Expression of intercellular cell adhesion molecule 1 and matrix metalloproteinase 9 in endometrium of pregnant mice with long-term exposure to low concentration of sevoflurane北大核心

BACKGROUND: Epidemiological studies have found that female workers who are exposed to waste sevoflurane for a long time have reduced fertility and increased incidence of abortion and fetal deformity. OBJECTIVE: To imitate the working environment of long-term exposure to waste sevoflurane and investigate the mechanism of embryo implantation disorder induced by low-concentration sevoflurane exposure by observing the expression of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 in endometrium of pregnant mice exposed to low concentrations of sevoflurane, attempting to provide a basis for clinical safe drug use and occupational protection and to lay a foundation for further research on the mechanism of inhalation anesthetics on embryo implantation at gene and molecular levels. METHODS: Forty female Kunming mice and sixteen male Kunming mice, aged 6 weeks, weighting (20±2) g, were caged separately. Forty female mice were randomly divided into experimental group and control group. Mice in the experimental group were exposed to 0.1% sevoflurane, 6 hours per day, while those in the control group were exposed to the air. Thirty days later, the female mice in estrus were caged with mature male mice at a rate of 2:1. Whether the female mice were pregnant was observed at 7:00 am on the second day after mating. The pregnant mice were kept independently in the original condition (n ≥ 8 pregnant mice in each group). Mouse uterus on day 4.5 of gestation was removed and sliced for histological observation. The expression of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 in endometrial tissue was detected by immunohistochemistry and statistically analyzed. The average integrated absorbance value of positive reactants was calculated. RESULTS AND CONCLUSION: In the experimental and control groups, 17 and 15 female mice were respectively found in estrus; 12 and 10 female mice respectively were found vaginal plugs after mating. Five and two female mice were found pseudopregnant on day 4.5 of gestation in the experimental and control groups, respectively. Therefore, there were 7 and 8 pregnant mice in the experimental and control groups, respectively, and the vacant value in the experimental group was replaced by the average value obtained in the same group, which would be subsequently used in the controlled trial. Immunohistochemical results showed that the endometrium (glandular epithelial cells, luminal epithelial cells and stromal cells) of all pregnant mice were positively stained brownish yellow, but the expressions of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 (0.019±0.007, 0.017±0.007, 0.015±0.005, 0.012±0.005) in the experimental group were significantly lower than those in the control group (0.032±0.014, 0.025±0.008, 0.021±0.007, 0.023±0.005) (P < 0.05). All these findings indicate that long-term exposure to 0.1% sevoflurane may affect the adhesion of mouse embryos to endometrium and the embryo implantation, which may be related to the inhibitory effects of sevoflurane on the expressions of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9, causing the imbalance in endometrial immunoregulation, the invasion of trophoblast cells into the endometrium and the inhibition of endometrial decidualization, and miscarriage and bleeding due to damaged vascular endothelium. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Huangqin decoction regulates autophagy to intervene with intestinal acute graft-versus-host disease in mice北大核心

BACKGROUND: How to use traditional Chinese medicine to intervene the imbalance of autophagy after intestinal mucosal barrier injury, so as to ultimately intervene the occurrence of gastrointestinal acute graft-versus-host disease, is an urgent problem to be solved after hematopoietic stem cell transplantation. OBJECTIVE: To verify the precise mechanism by which Huangqin Decoction interferes with acute intestinal graft-versus-host disease. METHODS: CB6F1 mice were randomly divided into normal control group, model control group, low-dose Huangqin Decoction group, medium-does Huangqin Decoction group and high-does Huangqin Decoction group, with 16 mice per group. CB6F1 mice in the model control group, low-dose Huangqin Decoction group, medium-does Huangqin Decoction group and high-does Huangqin Decoction group were infused with mononuclear cell suspension (bone marrow cell 8×107 + spleen cell 8×107) obtained from Balb/c mice via caudal vein within 4 hours after60Co whole body irradiation (radiation dose was 8 Gy). Different concentrations of Huangqin Decoction were given by gavage on the same day after modeling. The rats in the model control group and the normal control group were given the same volume of normal saline by gavage for 15 days. Eight hours after the last gavage, the small intestine tissues of six mice in each group were collected. PCR and western blot assay were used to detect the expression levels of LC3II/I, Beclin1 and P62. The pathological grading of small intestinal mucosa was scored by hematoxylin-eosin staining. The autophagic vesicle structure of small intestinal mucosal epithelial cells was observed by transmission electron microscope. The remaining 10 rats in each group (except the normal control group) were used to observe the clinical grading of acute graft-versus-host disease and record the survival time. RESULTS AND CONCLUSION: (1) After the application of Huangqin Decoction, the survival time of mice was significantly prolonged; the clinical acute graft-versus-host disease score was significantly decreased, and the pathological grading score of small intestinal mucosa was significantly decreased. The score of medium-does Huangqin Decoction group and high-does Huangqin Decoction group was significantly lower than that of model control group, but there was no significant difference between medium-does Huangqin Decoction group and high-does Huangqin Decoction group. (2) The LC3II/I and Beclin1 expression was significantly lower in the model control group than that in the normal control group (P < 0.01), and P62 expression was significantly higher than that in the normal control group (P < 0.01). Huangqin Decoction could promote the recovery of LC3II/I and Beclin1 levels and downregulate p62 levels (P < 0.01). (3) Under transmission electron microscope, the number of autophagic vesicles in the treatment group was significantly higher than that in the model control group, accompanied by the recovery of important organelles such as mitochondria. (4) The results confirm that by interfering autophagy related proteins, Huangqin Decoction can promote the recovery of autophagy in acute graft-versus-host disease, protect intestinal mucosal barrier and reduce intestinal rejection after transplantation and has promise as a new treatment for acute graft-versus-host disease. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Epidemiological analysis of femoral neck fractures in 179 patients based on the case data from the general hospital of Tianjin Medical University between 2013 and 2015北大核心

BACKGROUND: With an aging population increasing, the incidence of senile femoral intertrochanteric fractures is on a rise because of osteoporosis. Due to the aged usually accompanied with systematic diseases, conservative treatment will lead to high mortality after long-term bedridden. Thereafter, early surgery is recommended. OBJECTIVE: To investigate the incidence of femoral intertrochanteric fractures and its epidemiological features. METHODS: The digital radiography data and basic information of 179 patients (over 50 years of age) with femoral intertrochanteric fractures admitted in the General Hospital of Tianjin Medical University from 2013 to 2015 were analyzed retrospectively. The data including age, gender, injury causes, fracture types, complications, treatment procedures, and hospitalization time were recorded and compared. RESULTS AND CONCLUSION: All the 179 cases of femoral intertrochanteric fractures were enrolled, including 66 (36.9%) males and 113 (63.1%) females. The mean age was (76.98±9.73) years, and the number of patients aged 80-90 years was the most (n=71, 39.7%). With the age increasing, the incidence of fall-induced hip fractures was increased. By AO classification, type 31-A1 was the most common fracture type (46.4%), and type 31-A3 was the least common type (22.9%). By Evans classification, type I was the most common type (50.3%), and type V was the least common type (2.2%). There were 93.3% patients underwent surgical treatment (167/179), and 6.7% received conservative treatment (12/179). In the age group of 51-60 years, the male patients were more than females; in the age group 61-70 years, the male patients were more than females except in 2013; in the age groups of 71-80, and 81-90 years, the female patients were more than males; in the age group of over 90 years, there was no significant difference between female and male patients. These results manifest that the majority of hip fracture patients are the elderly, and slipping and osteoporosis are the leading causes. In spite of accumulating operative risks with aging, surgical treatment remains the predominant management strategy. Besides, the incidence of femoral intertrochanteric fractures shows a trend of increase yearly, with the highest incidence in the age group of 71-90 years, especially in females. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Diffuse distribution of bone cement in percutaneous vertebroplasty reduces the incidence of refracture of adjacent vertebral bodies北大核心

BACKGROUND: Percutaneous vertebroplasty is one of the effective treatments for osteoporotic vertebral compression fractures. The distribution of bone cement in the vertebral body will influence the clinical efficacy. OBJECTIVE: To investigate the influence of the distribution of bone cement in percutaneous vertebroplasty on the early postoperative outcomes after osteoporotic vertebral compression fractures. METHODS: A total of 132 patients, including 52 males and 80 females, with a mean age of (76.3±8.2) years who diagnosed as osteoporotic vertebral compression fractures in First Hospital of Shanxi Medical University from January 2017 to June 2019 were enrolled. All patients were divided into underdispersion group (n=54) and diffuse distribution group (n=78) according to the pattern of cement distribution on postoperative X-rays. Visual analogue scale scores postoperatively, the height of anterior edge and midline of injured vertebrae, Cobb angle of local kyphosis and the incidence of complications after 1-year follow-up were compared between the two groups. The trial was performed in accordance with the relevant ethical requirements for research in the First Hospital of Shanxi Medical University. RESULTS AND CONCLUSION: (1) The visual analogue scale scores were lower at 2 days, 1 and 6 months after operation than those before operation in the two groups (P < 0.05). The visual analogue scale scores at 1 month after operation in the underdispersion group were higher than those in the diffuse distribution group (P < 0.05), and there was no significant difference between the two groups at 2 days and 6 months after operation (P > 0.05). (2) Cobb angle and vertebral body height improved in both groups postoperatively compared to preoperatively (P < 0.05). The difference in Cobb angle and vertebral body height was not statistically significant between the two groups (P > 0.05). (3) The rate of bone cement infiltration was not significantly different between the two groups (P > 0.05). Incidence of recurrent fractures in adjacent vertebrae was lower in the diffuse distribution group than that in the underdispersion group (P < 0.05). (4) These findings confirm that percutaneous vertebroplasty is an effective treatment for osteoporotic vertebral compression fractures. The distribution of bone cement in the vertebral body will affect the surgical results. The bone cement is diffusely distributed, which may reduce the incidence of recurrent fractures in adjacent vertebrae. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Comparative study of traumatic heterotopic ossification in mice induced by Achilles tenotomy combined with skin burn injury and single Achilles tenotomy北大核心

BACKGROUND: At present, Achilles tenotomy model is an animal model mainly used for traumatic heterotopic ossification. However, this method requires a long time to form ectopic bone, and the size of the formed ectopic bone is always small. In addition, this method cannot accurately reproduce the systemic inflammatory state of most traumatic heterotopic ossification cases in clinic practice. OBJECTIVE: To verify the validity of the animal model of traumatic heterotopic ossification induced by Achilles tenotomy combined with skin burn injury, to compare this approach with single Achilles tenotomy, and to evaluate the practicability of the two methods. METHODS: Forty male C57BL/6 mice were randomly divided into two groups: Achilles tenotomy group (control group, n=20) and Achilles tenotomy+30% skin scald on the back group (experimental group, n=20). The survival rate and healing of surgical incisions of the mice in the two groups were recorded. Survival rate and wound healing in the two groups as well as skin recovery of burn injury in the experimental group were recorded. Micro-CT examination and Masson staining of the Achilles tendon was performed 8 weeks after surgery to observe the ectopic bone at the surgical site. Formation of ectopic bone was also observed in the two groups. RESULTS AND CONCLUSION: There was no death and wound infection in the two groups. The skin burn injury in the experimental group recovered well without ulceration. Micro-CT findings indicated that all mice in the experimental group developed traumatic heterotopic ossification, with obvious circular high-density shadow at the surgical site, and the volume of ectopic bone was (2.72±0.04) mm3. In contrast, only 17 mice developed traumatic heterotopic ossification in the control group, and the volume of ectopic bone was (0.65±0.08) mm3. There was a significant difference in the volume of ectopic bone between the two groups (P < 0.05). Masson staining showed that ectopic bone in both groups had bone trabecular and bone marrow structures, but the area of ectopic bone in the experimental group was significantly larger than that in the control group (P < 0.05). To conclude, Achilles tenotomy combined with skin burn injury can effectively induce traumatic heterotopic ossification earlier than single Achilles tenotomy in mice. This combination method has a higher successful rate and can produce larger size of ectopic bone, which can be an ideal method to establish an animal model of traumatic heterotopic ossification. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Impact of CCAAT enhancer binding protein α on the differentiation and apoptosis of acute myeloid leukemia HL60 cells

Objective To investigate the effect of CCAAT enhancer binding protein α(C/EBPα) on differentiation and apoptosis in the acute myeloid leukemia HL60 cells in vitro and in vivo and its possible mechanism. Methods The C/EBPα expression plasmid pEGFP-C/EBPα and empty control plasmid were respectively transfected into HL60 cells with cationic liposome as transfected group and empty plasmid transfected group, and untreated HL60 cells served as control group. The cells stably expressing the C/EBPα gene were obtained by G418 selection. The morphological changes were observed under light microscope following WrightGiemsa staining. MTT assay was employed to evaluate cell proliferation, and flow cytometry(FCM) was performed to analyze cell apoptosis. Meanwhile, the expression of c-myc was respectively detected by RT-PCR and Western blot both at the mRNA and protein level. Twenty BALB/c nude mice were divided into 3 groups in a completely randomized design: 7 mice in transfected group, 7 mice in empty plasmid transfected group and 6 in control group. Three kinds of cells including pEGFP-C/EBPα-HL60 cells, pEGFP -HL60 cells and the control HL60 cells were injected into mice separately through the subcutaneous. The mice were sacrificed at 20 d after injection. The mass and size of subcutaneous xenograft tumors were measured and the cell apoptosis of subcutaneous tumor were detected by TUNEL. Results The pEGFP-C/EBPα-HL60 cell line stably expressing the C/EBPα gene was screened out. Compared to either empty plasmid transfected group or control group, the expression of C/EBPα could promote cellular differentiation of HL60. FCM showed higher apoptotic rate in transfected group[ (21.9±4.5)%,P＜0.05 ] ,while (5.4±1.4)% in control group and (5.0±1.3)% in empty plasmid transfected group. c-myc expression was significantly down-regulated by C/EBPα both at the mRNA and protein level. The mass and size of tumors in transfected group were smaller than those in empty plasmid transfected group and control group [ (5.35±1.12)g and(25±4)mm in control group, (5.12±1.31)g and ( 18±3)mm in empty plasmid transfected group ,while (3.26±0.72)g and ( 11±2)mm in transfected group, all P＜0.05]. More apoptosis cells were found in subcutaneous tumor of transfected group(both P＜0.05). Conclusion C/EBPα can not only inhibit the proliferation, but also induce massive apoptosis of HL60 cells, meanwhile C/EBPα is a tumor suppressor of acute myeloid leukemia.     

植骨融合内固定修复连续双节段颈椎间盘突出症：钛网与椎间融合器的比较

BACKGROUND: Many studies have shown that different types of anterior cervical surgery in the treatment of two-level contiguous cervical disc herniation can obtain satisfactory results, but which method is the best has not yet reached a consensus. OBJECTIVE: To compare the efficacy and safety of three types of anterior cervical surgery for treating two-level contiguous cervical disc herniation.  METHODS: We retrospectively analyzed clinical data of 62 patients with two-level contiguous cervical disc herniation who underwent anterior decompression and fusion. These patients were assigned to three groups. Bone graft group received anterior cervical discectomy with autogenous iliac bone graft fusion. Titanium mesh group received anterior cervical corpectomy with titanium mesh fusion. Cage group received anterior cervical discectomy with cage fusion. Fusion rate of bone graft and improvement of neurological function (Japanese Orthopaedic Association Scores) were evaluated and compared after treatment in the three groups. Cervical vertebra anteroposterior and lateral images were used to measure height of anterior and posterior margin of vertebral body and Cobb angle changes of fusion segment. RESULTS AND CONCLUSION: All 62 patients were followed up and the follow-up time was ranged from 8 to 30 months. Operation time was significantly longer in the bone graft group than in the titanium mesh and Cage groups (P < 0.05). Intraoperative blood loss was larger in the bone graft group than in the titanium mesh and Cage groups (P < 0.05). Japanese Orthopaedic Association Scores were significantly improved after treatment (P < 0.05). No significant difference was found at different time points (P > 0.05). The fusion rate of bone graft was higher in the bone graft group than in the titanium mesh and Cage groups (P < 0.05) at 3 months after treatment, and bone union was found in the final follow-up. Height of anterior and posterior margin of vertebral body was significantly increased after treatment (P < 0.05). No significant difference in the increase of the height of anterior margin was detected among the three groups (P > 0.05). The increase in the height of posterior margin was higher in the Cage group than in the bone graft group and titanium mesh group (P < 0.05). Vertebral height loss of the anterior margin was higher in the bone graft group than in the titanium mesh and Cage groups, but vertebral height loss of the posterior margin was highest in the bone graft group, followed by titanium mesh group and Cage group at 3 months after treatment (P < 0.05). The increase value of Cobb angle was higher in the titanium mesh group than in the bone graft group and Cage group (P < 0.05). At 3 months after treatment, the altered value of Cobb angle was highest in the bone graft group, followed by titanium mesh group and Cage group (P < 0.05). No significant difference in the height of anterior and posterior margins of the vertebral body and Cobb angle was detectable between final follow-up and 3 months post-treatment (P > 0.05). These findings indicated that the three kinds of fusion method for treating two-level contiguous cervical disc herniation could obviously lessen nervous systems and improve cervical vertebra functions. In the bone graft group, operation time was long. Intraoperative blood loss was more. Postoperative height loss of the posterior margin of the vertebral body was visible. Cervical lordosis could be easily induced. Compared with the bone graft group, titanium mesh and Cage groups could better maintain the height and curvature of the cervical vertebra, but the Cage group had apparent advantages.  中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程      

青少年男子体操运动员主要关节的等速肌力特征

BACKGROUND: The gymnastic skill training of juveniles tends to be scientific and systematic, such as confirming the strength characteristics of joints and muscles and implementing training program pertinently based on the scientific diagnostic method. OBJECTIVE: To explore the isokinetic muscle strength characteristics of the trunk, hips and knees in juvenile male gymnasts. METHODS: Sixteen juvenile male gymnasts who were active athletes in Liaoning province were enrolled. ISOMED2000 isokinetic muscle strength test system was used to detect the muscle strength, and the test speed of trunk set as 30, 60 and 180 (°)/s, while 60, 180 and 300 (°)/s for the hips and knees. RESULTS AND CONCLUSION: At 30, 60 and 180 (°)/s, the hamstring/quadriceps ratio of trunk were 91.36±1.25, 87.77±3.74 and 78.20±4.70, respectively. At 60, 180 and 300 (°)/s, the hamstring/quadriceps ratio of the left hip was 65.55±4.38, 66.92±3.22 and 68.18±2.82, while that of the right hip were 57.40±4.43, 65.73±1.07 and 64.15±5.55. Additionally, the left flexor strength was significantly higher than that of the right, while the right extensor strength was significantly higher than that of the left at 60 (°)/s (P < 0.05). At 60, 180 and 300 (°)/s, the hamstring/quadriceps ratio was 50.88±4.98, 54.75±4.51 and 58.80±7.93 for the left knee, and 51.55±4.30, 55.20±5.08 and 58.43±5.93 for the right knee. In three test speeds there were no significant differences in flexor and extensor strength between two sides (P > 0.05). These results indicate that the rapid strength of the back especially of the flexor is insufficient markedly, and the basic strength of the extensor is weak. The basic strength of the left flexor in the hip is large, the same as the right extensor; the rapid strength of flexor is weak, and imbalance in the muscle strength between two sides appears. Fortunately, the muscle strength of the knee between two sides achieves balance, but there is still a certain deficiency in the rapid strength of the left flexor and the basic strength of the extensor on both sides. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

红花多糖对小鼠Lewis肺癌移植瘤生长及转移的影响

Objective To investigate the inhibitory effects of safflower polysaccharide (SPS) on tumor growth and metastasis of T739 mice transplanted with Lewis lung carcinoma cells, then explore the anti-tumor mechanism of action. Methods The xenografts derived from Lewis lung carcinoma cells were established in T739 mice. Inoculated mice were randomly divided into control group, low dose SPS group, moderate dose SPS group and high dose SPS group, daily oral administration, a total of 28 times. Tumor volume and weight were measured and lung metastatic foci of the mice were observed under microscope. MTT assay was used to investigate both the inhibitive effect of SPS on Lewis lung carcinoma cells and the influence on proliferation of T lymphocytes. Results There was no inhibitory effect of SPS on Lewis lung carcinoma cells in vitro. In vivo, SPS could promote proliferation of T lymphocytes and inhibit tumor growth and metastasis. There were significant differences when comparing the SPS groups with control group in terms of the volume, weight and lung metastatic foci of the transplanted tumor ( P ＜ 0.05 ). Conclusion SPS could inhibit the tumor growth and metastasis.The anti-tumormechanism of action was about related to increase the immunological function of mice.[Key words] Safflower Polysaccharide; Lewis lung carcinoma; Transplanted tumor; Lung metastatic     

骨桥蛋白对人膝骨关节炎软骨细胞透明质酸表达的影响

BACKGROUND: Both osteopontin and hyaluronic acid involve in the pathological process of osteoarthritis, resulting in the abnormal expression levels of various cytokines and enzymes. However, the relationship between the high expression of osteopontin and hyaluronic acid in chondrocytes remains unclear. OBJECTIVE: To investigate the effect of osteopontin on the expression of hyaluronic acid in human knee osteoarthritic chondrocytes in vitro by modulating the level of osteopontin. METHODS: Chondrocytes from human knee osteoarthritic cartilage were cultured in vitro, and were then divided into three groups: blank control group without any treatment; osteopontin group and and pontin siRNA group were treated with 1 mg/L recombinant human osteopontin and osteopontin siRNA, respectively. Expression levels of osteopontin, hyaluronic acid synthase 1, 2 and 3 mRNA were detected by real-time PCR, and the levels of hyaluronic acid were measured using ELISA. RESULTS AND CONCLUSION: Compared with the blank control group, the mRNA expressions of hyaluronic acid synthase 1, 2 and 3 were remarkably increased in the osteopontin group, while siRNA made the significantly inhibitory effects on the hyaluronic acid synthase 1, 2 and 3 mRNA expressions (P < 0.05). The level of hyaluronic acid in chondrocytes in the osteopontin group was significantly higher than that in the other two groups (P < 0.05). Our results suggest that osteopontin induces the synthesis of hyaluronic acid in osteoarthritic chondrocytes through upregulating the hyaluronic acid synthases expression levels. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.