Suppressed type 1, type 2, and type 17 cytokine responses in active tuberculosis in children

Type 1 cytokine responses are known to play an important role in immunity to tuberculosis (TB) in children, although little is known about other factors that might be important. In addition, children are more prone to developing extrapulmonary manifestations of TB than adults. To identify the immune responses important both in control of infection and in extrapulmonary dissemination, we examined mycobacterium-specific cytokine responses of children with pulmonary TB (PTB) and extrapulmonary TB (ETB) and compared them with those of healthy control children (HC). No significant differences were found in the cytokine responses either with no stimulation or following mycobacterial-antigen (Ag) stimulation between children with PTB and ETB. On the other hand, children with active TB compared with HC showed markedly diminished production of type 1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), 2 (interleukin 4 [IL-4] and IL-13), and 17 (IL-17A, IL-21, and IL-23)-associated cytokines with no stimulation and in response to mycobacterial antigens. This was not associated with significantly altered production of IL-10 or transforming growth factor β (TGF-β). Among children with ETB, those with neurologic involvement exhibited more significantly diminished Ag-driven IFN-γ and IL-17 production. Pediatric TB is characterized by diminished type 1, 2, and 17 cytokine responses, with the most profound diminution favoring development of neurologic TB, suggesting a crucial role for these cytokines in protection against pediatric tuberculosis.     

Autoimmunity and clinical course in children with type 1, type 2, and type 1.5 diabetes

AIMS: Both type 1 (T1D) and type 2 diabetes (T2D) are increasing in incidence in children; often an admixture of T1D and T2D features are present at diagnosis. We examined the relationship between diabetes autoantibodies (DAA), human leukocyte antigen (HLA), and clinical course in subjects grouped by clinical diabetes type. METHODS: Subjects 8-18 years old with T1D, T2D, and mixed clinical features (T1.5D), were studied at diagnosis. DAA were measured in all subjects; a subset of subjects underwent HLA genotyping. Clinical course was followed in 84% of subjects for 47.9+8.7 months. RESULTS: Eighty-nine percent of T1.5D subjects were positive for at least one DAA; 88% of HLA-typed subjects had risk HLA genotypes. Two subjects initially treated with oral agents were subsequently treated with insulin (50%); one had risk HLA, and the other was DAA positive. Thirty-three percent of T2D subjects were DAA positive and 93% were treated with oral agents at diagnosis. Three subjects were subsequently treated with insulin (21%); of these, two were DAA positive, and one had risk HLA. No subject who remained on diet therapy or oral agents had a combination of DAA-positivity and risk HLA genotype. CONCLUSIONS: Children clinically classified with T1.5D or T2D have a high frequency of autoimmune markers and T1D-associated HLA alleles which appears to indicate a more aggressive diabetes disease process, as has been shown for DAA-positive adults with phenotypic T2D.     

Expression of type 1 and type 2 mucins in colonic epithelial tumors

Expression of MUC-1 and MUC-2 was investigated with immunohistochemical staining (PAP-method) in 5 cases of adenomas and in 60 cases of colorectal adenocarcinomas. The expression of MUC-1 and MUC-2 can be useful for diagnosis and prognosis in patients with colorectal carcinoma.     

Manipulating the type 1 vs type 2 balance in type 1 diabetes

Virus infections cause a strong inflammatory reaction that is dominated by the expression of type 1 cytokines and chemokines. Such an aggressive immune response by the host is necessary to eliminate intracellular pathogens. However, because of this shift in the type 1 vs type 2 balance of the immune response, virus infections are potential candidates for triggering autoimmune diseases, such as type 1 diabetes (T1D), herpes stromal keratitis, or multiple sclerosis (MS). In this review we will focus on the pathogenesis of T1D in a virus-induced transgenic mouse model and discuss possibilities of how an aggressive type 1-dominated immune response can be restrained and autoimmunity be abrogated.     

Meniscus cells seeded in type I and type II collagen-GAG matrices in vitro.

The objective of this study was to determine the proliferative and biosynthetic activity of calf meniscus cells seeded in type I and type II collagen-glycosaminoglycan (GAG) copolymers with the overall goal to develop a cell-seeded implant for future investigations to improve the regeneration of the knee meniscus. The cell-seeded matrices were digested in protease and analyzed for GAG by a modification of the dimethyl-methylene blue method and assayed for DNA content. Other specimens were evaluated histologically after 1, 7, 14 and 21 days. Contraction of the same types of matrices, seeded with adult canine meniscus cells, was measured at the same time points. After three weeks, cells were observed throughout the type II matrix, whereas the type I matrix was densely populated at the margins. The cell morphology and the cell density after three weeks in both matrices was consistent with the normal meniscus. DNA assay for the type I matrix showed a 40% decrease over the first week and a final amount of DNA that was not significantly different from the initial value, whereas the type II matrix doubled its DNA content over the same time period. The cells continued their biosynthesis of GAG and type I collagen. GAG content of the type II matrix increased by 50% more than the type I matrix after three weeks. Over the same time period, the type I matrix displayed a significant shrinkage to approximately 50% of its initial value whereas in contrast, the type II matrix and the unseeded controls showed no significant shrinkage. The number of cells and the higher GAG synthesis in the type II matrix, and its resistance to cell-mediated contracture, commend it for future investigation of the regeneration of meniscus in vivo.     

The location and distribution of type A and type B atrial endings in cats

Summary In the attempt to explain the difference in discharge pattern of atrial endings, 131 endings were localized by punctate stimulation, 44 were type A, 77 type B and 10 of an intermediate type. All were located on the dorsal wall of the atria with none on the ventral wall or in the appendage. On the right side, 74% of type A were located in the atria and 63% of type B in or near the veins. On the left side, 67% of type A and 94% of type B were located in or near the veins. Thus, there appeared to be some difference in the location of type A and type B endings on the right side, but on the left side both types of endings were for the most part confined to the venous region. Further, on both right and left sides, these endings were present both in the central part of the atria and in or adjacent to veins. This leads to the suggestion that the difference in discharge patterns is not caused by the location but may be due to some other reasons, e. g. difference of arrangement in the atrial wall with respect to the contractile elements.     

A comparison of bezafibrate and clofibrate in type II B and type IV hyperlipoproteinemia

In 36 patients with primary hyperlipoproteinemia of type II B or IV the effect of bezafibrate, a new derivate of clofibrate, has been compared with the effect of clofibrate. In an open cross-over-study the effect of 1.5 g clofibrate p.d. has been compared with that of 450 mg bezafibrate p.d. for several months. The effect of bezafibrate on plasma triglyceride concentration and plasma cholesterol concentration was more pronounced than that of clofibrate. This difference was statistically significantly only in the concentration of plasma triglycerides of type IV patients. It is obvious that the difference between bezafibrate and clofibrate would have been more pronounced if the dose of bezafibrate had been in the optimal range. Serious side-effects caused by bezafibrate could not be observed.     

Differences in anger,hostility, and interpersonal aggressiveness in type A and type B adolescents

This study investigated self-reported anger, hostility, interpersonal aggressiveness, and self-confidence in 19 Type A and 11 Type B adolescent boys ages 15 and 16. It was hypothesized that Type As would report greater trait anger and aggressiveness, less confidence in interpersonal relating, and would endorse a pattern of expression of anger and aggressiveness that would differ from Type Bs. No significant differences were found between Type As and Type Bs on measures of global anger and aggressiveness, and no significant relationship between interpersonal hostility and self-confidence was demonstrated. Type As, however, were found to be more likely than Type Bs to report that they lose their temper and that they act in physically aggressive, verbally aggressive, and passive aggressive ways. Results were discussed in terms of the similarity of this pattern in Type A adolescent boys to that described for adult Type A men. © 1998 John Wiley & Sons, Inc. J Clin Psychol 54: 945–952, 1998.     

Interaction between collagen type I and type III in conditioning bundles organization.

Type I and type III collagen extracted from skin was purified by differential salt precipitation and chromatography. By heating to 37 degrees, type I formed after a lag phase a floppy and opalescent gel of high optical density and type III formed more rapidly a translucent and rigid gel of low optical density. Addition of type III to type I resulted in formation of gels of reduced optical density and lag phase related to the proportion of type III added. Phase contrast and scanning electronmicroscopy demonstrated the formation of thick bundles of type I, thin fibers of type III and bundles of intermediate size related to the proportion of type III. The relationship between collagen type and bundle architecture might prove most significant in conditioning the mechanical properties of the connective tissues in normal and pathological conditions.     

Long-term follow-up of renal transplantation in type 1 and type 2 diabetic patients

Summary This study evaluated the long-term outcome of renal transplantation in type 1 (n=25) and type 2 (n=18) diabetic patients. Overall postoperative survival at 1 year was 69% in type 1 diabetes and 75% in type 2; at 5 years it was 62% in type 1 diabetes and 58% in type 2. Death was due mainly to cardiovascular disease (60%) and septic gangrene (20%). Outcome was examined in terms of graft function, which was poor in the majority (86%) of patients who died. Patients with fatal outcome suffered major vascular complications prior to renal transplantation and frequently had impaired graft function. Metabolic control was better in patients with good graft function (HbA_1c < 6.2%) than in those with poor or no function of kidney transplant (HbA_1c > 9.8 %). In the absence of severe vascular complications renal transplantation may be the treatment of choice for both type 1 and type 2 diabetic patients with end-stage renal disease. Otherwise, renal transplantation is not able to improve the prognosis of patients with a history of severe vascular complications prior to renal replacement therapy.Abbreviations IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - ESRD end-stage renal disease - MI myocardial infarction     

实验性肝纤维化中I,III型胶原的形态学观察

Rats receiving intravenous injection of human albumin (4 mg/rat) once biweekly developed liver fibrosis. The lesion seemed to have little relation to hepatocellular injury. The incidence of liver fibrosis increased with the length of immunization, ranging 80%-86% after 30-60 days. The whole process of experimental liver fibrosis may be divided into three phases. The first is the initial stage of fibroplasia (from the first day to the time of 15 days after start of immunization). In this phase, Ito cells were activated and collagen type I and type III began to increase. The second is the activated stage of fibroplasia (from the 15th to the 60th day after the beginning of immunization), in which collagen type I and type III reached the maximum and myofibroblasts as well as 'transitional cells' proliferated with deposition of collagen fibers. The third phase is the stage of post-fibroplasia (the period after elimination of immunization). Collagen type III diminished gradually while collagen type I remained increasing. Our findings indicated that fibroplasia occurs at the very beginning of liver injury. This suggest that treatment of liver fibrosis must be considered simultaneously with treatment of acute hepatitis.     

Aberrant type I and type III collagen gene expression in human breast cancer in vivo

Increased synthesis and degradation of extracellular matrix components are associated with breast cancer development. This study evaluated type I and type III procollagen mRNA expression and the corresponding protein synthesis and maturation, as well as the tissue distribution of these collagens, in benign breast lesions, infiltrating ductal carcinomas, and their metastases by in situ hybridization and immunohistochemistry. In the benign lesions, the type I and type III collagen bundles were regularly organized and the expression of the corresponding mRNA was weak, indicating a relatively slow collagen turnover. In the malignant tumours, increased expression of type I and type III procollagen mRNAs was observed in the fibroblastic cells of the stroma; the malignant epithelial cells did not participate. The staining of corresponding newly-synthesized pN-collagens showed aberrant bundles in the invasive front of the malignant tumours. Newly-synthesized type I and type III procollagens were occasionally observed in fibroblastic cells, particularly in grade 2 and grade 3 tumours. Metastases of breast carcinoma resembled poorly differentiated primary tumours with respect to their collagen synthesis and deposition. The increased synthesis of fibrillar type I and type III procollagens may serve as a pathway for tumour invasion. The enhanced synthesis is associated with the formation of aberrant collagen bundles, which may be more readily degradable and may thus facilitate breast tumour invasion.     

Immunofluorescent assay of herpesvirus type 1 and type 2 antibodies in rabbit and human sera

Summary The immunofluorescent antibody technique was used to assay type-specific herpes simplex virus antibodies. Antibody responses were studied in three groups of patients: children with primary herpetic infections, neonates with generalized type 2 infection and adults with genital herpes infections. The results were compared with antibody responses seen in rabbits after experimental type 1 and 2 infections. In both rabbits and children with primary herpetic infections there was considerable cross-reaction, while in patients with genital herpes infections and in neonates there was very little cross-reaction.Preliminary report of this work was presented at the XVI Scandinavian Congress for Pathology and Microbiology, Reykjavik, Iceland 25–27 June 1970.     

Relation between sense of coherence and glycemic control in type 1 and type 2 diabetes

In this study, the authors examined the relation between glycemic control and sense of coherence (SOC) and the mediating role of psychological distress and of adherence to self-care behaviors in 67 people with type 1 and type 2 diabetes. In addition, 29 individuals without any chronic disease composed a control group. The authors determined glycemic control by glycosylated hemoglobin (HbA1c) measures. The participants answered a questionnaire that included questions about medical data, an adherence to self-care behaviors inventory, Derogatis' Brief Symptoms Inventory, and Antonovsky's SOC scale. People with diabetes showed higher levels of psychological distress than matched controls, but similar SOC scores. A path analysis revealed that SOC was indirectly related to glycemic control, through adherence to self-care behaviors and psychological distress. Adherence did not mediate the effect of psychological distress on glycemic control In addition, the type of diabetes of the subject was directly related to glycemic control. The model explained 38% of the variance of glycemic control. The results suggest a possible role of SOC in the psychological and physical wellbeing of people with diabetes. SOC should constitute a focus of further research, particularly studies of possible psychological intervention to enhance SOC in people with diabetes.     

Creatine kinase MB and citrate synthase in type I and type II muscle fibres in trained and untrained men

Summary Total creatine kinase (CK), creatine kinase MB (CK-MB) and citrate synthase (CS) were determined in isolated and pooled type I and type II skeletal muscle fibres. Determinations were made on biopsies from 3 sedentary men, 3 junior cyclists and 2 elite cyclists. CS and CK-MB activities were higher in the trained groups in both fibre types. The total CK activity was not related to training status, although it was lower in type I fibres than in type II fibres (p<0.05). The reverse relation was observed for CS and CK-MB activities (p<0.01). The ratio of type I/type II for CS was not related to training status, while the corresponding ratio for CK-MB increased with a greater degree of endurance training. For a given increase in CS activity, the increase in CK-MB activity was greater in type I fibres than in type II fibres (p<0.01). Thus, with endurance training there seems to be a specific adaptation for CK-MB, particularly in type I fibres.     

Differences in virus receptor for type I and type II feline infectious peritonitis virus

Summary.  Feline infectious peritonitis viruses (FIPVs) are classified into type I and type II serogroups. Here, we report that feline aminopeptidase N (APN), a cell-surface metalloprotease on the intestinal, lung and kidney epithelial cells, is a receptor for type II FIPV but not for type I FIPV. A monoclonal antibody (MAb) R-G-4, which blocks infection of Felis catus whole fetus (fcwf-4) cells by type II FIPV, was obtained by immunizing mice with fcwf-4 cells which are highly susceptible to FIPV. This MAb also blocked infection of fcwf-4 cells by type II feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible gastroenteritis virus (TGEV). On the other hand, it did not block infection by type I FIPVs. MAb R-G-4 recognized a polypeptide of relative molecular mass 120–130 kDa in feline intestinal brush-border membrane (BBM) proteins. The polypeptide possessed aminopeptidase activity, and the first 15 N-terminal amino acid sequence was identical to that of the feline APN. Feline intestinal BBM proteins and the polypeptide reacted with MAb R-G-4 (feline APN) inhibited the infectivity of type II FIPV, type II FECV, CCV and TGEV to fcwf-4 cells, but did not inhibit the infectivity of type I FIPVs. Accepted January 19, 1998 Received November 17, 1997     

Ionic currents underlying difference in light response between type A and type B photoreceptors

In Hermissenda crassicornis, the memory of light associated with turbulence is stored as changes in intrinsic and synaptic currents in both type A and type B photoreceptors. These photoreceptor types exhibit qualitatively different responses to light and current injection, and these differences shape the spatiotemporal firing patterns that control behavior. Thus the objective of the study was to identify the mechanisms underlying these differences. The approach was to develop a type B model that reproduced characteristics of type B photoreceptors recorded in vitro, and then to create a type A model by modifying a select number of ionic currents. Comparison of type A models with characteristics of type A photoreceptors recorded in vitro revealed that type A and type B photoreceptors have five main differences, three that have been characterized experimentally and two that constitute hypotheses to be tested with experiments in the future. The three differences between type A and type B photoreceptors previously characterized include the inward rectifier current, the fast sodium current, and conductance of calcium-dependent and transient potassium channels. Two additional changes were required to produce a type A photoreceptor model. The very fast firing frequency observed during the first second after light onset required a faster time constant of activation of the delayed rectifier. The fast spike adaptation required a fast, noninactivating calcium-dependent potassium current. Because these differences between type A and type B photoreceptors have not been confirmed in comparative experiments, they constitute hypotheses to be tested with future experiments.