Interstitial deletion of the short arm of chromosome 1: attempt to establish a clinical phenotype (46,XX,del (1)(p22p32))

A girl with a de novo interstitial deletion of the short arm of chromosome 1 (46,XX,del (1)(p22p32) is described with moderate developmental delay and minor phenotypic abnormality. These clinical manifestations are compared to previously reported patients with interstitial deletion of chromosome 1, in an attempt to identify a clinical phenotype which seems quite different from the syndrome linked to more terminal deletion of chromosome 1p, and perhaps from more proximal 1p deletion phenotype.     

Communication with close and distant relatives in the context of genetic testing for hereditary breast and ovarian cancer in cancer patients

The psychological aspects of genetic testing for hereditary breast and ovarian cancer (HBOC) in cancer patients (diagnostic genetic testing) have so far received less attention than predictive genetic testing in unaffected persons. Our study is aimed at gaining insight into the psychological aspects of diagnostic genetic testing and at formulating practical recommendations for counseling. Cancer patients often play a key role in the communication of information to relatives because they were the first individuals to be tested in the family. The present article focuses on the communication to close and distant relatives about the hereditary cancer, the genetic test and its result. Participants previously diagnosed with breast and/or ovarian cancer, with a family history of these cancers and who requested DNA-testing, were eligible for the study. Of the 83 eligible patients who could be contacted, 63 participated (response rate = 76%). Twenty-six participants were members of a family where a BRCA1 or BRCA2 mutation was detected. The DNA-analysis in the family of 37 participants had not revealed any mutation. Data were collected by semi-structured interviews and psychological tests and questionnaires. The dissemination of information was largely focused on first-degree relatives. Communication to distant relatives about the genetic test and its result was problematic. Other than the genetic test result and age as "objective" predictors of informing distant relatives, little and/or superficial contact seemed to be the major subjective barrier to informing distant relatives. Furthermore, the knowledge about HBOC of these messengers reveals several shortcomings. Communication within the family should receive special attention during counseling.     

Pneumolysin released during Streptococcus pneumoniae autolysis is a potent activator of intracellular oxygen radical production in neutrophils

Streptococcus pneumoniae is a major cause of otitis media, pneumonia, meningitis, and septicemia in humans. The host defense against this pathogen largely depends on bacterial killing by neutrophils. A peculiar property of pneumococci is their tendency to undergo autolysis, i.e., autoinduced disruption of the bacterial cell wall mediated by activation of the enzyme LytA, under stationary growth conditions. LytA is a virulence factor, but the molecular background for this has not been fully clarified. Here we examine how bacterial compounds released upon autolysis affect the production of reactive oxygen species (ROS) in neutrophils. We found that the S. pneumoniae strains A17 and D39 induced activation of the NADPH oxidase and the production of ROS in human neutrophils and that this activation was blocked when LytA was inactivated. The ROS-inducing bacterial substance released from autolyzed bacteria was identified as the cytoplasmic toxin pneumolysin. Further screening of clinical pneumococcal strains of various sero- and genotypes revealed that selected strains expressing toxins with reduced pneumolysin-dependent hemolytic activity had decreased abilities to induce ROS in neutrophils. Furthermore, a mutated form of purified pneumolysin lacking hemolytic and complement binding functions (PdT) did not induce any oxygen radical production. The ROS produced in response to pneumolysin formed mainly intracellularly, which may explain why this production was not detected previously. ROS released intracellularly may function as signaling molecules, modifying the function of neutrophils in bacterial defense.     

Molecular dipstick test for diagnosis of sleeping sickness

Human African trypanosomiasis (HAT) or sleeping sickness is a neglected disease that affects poor rural populations across sub-Saharan Africa. Confirmation of diagnosis is based on detection of parasites in either blood or lymph by microscopy. Here we present the development and the first-phase evaluation of a simple and rapid test (HAT-PCR-OC [human African trypanosomiasis-PCR-oligochromatography]) for detection of amplified Trypanosoma brucei DNA. PCR products are visualized on a dipstick through hybridization with a gold-conjugated probe (oligochromatography). Visualization is straightforward and takes only 5 min. Controls both for the PCR and for DNA migration are incorporated into the assay. The lower detection limit of the test is 5 fg of pure T. brucei DNA. One parasite in 180 microl of blood is still detectable. Sensitivity and specificity for T. brucei were calculated at 100% when tested on blood samples from 26 confirmed sleeping sickness patients, 18 negative controls (nonendemic region), and 50 negative control blood samples from an endemic region. HAT-PCR-OC is a promising new tool for diagnosis of sleeping sickness in laboratory settings, and the diagnostic format described here may have wider application for other infectious diseases.     

HRAS-related epidermal nevus syndromes: Expansion of the spectrum with first branchial arch defects

Epidermal nevus syndrome (ENS) comprises a heterogeneous group of neurocutaneous syndromes associated with the presence of epidermal nevi and variable extracutaneous manifestations. Postzygotic activating HRAS pathogenic variants were previously identified in nevus sebaceous (NS), keratinocytic epidermal nevus (KEN), and different ENS, including Schimmelpenning–Feuerstein–Mims and cutaneous-skeletal-hypophosphatasia syndrome (CSHS). Skeletal involvement in HRAS-related ENS ranges from localized bone dysplasia in association with KEN to fractures and limb deformities in CSHS. We describe the first association of HRAS-related ENS and auricular atresia, thereby expanding the disease spectrum with first branchial arch defects if affected by the mosaic variant. In addition, this report illustrates the first concurrent presence of verrucous EN, NS, and nevus comedonicus (NC), indicating the possibility of mosaic HRAS variation as an underlying cause of NC. Overall, this report extends the pleiotropy of conditions associated with mosaic pathogenic variants in HRAS affecting ectodermal and mesodermal progenitor cells.     

Action of some hypoglycaemic sulphonylureas on the oxygen consumption of isolated pancreatic islets of mice

Summary Cartesian divers were used to evaluate the effects in vitro of some hypoglycaemic Sulphonylureas on the oxygen consumption of isolated pancreatic islets. The islet specimens were obtained from obese-hyper-glycaemic mice, and consisted of over 90% B-cells. When incubated with Krebs-Ringer phosphate medium, the islet cells displayed an increased rate of respiration upon addition to the incubation medium of either tolbutamide (D860; 0.1 mg/ml) or glibenclamide (HB 419; 0.1 .g/ ml). The respiratory rate increased with the concentration of HB 419 in the range 0.001–0.1 g/ml, but did not exceed 120% of the respiration in pure phosphate medium. Whereas the physiological excretion product of D 860 did not affect the respiratory rate, the corresponding derivative of HB 419 was still effective in stimulating the oxygen uptake of the islets. When islets were incubated with glucose at a high concentration (3 mg/ml), the oxygen uptake was inhibited by addition of D 860, or its metabolite, or HB 419. The last drug slightly increased the respiration of islets incubated with glucose at a concentration of 1 mg/ml, and a marked stimulation was noted at a still lower glucose concentration, 0.5 mg/ml. Attempts to evaluate the effect of mannoheptulose on the respiratory response of the islets to hypoglycaemic Sulphonylureas produced inconclusive results. It is suggested that Sulphonylureas effect an increased rate of endogenous substrate oxidation in the B-cells of the pancreatic islets.This work was supported by the Swedish Medical Research Council (B68-12X-109-04) and the U.S.Public Health Service (Grant AM-05759-06). The skilful technical assistance of Miss Gunilla Lekselius and Miss Ing-Britt Brolen is greatfully acknowledged.     

Cytokines,matrix metalloproteinases and tissue inhibitor of metalloproteinases‐1 in gingival crevicular fluid from patients with Papillon‐Lefèvre syndrome

The aim of the present study was to compare concentrations of cytokines, matrix metalloproteinases (MMPs) and a metalloproteinase inhibitor (TIMP‐1) in gingival crevicular fluids (GCF) from sites with gingival inflammation in 28 young patients with Papillon‐Lefèvre syndrome (PLS), and in age‐ and gender‐matched controls. Each group consisted of 17 females and 11 males with a mean age of 11.0 years (range 4–22 years). In both groups, anterior upper sites with a clinical diagnosis of gingival inflammation and with pockets ≤3?mm were selected for sampling of GCF, which was carried out with filter disks inserted into the gingival crevice until saturated. The concentrations of cytokines (IL‐1α, IL‐1β, TNF‐α, and IL‐8), matrix metalloproteinases (MMP‐1, MMP‐3, MMP‐8, and MMP‐9), and their tissue inhibitor (TIMP‐1) were analysed using commercial ELISA kits. Significantly higher levels of IL‐1β (P?P?P?P?P?相似文献   

Erythropoiesis and Carbon Monoxide Production in Hodgkin''s Disease

Endogenous production of carbon monoxide (VCO), red cell survival and iron kinetics were studied in 15 subjects with Hodgkin's disease. The subjects were divided into two groups, namely: eight patients with anaemia (group A, haemoglobin (Hb) concentration less than 11.5 g/dl) and seven patients without anaemia (group B, Hb concentration greater than 11.5 g/dl). Red cell survival was not significantly different in the two groups being 91 +/- 40 days (mean +/- 1 SD) in group A and 111 +/- 54 days in group B. Relative VCO (mumol/mmol total body haem (TBH/d) was, however, significantly higher (0.01 greater than P greater than 0.001) in group A (20.7 +/- 4.7) compared to group B (12.0 +/- 3.8). When absolute VCO (mumol/d) was compared to the daily turnover of circulating red cell haemoglobin haem (Vhaem-c), the VCO/Vhaem-c quotient was 2.1 +/- 0.9 in group A and 1.2 +/- 0.3 in group B. Erythron turnover of iron (ET, mumol Fe/mmol TBH/d) was calculated through subtraction of the non-erythron turnover (NET) from the total plasma iron turnover (PIT). ET was significantly higher (0.05 greater than P greater than 0.01) in group A (39 +/- 21) than in group B (20 +/- 8). The conclusion drawn from the finding of significant increases in VCO and ET without and concomitant significant decrease in red cell survival in the anaemia group is that ineffective erythropoiesis, i.e. bone marrow haemolysis, seems to play an important role in the anaemia of Hodgkin's disease.     

Carbon Monoxide Production in Patients with Breast Carcinoma

Total haem catabolism has been studied through measurement of endogenous production of carbon monoxide (VCO) in 19 patients treated for breast carcinoma. The subjects were divided into three groups. Group A included six patients with haemoglobin (Hb) concentration greater than 11.5 g/dl and considered free from disease. Group B consisted of seven patients with distant metastases and Hb concentration greater than 11.5 g/dl and group C of six patients with distant metastases and anaemia (Hb concentration less than 11.5 g/dl). VCO in group A was 10.3 +/- 3.7 (mean +/- 1 SD) and in group B 9.0 +/- 2.5 mumol/mmol total body haem (TBH)/d. These values are not different from our normal values of 10.8 +/- 2.8 mumol/mmol TBH/d. In group C VCO was 21.1 +/- 3.1 (an increase of 100%). VCO was compared to daily catabolism of circulating red cell haemoglobin haem (Vhaem-c) in the VCO/Vhaem-c quotient. Vhaem-c was calculated from total circulating red cell haemoglobin haem (TBHb-c) and red cell survival. In group A and group B this quotient was 1.3 +/- 0.6 and 1.1 +/- 0.2, respectively, and in group C was 2.5 +/- 0.9. The difference between group A and B on one side and group C on the other side was significant (P less than 0.001). The 'extra' CO produced in patients with anaemia and disseminated disease (group C) was thought to originate from increased turnover of bone marrow haem, reflecting considerable ineffective erythropoiesis with destruction of haemoglobinized immature red cells. The results confirm earlier findings of a high VCO/Vhaem-c quotients in patients with anaemia secondary to Hodgkin's disease.