The histocompatibility antigens in patients with Beh?et's disease.

Twenty-one patients with Beh?et's disease were typed for HLA antigens. The controls were 50 subjects randomly chosen from a local population and 24 apparently healthy subjects of the same ethnic groupings as those of the patients. The study revealed significant differences in the frequencies of various antigens in the above three groups, the most obvious of them related to HLA-B5 and HLA-Bw35, HLA-B5 was demonstrated in 71% of the patients as compared with 18% in the local population group and 12.5% in the ethnically related healthy subjects. The incidences of HLA-Bw35 were 66.7%, 32% and 37.5% respectively. In 86% of the patients, at least one of these two antigens was present. It is suggested that besides contributing to the understanding of the disease process, the determining of associated specific antigens may constitute a further diagnostic acid in doubtful cases of Beh?et's disease.     

Proliferative response of T lymphocytes to mitogenic lectins in essential hypertension

Several studies in human and experimental models indicate the existence of a partial relationship between essential hypertension (EH) and the immune system. In this study, cellular immune functions were investigated in 13 patients with untreated and uncomplicated essential hypertension (EHP) and in 10 of their offspring (EHO) and compared to 13 age- and sex-matched normotensive controls (NC) and 10 of their offspring (NCO). The total number of T cells and T cell subsets were similar in all groups examined. In the EHP, basal lymphocyte transformation without lectins was significantly lower (1,126 +/- 261 cpm of [3H]-thymidine uptake) than in the NC (3,223 +/- 736, p less than 0.01); the response to both phytohemagglutinin (PHA) and concanavalin A (ConA) revealed reduced [3H]-thymidine uptake as compared with NC (21,890 +/- 5,432 compared to 64,574 +/- 9,723 for PHA and 10,488 +/- 2,621 compared to 37,334 +/- 8,148 for ConA, respectively, p less than 0.01). However, the ability to proliferate as a response to lectins was normal. This was leading to a normal stimulation index in both groups. In the EHO, non-significant decrease in basal transformation and reduced uptake with PHA (49,537 +/- 7,478) versus NCO (69,911 +/- 7,254) and NC (64,574 +/- 9,723) were found. These findings suggest that the proliferative response of T lymphocytes is partially suppressed in EH.     

Auditory brain stem responses in cerebellopontine angle tumors

The characteristic features of auditory brain stem responses (ABSR) are described in seven cases of cerebellopontine angle tumors: five acoustic neuromas, one congenital cholesteatoma, and one meningioma. An attempt is made to correlate the N₁ response with the degree of auditory nerve involvement, to gain information about the presence of brain stem displacement, and to evaluate the cranial extension of the lesion by recording responses to contralateral stimuli. The empirical nature of deductions based on crossed stimulation is emphasized. In tumors originating from the VIIIth nerve, the ABSR pattern is characterized by a well-defined N₁ complex, indistinct or absent additional responses, and prolonged brain stem conduction time (BSCT) on the affected side whenever its assessment is feasible. Recording from the affected side on stimulation of the contralateral side may show normal responses from stations central to the auditory nerve in cases of small-sized tumors. Medium or large tumors may be accompanied by abnormal N² and/or N₃ responses suggesting involvement of these stations.     

Invasive Meningococcal Disease: Patient and Strain Characteristics Set New Challenge for Prevention and Control

Summary Differences in the course of invasive meningococcal disease, in prevalence, case-to-carrier ratio, geographical pattern, age distribution and antibiotic resistance have been related to major serogroups and their serotypes. The relationship between Neisseria meningitidis serogroups and clinical manifestation, outcome and patient characteristics are assessed. All hospitalized patients in six major hospitals in central Isral with a verified meningococcal disease during 1990–1994 were included (n = 66). Their personal and clinical data and the results of bacteriological and serological tests of their blood and cerebrospinal fluid (CSF) were recorded. Meningococci were isolated from both blood and CSF, from blood alone, and from CSF alone in 60.6%, 18.2% and 21.2% of the cases, respectively. The highest proportion of isolations were from infants < 1 year (34.8%), followed by children aged 1 to 5 years (25.8%). Serogroup B prevailed in 62.1%, while group C and W135 accounted for 28.8% and 9.1%, respectively. Serogroup B predominated in children < 1 year, while in patients aged 5–22 years, C strains were the major pathogen (P < 0.001). Serogroup B accounted for 93% of the cases of meningitis, 58% of meningococcemia and 42% of fulminant meningococcemina, while group C strains were the major cause of fulminant meningococcemia (50%). The overall case fatality rate was 7.6%: fulminant meningococcemia 8.3%, and meningococcemia 10%. It was concluded that N. meningitidis group C continues to account for almost a third of the cases of meningococcal disease and is the major cause of fulminant meningococcemia. Received: August 17, 1998 · Revision accepted: January 24, 1999     

Biological evidence for inheritance of exceptional longevity

Subjects with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. In a case control study, we aim to determine phenotype and genotype of exceptional longevity in a genetically homogenous population (Ashkenazi Jews), and their offspring, while an age-matched control group of Ashkenazi Jews was used as control groups. We demonstrated that exceptional longevity and healthy aging in humans is an inherited phenotype across three generations. Moreover, we demonstrated that subjects with exceptional longevity and their offspring have significantly larger high-density lipoprotein (HDL) levels and particle sizes and low-density lipoprotein (LDL) levels that reflect on their health and cognitive function performance. This phenotype have led us to study candidate genes involved in lipoprotein metabolism, and to the implication of homozygosity for the 405 valine (V) allele of cholesteryl ester transfer protein (CETP). A markedly higher frequency of a functional CETP variant that led to increased particle sizes of HDL and LDL and thus a better health performance is the first example of a phenotype and an associated genotype in humans with exceptional longevity. Hopefully, this line of research will lead us to establish which genotype is necessary (although not necessary sufficient) for a prolonged disease-free aging.     

Immunosuppressive properties of follicular fluid and media conditioned by zygotes correlate with subsequent conception in in vitro fertilization

PROBLEM: Our objective in this study was to correlate immunosuppressive properties of follicular fluid (FF) and media conditioned by zygotes and early embryos with the occurrence of conception in an in vitro fertilization (IVF) program. METHOD OF STUDY: Fifty-seven IVF patients were studied. Donor lymphocytes were incubated with mitogens and FF from mature oocytes or conditioned media from zygotes and early embryos. Proliferation was assessed by radioactive thymidine incorporation. Proliferation Index (PI) was the ratio between radioactive labeling of lymphocytes incubated in the presence and absence of a mitogen. RESULTS: The FFs and media conditioned by zygotes from conception cycles had higher immunosuppressive activity than those from non-conception cycles. CONCLUSIONS: Immunosuppressive activity present in FF and media conditioned by zygotes may be a major determinant of conception in IVF, and may serve as a marker for embryo quality.     

The paradox of the insulin/IGF-1 signaling pathway in longevity

Ageing may be controlled by a genetic-hormonal system that may have originated from a very early common ancestor. One of the pathways that has been implicated in ageing is the insulin/insulin-like growth factor (IGF-1) signaling, which is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes, and mammalians. While disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly, mammals with genetic or acquired defects in insulin signaling pathway are at risk for age-related diseases and increased mortality. This contradiction can be explained by the acquisition of more complicated metabolic pathways in mammalians over evolution. Mammals have insulin/IGF-1 receptors in many organs, but their functions are opposite if they are located in the central nervous system or in the periphery; whereas lower species have insulin/IGF-1 receptors signaling mainly through the nervous system. Furthermore, mammalians have different and very specific receptors for insulin and IGF-1, with distinct pathways and diverse functions. Striking evidence suggests that decreased IGF-1 levels and signaling during early development, but not the insulin signaling may modulate longevity in many species. Thus, paradoxical outcomes follow the decrease of insulin and/or IGF-1 signal pathway in invertebrates and in mammals, prolonging life in the former and shortening it in the latter. In this review we focus on the downstream cascade of events in the insulin and IGF-1 signaling to identify specific pathways that are relevant to human longevity.     

Cardiac and neurologic complications identify risks for mortality for both men and women undergoing coronary artery bypass graft surgery.

BACKGROUND: Despite a number of studies showing that women and men respond to coronary artery bypass graft surgery differently, it is not known whether variables associated with mortality are the same for women and men. The purpose of this study was to identify variables independently associated with mortality for women undergoing coronary artery bypass graft surgery. METHODS: Single-institutional data were prospectively collected from 5,113 patients (1,558 or 30.5% women) undergoing coronary artery bypass graft surgery. The database was reviewed for patient characteristics and operative outcomes based on sex. Complications evaluated included low cardiac output syndrome (cardiac index < 2.0 l x min(-1) x m(-2) for > 8 h, regardless of treatment), stroke (new permanent global or focal motor deficits), Q-wave myocardial infarction, postoperative atrial fibrillation, and operative mortality. RESULTS: Women were older than men, and they were more likely to have preexisting hypertension, diabetes, and a history of stroke. Operative mortality for women was higher than for men (3.5% vs. 2.5%, P < 0.05). Compared with men, women were more likely to experience a postoperative myocardial infarction, stroke, and low cardiac output syndrome. When performing analysis on data from both sexes separately, low cardiac output syndrome, new stroke, myocardial infarction, and duration of cardiopulmonary bypass were independently associated with mortality for women and men both. Patient age was not independently associated with risk for mortality for women, but it was for men. However, when the authors combined both sexes in the logistic regression analysis, the age-sex interaction was not significant (P = 0.266), indicating that there was insufficient evidence to assert that age has a different effect on mortality for men and women. CONCLUSIONS: These data confirm that women have higher perioperative mortality after coronary artery bypass graft surgery compared with men. A higher frequency of cardiac and neurologic complications seem to account to a large extent for the higher operative mortality for women. Factors independently associated with perioperative mortality are generally similar for women and men.     

Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome

Purpose  

To report the performance of fluorescence in-situ hybridization in the setting of preimplantation genetic diagnosis in order to diagnose embryos affected by DiGeorge syndrome.