Recombinant human alpha lymphotoxin (tumor necrosis factor-beta) induces peripheral neutrophilia and lymphopenia in the rat.

Recombinant human alpha lymphotoxin (rLT) administered intravenously to Lewis rats induces peripheral neutrophilia and lymphopenia in a dose-response dependent fashion. A dose of 30,000 units of rLT induced a neutrophilia (1589 +/- 326 to 5554 +/- 1050 neutrophils/cu mm) and lymphopenia (10,368 +/- 992 to 4636 +/- 878 lymphocytes/cu mm) at 2 hours after injection that was highly significant (P less than 0.001 and P less than 0.001, respectively) in comparison with vehicle controls. The kinetics of the neutrophilia that peaked at 2 hours as well as of the lymphopenia were highly reminiscent of the neutrophilia and lymphopenia following intravenous administration of either recombinant human interleukin-1 (IL-1) alpha or beta to rats. The peripheral neutrophilia was accompanied by a significant depletion of bone marrow neutrophils (P less than 0.001), as is also known to occur after administration of IL-1. Systemic blood pressure was not affected by rLT, which suggested that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic-change-related release of adrenal hormones. Adrenalectomy did not alter the rLT-induced neutrophilia or lymphopenia, which suggested that rLT does not mediate its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones. Pretreatment of rats with dexamethasone, indomethacin, or aspirin also did not alter rLT-induced neutrophilia or lymphopenia, which suggested that rLT-induced hematologic effects were not mediated via arachidonic acid metabolites, in stark contrast to IL-1 induced neutrophilia, which is inhibited by both dexamethasone and indomethacin.     

Endobronchial HIV associated lymphoma.

A 27 year old HIV infected man presented with two days of haemoptysis. Flexible bronchoscopy revealed a large carinal mass partially obstructing the left and right main stem bronchi. Rigid bronchoscopy was required to make the diagnosis of large cell immunoblastic lymphoma.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

用于筛选天然产物中脲酶抑制剂的脲酶活性测试方法的建立

抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Ｂｅｒｔｈｅｌｏｔ试剂在９６孔培养板上检测重组脲酶活性，其灵敏度指标酚红法每ｍｇ酶蛋白引起的每分钟吸光度变化。△Ａ为６．９，而Ｂｅｒｔｈｅｌｏｔ法每ｍｇ酶蛋白引起的每分钟吸光度比值变化△Ａ为３１３。结果表明用Ｂｅｒｔｈｅｌｏｔ试剂检测重组脲酶活性适宜在９６孔培养板上大规模筛选天然产物中的脲酶抑制剂。     

Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study

Sixteen cohorts of men aged 40–59 years at entry were examined with the measurement of some risk factors and then followed-up for mortality and causes of death for 25 years. These cohorts were located in the USA (1 cohort), Finland (2), the Netherlands (1), Italy (3), the former Yugoslavia (5), Greece (2), and Japan (2), and included a total of 12,763 subjects.Large differences in age-adjusted coronary heart disease (CHD) death rates were found, with extremes of 45 per 1000 in 25 years in Tanushimaru, Japan, to 288 per 1000 in 25 years in East Finland. In general, higher rates were found in the US and Northern European cohorts as compared to the Southern European and Japanese cohorts. However, during the last 10 years of follow-up large increases of CHD death rates were found in some Yugoslavian areas. Out of 5 measured entry characteristics treated as age-adjusted levels (serum cholesterol, systolic blood pressure, cigarette smoking, body mass index and physical activity at work), only serum cholesterol was significant in explaining cohort differences in CHD death rates.Over 50% of the variance in CHD death rates in 25 years was accounted for by the difference in mean serum cholesterol. This association tended to decline with increasing length of follow-up, but this was due to the great changes in mean serum cholesterol in the two Jugoslavian cohorts of Velika Krsna and Zrenjanin. When these two cohorts were excluded the association increased with time.Changes in mean serum cholesterol between year 0 and 10 helped in explaining differences in CHD death rates from year 10 onward.It can be concluded that this study suggests that mean serum cholesterol is the major risk factor in explaining cross-cultural differences in CHD.     

Longevity of man: relative weight and fatness in middle age

By February, 1948, examinations in the Twin Cities Prospective Study were completed on 284 executive men, then aged 45-55 and "healthy". In 35 years 183 died, 110 were alive, one was lost. Entry body fatness, indicated by body mass index, skinfold thickness at three sites, relative girth, and body density, did not significantly discriminate the 35-year dead from survivors. Age at death was not related to any fatness measure. The multiple logistic equation in five solutions using age, blood pressure and smoking plus each fatness item separately, found no discrimination of dead from survivors by any fatness measure. In other long time prospective studies, two suggested excess mortality at far extremes of over- and under-weight, several found survivors significantly fatter than the dead, others found no relation between fatness and longevity. Framingham reported fatness a risk factor for death when allowance is made for smoking but that singular claim has been criticized.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.