Binding of heme by glutathione S-transferase: a possible role of the erythrocyte enzyme

Human erythrocyte glutathione S-transferase activity is inhibited, probably competitively, by hemin with a Ki of 10(-7) M. It is postulated that glutathione S-transferase functions physiologically as a hemin-binding and/or transport protein in developing erythroid cells.     

The surgical hypertensive patient

We reviewed the pathophysiology and treatment of hypertensionin a recent edition of this journal (see key references). Inthis article, we discuss the management of the hypertensivepatient presenting for surgery and anaesthesia.     

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1- infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high- risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.     

Cerebral Tuberculoma

SUMMARY Intracranial tuberculoma has become a rarity. It remains a curable lesion that responds well to medical therapy. Although diagnosis in developed countries is often made only postoperatively, early and effective treatment can be instituted if a high index of suspicion is maintained and diagnostic criteria are looked for. A case is presented which illustrates the difficulties in reaching a diagnosis, and a review of the literature is given.     

Deletions of the cyclin-dependent kinase inhibitor genes p16INK4A and p15INK4B in non-Hodgkin's lymphomas

The tumor suppressor genes p16INK4A and p15INK4B map to the 9p21 chromosomal locus and are either homozygously deleted or mutated in a wide range of human cancer cell lines and tumors. Although chromosome 9 abnormalities have been described in non-Hodgkin's lymphomas (NHLs), to date, the mutational status of these genes has not been determined for these malignancies. A total of five cell lines and 75 NHLs were examined for homozygous deletions or point mutations in the coding regions of both the p15 and p16 genes using Southern blot and/or polymerase chain reaction-single-strand conformation polymorphism analyses. Homozygous deletions of either the p16 gene or both the p15 and p16 genes were observed in one diffuse large B-cell lymphoma cell line and two uncultured lymphomas consisting of one large B-cell and one mixed T-cell lymphoma. In contrast, point mutations were not detected in either the cell lines or lymphomas. These results indicate that the rate of alterations in the p15 and p16 genes is low for lymphomas, but loss of p16 and/or p15 may be involved in the development of some lymphomas.     

Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.     

乐胃煎逆转胃癌前病变AgNOR及细胞图像分析

目的研究乐胃煎逆转胃癌前病变不完全结肠型肠化和／或中度异型增生的疗效．方法胃镜病理证实为不完全结肠型肠化和／或中度异型增生４６例．治疗组３０例用乐胃煎，对照组１６例用德诺（Ｄｅ＿Ｎｏｌ）．治疗前后胃镜活检胃窦固定部位粘膜标本作ＡｇＮＯＲ染色及细胞图像分析．结果乐胃煎对不完全结肠型肠化及中度异型增生总有效率均高于Ｄｅ＿Ｎｏｌ，分别为７２％比２５％（Ｐ＜００５）和８９５％比４４４％（Ｐ＜００５）．乐胃煎治疗前后，ＡｇＮＯＲ计数分别为７３０±１１６和４８１±１５０（Ｐ＜００１），Ｄｅ＿Ｎｏｌ组为７７３±０９２和７０５±１０２（Ｐ＜００１）．两组治疗前后ＡｇＮＯＲ计数差值均数相比，统计学上也有显著性差异，分别为２５２±１５４和０６９±０４８（Ｐ＜００１）．乐胃煎组中２０例作细胞图像分析，治疗后各参数（长轴、短轴、核浆比、结构异型指数等）均有不同程度的降低，有显著性差异．结论乐胃煎确有较好地逆转胃癌前病变的功效．     

Use of the gel agglutination technique for determination of fetomaternal hemorrhage

BACKGROUND: Adequate administration of Rh immune globulin requires an accurate determination of the number of D-positive cells in the circulation of D-negative women. Although several tests have been described for the detection of fetomaternal hemorrhage, there is still a need for a rapid, simple, and clinically relevant screening test. STUDY DESIGN AND METHODS: Serial dilutions of a monoclonal anti-D were incubated with stock solutions (0.2 mL) of adult D-negative red cells in the absence or presence of various amounts of fetal D-positive cells (0.1, 0.2, 0.3, 0.4, and 0.5%). After incubation, the supernatants were tested against D-positive red cells by using the new, gel agglutination technique (GAT). After the GAT was adapted to detect D-positive cells at concentrations of > or = 0.2 percent, unselected postpartum samples from D-negative women (n = 420) who delivered D-positive infants were analyzed by both the new test and the Kleihauer-Betke test (KBT). RESULTS: Three of a total of 420 postpartum samples were positive (> or = 0.4% fetal cells), and 406 were negative in both tests. One had 0.5- percent fetal cells in the KBT and gave negative results in the GAT. The latter test was, however, performed after administration of Rh immune globulin. The KBT gave false-positive results in two cases, because of hereditary persistence of hemoglobin F, and the GAT gave a false-positive reaction in one case because of a maternal weak D variant. In the remaining seven cases, the KBT results were only weakly positive (0.2%) and could not be attributed solely to D positive red cells. CONCLUSION: The GAT is suited for routine screening. It provides rapid and specific detection of D-positive red cells at clinically relevant concentrations. The test may (rarely) yield false-negative results due to insufficient administration of Rh immune globulin before testing.     

Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.