Transforming proteins of fujinami and PRCII avian sarcoma viruses have different subcellular locations

The subcellular locations of transforming proteins encoded by the related avian sarcoma viruses, PRCII and Fujinami sarcoma virus (FSV), were compared by cell fractionation and by indirect immunofluorescence. Whereas both viruses encode gag-fps proteins associated with tyrosine-specific kinase activity, FSV is more highly tumorigenic than PRCII in vivo. Cell fractionation studies showed that the PRCII transforming protein, P105, became associated with the high-speed particulate fraction shortly after synthesis. However, PRCII P105 did not fractionate with the plasma membrane marker, but rather with high-density membranes. It is unique in this subcellular localization among viral tyrosine kinases. This membrane association was found to be relatively insensitive to salt concentration and did not require divalent cations. Immunofluorescent studies, using anti-fps serum, showed that the PRCII protein was present in discrete, large, cytoplasmic patches, as well as in a juxtanuclear location. In contrast, FSV-encoded P130 was found to fractionate with the plasma membrane marker when cells were analyzed in low salt in the presence of magnesium. However, at higher salt concentrations and in the absence of magnesium, the bulk of P130 was found to be soluble. Immunofluorescent staining of FSV P130 revealed a diffuse, cytoplasmic pattern that was distinct from that of the PRCII product. The observed difference in the subcellular localization of these transforming proteins may be the cause of the difference in tumorigenicity between the two viruses.     

Cellular changes associated with triton WR-1339 accumulation in rat hepatocytes. II. Lysosomal triton WR-1339 accumulation.

Following a single intraperitoneal injection, Triton WR-1339 accumulated in rat hepatocyte lysosomes. The accumulation phenomenon followed a two-step process: (1) Sequestration of Triton and subsequent enlargement of lysosomes which occurred through 48 hr post-injection. (2) Fusion of lysosomes to form swollen, electron-lucid lysosomes which occurred from about 48 hr through 8 days post-injection. During the first phase, the dense lysosomal matrix was pushed to the periphery of the lysosome during enlargement. During phase 2 prominent swelling or enlargement of the lysosomes and increasing cellular damage was observed. From injection to 8 days post-injection, the number and size of the lysosomes increased. Hypertrophy of the Golgi apparatus, possibly associated with increased packaging, accompanied the increase in lysosome number. Lysosomal Triton accumulation exhibits morphological characteristics similar in many respects to storage diseases.     

Human Peripheral Eosinophils with Receptors for IgM: Demonstration and Ultrastructural Morphology

Receptors for IgM were detected on peripheral blood human eosinophils by a rosette technique with ox red blood cells coated with the IgM fraction of the specific immunserum. Between 14 % and 43 % (mean 27 %) FcµR positive cells were found after an overnight incubation period at 37°C by using this technique. The specificity of the receptors for IgM was assessed by studying the inhibitory capacity of purified human IgM in the rosette assay. From an ultrastructural point of view, the EA^M rosette-forming cells are mature eosinophlic granulocytes characterized by a nucleus with a variable number of lobes and a certain number of «first type» granules partially or totally devoid of their content.     

首次及重复感染HCV后抗体及HCV RNA的动态观察

本文报道对首次感染ＨＣＶ的１４人与重复输入含ＨＣＶ血的１１位感染者进行长达一年半的动态观察，总结出输入大量含ＨＣＶ血后导致的感染者在自然状态下ＨＣＶ ＲＮＡ及抗体变化的规律。７／８再次输入４００ｍｌ以上含ＨＣＶ血的感染者，其自身存在的高滴度抗体在受血后１～３个月下降０．５～１．０ＯＤ值。首次输出含ＨＣＶ血的感染者中，１１／１４的感染者３个月内ＡＬＴ高于参考值的３倍以上，而再次输入含ＨＣＶ血的患者中     

Protective monoclonal antibodies define maturational and pH-dependent antigenic changes in Sindbis virus E1 glycoprotein

Monoclonal (MC) antibodies specific for either the EI or E2 glycoproteins of Sindbis virus (SIN) were used to probe for differences in the surface topography of SIN epitopes between infected cells and mature virions. Employing an enzyme-linked immunosorbent assay (ELISA) in which binding of individual peroxidase-labeled MC antibodies to immobilized (solid-phase) detergent-disrupted SIN was inhibited specifically by one or more unlabeled antibodies, viral epitopes could be grouped into six spatially distinct antigenic sites--five on E1, designated a through e, and one site on E2. All six sites were represented on the surfaces of SIN-infected cells as shown by the complement (C')-dependent lysis mediated by antibodies of the corresponding epitope specificities. In contrast, virus-neutralizing (NT) activity was restricted to antibodies specific for epitopes on E2 and on site c of E1, irrespective of the presence of added C' and an antiserum against mouse immunoglobulins. That E1 sites a, b, d, and e became inaccessible to antibody binding was shown by a competitive-inhibition ELISA. Whereas all MC antibodies were inhibited from binding to solid-phase SIN when premixed with detergent-treated virions, only those having NT activity could be competitively inhibited by intact virions. Sites E1-d and E1-e could be exposed not only by detergent disruption but also by lowering the virion pH from 7.2 to 6.0. These collective results indicate that a majority of immunologically relevant E1 epitopes present on SIN-infected cell surfaces become cryptic during SIN maturation and, except at low pH, remain undetectable on virion surfaces.     

β Chain deficiency in three patients with dysfunctional C8 molecules

Structural and functional studies were performed on a dysfunctional C8 molecule present in the serum of two siblings and an unrelated individual. The C8 in these three sera exhibited a pattern of partial immunologic identity with C8 in normal serum but was devoid of functional activity. The C8 was immunoprecipitated from the three sera and from a control serum with an antihuman C8 antiserum and analyzed by SDS-PAGE using highly purified human C8 as a reference. A selective absence of a band of 62,000 mol. wt was observed in the immunoprecipitates from the sera containing dysfunctional C8. Experiments performed with the purified α-γ and γ subunits showed that the hemolytic activity of the C8 deficient sera could be reconstituted by the addition of the β chain but not the α-γ dimer. Binding of the dysfunctional C8 to C$\text{567}$ was excluded by the following observations: (1) EAC 1–7 treated with the C8 deficient sera and then washed could not be lysed after the addition of the β subunit and C9; and (2) the abnormal molecules did not interfere with the consumption of normal C8 by the soluble complex SC5b-7.     

Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study

Summary To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100–115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty-four patients [16 m, age 54 (7) y] completed the study.As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively.DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo.The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives.     

Survival effect of systemic therapy on patients developing metastatic breast carcinoma

A multivariate analysis was performed to assess the effect of post-relapse systemic therapy on a series of patients with metastatic breast cancer who at initial presentation had no detectable metastases (M), were 70 years of age, presented with unilateral localized disease and no other associated malignancy, and were treated between 1965 and 1984 with successive protocols for primary disease and subsequently developed distant metastasis. All 760 patients analyzed relapsed with at least one metastasis, and were studied retrospectively with no selection criteria according to any specific protocol. All had recorded clinical data on menopause, stage, clinical tumor aggressiveness (PEV), initial chemo or hormonal therapy, and time to relapse, and had ongoing follow up at our Center, with salvage chemotherapy and/or hormonal therapy having been given to some but not all patients.A brief metastasis-free survival (p < 0.000001), and factors associated with electing pre-relapse chemotherapy (p < 0.000001) were associated with shortened post-relapse survival, while post-relapse therapy (chemo p < 0.0001, and hormonal p < 0.00001, replacing chemotherapy in the model) apparently increased post-relapse survival in the group overall. This result was similar in the inoperable patient group [with inflammatory breast carcinoma an additional risk factor (p < 0.0005)], as well as the operable group. However, in the operable group, when the pathologic criteria of histologic grade and nodal status were introduced into the analysis, post-relapse therapy was not seen to be an important factor for survival in any subgroup. Histograde (p < 0.000001), nodal status (p < 0.0001), metastasis-free survival (p < 0.001), and menopausal status (p = 0.03) were the only significant factors for post-relapse survival.     

原发性高血压和动脉硬化性脑梗死及腔隙性脑梗死患者的HLA-DQA1遗传易感性

目的　探讨原发性高血压(EH)、动脉粥样硬化性血栓性脑梗死(ABI)及腔隙性脑梗死(LS)患者HLA-DQA1位点的基因分型及其遗传易感性。方法　采用PCR-SSP方法对EH、ABI及LS共155例患者和正常对照64人进行HLA-DQA1位点的基因分型和遗传易感性分析。结果　EH、ABI及LS组的HLA-DQA1*0301基因频率均明显高于正常对照组,分别为33.6538对17.9688,36.5854对17.9688,33.0645对17.9688（P<0.01）,而HLA-DQA1*0103基因频率却明显低于正常对照组(P<0.05或P<0.01)。结论　HLA-DQA1*0301等位基因可能与EH、ABI及LS的遗传易感性相关,而HLA-DQA1*0103等位基因可能与其保护性相关。     

注射用克林霉素磷酸酯的稳定性研究

目的：对影响注射用克林霉素磷酸酯稳定性的各种因素进行考察,方法：采用高效液相色谱法测定注射用克林霉素磷酸酯的稳定性。结果：温度对本制剂稳定性有影响,对光稳定性较好。结论：本制剂应于凉暗干燥处贮存。