双特异抗体介导的人单核—巨噬细胞对荷人肝癌裸鼠的抑制作用

观察双特异性单克隆抗体介导的人单核－巨噬细胞在裸鼠体内对肝癌生长的抑制作用。用化学交联法制备双特异性单克隆抗体ＨＡｂ１８－ＭＡｂ７及ＨＡｂ１８Ｆ（ａｂ）２－ＭＡｂ７Ｆ（ａｂ＇＿２，并将其与单核－巨噬细胞－同注入荷人肝癌裸鼠体内，观察肿瘤体积的变化。     

Ontogeny and thymus-dependence of T cell surface antigens in Xenopus : flow cytometric studies on monoclonal antibody-stained thymus and spleen

Recently generated anti-Xenopus T cell monoclonal antibodies (mAbs) to the 120 kDA XTLA-1 determinant and against the putative CD5 and CD8 homologues, together with anti-IgM and anti-MHC class II mAbs, are used in dual colour flow cytometric experiments to characterize cell surface antigenic expression on lymphocytes in thymus and spleen of Xenopus laevis during larval and early adult life and also in metamorphosis-inhibited animals. Histological confirmation of T cell emergence early in larval ontogeny is supplied by cryostat sections stained for CD8. Five-day thymectomy i.e. prior to T-lineage cell differentiation in the thymus, abolishes T cell marker expression in the spleen for up to 1 year. Moreover, late larval (20 days) or early adult (3 months) thymectomy (i.e. removal after peripheralization of T cells has occurred) also leads to severe depletion of mAb-defined T cells in the spleen.     

Effects of age and age-related hearing loss on the neural representation of speech cues.

OBJECTIVE: To examine the effects of aging and age-related hearing loss on the perception and neural representation of a time-varying speech cue. METHODS: P1, N1 and P2 cortical responses were recorded from younger and older normal-hearing adults, as well as older adults with age-related hearing loss. Synthetic speech tokens representing 10 ms increments along a /ba/-/pa/ voice-onset-time (VOT) continuum were used to evoke the responses. Each participant's ability to discriminate the speech tokens was also assessed. RESULTS: Compared with younger participants, older adults with and without hearing loss had more difficulty discriminating 10 ms VOT contrasts. In addition, both older groups elicited abnormal neural response patterns. There were no significant age-related findings for P1 latency; however, N1 latencies were prolonged for both older groups in response to stimuli with increased VOT durations. Also, P2 latencies were delayed for both older groups. The presence of age-related hearing loss resulted in a significant increase in N1 amplitude in response to voiceless stimuli. CONCLUSIONS: Aging and age-related hearing loss alter temporal response properties in the central auditory system. Because both older groups had difficulty discriminating these same speech stimuli, we conclude that some of the perceptual difficulties described by older adults might be due to age-related changes regulating excitatory and inhibitory processes. SIGNIFICANCE: Some of the speech understanding difficulties expressed by elderly adults may be related to impaired temporal precision in the aging auditory system. This might explain why older adults frequently complain that wearing a hearing aid makes speech louder, but does not necessarily improve their ability to understand speech.     

Obesity in youth and middle age and risk of colorectal cancer in men

To investigate an association between colon cancer and obesity during early adulthood—a potentially important period in the etiology of this disease—the authors assembled, by computer linkage, a population-based historical cohort of 52,539 men born between 1913 and 1927 residing in Hawaii (USA), for whom weight and height had been recorded in 1942–43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 737 incident cases of colorectal cancer for 1972–86. An average of 3.8 cancer-free controls were matched to each case on month and year of birth and ethnicity of the parents. A case-control analysis in each anatomic subsite of the large bowel revealed that both early and middle-age body mass increased the risk of sigmoid cancer in men in a dose-dependent fashion. The odds ratios (OR) for sigmoid cancer for the highest compared with the lowest tertiles of Quetelet index were: 2.1 (95 percent confidence interval [CI]=1.4–3.2) and 1.7 (CI=1.1–2.5), at ages 15–29 and in prediagnostic years, respectively. These associations were additive and idependent of socioeconomic status. Men who were above the median Quetelet index in 1942 and 1972 had an OR of 2.7 (CI=1.8–4.0), compared with those who were below the median in both periods. This study provides further evidence for an association of obesity with colon cancer in men and suggests that this association is limited to the sigmoid colon and may be related to both early and late events of colon carcinogenesis.The authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii. Address correspondence to Dr Le Marchand, Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA. This work was supported in part by Public Health Service grant 5-R29-CA44503 and contract NO1-CN-55424 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.     

Use of a somatostatin analogue, octreotide acetate, in the management of acute gastrointestinal graft-versus-host disease

PURPOSE: Because the secretory diarrhea of acute graft-versus-host disease (GvHD) of the gut induces serious metabolic and nutritional disturbances, this study was initiated to assess the use of a somatostatin analogue, octreotide acetate, as adjunctive therapy for severe GvHD of the gut with massive diarrhea. PATIENTS AND METHODS: In a pilot study, six patients with biopsy-confirmed acute gut GvHD after allogeneic bone marrow transplantation received octreotide 50 to 250 micrograms three times a day subcutaneously. RESULTS: Three of the six treated patients had a prompt and dramatic reduction in stool volume within 1 to 3 days of initiation of octreotide therapy. CONCLUSIONS: Somatostatin and its analogues have been used successfully in diarrheal states by antagonism of neuropeptide overproduction, although other potential therapeutic mechanisms include inhibition of fluid secretion, enhanced salt absorption, and inhibition of gut motility. Somatostatin and its analogues may be promising adjunctive agents in the treatment of gastrointestinal GvHD, although assessment in a controlled trial will be required to confirm their therapeutic efficacy.     

Staphylococcal toxins: screening of burn wound isolates and evidence for alphahaemolysin production in the burn wound

Culture filtrates of Staphylococcus aureus strains isolated from burn patients were examined for cytotoxic activities. A large molecular weight cytotoxin (MW=253000 daltons) that exhibited cytotoxicity for human foreskin cells and haemolytic activity against human and rabbit erythrocytes was identified. The cytotoxic activity could be completely neutralized by antiserum formed against the cytotoxin. Further characterization of the molecule by isoelectric focusing revealed that the cytotoxin was composed of at least two toxic factors of smaller molecular weight. Both factors exhibited cytotoxicity to tissue-culture cells. however, one factor lysed rabbit but not human erythrocytes whereas the other factor had the opposite haemolytic pattern. The cytotoxicity of each factor was neutralized by the antiserum formed against the cytotoxin. A cytotoxic factor that exhibited haemolytic activity for rabbit erythrocytes, and that was neutralized by the cytotoxin antiserum, was identified in burn wound extracts of mice infected with Staph. aureus. On the basis of molecular weight and isoelectric focusing data, we conclude that the large molecular weight cytotoxin was composed of an aggregation of alpha-haemolysin and another presently unidentified toxic molecule, possibly delta-toxin. Alpha-haemolysin appears to be produced in vivo during experimental staphylococcal burn wound infection.     

实验性室间隔缺损心肌血管紧张素Ⅱ受体表达的变化

目的　探讨实验性室间隔缺损 ( VSD)动物左右心室心肌血管紧张素 受体的改变。方法　建立猪实验性室间隔缺损动物模型 ,术后 1月取左右心室组织 ,通过放射性配体受体结合分析法测定每 10 6个细胞上血管紧张素 受体 ( AT1 R、AT2 R)的最大结合量 ( Bmax)和平衡解离常数 ( KD)。结果　假手术组与正常组动物受体的 Bmax和KD改变无统计学意义 ,手术组动物左室 AT1 R、右室 AT1 R和 AT2 R的 Bmax值 (分别为 188.42± 13 3 .97、2 72 .14±2 3 2 .74、40 .42± 3 4.76fmol/ 10 6 ,对照组 AT1 R和 AT2 R的 Bmax值左室为 2 9.2 0± 19.5 0和 2 .90± 0 .64 ,右室为76.72± 5 1.2 1和 9.63± 1.2 7fm ol/ L )增高明显 ( P<0 .0 5 )。结论　心内左向右所引起的心室容量负荷过重 ,导致AT1 R的表达增高 ,是 VSD心室肥厚及重构的重要机制 ;AT2 R在右心室表达增高 ,可能是中等程度容量负荷的VSD容易出现左室肥厚而非右室肥厚的原因