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Biomedical subjects

M Sherman

Publications and source records attributed to M Sherman.

At least 91 records · Page 5Linked to original sources
PubMed1993

Inorganic pyrophosphate gives a membrane potential in yeast mitochondria, as measured with the permeant cation tetraphenylphosphonium.

Evidence for a membrane potential (delta psi) generating capacity of inorganic pyrophosphate (PPi) with inorganic pyrophosphatase in mitochondria from the yeast Saccharomyces cerevisiae is presented. Addition of PPi increases the accumulation of the permeant cation tetraphenylphosphonium (TTP+) in mitochondria, as measured with a TPP(+)-selective electrode or using [3H]TPP+. This accumulation is strongly inhibited by the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) but not by oligomycin, whereas accumulation of TPP+ induced by ATP is strongly inhibited by both FCCP and oligomycin. The values of delta psi obtained upon addition of PPi were similar to those obtained when yeast mitochondria were energized by NADH or ATP. Energization of the wild type yeast mitochondria with ATP resulted in higher delta psi values than those achieved when PPi was hydrolyzed, whereas the effect of PPi was more pronounced in mitochondria from a pyrophosphatase (PPase) overproducing yeast strain. These results clearly indicate that PPi is significant as an energy donor and that the yeast mitochondrial PPase, the gene for which we have recently cloned and sequenced, may participate in energy transfer reactions.

Adenosine Triphosphate↗
PubMed1993

The v-raf oncogene enhances tumorigenicity and suppresses differentiation in vivo in a rat hepatocyte cell line.

raf oncogenes have been implicated in hepatic carcinogenesis. We studied the effects of the v-raf of murine retrovirus 3611-MSV on the growth and differentiation of a simian virus 40 (SV40)-immortalized rat liver cell line (ALB-8) which maintained many of characteristics of differentiated hepatocytes. Cells were co-transfected with v-raf and the neo gene followed by selection with G418 for transfectants. In culture, the expression of v-raf stimulated cell proliferation without altering cell morphology or expression of liver-specific genes: albumin, fibrinogen, alpha-1-antitrypsin and alpha-1-acid glycoprotein. The v-raf-transfected cells induced rapidly growing tumors in 100% of nude mice, while control DNA-transfected cells were only weakly tumorigenic, producing slowly growing tumors in 2/7 mice after a long latency. These slowly growing tumors were histologically moderately to well-differentiated hepatocellular carcinomas in which the liver-specific genes were highly expressed. In contrast, v-raf-induced tumors were histologically poorly differentiated and showed a dramatic decline in the expression of the liver-specific genes. In a tumor cell culture established from a v-raf-induced tumor, however, expression of the liver-specific genes was coordinately recovered. These observations indicate that v-raf is capable of inducing progression of SV40-immortalized hepatocytes into highly malignant cells and the progression is accompanied by loss, in vivo, of the hepatic differentiation.

Albumins↗
PubMed1993

One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome.

PURPOSE: One hundred autotransplants for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were examined prospectively to identify variables with prognostic significance. PATIENTS AND METHODS: Ninety-six patients with relapsed or refractory HD or NHL underwent 100 autotransplants. Patients received high-dose carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem-cell rescue. RESULTS: The 3-year actuarial event-free survival (EFS) rate for the 47 HD patients is 49%, with a median followup duration of 2 years. For the 53 NHL patients, the 3-year actuarial EFS rate is 40%, with a median follow-up duration of 19 months. By multivariate analysis, minimal disease on admission (all areas < or = 2 cm) is associated with improved EFS (HD, P = .003, NHL, P = .03). The projected EFS rate for HD patients entering with minimal disease is 70% versus 15% for patients with bulky disease (P = .0001). The projected EFS rate for NHL patients with minimal disease is 48% versus 25% for patients with bulky disease (P = .04). Posttransplant involved-field radiotherapy, administered to 26 of the last 61 patients, was associated with an improved EFS rate for NHL patients (P = .015). The BEAC regimen was well tolerated by patients who entered the study with minimal disease (mortality rate, < 5%), but caused significant toxicity in patients with bulky disease (mortality rate, 25%). CONCLUSION: Disease burden before autotransplantation is an important predictor of regimen-related toxicity and EFS. Posttransplant involved-field radiotherapy may improve outcomes in select patients with NHL. The BEAC regimen is safe and effective, particularly for patients with minimal disease.

Actuarial Analysis↗
PubMed1993

Extra-articular augmentation for residual hip dysplasia. Radiological assessment after Chiari osteotomies and shelf procedures.

The Chiari osteotomy and various shelf procedures are used to augment the weight-bearing area in dysplastic acetabula. The new articular surface derives by metaplasia from the acetabular rim and joint capsule, and is therefore of poorer quality than congruous hyaline cartilage. We reviewed 32 patients after augmentation procedures, using conventional radiographs and three-dimensional reconstruction from CT scans. We showed that Chiari osteotomy and shelf procedures generally achieve less than complete cover, especially over the posterolateral quadrant of the femoral head. Our results suggest that alternative methods which reorientate the whole of the acetabulum are the treatment of choice. Augmentation procedures remain as a salvage option when reorientation is inappropriate or the original hyaline cartilage surface is absent, as in subluxed joints with a secondary acetabulum. Computerised assessment is recommended before operation to assess existing cover and the possible extent of provision of new cover.

Adolescent↗
PubMed1992

ras transformation of simian virus 40-immortalized rat hepatocytes: an in vitro model of hepatocarcinogenesis.

Primary rat hepatocytes were transfected with simian virus 40 DNA and cultured in a chemically defined medium. Proliferating colonies developed after 2-3 weeks. Three cell lines were established by cloning albumin-secreting colonies, as identified by an immunooverlay assay. Two of the cell lines, ALB-6 and ALB-8, expressed all five liver-specific mRNAs studied, albumin, alpha-1-antitrypsin, fibrinogen, alpha-1-acid glycoprotein, and histidase. ALB-6 cells were nontumorigenic in nude mice while ALB-8 cells were weakly tumorigenic with only one of four injected nude mice developing a slowly growing tumor. Further transfection of ALB-6 and ALB-8 cells with an activated c-Ha-ras or N-ras oncogene resulted in strongly tumorigenic cells. The tumors induced by ras-transformed ALB-6 cells were moderately differentiated hepatocellular carcinomas. The tumors derived from ras-transformed ALB-8 cells were poorly differentiated, while the slowly growing tumors induced by untransfected or control DNA-transfected ALB-8 cells were well-differentiated trabecular hepatocellular carcinomas, suggesting histological dedifferentiation of cells following ras transformation. However, the synthetic capabilities of the cells were not lost in that the ras-transfected cultures and the tumors induced by ras-transformed cells retained the ability to synthesize the five liver-specific mRNAs. Thus we have developed an in vitro model of carcinogenesis in which, by sequential exposure to SV40 DNA and a ras oncogene, primary rat hepatocytes are transformed.

Animals↗
PubMed1992

Post-transplant recurrent hepatitis B viral liver disease. Viral-burden, steatoviral, and fibroviral hepatitis B.

Recurrence of hepatitis is a well-documented complication of hepatitis B liver disease, post-transplantation. It is well established also that the earliest hepatocellular change is the appearance of hepatitis B viral (HBV) markers and that the disease is rapidly progressive. In this article on 17 liver transplants in 16 HBV positive patients with long-term follow-ups (100-1234 days), the distinctive pathologic features of this disease are emphasized: the extreme viral load, the steatosis, and/or fibrosis. An attempt to quantitate the magnitude of the viral burden was made and the result was a staggering figure. In one patient, an estimated 10(18) HBV core particles were present in the liver. One of two patterns of progression were noted. In four patients in addition to the massive nuclear hepatitis B core antigen (HBcAg) and cytoplasmic hepatitis B surface antigen (HBsAg) positivity, superimposed hepatitic changes led to diffuse hepatic fibrosis (fibroviral hepatitis B); and in another six patients, extraordinary hepatocellular viral marker positivity and steatosis were the hallmarks (steatoviral hepatitis B). Steatosis is not usually considered a feature of HBV liver pathology. These results suggest that more than one type of posttransfusion recurrent hepatitis B liver disease exists pathologically.

Fatty Liver↗
PubMed1991

Head and neck surveillance program for factory personnel exposed to asbestos.

Personnel at a local factory that manufactures brake linings and discs in which asbestos is a major component were requested to participate in an on-site surveillance program to detect head and neck abnormalities, specifically cancer. Demographic data included smoking histories and job descriptions that could be delineated into high- and low-asbestos exposure groups. In the first year, 322 factory workers had no cancer identified but 15% had laryngeal abnormalities, mostly laryngitis. Ninety-seven percent of those workers with abnormal findings were smokers, but there were a significant number in the high-asbestos group irrespective of smoking histories. From this report, high-risk individuals were identified and requested to continue in the program for monitoring. In the subsequent 3 years, these individuals and new personnel were examined. Similar results were obtained in that laryngitis was noted in 24% (95% of whom were smokers) with a stronger statistical association with the high-asbestos group. More important, one person previously identified as high-risk was noted to have stage I squamous cell carcinoma and was treated with radiotherapy. The results of this program suggest that individuals at high risk for the development of head and neck cancer can be identified and that such surveillance programs should be implemented in similar arenas.

Adult↗
PubMed1991

Chronic reactive airway disease following acute chlorine gas exposure in an asymptomatic atopic patient.

While chlorine gas inhalation has previously been reported to cause temporary mucous membrane irritation, acute pneumonitis, pulmonary edema, and transient bronchospasm, there is controversy about the existence of long-term pulmonary sequelae. We report the case of a 25-year-old man in whom chronic, recurrent asthma developed after exposure to a chlorine gas leak in an enclosed space. His course since the exposure has been notable for frequent exacerbations necessitating chronic corticosteroid therapy and multiple hospitalizations. To our knowledge, the persistence of symptoms years after the exposure is unique in the literature.

Accidents, Occupational↗
PubMed1990

Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects.

Forty-nine patients with active rheumatoid arthritis completed a 24-week, prospective, double-blind, randomized study of dietary supplementation with 2 different dosages of fish oil and 1 dosage of olive oil. Clinical evaluations were performed at baseline and every 6 weeks thereafter, and immunologic variables were measured at baseline and after 24 weeks of study. The 3 groups of patients were matched for age, sex, disease severity, and use of disease-modifying antirheumatic drugs (DMARDs). Subjects continued receiving DMARDs and other background medications without change during the study. Twenty patients consumed daily dietary supplements of n3 fatty acids containing 27 mg/kg eicosapentaenoic acid (EPA) and 18 mg/kg docosahexaenoic acid (DHA) (low dose), 17 patients ingested 54 mg/kg EPA and 36 mg/kg DHA (high dose), and 12 patients ingested olive oil capsules containing 6.8 gm of oleic acid. Significant improvements from baseline in the number of tender joints were noted in the low-dose group at week 24 (P = 0.05) and in the high-dose group at week 18 (P = 0.04) and 24 (P = 0.02). Significant decreases from baseline in the number of swollen joints were noted in the low-dose group at weeks 12 (P = 0.003), 18 (P = 0.002), and 24 (P = 0.001) and in the high-dose group at weeks 12 (P = 0.0001), 18 (P = 0.008), and 24 (P = 0.02). A total of 5 of 45 clinical measures were significantly changed from baseline in the olive oil group, 8 of 45 in the low-dose fish oil group, and 21 of 45 in the high-dose fish oil group during the study (P = 0.0002). Neutrophil leukotriene B4 production decreased by 19% from baseline in the low-dose fish oil group (P = 0.0003) and 20% in the high-dose group (P = 0.03), while macrophage interleukin-1 production decreased by 38.5% in the olive oil group (P not significant), 40.6% in the low-dose group (P = 0.06), and 54.7% in the high-dose group (P = 0.0005). Tritiated thymidine incorporation in peripheral blood mononuclear cells after stimulation with concanavalin A increased significantly in all 3 groups after 24 weeks, compared with baseline values. We conclude that the clinical benefits of dietary supplementation with omega-3 fatty acids are more commonly observed in patients consuming higher dosages of fish oil for time intervals that are longer than those previously studied. Dietary supplementation with olive oil is also associated with certain changes in immune function, which require further investigation.

Arthritis, Rheumatoid↗
PubMed1990

San Diego Suicide Study: the adolescents.

The San Diego Suicide Study involved psychological autopsy and toxicological examination of 283 suicides. Of the 133 consecutive cases under age 30, 14 were under age 20. In this paper, detailed data on the 14 adolescent cases are presented and the findings compared to other studies.

Adolescent↗
PubMed1989

Tissue-specific activity of heterologous viral promoters in primary rat hepatocytes and Hep G2 cells.

In preparation for studies using gene transfer, we have identified transcriptional control elements which are active in primary rat hepatocytes. We used plasmids which were constructed so that the promoter or enhancer of interest initiated transcription of the bacterial chloramphenicol acetyltransferase (CAT) gene. Plasmids were introduced into primary rat hepatocytes in culture, into Hep G2 cells and other human and animal cell lines and into bone marrow stromal cells, and CAT activity was assayed after 48 hr. In primary rat hepatocytes, the highest CAT activity was obtained with plasmids carrying the Rous sarcoma virus long terminal repeat (pRSVCAT), or the SV40 early region promoter and enhancer (pSV2CAT). Hepatocytes carrying the murine cytomegalovirus immediate early promoter (pUCRNmCMVX/HCAT) also had appreciable CAT activity. No CAT activity was detected in rat hepatocytes carrying pSVOCAT (a promoterless construct), pUCRNtKCAT (herpes simplex thymidine kinase gene promoter), pLPVCAT (lymphocytotrophic papovavirus promoter) and pHBV1CAT (hepatitis B virus enhancer and core gene promoter). Therefore, for future studies of gene transfer in primary rat hepatocytes, the Rous sarcoma virus long terminal repeat or the SV40 early region promoter and enhancer can be effectively used to drive gene expression. Hep G2 cells carrying pHBV1CAT had high CAT activity. Hep G2 cells carrying pHBV2CAT (similar to pHBV1CAT, but with the hepatitis B virus sequences in reverse orientation with respect to the CAT sequences) and pHBV3CAT (similar to pHBV2CAT, but hepatitis B virus sequences are separated from the CAT sequences by about 700 bases) also expressed CAT activity, but not as strongly as with pHBV1CAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Development and evaluation of a system of microencapsulation of primary rat hepatocytes.

To determine the in vitro function of microencapsulated hepatocytes, viable hepatocytes were isolated from rats and encapsulated within biocompatible alginate-polylysine membranes for in vitro studies. Urea formation, prothrombin and cholinesterase activity, the incorporation of tritiated leucine into intracellular proteins and the immunolocation of synthesized albumin were monitored in culture. Despite a decrease in some of these activities, the cultured hepatocytes continued to function throughout the 5-week observation period, producing and excreting urea, prothrombin and cholinesterase activity into the medium. In addition, albumin could be demonstrated within encapsulated hepatocytes for up to 5 weeks. Scanning and transmission electron microscopy showed the cells to be embedded within the alginate matrix and to retain a globular shape.

Albumins↗
PubMed1989

Role of lysine methylation in the activities of elongation factor 1 alpha.

Previous work in our laboratory has demonstrated that 19% of the lysine residues in the protein synthesis elongation factor (EF-1 alpha) are methylated when the factor is purified from the mycelial form of the fungus Mucor racemosus. However, the same factor, when purified from spores of M. racemosus, is largely unmethylated. Despite its wide-spread occurrence in a great number of basic proteins, the functional significance of lysine N-methylation remains poorly understood. Spore and mycelial forms of EF-1 alpha were therefore compared in a series of assays to determine their relative affinities for various substrates and cofactors known to interact with the factor during the elongation cycle. The results suggested that hypomethylated and fully methylated EF-1 alpha had equal affinities for GTP, aminoacyl-tRNA, and ribosomes. Also, methylation did not appear to affect the accuracy of translation in an in vitro system. However, experiments did suggest that methylation may affect the ability of the factor to form complexes with other subunits (EF-1 beta gamma) which are known to enhance the overall rate of protein synthesis.

Amino Acyl-tRNA Synthetases↗
PubMed1989

Epinephrine improves expiratory flow rates in patients with asthma who do not respond to inhaled metaproterenol sulfate.

One hundred patients with acute asthma and peak expiratory flow rates (PEFR) less than 150 L/min were randomized and treated in a double-blind treatment protocol with either metaproterenol sulfate aerosol (MPA) inhalation and placebo injection or epinephrine injection (EPI) and inhaled placebo at entry and at 30 and 60 minutes, and then were treated with the crossover comparison regimen at 120, 150, and 180 minutes. The two groups had similar entry PEFRs and FEV1 (MPA, 112 L/min; 0.94 L, respectively; EPI, 111 L/min; 0.85 L, respectively) and similar plasma theophylline levels (MPA, 12.2 micrograms/ml; EPI, 13.8 micrograms/ml). PEFR and FEV1 were measured every 30 minutes for 4 hours. Mean expiratory flow rates among both groups were similar at entry and at 120 and 240 minutes. At 120 minutes, flow rates had improved in 28/46 MPA-treated patients (61%) and 48/54 EPI-treated patients (89%). Among these improved patients, flow rates were significantly higher in the MPA-treated group. At 120 minutes, 18/46 MPA-treated patients (39%) and 6/54 EPI-treated patients (11%) had PEFRs less than 120 L/min and PEFR and FEV1 less than 120% of baseline values (p less than 0.01). In 13 of these 18 MPA-treated patients who did not improve compared to 1/6 EPI-treated patients who did not improve, PEFRs were greater than 120 L/min, and PEFR and FEV1 had increased 20% or more above baseline values after treatment with the crossover comparison regimen (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1989

Affect and cognition in autism.

An array of six photographs of the same woman was used to assess the ability of 18 autistic, 14 nonautistic mentally retarded, and 18 normal preschool subjects to use affect- and activity-related concepts in the solution of cognitive tasks. The Total Performance Level of the autistic and mentally retarded subjects did not differ significantly. Autistic subjects performed imitation, directed action, and description tasks less well in the affect mode. The findings are consistent with other studies, suggesting an impairment in the expression of emotion in autism.

Adolescent↗