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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 253 records · Page 14Linked to original sources
PubMed1991

Nuclear and flow cytometric characteristics associated with overexpression of the c-erbB-2 oncoprotein in breast carcinoma.

The overexpression of the c-erbB-2 oncoprotein is now thought by most authors to be associated with adverse prognosis in breast carcinoma. In this study, we investigate the relationship between overexpression of the c-erbB-2 oncoprotein and nuclear size by morphometry in a series of 150 human breast carcinomas, comprising 65 cases of ductal carcinoma in situ (DCIS) and 85 cases of invasive adenocarcinoma. The mean nuclear size for c-erbB-2 positive cases of DCIS was 54.8 micron 2 and invasive carcinoma was 52.1 micron 2 respectively, in contrast with 41.6 micron 2 and 42.5 micron 2 for c-erbB-2 negative cases of DCIS and invasive carcinoma respectively. Flow cytometric examination of DNA in a subset of 91 of these tumours showed no association between tumour cell aneuploidy and c-erbB-2 overexpression. S-phase fraction could be calculated on 20 cases of DCIS and 48 invasive carcinomas. There was a strong association between c-erbB-2 overexpression, S-phase fraction (p less than 0.001) and proliferative index (p less than 0.001) in 20 cases of DCIS. A weak association of S-phase fraction and c-erbB-2 overexpression was seen in 48 invasive carcinomas (p = 0.047). This study confirms the subjective impression that there is a relationship between large tumour cell nuclear size and an overexpression of the c-erbB-2 oncoprotein, and also shows an association with increased tumour cell proliferation.

Adenocarcinoma↗
PubMed1991

Self-differentiation of human fetal lung organ culture: the role of prostaglandins PGE2 and PGF2 alpha.

Addition of PGE2, but not PGF2 alpha, to fetal lung organ cultures accelerates the process of self-differentiation with increased dilatation of terminal airsacs and differentiation of the epithelial lining. Indomethacin reduces the endogenous production by organ cultures of PGE2, PGF2 alpha, 13,14-dihydro-15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2 alpha and retards the process of self-differentiation. Prolonged exposure of cultures to indomethacin results in cell necrosis. Indomethacin inhibition of self-differentiation can be reversed and accelerated by the addition of PGE2. Addition of PGF2 alpha in the presence of indomethacin prevents indomethacin-associated cell necrosis but does not accelerate dilatation or differentiation beyond that of cultures in sera-free media without additions. We propose that the endogenous production of PGE2 is a key process in the mechanism of self-differentiation of human fetal lung in organ culture.

Cell Differentiation↗
PubMed1991

Activation of the L1 late H2B histone gene in blastula-stage sea urchin embryos by Antennapedia-class homeoprotein.

The L1 late H2B histone gene of the sea urchin Strongylocentrotus purpuratus is transcriptionally activated in late blastula stage embryos by a mechanism that depends on an enhancer element located 3' of the gene (Zhao et al., 1990). A protein factor, designated H2B abp 1, binds this element at a site that resembles the consensus recognition sequence of Antennapedia-class homeodomain proteins. We demonstrate here that Antennapedia (Antp) and Hbox4 proteins, members of the Antennapedia class of homeoproteins from Drosophila and sea urchin respectively, bind the L1 H2B abp 1 site, and that the Drosophila Antp protein acts through this site to trans-activate the L1 H2B gene, in vivo. In addition, RNA gel blot analysis demonstrated that Hbox4 transcripts accumulate in developing embryos with a time course that closely resembles that of H2B adp 1 DNA binding activity and the activity and the transcription rate of the L1 late H2B gene. Finally, we show that antibody prepared against the sea urchin Hbox4 protein, a member of the Abd-B subclass of the Antennapedia class, specifically inhibits binding of the H2B abp 1 factor to the L1 H2B enhancer, suggesting that H2B abp 1 is encoded by Hbox4 or a closely related gene.

Animals↗
PubMed1991

c-erbB-2 oncoprotein expression in primary and advanced breast cancer.

Immunoreactivity for c-erbB-2 oncogene product expression has been investigated in patients with breast cancer using the polyclonal antibody 21N. Three series of patients were studied, 602 presenting with primary operable cancer, 57 with stage 3 and 123 with stage 4 disease. Representative tissue sections of each primary tumour were stained using a standard immunoperoxidase technique. Invasive tumour membrane immunoreactivity was assessed and identified in 15% of patients with primary operable cancer and 20% in the advanced breast cancer group. The results demonstrate a relationship between poorer survival and oncogene expression in all three patient groups. Patients in the primary operable cancer group with membrane oncoprotein expression had a poorer outcome, 35% 10-year survival, compared with those in which membrane expression was absent, 55% 10-year survival. The median survival of patients with stage 3 disease with c-erbB-2 membrane positivity was 17 months compared to 24 months with membrane negativity. In stage 4 disease median survival with membrane expression was 8.8 months compared to 19.7 months with no membrane expression. In addition in the series of primary cancers a correlation existed between histological grade and membrane immunoreactivity. Multivariate analysis showed histological grade to be a more powerful prognostic factor than c-erbB-2 protein expression. In conclusion, this study demonstrates, in a large series of patients presenting to one centre, that c-erbB-2 protein expression is a prognostic indicator in patients with primary operable and advanced breast disease.

Breast Neoplasms↗
PubMed1991

Pain and addiction.

In a society which is drug-orientated yet is committed to a 'War on Drugs', guidelines for prescribing narcotic analgesics are marked by division and inconsistency. A fear of engendering an addiction leads to anxiety in doctors about prescribing these analgesics and to the inadequate treatment of pain. The concept of 'addiction' is derived from an essentially moralistic view of drug use, and serves as a barrier to effective treatment of chronic non-malignant pain. A biopsychosocial approach to disease provides a better basis for treatment of this type of pain.

Journal Article↗
PubMed1991

Intracytoplasmic lumina--a useful diagnostic feature of adenocarcinomas.

The monoclonal antibody NCRC-11, which has epithelial membrane antigen (EMA)-like immunoreactivity, was used to identify intracytoplasmic lumina in a series of 105 adenocarcinomas from various sites and in 283 breast carcinomas; 55% of the non-breast carcinomas and all breast carcinomas except one of spindle cell type contained intracytoplasmic lumina. The highest frequency (16.4% of tumour cells) was found in invasive lobular carcinoma of the breast. The use of antibodies with EMA reactivity is advocated in the routine investigation of metastatic and undifferentiated tumours.

Adenocarcinoma↗
PubMed1991

Lithium carbonate and mood disorder in recently detoxified alcoholics: a double-blind, placebo-controlled pilot study.

The effects of lithium carbonate were assessed in a double-blind, placebo-controlled study of a small group of recently detoxified alcoholics. The patients were treated during their 2nd and 3rd week of abstinence. A previous study demonstrated the existence in these patients of a syndrome of mildly elevated psychomotor rate, including irritability, grandiosity, an increased need for social contact, loquaciousness, and sexual preoccupation. The intensity of this syndrome was significantly decreased by treatment with low dose lithium carbonate, with no effect of placebo treatment.

Adult↗
PubMed1990

Effect of intravenous streptokinase on early mortality in patients with suspected acute myocardial infarction. A meta-analysis by anatomic location of infarction .

PURPOSE: To determine the effect of intravenous streptokinase on early mortality in patients with suspected acute anterior and acute inferior myocardial infarctions. DATA IDENTIFICATION: A literature search of English-language studies on the use of intravenous streptokinase in the treatment of suspected acute myocardial infarction for the period 1966 to 1989 using Medlars II and the bibliographies of relevant articles. In a number of instances, additional details on early mortality by location of myocardial infarction were provided by the authors. STUDY SELECTION: Of 140 originally identified articles, 6 that specifically met our inclusion criteria were selected: randomized trials that used intravenous streptokinase in a dose of 1.5 million units, with or without additional agents, compared with a group that differed only by the absence of streptokinase. Trials were selected by review of the methods section without regard for the results. DATA EXTRACTION: Data were extracted independently by two observers using specific methodologic criteria for infarct location and early mortality. After they conferred, the observers agreed completely on the data. RESULTS OF DATA SYNTHESIS: Among the 9155 patients with suspected acute anterior myocardial infarction, the mortality rate in the control group was 17.4%. In contrast, patients treated with streptokinase had a 12.5% mortality. The mean risk difference was -4.8% (95% CI, -7.5% to -2.1%) and the summary risk ratio was 0.72 (CI, 0.65 to 0.79). A total of 9650 patients with suspected inferior infarction had a mortality rate in the control group of 7.6% [corrected]. The mortality for streptokinase-treated patients was 6.6%. The mean risk difference was -0.8% (CI, -1.8% to 0.2%) and the summary risk ratio was 0.87 (CI, 0.76 to 1.01). CONCLUSIONS: Intravenous streptokinase clearly confers a protective effect against early mortality in patients with suspected acute anterior myocardial infarction. The magnitude of this effect is on the order of a 5% absolute reduction in risk of death by 21 to 35 days. For these patients, 21 need to be treated to save 1 additional life. For patients with suspected acute inferior infarction, the benefit of treatment on reducing early mortality is of smaller magnitude and less certain. These patients have an estimated absolute reduction of early mortality of approximately 1%, which would require treating 125 patients to save 1 additional life.

Humans↗
PubMed1990

Hepatitis C virus in intravenous drug users.

Sera from 172 intravenous drug users were tested for the presence of antibodies to hepatitis C virus (anti-HCV). The results were analysed in relation to aspects of the history of drug use and evidence of liver disease. The presence of anti-HCV was strongly associated with duration of intravenous drug use. Two-thirds of patients were anti-HCV seropositive within two years of commencing regular intravenous drug use, and there was 100% seropositivity among people injecting drugs for more than eight years. Seropositivity for hepatitis C virus closely paralleled exposure to hepatitis B virus, which was also endemic in this population. In contrast, only one patient tested positive for antibodies to the human immunodeficiency virus. The presence of anti-HCV correlated poorly with biochemical markers of hepatitis. About half the patients with anti-HCV had normal serum levels of alanine aminotransferase, whereas an abnormal liver biochemistry was frequently observed in anti-HCV seronegative subjects. Previous studies of non-A, non-B hepatitis that have used abnormal liver biochemistry as a marker have underestimated the prevalence of chronic hepatitis among intravenous drug users; the use of a specific screening test reveals that infection with hepatitis C virus is very common in this population.

Adult↗
PubMed1990

Heroin users seeking methadone treatment.

Seven hundred and sixty-seven patients applying to enter public methadone programmes in the western suburbs of Sydney underwent assessment in the Drug and Alcohol Unit at Westmead Hospital between 1986 and 1988. These patients had long histories of illicit drug use and most were involved in crime, prostitution and a drug subculture. Many abused multiple drugs, and almost all had been exposed to hepatitis B virus. However, human immunodeficiency virus (HIV) seropositivity rate was low. Methadone programmes, at least in Sydney's western suburbs, attract a very disadvantaged population for whom rehabilitation is likely to be a difficult, long-term process.

Adult↗
PubMed1990

The alpha and pi isoenzymes of glutathione S-transferase in human fetal lung: in utero ontogeny compared with differentiation in lung organ culture.

Polyclonal antisera to the alpha and pi isoenzymes of glutathione S-transferase have been used in immunohistochemical studies of developing human lung. In utero expression of the pi set was down-regulated in distal airway cells and the first appearance of pi-negative cells coincided with phenotypic differentiation. In contrast, in the early phase of fetal lung organ culture pi isoenzyme was detected in all differentiated epithelial cells and only as culture progressed did focal negativity develop. The alpha set showed no developmental changes in utero or in organ culture.

Down-Regulation↗
PubMed1990

Leukemia following chemotherapy for ovarian cancer.

An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known.

Antineoplastic Agents↗
PubMed1990

Leukemia following Hodgkin's disease.

To investigate the effect of different treatments for Hodgkin's disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case-control study of 163 cases of leukemia following treatment for Hodgkin's disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkin's disease but in whom leukemia did not develop. The use of chemotherapy alone to treat Hodgkin's disease was associated with a relative risk of leukemia of 9.0 (95 percent confidence interval, 4.1 to 20) as compared with the use of radiotherapy alone. Patients treated with both had a relative risk of 7.7 (95 percent confidence interval, 3.9 to 15). After treatment with more than six cycles of combinations including procarbazine and mechlorethamine, the risk of leukemia was 14-fold higher than after radiotherapy alone. The use of radiotherapy in combination with chemotherapy did not increase the risk of leukemia above that produced by the use of chemotherapy alone, but there was a dose-related increase in the risk of leukemia in patients who received radiotherapy alone. The peak in the risk of leukemia came about five years after chemotherapy began, and a large excess persisted for at least eight years after it ended. After adjusting for drug regimen, we found that patients who had undergone splenectomy had at least double the risk of leukemia of patients who had not, and an advanced stage of Hodgkin's disease carried a somewhat higher risk of leukemia than Stage I disease. We conclude that chemotherapy for Hodgkin's disease greatly increases the risk of leukemia and that this increased risk appears to be dose-related and unaffected by concomitant radiotherapy. In addition, the risk is greater for patients with more advanced stages of Hodgkin's disease and for those who undergo splenectomy.

Antineoplastic Agents↗
PubMed1990

Prenatal diagnosis: current status and future trends.

Many of the major single-gene disorders in man can now be detected in utero using restriction fragment length polymorphisms (RFLPs). This approach is based on the knowledge of established linkage between RFLPs and mutations in an adjacent gene. The development of the polymerase chain reaction has altered the available approaches to this problem. This technique permits very rapid detection of the specific mutation from small amounts of starting material and may enable us to detect the genotype from fetal cells in maternal blood or from single cells in embryos before implantation. This may lead to the selection of embryos that lack a defect before they are implanted, avoiding the need for termination of pregnancy. Perhaps the greatest ethical challenge related to the application of these techniques will come with the understanding of the genetic basis for common polygenic disorders. The clarification of the multiple genetic factors responsible for a large part of susceptibility to diseases such as diabetes mellitus, rheumatoid arthritis or ischaemic heart disease will be greatly facilitated by a one-centimorgan genetic map. The strategy involved in establishing such a map, using the polymerase chain reaction, and then the identification of genetic loci responsible for susceptibility to a typical polygenic disease (insulin-dependent diabetes mellitus), is discussed. The ability to identify individuals at high risk of developing such diseases may present opportunities for early intervention.

Female↗
PubMed1990

Clinicians' self-reported reactions to psychiatric emergency patients: effect on treatment decisions.

Masters-level social work clinicians at two urban psychiatric emergency services self-rated their cognitive reactions and conscious feelings toward a total of 783 patients. Negative self-reported affect toward patients was related to their displaying overt psychotic symptoms, having a final diagnosis of substance abuse, being impulsive, unemployed, or having a history of criminal behavior. However, clinicians' reactions did not enter into the model predicting hospitalization, which included opinion of family and friends, degree of psychopathology, suicidal ideation and lack of social supports as the major predictors of whether or not a patient would be hospitalized.

Adult↗
PubMed1990

The treatment and long-term prognosis of children with intracranial tumors: a study of 610 cases, 1950-1981.

Six hundred and ten children aged under 16 years with intracranial tumors were referred for radiotherapy between 1950 and 1981: 579 were new cases and 31 had recurrent disease after primary treatment elsewhere. Radiotherapy was completed in 93% of all cases. The actuarial survival rate for all new cases was 53% at 5 years, 46% at 10 years, 40% at 20 years, and 39% at 30 years. The oldest children (10-15 years) had the best survival and the youngest (0-2 years) had the worst survival. Children treated with megavoltage x-ray equipment (1970 to 1981) had a significantly greater survival than those treated with orthovoltage X rays (1950-1969). Overall, a direct correlation was found between survival and maximum radiotherapy dose. Children having a total excision of the tumor prior to radiotherapy showed a greater survival than those treated by a subtotal or partial tumor removal. Children treated by radiotherapy alone had a survival comparable to those treated by sub-total excision and radiotherapy. There is a striking difference in survival expectation depending on initial functional category (I to III). The overall survival rates of 428 children completing treatment for glioma were 49% at 5 years, 43% at 10 years, and 40% at 15 years. The results according to certain specific tumor sites within the cerebral hemispheres are reported. Age is an important prognostic factor in low grade and also high grade astrocytomas, children having longer survivals than adults. Sub-total or partial excision of craniopharyngiomas combined with radical radiotherapy appears to give the best long-term results. Of 73 new cases, the 5-, 10-, and and 15-year survival rates were 92%, 84%, and 79%. Recurrent craniopharyngiomas treated by surgery alone can be salvaged by further conservative surgery and radical radiotherapy. Optic gliomas are slow growing low grade astrocytomas. Survival rates at 5, 10, and 15 years for 20 children with mostly chiasmal lesions were 89%, 89%, and 78%, respectively. In 73 children with brain stem tumors, 17% remained alive for up to 15 years. The risk of CNS seeding from intracranial ependymomas depends on site of origin and grade of malignancy, with 50% incidence occurring in cases with high grade lesions situated in the posterior fossa. Survivals at 5, 10, and 15 years in 51 children were 51%, 40%, and 31%. Adjuvant chemotherapy improves survival.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗