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Biomedical subjects

B Jones

Publications and source records attributed to B Jones.

At least 379 records · Page 21Linked to original sources
PubMed1991

Human immunodeficiency virus infection among Peace Corps volunteers in Zaire. No evidence for unusual modes of transmission.

A prospective study of US Peace Corps volunteers (PCVs) serving in Zaire, central Africa, was undertaken to determine the risk of human immunodeficiency virus (HIV) and hepatitis B virus infection in an acquired immunodeficiency syndrome-aware expatriate population living in an area of high endemicity for both diseases. Of the 338 PCVs who served in Zaire between October 1985 and May 1988, 282 (83%) were enrolled, representing 7776 volunteer-months of service. Analyses of serum samples for HIV and hepatitis B virus were performed on enrollment and at completion of service. All PCVs received extensive education and counseling regarding HIV and acquired immunodeficiency syndrome throughout their stay in Zaire. There were no documented seroconversions to HIV among 282 PCVs who lived in Zaire for periods ranging from 1 to 81 months, with a mean length of stay of 27.4 months. Of the 14 (6.2%) of 226 PCVs tested who had at least one positive serologic marker for infection with hepatitis B virus, none was documented to have seroconverted during service. During the study period, the rate of all sexually transmitted diseases among PCVs in Africa decreased from 131 to 68 per 1000 study population per year, and there were 52 cases of confirmed malaria among volunteers in Zaire. These data suggest that the risk of acquiring infection with HIV or hepatitis B virus in PCVs in Zaire is very low, and there is no evidence for unusual modes of transmission.

Adult↗
PubMed1990

Midline facial defects with ocular colobomata.

We describe 5 children with midline facial anomalies and iris colobomata reminiscent of frontonasal "dysplasia." Two patients have, in addition, abnormalities of the eyelids and one of them probably has the rare autosomal recessive condition frontofacionasal "dysplasia." The patients may have a new syndrome of midline facial defects, iris colobomata, and mental retardation.

Abnormalities, Multiple↗
PubMed1990

Ectopic expression from the Deformed gene triggers a dominant defect in Drosophila adult head development.

Drosophila adults carrying a dominant allele of the Deformed locus (DfdD) have a mutant phenotype in which lower eye and orbital structures of the adult head are eliminated. The molecular defect responsible for this dominant mutation is a large, transposon-flanked, fragment of DNA inserted downstream of the Deformed (Dfd) transcription unit. The downstream transposon-flanked insert causes the inappropriate activation of Dfd gene expression in a subset of the cells of the eye imaginal disc, resulting in their abnormal development, and in the loss of lower eye structures from the adult head. A chromosome selected for its reversion of the dominant phenotype is missing a portion of the transposon-flanked insert and reverts to a normal expression pattern of Dfd in the eye-antennal disc. Additional evidence that the dominant head phenotype is caused by ectopic expression of Dfd in the eye disc derives from experiments showing that a DfdD-like phenotype can be induced by ectopic expression of a Dfd gene under heat shock promoter control.

Animals↗
PubMed1990

Spread of herpes simplex virus type 1 in the central nervous system during experimentally reactivated encephalitis.

Because many of the features of reactivated herpes simplex virus type 1 (HSV-1) central nervous systems (CNS) infections in vivo are incompletely understood, we used an animal model to study the development of the morphological, ultrastructural, radiological and immunological changes which occurred during acute and experimentally reactivated diseases. Rabbits were intranasally inoculated with HSV-1, and their latent trigeminal ganglionic and CNS infections were reactivated by intravenous injection of cyclophosphamide and dexamethasone. Technetium brain scans were performed to localize areas of blood-brain barrier breakdown, and cerebrospinal fluid (CSF) was analysed for IgG content by radial immunodiffusion assays. Nervous system tissues were studied by in situ hybridization and by immunofluorescent, light and electron microscopic techniques. Diffuse uptake of technetium was observed as HSV-1 spread transsynaptically into the brain during the acute phase of infection, and viral antigens and nucleic acids were detected in both the CNS olfactory and trigeminal systems. During latency, viral RNA was detected in the nuclei of neurons within the CNS olfactory cerebral and entorhinal cortices, indicating that HSV-1 became latent within the same CNS structures that were involved during the acute phase of infection. Following drug-induced reactivation, the brain scans revealed a more focal breakdown of the blood-brain barrier, and both neurons and neuronal processes in the entorhinal and olfactory cortices contained viral nucleic acids which correlated with the ultrastructural presence of HSV-1 virions. During the reactivated phase of infection a marked increase in the CSF IgG index occurred without an increase in the CSF: serum albumen ratio indicating a prompt intrathecal response in infected rabbits as compared to controls. To some extent, the CSF IgG index reflected the degree of histopathological damage.

Animals↗
PubMed1990

Treatment of epidemic Kaposi's sarcoma with combination chemotherapy (vincristine and bleomycin) and zidovudine.

Advanced AIDS-associated Kaposi's sarcoma often requires systemic cytotoxic chemotherapy. Despite high response rates, the majority of the patients die of opportunistic infections (OIs). Effective anti-retroviral agents in combination with cytotoxic chemotherapy may be useful in preventing the development of OIs in addition to increasing the tumor response. Twelve patients with extensive EKS were treated with a non-myelosuppressive drug regimen consisting of bleomycin and vincristine (BV) in combination with the anti-retroviral agent, zidovudine (ZDV). The dose of ZDV was 200 mg orally every four hours (full dose) in eight patients (Group I) or 100 mg orally every four hours (half dose) in four patients (Group II). Toxicity was acceptable with only 3 patients (all from Group I) requiring blood transfusions. ZDV dose reduction due to granulocytopenia was required in 6 patients (5 in Group I and 1 in Group II). Only two patients developed OIs during 27.5 cumulative months of therapy. The overall response rate was 83% in both groups with 4 patients achieving complete remission (CR) and 6 patients acheiving a partial remission (PR). We conclude that a combination of (BV) chemotherapy and ZDV can be used safely with high response rates. Prospective studies of such combination regimens are currently in progress.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Absence of placebo response in obsessive-compulsive disorder.

Analyses in 30 patients with a diagnosis of obsessive-compulsive disorder given single-blind placebo over a 2-week period and of 12 of these patients who continued treatment on double-blind placebo for an additional 10 weeks revealed virtual absence of improvement on both clinician and self-rating scales of obsessions, compulsions, phobias, depression, and anxiety. This result would imply that the contribution of the placebo effect to the pharmacotherapy of patients with obsessive-compulsive disorder is negligible although considerable effort and work is still required to reliably identify one of four panic disorder with agoraphobia patients who respond to placebo. The placebo response thus presents a clear distinction between these two phenomenologically complex anxiety disorders.

Adolescent↗
PubMed1990

Frontonasal dysplasia or craniofrontonasal dysplasia and the Poland anomaly?

We describe a 10-year-old girl with features of a frontonasal dysplasia and a right-sided Poland anomaly. As there has been one previous case report of pectoral muscle hypoplasia in association with craniofrontonasal dysplasia, the relationship between these two conditions is discussed.

Abnormalities, Multiple↗
PubMed1990

Distribution of labelled cysteine and methionine in the matrix of the stratum medium of the wall and in the laminar layer of the equine hoof.

The distribution of 35-S-labelled cysteine and methionine in the epidermis of the equine hoof following 2 hours of intra-arterial injection was studied by microautoradiography. Material for autoradiography was obtained by biopsy about 1 hour after termination of the intra-arterial injection and also 10 and 40 days later. In the specimens obtained one hour after the injection of labelled cysteine and methionine, the amount of radioactivity in the matrix and in the most proximal part of the laminar layer was very high. There was a clear difference between the distribution of the two labelled amino acids in the keratinizing epidermis of the hoof. Cystine was located mainly in keratinocytes of the keratogenous zone in the matrix and in the nucleated keratinocytes that formed the incompletely keratinized basal part of the primary epidermal laminae and covered the lateral surface of the outer, fully keratinized part of those laminae. Methionine was located mainly in the stratum basale and in the stratum spinosum of the matrix and in the secondary epidermal laminae of the laminar layer. In the specimens obtained 10 days after injection of labelled cysteine a considerable number of keratinocytes, both in the matrix and in the laminar layer, had attained terminal differentiation with residual labelling. Neither in the cysteine specimens obtained after 40 days or in the methionine specimen obtained after 10 days was radioactivity significantly above the basal level observed in the hoof epidermis. The possible importance of the results for research on the pathogenesis of laminitis and on the growth of the hoof is discussed.

Animals↗
PubMed1990

A controlled dose-ranging study of remoxipride and haloperidol in schizophrenia--a Canadian multicentre trial.

The efficacy and side-effect profile for three dose ranges of remoxipride were compared with haloperidol in 242 schizophrenic inpatients in 13 centres. All patients were in a productive phase of schizophrenia according to DSM-III criteria. Relative efficacy of low dose (30-90 mg daily) vs middle dose (120-240 mg daily) vs high dose (300-600 mg daily) was compared with the standard dose of haloperidol (15-45 mg daily), as were the side effects. It was concluded that the therapeutic efficacy of remoxipride was comparable to that of haloperidol for acute episodes of schizophrenia; that the low dose range was significantly less effective than the higher ranges; that there was a clear advantage of remoxipride over haloperidol with respect to incidence and severity of extrapyramidal symptoms. The general safety profile of remoxipride as assessed from clinical chemistry, haematology, and cardiovascular variables suggests that remoxipride in the dose ranges studied can be used safely for the treatment of schizophrenic patients.

Acute Disease↗
PubMed1990

Recognition by the DNA repair system of DNA structural alterations induced by reversible drug-DNA interactions.

Ditercalinium (NSC 335153) was synthesized as a bifunctional DNA intercalator. It is made of two 7-H pyridocarbazole rings joined by a rigid bis-ethyl bispiperidine chain. It binds to DNA with high affinity and elicits anti-tumor activity on a variety of animal tumors. 1H n.m.r. studies of ditercalinium bis-intercalated into d(CpGpCpG)2 have shown that the intercalation process occurs from the large groove of the DNA helix while the two intercalated rings are separated by two base pairs. Because of the linking chain rigidity of ditercalinium, DNA conformation has to be altered to permit the intercalation of the two rings. DNA must be bent toward the minor groove. In E. coli, ditercalinium elicits a specific toxicity on polA strains which is suppressed by an additional uvrA mutation. In vitro, the purified UvrA and UvrB proteins bind to the DNA-ditercalinium complex in an ATP dependent manner. The UvrABC complex induces single-strand nicks, but only when ditercalinium is bound to negatively supercoiled DNA. The life-time of the UvrAB-DNA-ditercalinium complex is greater than 50 min when free ditercalinium concentration is maintained constant in the incubation medium. The cytotoxicity of ditercalinium in E. coli results from the induction of a futile and abortive DNA repair. The reversible ditercalinium-DNA complex mimics a bulky DNA lesion, yet the UvrABC endonuclease is unable to cope with a reversible lesion since it cannot eliminate the causative agent. The interaction of UvrA and UvrB proteins has also been studied with DNA and other DNA-binding drugs forming high-affinity complexes such as distamycin. The Uvr protein recognition process appears to be associated with specific DNA structural alterations. In eukaryotic cells, ditercalinium is concentrated in mitochondria. Mitochondrial DNA is rapidly and totally degraded. Mitochondrial DNA coded proteins being no longer synthesized, the respiratory chain is progressively inactivated. The stimulation of the glycolytic pathway allows the cells to continue growth for several generations. Dihydro-orotate dehydrogenase is located in the inner membrane of mitochondria and its activity is dependent on mitochondria energization. It becomes inactive after ditercalinium treatment. A drop of the pyrimidine pool is then observed. Complementation of treated cells with uridine decreases 10-fold the ditercalinium toxicity. The cellular delayed toxicity of ditercalinium results from the slow induction of a pyrimidineless state associated with the progressive inactivation of mitochondria. The results show that DNA structural alterations induced by reversible drug-DNA complexes can be recognized by DNA repair enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Characterization of a bovine leucocyte differentiation antigen of 145,000 MW restricted to B lymphocytes.

A new bovine B-cell differentiation antigen is described that is detected by three monoclonal antibodies (mAb). The antigen is not an immunoglobulin and is precipitated from peripheral B cells as a molecule with an approximate molecular weight (MW) of 120,000 or 145,000 before and after reduction, respectively. Data obtained from two-colour cytofluorimetry and immunohistochemistry confirmed that the antigen was found only on mature B cells and on cells with dendritic morphology in the follicles of the organized lymphoid tissues. Its level of expression is directly correlated with that of IgM on peripheral blood B cells and Theileria parva-transformed B cells. The marker was also expressed on the peripheral cells which expressed surface IgG. Based on the antigen's cellular distribution, biochemistry and histochemistry, it is considered to be analogous to the human CD21 antigen.

Animals↗
PubMed1990

Interferon-alpha maintenance therapy after cytotoxic chemotherapy for treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma.

A prospective phase I clinical trial with recombinant interferon-alpha-2b as maintenance therapy after cytotoxic chemotherapy was conducted. Twenty-one homosexual and bisexual males with extensive mucocutaneous or visceral epidemic acquired immunodeficiency syndrome (AIDS)-Kaposi's sarcoma (KS) were studied. After a complete response (6 patients) or partial response (15 patients) from chemotherapy consisting of Adriamycin (20 mg/m2), bleomycin (10 U/m2), and vincristine (1.4 mg/m2; 2 mg maximum), patients were given interferon-alpha (IFN-alpha) in an attempt to prolong disease-free survival. Three dose levels of daily IFN-alpha were tested: 5, 10, and 15 million U. The maximum tolerated dose was 10 million units. Dose-limiting toxicities included recurrent grade 3 fatigue, diarrhea, and fever, which resulted in the termination of therapy in eight patients (38%). Hematologic toxicities were infrequent (four patients; 19%). Responses were observed in two patients on IFN-alpha, both at the 10-million-U dose level. The median duration of response on IFN-alpha therapy following chemotherapy was 8 weeks (range, 3-11). We conclude that the duration of IFN-alpha maintenance response following cytotoxic chemotherapy is short with response to residual disease observed in a minority of cases at this dose and schedule. Additional trials of maintenance therapy in patients with advanced AIDS-KS combining antiretroviral agents are in progress.

Acquired Immunodeficiency Syndrome↗