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Biomedical subjects

R Stephens

Publications and source records attributed to R Stephens.

At least 145 records · Page 8Linked to original sources
PubMed1982

DNA sequence relationship of the baboon endogenous virus genome to the genomes of other type C and type D retroviruses.

Baboon endogenous virus (BaEV) is a type C retrovirus present in multiple proviral copies in the DNA of baboons. Although interspecies antigenic determinants present on reverse transcriptase and gag proteins are shared among all mammalian type C viruses, no nucleic acid homology between BaEV and other type C viruses (except RD-114) has been found in conventional liquid hybridization experiments. In this study, we used restriction fragments of cloned BaEV DNA immobilized on nitrocellulose to test for relatedness with [(32)P]cDNA's of various type C and type D viruses. We detected the following distant relationships previously found only through immunological and protein sequencing techniques: (i) eight type C viral cDNA's (the endogenous virus of rhesus monkeys, feline leukemia virus, simian sarcoma virus, gibbon ape leukemia virus, Rauscher murine leukemia virus, BALB-2, NZB, and RD-114) and two type D viral cDNA's (Mason-Pfizer monkey virus and squirrel monkey retrovirus) were able to hybridize with cloned BaEV DNA; (ii) the eight type C probes hybridized to restriction fragments spanning most of the BaEV genome, but only RD-114 hybridized to fragments within the 1.9 kilobases at the 3' end of the genome; (iii) the two type D probes hybridized primarily to fragments within the 1.9 kilobases at the 3' terminus and weakly or not at all elsewhere; and (iv) [(32)P]cDNA's of several other oncornaviruses (mouse mammary tumor virus, equine infectious anemia virus, bovine leukemia virus, and reticuloendotheliosis virus) exhibited no homology with BaEV DNA. DNA sequence analysis has allowed us to orient the BaEV restriction map with the genetic map at both ends of the genome. Homologies between retroviral cDNA's and BaEV clone restriction fragments could thus be related to specific BaEV genes. Whereas type C cDNA's hybridized to fragments from gag, pol, and the pol-env junction, squirrel monkey retrovirus cDNA hybridized only to a fragment coding for the p15E portion of env. Mason-Pfizer monkey virus cDNA also hybridized within the p15E region, but exhibited homology to the 3' half of gp70 as well. These results are discussed relative to previously reported antigenic relatedness of retroviral proteins. The data suggest that BaEV represents an important link in oncornavirus evolution.

Base Sequence↗
PubMed1982

Metachromatic leucodystrophy: review of 38 cases.

Clinical and laboratory features of 38 children suffering from metachromatic leucodystrophy (MLD) are reported. Twenty-four children with the late infantile form of MLD presented between ages 6 and 25 (mean 17) months with a delay or deterioration in walking, followed by a general loss of abilities. There was severe handicap by age 3 years and death occurred between 5 months and 8 years after presentation. Neurological signs at the time of diagnosis were varied. Motor nerve conduction velocity was slowed in the 18 children tested. The disease became evident at a later age in 14 children. One boy presented at 13 years, while in the remainder there appeared to be two clinical patterns of the disease which could be termed (1) early juvenile or intermediate and (2) juvenile MLD. In 7 children with early juvenile or intermediate MLD a gait disorder developed between ages 4 and 6 (mean 5) years. This was accompanied in 4 children, and followed between 8 and 26 months later in the remaining 3, by loss of other abilities. Neurological signs were varied. Motor nerve conduction velocity was slowed in 2 of the 5 patients tested. Six children with juvenile MLD presented between ages 6 and 10 years with educational or behavioural difficulties. Motor disorders arose from 6 months to 4 years later. Neurological signs at the time of diagnosis, although mixed, were predominantly extrapyramidal and motor nerve conduction velocity was slowed in 2 of the 3 children tested. In the early juvenile form of MLD, progression of the disease was slower than in the late infantile form and death occurred between 31/2 and 18 years after presentation. Only one-third of patients had fits and these tended to be a late feature.

Child↗
PubMed1981

Exposure to lead.

Explore the source record for details and available documents.

Air Pollutants↗
PubMed1981

Antenatal diagnosis of Niemann-Pick disease in a twin pregnancy.

An Ashkenazi Jewish woman had a child with Niemann-Pick disease in her first marriage. She subsequently remarried a man who was also heterozygous for the condition and conceived twins. Prenatal diagnostic tests were performed and one twin was shown to be homozygous and the other heterozygous for Niemann-Pick disease. The problems of prenatal diagnosis and counselling in twin pregnancies are discussed.

Diseases in Twins↗
PubMed1980

Combination chemotherapy, radiotherapy, and BCG immunotherapy in extensive (metastatic) small cell carcinoma of the lung. A Southwest Oncology Group study.

From November 1976 to November 1978, the Southwest Oncology Group treated 254 patients with extensive (metastatic) small cell carcinoma of the lung with combination chemotherapy and radiotherapy with and without BCG immunotherapy. Patients receiving BCG achieved a response rate of 50% versus those patients not receiving BCG of 46% (P = .704). Response duration was 20 weeks for the BCG arms and 23 weeks for the no-BCG arms; survival was 28 weeks for the BCG arms versus 29 weeks for the no-BCG arms. An adverse effect in patients surviving more than one year was detected; those continuing to receive BCG had significantly shorter survival, 60 weeks versus 85 weeks (P = .019). Toxicities of the programs were not affected by the addition of BCG immunotherapy. It appears that BCG immunotherapy has no beneficial effect on response rate or duration of response in programs using chemotherapy and radiotherapy for control of metastatic small cell carcinoma of the lung. In addition, because of the adverse effect on long-term survival, we do not recommend the addition of BCG immunotherapy as a treatment modality in this tumor type.

Antineoplastic Agents↗
PubMed1980

Cis-platinum therapy of previously treated head and neck cancer: the Southwest Oncology Group's two-dose-per-month outpatient regimen.

The Southwest Oncology Group tested an outpatient Cis-platinum regimen in patients with carcinoma of the head and neck. Courses which consisted to two doses, a week apart, were scheduled to be given at 4-week intervals. Eighty-nine poor risk head and neck cancer patients, who had received extensive prior therapy with surgery, radiation, and/or multiple drugs were studied. Sixteen (18% of all entered and 25% of the 65 fully evaluable) had objective tumor regression. The median duration of response was 136 days. Toxicity was moderate. Myelosuppression was minimal with only 3% of patients exhibiting leukocyte nadirs below 2,000 and less tha 2% experiencing platelet counts below 50,000. Significant, but reversible, impairment of renal function occurred in 8% of patients. Individual susceptibility to such renal toxicity appears to have been predictable. This simple outpatient program with its effectiveness and minimal toxicity in poor risk patients deserves further utilization.

Adult↗
PubMed1980

Feasibility studies of oncornavirus production in microcarrier cultures.

Studies conducted with virus-infected monolayer cell cultures have demonstrated the feasibility of producing several tumor-associated viruses in microcarrier (mc) cultures (Sephadex G50 beads treated with DEAE-chloride). The efficiency of cell adherence to mc varied with the cell type, the pH of the growth medium, and the stirring force applied to keep the mc in suspension. Most cells attached firmly to the mc and could not be removed easily with routine trypsinization procedures. Techniques using Enzar-T and Pronase were effective in detaching cells from mc in 10 to 15 min while retaining 95% cell viability. After detachment, Ficoll gradients were used for rapid and complete separation of viable cell suspensions from the mc. Retrovirus production in large volumes of mc cultures was investigated with periodic harvesting of growth fluids. Physical, biochemical, and biological properties of the Mason-Pfizer monkey virus and the RD114 virus recovered from the mc cultures were identical to those produced in conventional cultures. The utilization of mc has several applications in research and short-term cultures, but the as-yet-unsolved technical problems met were found to be serious limitations when attempting mass cell culturing on a long-term basis.

Animals↗
PubMed1979

Phase I-II study of ftorafur and methyl-CCNU in advanced colorectal cancer.

The combination of Ftorafur (NSC-148958) and methyl-CCNU (NSC-95441) was evaluated in 36 patients with advanced colorectal cancer. The principle toxicities encountered were myelosuppression, gastrointestinal, and neurological. There were no complete responses and only 5/34 (14.7%) patients achieved a partial response. Methyl-CCNU and Ftorafur does not appear to be an effective combination in advanced adenocarcinoma of the colon and rectum.

Adenocarcinoma↗
PubMed1979

Relationship between monocytosis and T-lmphocyte function in human cancer.

This study was designed to: 1) determine the relative number of monocytes in mononuclear cell suspensions derived from the peripheral blood of cancer patients and 2) ascertain if any relationship existed between the numbers of monocytes in those cell suspensions and T-lymphocyte function. Monocytes were quantitated by morphology verified by phagocytosis of antibody-coated erythrocytes. A significant difference (P less than or equal to 0.01) existed between the number of monocytes in suspensions from normal individuals (26.2 +/- 4.3) and cancer patients (38.0 +/- 13.4). The cancer patients were divided into 2 groups: 1) those who exhibited normal in vitro T-cell responses to phytohemagglutinin and 2) those in whom responses were significantly suppressed. The mean number of monocytes in suspensions from the cancer patient group with normal responses was 29 +/- 9, whereas that from the cancer patients with suppressed responses was 47 +/- 11, a highly significant difference (P less than or equal to 0.01). Therefore, the study demonstrated two things: 1) Mononuclear cell suspensions derived from cancer patients exhibited significant monocytosis relative to those from normal individuals and 2) a strong correlation existed between monocytosis and suppressed T-lymphocyte function in vitro.

Cell Communication↗
PubMed1979

Characterization of a retrovirus isolated from normal mink cells co-cultivated with a dog mammary tumour.

A retrovirus antigenically distinct from known type C, B and D viruses was isolated from normal mink (Mustela vison) lung cells that had been co-cultivated with 5-iododeoxyuridine- and dexamethasone-treated dog mammary tumour cells. Cytogenetic studies of the virus-releasing co-culture showed mitotic figures identical to the normal mink cell line (MvlLu) with the exception of a low frequency of cells with extensive chromosomal breakage and uncoiling. The new virus bands at a buoyant density of 1.16 g/ml, contains 60S RNA and a reverse transcriptase which prefers Mn2+ over Mg2+ for the synthesis of DNA. This enzyme utilizes poly(rA).oligo(dT) more efficiently than poly(dA).oligo(dT) and is also able to synthesize DNA copies from the endogenous RNA. Morphologically, it is a typical type C virus. Filtered virus readily infects mink, dog and other mammalian cells indicating the amphotropic nature of its cell growth requirement. Hybridization studies showed that normal mink DNA contains multiple copies of proviral sequences of this newly isolated virus. Serological analyses indicate that the mink endogenous virus contains in its core protein, in addition to the interspecies type-C determinant, an antigenic component related to one of the determinants found in the feline leukaemia virus p30 protein. This determinant is not present in the Rauscher leukaemia virus, RD114 virus or simian sarcoma virus.

Animals↗
PubMed1979

The Börjeson-Forssman-Lehmann syndrome: a new case.

A new case of the Borjeson-Forssman-Lehmann syndrome is described with details of anthropometry, dermatoglyphs, endocrine function studies and mental state. Comparisons are made with the five previously reported cases. The diagnosis is based on the clinical appearance. Endocrine studies gave normal results and the patient's short stature is not due to growth hormone deficiency. There is no evidence for primary hypogonadism.

Abnormalities, Multiple↗
PubMed1979

Electroencephalographic change in Parkinsonian patients treated with levodopa-carbidopa.

Our findings in a relatively small series of cases seem to confirm a lack of statistically significant EEG changes when Carbidopa is combined with Levodopa in the therapy of patients with Parkinson's disease. There appears to be a slight increase in basic background frequency which was one of the earlier findings when Levodopa was first used clinically. From the literature surveyed there appears to be a definite lack of consistency in the effects of Levodopa therapy on the electroencephalogram and on the clinical status of the patients followed. We think this well may be explainable by the fact that no large study has been accomplished in which a neuroanatomical (pathological) correlation has been done with both the clinical and the EEG data. Neurological examination and the electroencephalogram are both clinical tools and have yet to be closely reviewed with the added parameter of neuro-pathologic investigation in this new day of therapy for Parkinson's disease.

Aged↗
PubMed1979

Phase II evaluation of hexamethylmelamine in advanced breast cancer: a Southwest Oncology Group study.

Ninety-eight patients with metastatic breast cancer, heavily pretreated with other agents, were entered in a phase II trial of hexamethylmelamine (HEX). Patients were randomized to receive HEX alone or combined with prophylactic pyridoxine. There was a 2% response rate in 89 partially or fully evaluable patients. Seven percent of these patients developed neurologic toxicity which occurred in the HEX-alone group only.

Aged↗
PubMed1977

Productive Epstein-Barr viral infection of the human lymphoblastoid cell line 6410 with release of early antigen inducing and transforming virus.

The human lymphoblastoid cell line 6410 was superinfected with P3HR-1 derived Epstein-Barr virus. Subsequent to the first cycle of infection, characterized by early (EA) and virus capsid (VCA) antigen synthesis, the culture, designated 6410-EBV, continued to synthesize VCA. Further immunofluorescence and electron microscopic examination over 18-24 months showed the 6410-EBV culture to be productively infected with EBV. Virus was recovered, in quantity, from the culture fluids and assayed for ability to induce EA synthesis in Raji cells and to transform human umbilical cord lymphocytes. The virus was found to possess both properties, in contrast to P3HR-1 virus which only induces EA. HLA and karyologic analyses of P3HR-1, 6410 and 6410-EBV cultures showed relatedness of 6410-EBV to 6410 cells and dissimilarity to P3HR-1. The biologic activity data coupled with the cytologic analyses confirm a productive infection of the target cells. The reason for differences in biologic activity between the infecting (P3HR-1) and progeny virus is unresolved. It may be speculated that the endogenous EBV genome of 6410 cells was activated and gave rise to a different strain of EBV or to a mixed progeny-parent population as a result of dual infection. Alternatively, the parent strain of virus may have been modfied as a result of interaction with the new host cell.

Antigens, Viral↗
PubMed1977

Comparative studies on EBV antigens by immunofluorescence and immunoperoxidase techniques.

Three groups of EBV antigens, VCA, MA and EA, were compared by the techniques of electron microscopic immunoperoxidase (IP) and immunofluorescence (IF). P3HR-1 and EBV superinfected Raji cells served as targets for labelled sera from patients with BL, NPC and IM or from healthy donors. 125I peroxidase-labelled antibodies were also prepared to determine, autoradiographically, the penetration of the complex into the cell system, and to monitor the incubation and washing procedures. The development of a gentle sedimentation technique proved critical in handling the fragile target cells. VCA and MA were readily identified and localized by both procedures without significant modification of the basic techniques. Indentification of early antigens by IP required modification of the fixation method to include a brief treatment in acetone. The diffuse early antigen (EAD) was found to be associated with cellular ribosomes.

Antigens, Viral↗