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Biomedical subjects

C J Williams

Publications and source records attributed to C J Williams.

214 records · Page 12Linked to original sources

RNase H and RNA-directed DNA polymerase: associated enzymatic activities of murine mammary tumor virus.

The RNA-directed DNA polymerase of murine mammary tumor virus, a type B RNA tumor virus, was purified sequentially through DEAE-cellulose, phosphocellulose (step gradient), and phosphocellulose (linear salt gradient) chromatography followed by glycerol sedimentation centrifugation. During all stages of purification, coincident peaks of RNA-directed DNA polymerase activity, templated by polyribocytidylate-oligodeoxyguanidylate, and RNase H digestion of [3H]polyriboadenylate-polydeoxythymidylate were observed, and both enzymatic activities displayed a cation preference for magnesium. Under conditions that removed adventitiously associated nucleases, RNase H activity was found to co-purify with polymerase. The specificity of this nuclease was assayed with various prepared substrates, which indicated that the polymerase-associated RNase H activity was directed only against the RNA strand of an RNA-DNA hybrid. It is highly probable that RNase H (RNA-DNA hybrid: ribonucleotide-hydrolase, EC 3.1.4..34) and RNA-directed DNA polymerase of type B viruses are associated enzymatic activities analogous to those observed for avian and mammalian type C RNA tumor viruses.

Mammary Tumor Virus, Mouse↗

Effects of level of dietary sulfur on the growth performance and blood mineral profile of sheep fed urea-supplemented corn silage.

Several blood constituents were measured in whether receiving a basal diet of corn silage, urea and a mineral-vitamin supplement to which various levels of sulfur (S) were added. The amounts of S in the total diets were: .16, .26, .38, .47 and .57% of dry matter. After a six-month experimental period, the levels of copper and iron in the plasma and of urea and manganese in the blood had been effected, lower levels being associated with higher levels of dietary S. Plasma zinc and magnesium levels showed a quadratic response to dietary S levels. However , plasma calcium levels and blood selenium levels were not significantly affected. Plasma sulfate-S content was higher in those animals receiving higher levels of S in the diet. The quantity of S ingested did not significantly affect voluntary feed intake, growth rate, or diet digestibility; however, nitrogen retention was lowered. The higher dietary S levels resulted in higher urinary excretion of the element, while fecal S remained unchanged.

Animal Nutritional Physiological Phenomena↗

Acute Listeria monocytogenes osteomyelitis.

The presentation and management of a case of acute Listeria monocytogenes osteomyelitis in a lady with acute lymphoblastic leukaemia are described. The literature on Listeria infection is briefly reviewed, and the importance of scrutinizing diphtheroid-like isolates in the laboratory is stressed.

Acute Disease↗

Cellular hypersensitivity of gp55 of RIII-murine mammary tumor virus and gp55-like protein of human breast cancers.

Previous studies suggested that immunogenic breast cancer tissues contained a component(s) that is antigenically similar to some component of murine mammary tumor virus (MuMTV) and resembles the glycoprotein, M.W. 55,000 (gp55), of RIII-MuMTV in molecular weight and charge density. This investigation measured in vitro cellular hypersensitivity responses of breast cancer patients to RIII mouse milk, purified RIII-gp55, C3H-MuMTV, autologous and homologous breast cancer tissues, gp50 of A-MuMTV, and preparations of Rauscher leukemia virus and Mason-Pfizer monkey virus. Particular attention was paid to cross-reactivity between gp55 and the other targets. The data indicate that responsiveness to C3H-MuMTV and RIII milk are linearly correlated with responsiveness to gp55. A preferential relationship was demonstrable between responses to gp55 and to those breast cancer tissues containing a gp55-like protein component (S-p50). The critical role of a gp55-like protein as the antigen responded to by breast cancer patients' in leukocytes was also suggested by the ability of anti-gp55 antiserum to decrease leukocyte responsiveness to RIII-gp55, C3H-MuMTV, and breast cancer tissues. In vitro cellular hypersensitivity against RIII-gp55 was preferentially found in prognostically favorable cases with immunogenic lesions. Further studies are needed to test the possibility that gp55 might be of value in the immunodiagnosis of early breast cancer, the monitoring of prognostically significant cellular hypersensitivity, and the induction of such hypersensitivity (immunoprophylaxis).

Animals↗

Prognostically significant protein components of human breast cancer tissues.

Cryostat sections of clinicopathologically characterized breast cancer tissues were eluted with phosphate-buffered 0.9% sodium chloride solution, pH 7.2. The proteins were then characterized by polyacrylamide gel electrophoresis with and without prior treatment with sodium dodecyl sulfate. Approximately 65% of the brease cancer tissue eluates contained a prominent protein fraction with a molecular weight of 47,000 to 55,000 (p50). No such component was found in 15 of 17 eluates of benign breast tissue. Charge density studies disclosed that the p50 component included three populations of proteins that could be characterized according to the migration relative to gp55 derived from RIII murine mammary tumor virus, namely, fast (F-p50), intermediate (I-p50), and slow (S-p50). Prognostically favorable pathological characteristics, i.e., stage, nuclear grade, and lymphoreticuloendothelial responses, were proportionately most frequently found among S-p50 bbreast cancers and were least frequently found among F-p50 breast cancers. It appears that the S-p50 component acts in vivo as a prognostically significant immunogen. Further knowledge of the relationship between protein characteristics and clinicopathological features of human breast cancers would contribute to our understanding of mammary carcinogenesis and biological behavior.

Breast Neoplasms↗

A report on a prospective trial of no initial therapy in patients with initial therapy in patients with asymptomatic favourable prognosis non-Hodgkin's lymphoma.

Thirty-one (58 per cent) of a group of fifty-three unselected patients with stage II-IV favourable prognosis non-Hodgkin's lymphoma were regarded as being eligible for a prospective study of no initial therapy. Seventeen of these patients (55 per cent) have required no treatment for periods from 6 + -47 + months, (median 18 months) and fourteen patients have been treated with chemotherapy for progressive disease after a period varying from 3-40 months (median 9.5 months). Selected asymptomatic patients with non-bulky disease may be suitable for no initial therapy. Randomized prospective trials will be needed to test whether survival is affected by delaying therapy.

Adolescent↗

Bone marrow examination in small cell carcinoma of the bronchus: an unnecessary procedure?

One hundred and thirty-seven patients with small cell carcinoma of the bronchus underwent bone marrow trephine and/or aspirate examination as part of their clinical staging. Twenty-four patients (17.5 per cent) were found to have malignant marrow infiltration. In no case was this an isolated finding of metastatic disease, indeed most patients had gross metastatic spread to liver and/or bone. Marrow infiltration has not been shown to be a major prognostic factor in response to chemotherapy or survival in previous studies. We recommend that this staging procedure be discontinued in routine clinical practice, and instead be confined to specific indications in clinical trials.

Bone Marrow Examination↗

Mediastinal germ cell tumour associated with malignant histiocytosis and high rubella titres.

Two further cases of a haematological malignancy are reported in patients with mediastinal germ cell tumours. Two young men developed bone marrow infiltration with histiocytes showing erythrophagocytosis shortly after subtotal excision of a malignant teratoma of the anterior mediastinum. Serial viral titres showed a rise in rubella antibody titres by haemoagglutination inhibition in both cases, antirubella IgG (ELISA) in one case and rubella RH zone in the other, in the absence of detectable IgM rubella antibodies. In case 1 a diagnosis of virus associated haemophagocytic syndrome was made and he was treated with interferon and steroids. In case 2 the diagnosis was initially idiopathic thrombocytopenia purpura but he deteriorated on steroids, and was subsequently unsuccessfully treated with chemotherapy and gamma globulin infusions. The disease ran a rapid downhill course with progressive marrow failure and they both died 5 months after diagnosis. Review of the presenting histology, the progressive course of the disease and post mortem histology, suggests that they had malignant histiocytosis. The association between mediastinal teratoma and haematological malignancy is of biological importance. Serial viral titres should be measured in patients with malignant histiocytosis to see if there is a raised rubella titre. Such viral studies are also warranted where there is an association between a mediastinal germ cell tumour and haematological malignancy.

Adult↗

Temperature-dependent hysteresis in somatosensory and auditory evoked potentials.

Fourteen adult patients undergoing open heart surgery under induced hypothermia had median nerve, short-latency somatosensory evoked potentials (SSEPs) recorded during cooling (from 36 degrees C to 19 degrees C) and subsequent rewarming. Similar data on another group of patients who had brain-stem auditory evoked potentials (BAEPs) were also analyzed. Hypothermia produced increased latencies of the major SSEP and BAEP components and the latencies returned to normal with subsequent warming. The temperature-latency relationship during the cooling phase was significantly different from that during the warming phase. For SSEP components the temperature-latency relationship was linear during cooling and curvilinear during warming, whereas for BAEP it was curvilinear both during cooling and warming. Furthermore, the regression curves were different during the two phases of temperature manipulation, particularly for temperatures below 30 degrees C both for SSEP and BAEP components. At the onset of warming there was an initial exaggerated warming response on the evoked potential (EP) latencies and amplitude of the EP components. The temperature-latency regression curves were uniformly less steep during the warming phase compared to those during cooling. These findings suggest the existence of hysteresis in the relationship between temperature and EP latencies. The latencies at a given temperature below 30 degrees C depend on whether that temperature is reached during cooling or during warming.

Acoustic Stimulation↗

Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta.

Cloned probes specific for unique genes have proven to be powerful tools in defining the nature of genetic diseases such as the thalassaemias and growth hormone deficiencies. A similar approach should be useful in defining heritable diseases of type I collagen, the heterotrimer of two alpha 1(I) chains and one alpha 2(I) chain, which is the most abundant member of the collagen family of proteins. Recently, cloned cDNAs and genomic DNAs for the two polypeptide chains of the type I collagen have become available and have been used to elucidate the chromosomal location of the corresponding genes. Here, we have used several of these cloned DNAs to demonstrate the presence of an internal deletion of about 0.5 kilobases (kb) in one allele for the pro alpha 1(I) chain in a patient with osteogenesis imperfecta (OI), a group of heritable disorders which are characterized by brittle bones but which are highly heterogeneous both phenotypically and biochemically.

Animals↗

First-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q.

Osteoporosis is characterized by low bone density, and osteopenia is responsible for 1.5 million fractures in the United States annually. In order to identify regions of the genome which are likely to contain genes predisposing to osteopenia, we genotyped 149 members of seven large pedigrees having recurrence of low bone mineral density (BMD) with 330 DNA markers spread throughout the autosomal genome. Linkage analysis for this quantitative trait was carried out using spine and hip BMD values by the classical lod-score method using a genetic model with parameters estimated from the seven families. In addition, non-parametric analysis was performed using the traditional Haseman-Elston approach in 74 independent sib pairs from the same pedigrees. The maximum lod score obtained by parametric analysis in all families combined was +2.08 (theta = 0.05) for the marker CD3D on chromosome 11q. All other combined lod scores from the parametric analysis were less than +1.90, the threshold for suggestive linkage. Non-parametric analysis suggested linkage of low BMD to chromosomes 1p36 (Zmax = +3.51 for D1S450) and 2p23-24 (Zmax = +2.07 for D2S149). Maximum multi-point lod scores for these regions were +2.29 and +2.25, respectively. A third region with associated lod scores above the threshold of suggestive linkage in both single-point and multi-point non-parametric analysis was on chromosome 4qter (Zmax = +2.95 for D4S1539 and Zmax = +2.48 for D4S1554). Our data suggest the existence of multiple genes involved in controlling spine and hip BMD, and indicate several candidate regions for further screening in this and other independent samples.

Bone Density↗

High density lipoprotein cholesterol. A 16-year longitudinal study in aging male twins.

The National Heart, Lung, and Blood Institute Twin Study is a collaborative, longitudinal study of white, male twins who were veterans of World War II and were born between 1917 and 1927. The twins were selected from the National Academy of Sciences/National Research Council Twin Panel and were examined three times (1969-73, 1981-82, and 1986-87). At all three exams, the dizygotic (DZ) twins were found to have a greater total variance for high density lipoprotein cholesterol (HDL-C) than the monozygotic (MZ) twins (p less than 0.05). DZ variance estimates were also larger than the variance of singletons from the second National Health and Nutrition Examination Survey. At the third exam, HDL-C was divided by precipitation into HDL2 and HDL3 fractions, and HDL2 was found to be the primary cause of the greater DZ total variance (DZ/MZ HDL2 variance = 2.22). The DZ/MZ variance ratio decreased 9% after adjustment of HDL2 for correlations with plasma triglycerides, alcohol consumption, smoking, exercise, and body mass index measured at the third exam. Postulated causes of the difference between MZ and DZ total variances include World War II induction screening, environmental influences unique to one zygosity, and genetic factors related to twinning. Further understanding of the etiology of this striking difference between MZ and DZ twin variance for HDL-C fractions could lead to more effective methods of decreasing the complications of arteriosclerosis.

Adult↗

Chromosomal abnormalities and gene amplification in renal cancers induced in rats by nickel subsulfide.

Nickel subsulfide (alpha Ni3S2) was administered to male Fischer-344 rats by unilateral intrarenal (i.r.) injection (20 mg per rat) to establish the time-course of alpha Ni3S2-induced erythrocytosis and to identify chromosomal abnormalities and molecular genetic aberrations in ensuing renal cancers. Blood hematocrit values were increased in alpha Ni3S2-treated rats during two to 36 weeks post-injection, attained a maximum of 77 percent (SD +/- 5) at 16 weeks (vs 51 +/- 3 percent in vehicle controls), and returned to baseline at 40 weeks. Within 21 months, malignant neoplasms (five sarcomas, one carcinoma) occurred in the injected kidneys of 6/28 alpha Ni3S2-treated rats (vs 0/13 controls). Cytogenetic analyses of direct preparations or primary cell cultures showed prominent chromosomal aberrations in three neoplasms, with rearranged marker chromosomes, polyploidy, and in one case an homogeneously staining region (HSR). Assays for gene amplification were performed with probes for murine erythropoietin (EPO) gene and H-ras, c-fos, c-myc, and N-myc oncogenes, using deoxyribonucleic acid (DNA) samples isolated from injected kidneys and renal neoplasms, as well as from the contralateral, non-injected kidneys. No consistent pattern was found; in one sarcoma, N-myc was amplified six-fold and c-fos was amplified two-fold; in another sarcoma, H-ras, c-fos, and EPO were amplified two-fold. This study shows that (a) karyotypes of 3/6 renal neoplasms of alpha Ni3S2-treated rats contained prominent marker chromosomes, (b) oncogene amplification was noted in 2/6 renal neoplasms, and (c) the EPO gene was not consistently amplified in DNA from the injected kidneys of alpha Ni3S2-treated rats during the initiation of erythrocytosis, or in subsequent renal neoplasms.

Animals↗