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Biomedical subjects

C Bishop

Publications and source records attributed to C Bishop.

At least 73 records · Page 4Linked to original sources

In vivo metabolism of proapolipoprotein A-I in Tangier disease.

Tangier disease is a rare familial disorder characterized by extremely low levels of apolipoprotein A-I (apoA-I) and high density lipoproteins (HDL). In normal subjects, proapoA-I is secreted into plasma and converted to mature apoA-I by the cleavage of the amino-terminal six amino acids with the major isoprotein in plasma being mature apoA-I. In contrast, in Tangier disease there is a marked relative increase of proapoA-I as compared with mature apoA-I. ProapoA-I and mature apoA-I were isolated from normal and Tangier disease subjects, radio-labeled, and autologous apoA-I isoproteins injected into normal and Tangier subjects. The in vivo catabolism and conversion of proapoA-I and mature apoA-I in normal and Tangier disease subjects were quantitated. A comparison of the rate of catabolism of apoA-I isoproteins from plasma revealed a significantly faster rate of catabolism of both isoproteins of apoA-I in Tangier subjects when compared with normal subjects. The fractional conversion rate of proapoA-I to mature apoA-I was 3.9 d-1 in normal subjects and 3.6 d-1 in Tangier subjects. The results indicate that (a) apoA-I enters plasma as the pro isoprotein in both normal and Tangier subjects, (b) Tangier disease subjects have a normal fractional rate of conversion of proapoA-I to mature apoA-I, (c) proapoA-I is catabolized at the same rate as mature apoA-I in Tangier subjects, and (d) Tangier subjects catabolize both pro and mature apoA-I at a much greater rate than do normal subjects. Therefore, the relative increase in proapoA-I in Tangier disease is due to a marked decrease in mature apoA-I resulting from rapid catabolism of both pro- and mature apoA-I and not to defective conversion of proapoA-I to mature apoA-I.

Adult↗

Mapping the mouse X chromosome: possible symmetry in the location of a family of sequences on the mouse X and Y chromosomes.

Major advances in our knowledge of the genetic organization of the mouse X chromosome have been obtained by the use of interspecific crosses involving Mus spretus-derived strains. This system has been used to study sequences detected by three probes 80Y/B, 302Y/B and 371Y/B isolated from a mouse Y-chromosome library which have been shown to recognize both male-female common and male-female differential sequences. These patterns are due to the presence of a family of cross-reacting sequences on the mouse X and Y chromosomes. Detailed genetic analysis of the localization of the X-chromosome-specific sequences using both a somatic cell hybrid panel and an interspecific mouse cross has revealed the presence of at least three discrete clusters of loci (X-Y)A, (X-Y)B and (X-Y)C. Two of these clusters, (X-Y)B and (X-Y)C, lie distally on the mouse X chromosome, the other cluster (X-Y)A being situated close to the centromere. In situ hybridization shows a striking symmetry in the localization of the major sequences on both the X and Y chromosomes detected by these probes, hybridization being preferentially localized to a subcentromeric and subtelomeric region on each chromosome. This striking localization symmetry between the X and Y chromosome sequences is discussed in terms of the extensive pairing of the X-Y chromosomes noted during meiosis.

Animals↗

Human preproapolipoprotein C-II. Analysis of major plasma isoforms.

Apolipoprotein C-II plays a major role in lipid metabolism as a cofactor for lipoprotein lipase, the enzyme involved in the hydrolysis of triglyceride-rich lipoproteins. Apo-C-II is initially synthesized as a 101 amino acid protein that undergoes subsequent cotranslational cleavage of a signal peptide. Post-translational processing of apo-C-II has not been previously described. In this manuscript we identify four major plasma isoforms of apo-C-II by two-dimensional gel electrophoresis and immunoblot analysis that result from post-translational modification of apo-C-II. Neuraminidase studies have shown that two of these isoforms are early secreted sialic acid containing glycoproteins. Amino acid compositional and amino-terminal analysis have established that the major plasma isoform of apo-C-II is proapo-C-II. Proapo-C-II undergoes proteolytic cleavage of its amino-terminal hexapeptide to generate the mature form of apo-C-II. Thus, apo-C-II appears to be secreted as a carbohydrate containing proprotein that then undergoes deglycosylation and proteolytic cleavage to generate mature apo-C-II, a minor isoform in plasma. An improved understanding of the structural relationship of the various plasma isoforms of apo-C-II will help to elucidate the mechanisms involved in normal, as well as defective, processing of apo-C-II.

Amino Acids↗

Cloning of DNA libraries from mouse Y chromosomes purified by flow cytometry.

To purify mouse Y chromosomes by flow cytometry, a male cell line containing the Robertsonian translocation Rb(9.19)163H has been established by SV40 transformation. Flow karyotypes obtained from these cells exhibit a well-isolated peak of fluorescence corresponding to the single Y chromosome, clearly distinct from that of chromosome 19. From this peak, 650,000 chromosomes were sorted, and two restriction fragment libraries were constructed from the DNA of the sorted chromosomes. The characterization of several Y-specific fragments has shown that the Y DNA was enriched at least 36-fold. Furthermore, given that there are likely homologies between the X and Y chromosomes, we can assume that this calculated value of the purification factor is an underestimation and that the Y DNA was more highly purified by flow sorting.

Animals↗

Isolation and characterization of apolipoproteins A-I, A-II, and A-IV.

A number of different analytical techniques are now available for the isolation of apoA-I, apoA-II, and apoA-IV. The choice of a particular technique is dependent on the instrumentation available, and the quantity of isolated apolipoprotein required. The isolation and characterization of the separate isoforms and the precursor isoproteins of the individual apolipoproteins are detailed, and methods for the evaluation of the purity of the separate apolipoproteins presented. A method for the evaluation of apolipoproteins in plasma is now available which permits the identification of structural variants of plasma apolipoproteins in patients with dyslipoproteinemias.

Amino Acid Sequence↗

A human Y-linked DNA polymorphism and its potential for estimating genetic and evolutionary distance.

A human DNA sequence (p12f2), derived from a partial Y-chromosome genomic library and showing homology with the X and Y chromosomes and with an undetermined number of autosomes, detected two Y-specific restriction fragment length variants on male DNA that had been digested with Taq I and Eco RI. These variants may have been generated through a deletion-insertion mechanism and their pattern of holoandric transmission indicates that they represent a two-allele Y-linked polymorphism (RFLP). By means of DNA from patients with inborn deletions in chromosome Y, this polymorphic DNA site was mapped to the interval Yq11.1-Yq11.22. The frequency of the rarest allele was about 35 percent in Algerian and Sardinian human males, whereas it was only 4 percent among Northern Europeans. The p12f2 probe also detected Y-specific DNA fragments in the gorilla and chimpanzee. In view of the monosomy of the Y chromosome in mammalian species, Y-linked RFLP's may prove to be more useful than autosomal or X-linked markers in estimating genetic distances within and between species.

Base Sequence↗

Extensive DNA sequence homologies between the human Y and the long arm of the X chromosome.

It has been proposed that sequence homology should exist between the short arms of the human sex chromosomes, in the regions pairing at meiosis. Out of 40 clones picked at random from a collection of non-repetitive DNA sequences derived from the human Y chromosome, we have found nine sequences which show very high homology with sequences located on the X chromosome. All nine probes originate from the euchromatic part of the Y chromosome. All the homologous sequences are located within the Xq12-Xq22-24 region. None of them map to the short arm of the X chromosome. We conclude that an important part of the euchromatic region of the Y chromosome is homologous to the middle of the X chromosome long arm, possibly as a result of recent translation event(s).

Animals↗

Model peptidergic systems at the insect neuromuscular junction.

The emergence of neuropeptides as a prominent neurotransmitter class raises fundamental new questions about modes of chemical signaling in the nervous system. These relate to the large number of peptides, their co-localization in neurons and to novel actions at innervated targets. Synaptic preparations in insects offer excellent experimental models for studies of multiple transmitters and their joint actions at uniquely identified nerve-muscle junctions. Peptidergic systems in insects are reviewed with particular reference to two identified neuromuscular preparations which demonstrate cotransmitter actions of peptides and "classical" neurotransmitter substances.

Animals↗

Methicillin-resistant Staphylococcus aureus (MRSA): risk and outcome of colonized vs. infected patients.

A retrospective study of 204 patients culture positive for methicillin-resistant Staphylococcus aureus compared infected and colonized patients. Seventy-eight patients were colonized and never developed infection (C), 24 were colonized and subsequently infected (C----I), and 102 patients had 1 or more nosocomial infections with MRSA at time of first culture (I). The most prevalent sites of infection were wound (26.5%) and blood-stream (20.7%), whereas the respiratory tract and surgical wounds were both frequent sites of colonization. Stepwise discriminant analysis found the most important factors in differentiating likelihood of colonization vs. infection were recent prior hospitalization, history of wound debridement, and number of invasive procedures. Ten percent of (C) died and 25.5% of (I) died. MRSA contributed to death in 57.6% of the (I) deaths (p less than .05). These results underscore the importance of differentiating (C) vs. (I) in hospitals where MRSA is endemic so that early specific treatment may be initiated. Risk factors for infection should be discriminated from those for acquisition of the organism.

Cross Infection↗

Extensive sequence homologies between Y and other human chromosomes.

Twenty-six human Y-chromosome-derived DNA sequences, free of repetitive material, were used to probe male and female genomic blots. We present data from a detailed analysis and chromosomal location of the bands detected by such probes, which demonstrate extensive DNA sequence homology between the mammalian sex chromosomes and autosomes. Under stringent conditions, nine Y-derived probes reacted exclusively with the Y chromosome, 12 probes detected homologous sequences present on both the Y and the X, four probes detected homologies between Y and autosome(s) without any X counterpart and, finally, one probe hybridized to homologous sequences on Y, X and autosome(s). These data are consistent with the hypothesis of a common evolutionary origin for the mammalian sex chromosomes and reveal structural similarities between Y-located and autosomal non-repetitive sequences.

Base Sequence↗

True histiocytic lymphoma. A report of four cases.

Clinical, morphologic, cytochemical, immunologic, and ultrastructural features of four cases of true histiocytic lymphoma are described. The neoplastic cells were large, ranging from 20 to 45 mu in diameter with round, folded, or convoluted nuclei, and abundant eosinophilic cytoplasm. They exhibited diffuse nonspecific esterase activity. Diffuse acid phosphatase activity was present in two cases so tested. Muramidase activity was present in half of the cases. Finely granular PAS-positive material was seen in the cytoplasm. Methyl green-pyronin positivity was variable. An occasional neoplastic cell showed erythropagocytosis in one case. Malignant cells either contained no cytoplasmic immunoglobulins (three cases) or had immunoglobulins of multiple classes (one case). Surface markers were studied in two cases; they were absent in one case, and were of multiple classes in another case. Ultrastructurally the neoplastic cells had lysosomal granules in three cases so examined, and phagolysosomes, phagocytized material and residual bodies in one of three cases so studied. Patients ranged in age from 28 to 60 years. Two patients had extralymphatic tumors. Survival of more than 5 years was seen in one patient.

Adult↗

Essential thrombocythemia: a clonal disorder of hematopoietic stem cell.

We studied 5 patients with essential thrombocythemia utilizing glucose-6-phosphate dehydrogenase (G-6-PD) enzyme as a cell marker for determining clonality. One of the patients was found to be heterozygous for isoenzymes B and A in the nonhaemopoietic tissues such as fibroblasts, but manifested only isoenzyme type B in the erythrocytes, neutrophils, and platelets. Our studies support the concept that essential thrombocythemia is a clonal disorder arising in a multipotent stem cell.

Blood Platelets↗

How nursing homes behave: a multi-equation model of nursing home behavior.

This paper estimates a multi-equation model of nursing home behavior using the 1973 NCHS National Nursing Home Survey for data. The paper investigates empirically the effects of public reimbursement and regulatory policies, as well as other exogenous factors, on the following dependent variables: (1) average operating cost; (2) nursing hours per patient-day; (3) an index of rehabilitation-type services; (4) the occupancy rate; (5) the mix of public and private patients; and (6) the rate charged to private patients. The results dramatize the importance of endogeneity concerns in nursing home behavior. Rate setting and many regulations are shown empirically to have unintended and often undesired consequences on cost and other policy criteria of interest. While there has been anecdotal evidence of such system-wide interdependencies, this study affirms that such possibilities must be taken seriously. Rational nursing home regulation cannot proceed apart from a comprehensive understanding of the nursing home behavioral environment.

Bed Occupancy↗

Why do nursing home costs vary? The determinants of nursing home costs.

Since the costs of nursing home care are a major component of the rapidly rising costs of health care, it is appropriate to base public policy discussions about cost containment on the determinants of nursing home costs. This article investigates the determinants of nursing home operating costs and reviews the results of 11 related econometric cost analyses conducted by the authors. Single-equation cost analyses are developed for nursing homes in three states and in the nation. The cost results of a multi-equation model of nursing home behavior are also reviewed. The analyses indicate that facility size and occupancy rate are minimally important in determining cost variation. Facility characteristics, particularly type of facility and ownership, are important variables. Nonprofit facilities consistently had higher costs than for-profit facilities, after controlling for patient mix and service differences, and, in one analysis, for a measure of quality.

Costs and Cost Analysis↗