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Biomedical subjects

T Chapman

Publications and source records attributed to T Chapman.

At least 55 records · Page 3Linked to original sources

Long-term adaptive responses to dietary protein restriction in chronic renal failure.

Six patients with chronic renal failure (glomerular filtration rate 18 +/- 2 ml/min) underwent two 10-day admissions separated by at least 1 yr of outpatient therapy with a very low-protein diet (VLPD) providing 0.28 g protein.kg-1.day-1 plus an amino acid-ketoacid supplement. During each Clinical Research Center admission, subjects completed a 5-day nitrogen balance (BN), and whole body protein turnover was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Outpatient dietary protein compliance was very good (25 vs. 20 g protein/day or 125% goal), whereas energy intake was only 69% of goal (24 vs. 35 kcal.kg-1.day-1). During the 16 +/- 2 mo of dietary therapy, there were no changes in serum proteins or anthropometrics. BN after > or = 1 yr of dietary therapy was neutral and did not differ from initial values (+0.46 +/- 0.20 vs. +0.55 +/- 0.19 g N/day). Similarly, rates of whole body protein synthesis, degradation, and leucine oxidation after long-term therapy with the VLPD regimen did not differ from baseline values, and neutral BN was maintained by a marked suppression of amino acid oxidation and postprandial inhibition of protein degradation. This is the first evidence that the compensatory changes in whole body protein turnover activated in response to dietary protein restriction are sustained during long-term therapy.

Adaptation, Physiological↗

Replacement of the conserved G.U with a G-C pair at the cleavage site of the Tetrahymena ribozyme decreases binding, reactivity, and fidelity.

There is a phylogenetically conserved G.U pair at the 5'-splice site of group I introns. When this is mutagenized to a G-C pair, splicing of these introns is greatly reduced. We have used a ribozyme derived from the Tetrahymena group I intron to compare the binding and reactivity of oligonucleotides that form either a G.U or a G-C pair at this position. Ribozyme binding of oligonucleotides at 42 degrees C was measured by native gel electrophoresis and equilibrium dialysis. Binding of GGCCCUCC (C(-1)P), which base-pairs with the ribozyme guide sequence to form a G-C at the cleavage site, was 10-fold weaker than the binding of GGCCCUCU (U(-1)P), which maintains the conserved G.U pair at the cleavage site. This is surprising since a terminal G-C enhances the binding between oligonucleotides by 20-fold relative to a terminal G.U. Thermal denaturation studies indicate that C(-1)P and several analogs with deoxy substitutions bind the guide-sequence oligonucleotide, GGAGGGAAA, as strongly as they bind the ribozyme. In contrast, U(-1)P binds 240-fold more strongly to the ribozyme than to GGAGGGAAA, a difference that is decreased by deoxy substitutions. Thus, while U(-1)P binds the ribozyme through a combination of base-pairing and specific 2-OH and other tertiary interactions, C(-1)P may bind by base-pairing alone. The substrate GGCCCUCCAAAAA (C(-1)S) is cleaved 100-fold more slowly than GGCCCUCUAAAAA (U(-1)S) and also has a higher propensity to be cleaved at the wrong nucleotide position.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A hyphal-specific chitin synthase gene (CHS2) is not essential for growth, dimorphism, or virulence of Candida albicans.

In the dimorphic fungus Candida albicans, the CHS2 gene encodes a chitin synthase that is expressed preferentially in the hyphal form. Gene disruption of CHS2 in this diploid asexual fungus was achieved by the "ura-blaster" protocol described for Saccharomyces [Alani, E., Cao, L. & Kleckner, N. (1987) Genetics 116, 541-545]. This involves the sequential disruption of multiple alleles by integrative transformation with URA3 as a single selectable marker. After disrupting the first CHS2 allele, the Ura- phenotype was recovered through cis recombination between repeated hisG sequences that flanked the URA3 marker in the disruption cassette, which was then used again to disrupt further CHS2 alleles. This method of gene disruption is well suited to the mutational analysis of this genetically recalcitrant human pathogen. Three rounds of disruption were required, suggesting that the strain SGY243 is triploid for the CHS2 locus. The resulting homozygous delta chs2::hisG null mutants were viable and made germ tubes with a normal morphology. The germ tubes were formed more slowly than parental strains in serum-containing medium and the germinating cells had a 40% reduction in their chitin content compared to germ tubes of the parent strain. The chitin content of the yeast form was not affected. A prototrophic strain of the chs2 null mutant was not attenuated significantly in its virulence when tested in normal and immunosuppressed mice.

Animals↗

Adaptive responses to very low protein diets: the first comparison of ketoacids to essential amino acids.

Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days before hospital admission and following a four-day equilibration, a five-day nitrogen balance (BN) was performed. Whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Even though the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Nitrogen conservation with KA was due to a reduction in urea nitrogen appearance. Rates of WBPT measured during fasting and feeding did not differ between the KA or EAA regimens. During both regimens, feeding decreased protein degradation, whereas protein synthesis was unchanged. Although feeding stimulated leucine oxidation, rates were 50 to 100% lower than reported in CRF patients consuming 0.6 or 1.0 g protein/kg/day. Thus, neutral Bn with the VLPD regimen is achieved by a marked reduction in amino acid oxidation and a postprandial inhibition of protein degradation.

Adaptation, Physiological↗

Molecular physiology of CFTR Cl- channels in heart.

Recent electrophysiological data suggests a number of similarities in the properties of cAMP-dependent Cl- channels in heart and cAMP-dependent Cl- channels encoded by the cystic fibrosis transmembrane conductance regulator (CFTR) gene product in various epithelial cells. We tested the hypothesis that cAMP-dependent Cl- channels in heart may be due to cardiac expression of CFTR by amplification and sequencing of several regions of CFTR from myocardial tissue derived from various species and areas of the heart. Regions corresponding to the first nucleotide binding domain (NBD1), transmembrane segments I-VI (TS I-VI), transmembrane segments VII-XII (TS VII-XII), and the regulatory domain (R domain) were amplified and sequenced from rabbit ventricle (see Fig. 1). Comparison of the known amino acid sequence of human epithelial CFTR with the deduced sequence from rabbit heart indicated deletion of exon 5 in the first cytoplasmic loop of TS I-VI suggesting that CFTR is an alternatively spliced isoform in rabbit ventricle. Outside of the alternatively spliced region, the heart CFTR Cl- channel isoform displayed greater than 95% identity to human epithelial CFTR Cl- channels. We have also compared the molecular distribution of the CFTR gene product to the distribution of cAMP-dependent Cl- channels in native cardiac myocytes derived from various species and areas of the heart. Amplification of regions corresponding to NBD1, R domain, and TS VII-XII from atrium and ventricle of guinea pigs, rabbit, and dog hearts exhibited a distribution which closely matched the distribution of cAMP-dependent Cl- channels assessed using electrophysiological techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

No reduction in the cost of mating for Drosophila melanogaster females mating with spermless males.

Drosophila melanogaster females can incur a cost of mating, manifested as a decrease in longevity and lifetime reproductive success. We investigated whether the cost of mating was a cost of storing and/or receiving sperm by using two types of males that do not transfer sperm (transformer pseudomales and the male offspring of homozygous tudor mothers). Females that were intermittently exposed to males that did and did not transfer sperm did not differ in lifespan, in the absence of any differences in other costly aspects of reproduction, showing that there was no cost to receiving sperm. There was a cost of mating with spermless males; this suggested a potential cost of receiving accessory fluid. However, it was not possible to distinguish this possibility from other explanations, e.g. female injury at mating and the transfer of parasites. The reasons why females continuously exposed to males remated more than was in their reproductive interests is discussed.

Animals↗

Early prenatal diagnosis of type II cystic adenomatoid malformation of the lung: sonographic and histological findings.

Cystic adenomatoid malformation is a rare abnormality of the fetal lung. Depending on the size and histology of the cyst, it is classified as type I, II or III. With improving ultrasound technology, prenatal diagnosis during the mid-trimester is now possible; however, the earliest previous reports of type II cases have been at 23-24 weeks' gestation. We here report cases diagnosed at 19.5 and 20.5 weeks. In contrast to the appearance of multiple small cysts seen later in pregnancy, these cases showed a predominance of marked hyperechogenicity, usually associated with type III malformations, with small areas of lung involved by sonographically detectable cysts. Both families chose pregnancy termination. Sonographic findings, counselling, and histology are presented and discussed.

Journal Article↗

Child panic revisited.

Childhood panic attacks and panic disorder were assessed retrospectively in adult anxiety clinic patients (N = 343) and their adult relatives (N = 560). Only nine (1%) of the 903 subjects were judged to have experienced spontaneous panic attacks before age 13 by clinically trained interviewers. The narrative summaries of these cases were reviewed, and only three of nine provided convincing descriptions of spontaneous panic attacks in childhood. The authors conclude that prepubertal spontaneous panic attacks are rare, and that retrospective assessments of panic phenomena are difficult, even among adequately trained mental health professionals.

Adolescent↗

Chitin biosynthesis in Candida albicans grown in vitro and in vivo and its inhibition by nikkomycin Z.

An N-acetyl-D-[14C]glucosamine radiolabel incorporation assay has been used to monitor chitin biosynthesis in whole cells of Candida albicans both in vitro and in vivo in two different mouse infection models, one using the peritoneal cavity as a chamber in which to add and retrieve cells and the other using infected kidneys. Specific labeling of chitin in alkali-insoluble material was confirmed by chitinase digestion, analysis of acid hydrolysates, and the use of nikkomycin Z as a probe. Nikkomycin Z was shown to strongly inhibit chitin biosynthesis in C. albicans grown in vitro and in vivo in both models. This demonstrates that nikkomycin Z-susceptible chitin synthase activity is present in C. albicans when the fungus is in its pathogenic state in vivo. The limited use of nikkomycin as a therapeutic agent is discussed.

Aminoglycosides↗

The nurse's role in neuroleptic medications.

1. A questionnaire study of schizophrenia sufferers' (N = 132) views on medication, contrary to expectations, revealed generally favorable attitudes. Clients seemed to understand the fine balance between costs and benefits better than many health-care professionals imagine. 2. Because nurses spend more time communicating with clients than physicians, they are ideally placed to find out how patients perceive neuroleptic therapy, and to provide information, advice, and counseling support. 3. There is a strong case for asserting that mental health nurses should extend their role in monitoring the effects of medication on their clients.

Antipsychotic Agents↗

Colonoscopic removal of a gallstone obstructing the sigmoid colon.

For the patient with a single gallstone obstructing the colon, this technique offers nonoperative relief of the obstruction, allowing definitive operative therapy to be accomplished at a later time on a more elective basis. The patient should be carefully observed during the interval for intervening recurrent gallstone ileus.

Aged↗

Do the right thing for the community. Interview by Howard Larkin.

When the area surrounding Greater Southeast Community Hospital, Washington, DC, changed from a middle-class commuter neighborhood to one populated mainly by the poor and elderly in the early 1970s, hospital officials decided to stay and serve where they were needed most. The 450-bed hospital now sponsors a wide variety of health and community development programs. In recognition of its commitment to community service, Greater Southeast Community Hospital was awarded this year's Foster G. McGaw Prize by the American Hospital Association, Chicago, and the Baxter Foundation, Deerfield, IL. Thomas Chapman, president of Greater Southeast Community Hospital, recently talked about the importance of community service with Hospitals finance coordinator Howard Larkin.

Awards and Prizes↗

An imbalance in sex chromosomes alters cell survival of human skin fibroblasts exposed to ionizing radiation in vitro.

We report that a cell clone with a 45,X(-Y) karyotype, obtained from a male individual who is a gene carrier for hereditary adenomatosis of the colon and rectum (ACR), was considerably more resistent to gamma-ray irradiation (D0 range 184-240) than were diploid ACR skin fibroblasts (SF) obtained from sister biopsies of the same individual or of normal controls (D0 range 90-125). In addition, cell clones obtained from a Turner's syndrome female patient and from a female patient with focal endometrial hyperplasia, each with a 45,X(-X) karyotype, were abnormally resistent to gamma-ray irradiation (D0 range 168-195). These results may suggest an association between the status of the sex chromosomes and an altered response to gamma-ray-induced cytotoxicity of human SF.

Adenoma↗

Cystic adventitial disease of the popliteal artery.

Cystic adventitial disease of the popliteal artery is a rare but well recognized cause of arterial occlusive changes producing disabling symptoms in young patients. We have described a 37-year-old long-distance runner who noticed progressive decrease in the function of his right leg over a period of several months. The presence of an arterial occlusive lesion was difficult to define on clinical grounds, but was confirmed with noninvasive vascular studies and angiography. Surgical treatment by resection of the diseased segment and end-to-end saphenous vein interposition graft yielded excellent results.

Adult↗