Search PubMed⌕ Search

Biomedical subjects

R White

Publications and source records attributed to R White.

At least 253 records · Page 14Linked to original sources
PubMed1993

Nontuberculous mycobacterial infections in continuous ambulatory peritoneal dialysis patients.

Nontuberculous mycobacterial infections are a rare but clinically important cause of infections in continuous ambulatory peritoneal dialysis (CAPD) patients. We describe seven cases of catheter-related nontuberculous mycobacterial infections associated with CAPD. Six patients had Mycobacterium fortuitum infections and one had a Mycobacterium kansasii infection. Three patients presented with peritonitis, three presented with exit site infections, and one developed an infection at the exit site after catheter removal. There were no specific clinical findings that differentiated these infections from those caused by common bacterial pathogens. Initial routine peritoneal dialysis fluid and exit site cultures were negative in two patients and grew M fortuitum in four patients and M kansasii in one patient. M fortuitum and M kansasii were sensitive to amikacin, and M fortuitum was sensitive to ciprofloxacin when tested. Sensitivities to other antibiotics were variable. All patients were treated with a combination of antibiotics from 3 weeks to 6 months. Catheter removal was necessary for cure of the infection in all patients with peritonitis and in a majority of patients with exit site infections. The majority of patients changed to hemodialysis after catheter removal. Two patients remained on CAPD, with follow-up ranging from 2 months to 4 years. One patient has received a successful renal transplant. In conclusion, M fortuitum is the most common nontuberculous mycobacterial catheter-related infection in CAPD patients. Nontuberculous mycobacterial infections should be considered in the differential diagnosis of any culture-negative infection associated with CAPD. In patients with infections secondary to M fortuitum, our findings suggest that amikacin and ciprofloxacin are the initial antibiotics of choice until antibiotic sensitivities are available.

Aged↗
PubMed1993

Identical APC exon 15 mutations result in a variable phenotype in familial adenomatous polyposis.

Germ-line mutations in the adenomatous polyposis coli (APC) gene result in familial adenomatous polyposis coli (APC), an inherited syndrome that predisposes affected individuals to early onset of colorectal cancer. Somatic APC mutations also have been detected in sporadic colon tumors. We have used single strand conformational polymorphism (SSCP) analysis to scan a region of the APC gene that frequently is mutated in both APC and sporadic colorectal cancer. Four truncating mutations were found between codons 1060 and 1327 in 17 of 68 unrelated APC individuals. Fourteen of these persons carried either of two previously described five-nucleotide deletions which represent about 20% of APC mutations in these pedigrees. Patients with mutations in this region of exon 15 develop a classic APC colonic phenotype with multiple, diffuse adenomas developing by the second or third decade. However, the density of adenomas and the extracolonic disease manifestations associated with this syndrome are variable among individuals with identical APC mutations.

Adenomatous Polyposis Coli↗
PubMed1993

A method for accurate amplification of polymorphic CA-repeat sequences.

Anomalous PCR products are often produced during the amplification of d(CA)n.d(TG)n sequences. Upon denaturing polyacrylamide gel electrophoresis, these products yield a ladder-like pattern that can complicate genotypic interpretation. We have developed two related techniques, referred to as two- and three-stage linear amplification (2-SLA and 3-SLA, respectively), which largely overcome this problem and yield readily interpretable banding patterns.

Adenine↗
PubMed1993

Determination of residual 4'-aminomethyl-4,5',8-trimethylpsoralen and mutagenicity testing following psoralen plus UVA treatment of platelet suspensions.

Psoralens and UVA light have been used in the laboratory to study the inactivation of viruses that may be infrequently present in platelet concentrates that are prepared for transfusion. In order to evaluate safety aspects of the treatment of platelet suspensions with 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), we have investigated the residual levels and mutagenic potential of AMT after UVA phototreatment. 4'-aminomethyl-4,5',8-trimethylpsoralen, at a final concentration of 40 micrograms/mL, was added to platelet suspensions which contained 16% plasma and a synthetic medium. Platelet suspensions containing AMT were irradiated with up to 7.2 J/cm2 UVA light under normal oxygen levels. Residual levels of AMT were determined by HPLC and a bioassay based on bacteriophage phi 6 inactivation. The photodestruction of AMT or its activity by UVA was characterized by a D37 value of 0.6 and 0.3 J/cm2 with HPLC or bioassay, respectively. At 2.4 J/cm2 UVA, which results in approximately 5 log10 inactivation of vesicular stomatitis virus (VSV) and retention of platelet in vitro properties, 12% (HPLC) to 9% (bioassay) AMT remained. Like other psoralens, AMT was found to bind to serum proteins as shown by ultrafiltration. Results are consistent with approximately 36% of the initial drug load binding primarily to serum albumin. It was determined using 3H-AMT that 9 to 18% of radioactivity was bound to platelets in the absence of irradiation. Similar fractions (13 to 18%) of AMT were bound to platelets after 3.6 J/cm2 UVA irradiation, and 8 to 10% of total AMT was associated with saline-washed irradiated platelets and is presumably tightly bound.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophages↗
PubMed1993

Differential regulation of cellular activities by GTPase-activating protein and NF1.

The regulation of the GTPase activity of the Ras proteins is thought to be a key element of signal transduction. Ras proteins have intrinsic GTPase activity and are active in signal transduction when bound to GTP but not following hydrolysis of GTP to GDP. Three cellular Ras GTPase-activating proteins (Ras-gaps) which increase the GTPase activity of wild-type (wt) Ras but not activated Ras in vitro have been identified: type I and type II GAP and type I NF1. Mutations of wt Ras resulting in lowered intrinsic GTPase activity or loss of response to cellular Ras-gap proteins are thought to be the primary reason for the transforming properties of the Ras proteins. In vitro assays show type I and type II GAP and the GAP-related domain of type I NF1 to have similar biochemical properties with respect to activation of the wt Ras GTPase, and it appears as though both type I GAP and NF1 can modulate the GTPase function of Ras in cells. Here we report the assembling of a full-length coding clone for type I NF1 and the biological effects of microinjection of Ras and Ras-gap proteins into fibroblasts. We have found that type I GAP, type II GAP, and type I NF1 show markedly different biological activities in vivo. Coinjection of type I GAP or type I NF1, but not type II GAP, with wt Ras abolished the ability of wt Ras to induce expression from an AP-1-controlled reporter gene. We also found that serum-stimulated DNA synthesis was reduced by prior injection of cells with type I GAP but not type II GAP or type I NF1. These results suggest that type I GAP, type II GAP, and type I NF1 may have different activities in vivo and support the hypothesis that while type I forms of GAP and NF1 may act as negative regulators of wt Ras, they may do so with differential efficiencies.

Animals↗
PubMed1993

Identification of residues in the estrogen receptor that confer differential sensitivity to estrogen and hydroxytamoxifen.

We have generated mutant mouse estrogen receptors which differ in their sensitivity to estrogen and the antiestrogen 4-hydroxytamoxifen. Mutation of the glycine at position 525 and the methionine and/or serine at positions 521/522 virtually abolishes the ability of the receptor to bind estradiol and stimulate transcription. In contrast, the mutant receptors retain the partial agonist activity exhibited by the wild-type receptor in the presence of 4-hydroxytamoxifen. The mutations do not affect the expression and DNA-binding activity of the receptor, but do abolish the estrogen-induced increase in the mobility of the receptor-DNA complex observed with the wild-type receptor. Other mutant receptors that were able to bind and stimulate transcription in the presence of estradiol also failed to show the agonist-induced increase in the mobility of the receptor-DNA complex, suggesting that it is unlikely to reflect the formation of a hormone-dependent transcriptional activation function.

3T3 Cells↗
PubMed1993

The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling.

The mouse estrogen receptor was shown to be constantly shuttling between the nucleus and cytoplasm although under steady-state conditions it is detected predominantly in the cell nucleus in both the absence and presence of estradiol. Shuttling was demonstrated by monitoring the transfer of protein between nuclei in heterokaryons and by examining the subcellular distribution of mutant receptors. In the presence of the partial antiestrogen 4-hydroxytamoxifen the receptor was retained in the nucleus whereas it accumulated in the cytoplasm when cells were treated with the pure antiestrogen ICI 182780. The effect of the pure antiestrogen was to inhibit nucleocytoplasmic shuttling of the receptor by blocking its nuclear uptake. Thus although ligand binding is not required by the estrogen receptor to undergo nucleocytoplasmic shuttling, this process can be disrupted by the binding of a pure antiestrogen.

Amino Acid Sequence↗
PubMed1993

Medical maintenance: a pilot study.

In a one year study, 130 methadone maintained subjects with a six month history of good treatment performance were assigned randomly to an experimental condition of one monthly non-random urine screen, one monthly counseling session, one monthly doctor visit, two times per month methadone pick up, a quarterly true random urine screen and participation in a diversion control program or to a control condition of staying under standard conditions for six months and then being transferred to the experimental condition for six months. Results of urine screens and scores on the Addiction Severity Index (ASI) at entrance and six month intervals showed no differences between groups. Three out of four subjects completed the year in good standing. Subject satisfaction was such that the IRB judged that return to standard conditions would be a hardship. Experimental conditions were cheaper such that resources freed up could be applied to the HIV epidemic.

Adult↗
PubMed1993

Microbial hydroxylation and glucuronidation of the angiotensin II (AII) receptor antagonist MK 954.

The microbial metabolism of MK 954 (Fig. 1), a novel nonpeptide angiotensin II receptor antagonist, was investigated using 40 microorganisms in an initial screen for cultures that will produce metabolites similar to those produced in the mammalian liver. The microbial transformation occurred under aerobic conditions in shake flasks incubated at 27 degrees C. Three metabolites of MK 954 were isolated and identified as the 1'-hydroxy M2, 3'-hydroxy M1, and glucuronic acid conjugated M3 derivatives. The structures of the metabolites were established by UV, 1H-NMR spectroscopy and FAB-MS spectrometry and are identical to metabolites produced by incubation of MK 954 with mammalian liver slices.

Actinomycetales↗
PubMed1993

Thoracic organ transplants in the United States from October 1987 through December 1992: a report from the UNOS Scientific Registry for Organ Transplants.

1. In 1992, there were 2,171 heart, 48 heart-lung, and 535 lung transplants performed in the United States. The number of lung transplants increased by about 32% over 1991, whereas heart transplants only increased by about 2% over 1991. The number of heart-lung transplants decreased in 1992. 2. The number of programs performing heart and lung transplants has continued to increase: about 16% in heart and about 280% in lung, since 1988. 3. The most frequently reported primary indications for transplant were: coronary artery disease (44%) and cardiomyopathy (41%) in heart; cystic fibrosis (40%) in double lungs; emphysema/COPD (35%) in single lungs; and congenital/Eisenmenger's syndrome (36%) in heart-lung. 4. Between 1988 and 1992, the following groups showed significant increases for heart and lung transplants: pediatric transplants, non-White recipients, non-White donors, older donors, and local utilization. 5. For the entire period covered by this report, overall one-year patient survival rates were: heart 82.3%, single lung 70.1%, double lung 66.4%, and heart-lung 58.7%. There has been little change in one-year heart transplant survival rates during this time. Survival rates for lung and heart-lung transplants increased dramatically between 1988 and 1990, but have declined slightly since then.

Adolescent↗
PubMed1993

A CA-repeat polymorphism close to the adenomatous polyposis coli (APC) gene offers improved diagnostic testing for familial APC.

Presymptomatic genetic testing for the presence of a mutant allele causing familial adenomatous polyposis coli (APC) has been difficult to perform effectively in the past because DNA markers surrounding the APC gene on chromosome 5q have not been very informative. We report results of genetic linkage studies on both research families and clinical families by using D5S346, a highly polymorphic dinucleotide (CA)-repeat locus 30-70 kb from the APC gene. Linkage analysis with this marker in a large APC pedigree showed an increase of at least 9.0 LOD units, in likelihood of linkage of the disease-causing allele to the APC locus, when compared with the highest LOD score attained with any other closely linked marker. When the first 14 APC families that requested genotypic analysis by the DNA Diagnostic Laboratory at the University of Utah were tested with D5S346, 20 of the 31 at-risk individuals were identified as either carriers or noncarriers of an APC-predisposing allele. We see this marker as an important tool for research studies and for the presymptomatic diagnosis of APC.

Adenomatous Polyposis Coli↗
PubMed1993

Becoming a successful division psychiatrist: guidelines for preparation and duties of the assignment.

Little attention is given in psychiatry residency programs to preparing graduates to occupy division psychiatry slots. The first part of this paper discusses several guidelines: preparations to make before leaving for a new post; immediate steps to take upon arrival; the place of the Division Mental Health Service in a division structure; and general observations about how best to obtain credibility with line soldiers. The second part focuses on general and specific duties of the assignment, and discusses some common clinical problems. The paper is intended to help the new division psychiatrists have an effective and productive tour. Many sections will be applicable to general medical officers and other health care workers leaving for a division assignment.

Adolescent↗
PubMed1993

Germ-line mutations in the first 14 exons of the adenomatous polyposis coli (APC) gene.

The first 14 exons of the APC gene have been screened by the denaturation gradient gel electrophoresis method in 160 unrelated patients with familial adenomatous polyposis coli (APC) syndrome. Four polymorphic variants corresponding to silent mutations not associated with the disease phenotype were observed. Mutations predicted to alter the coding property of the APC gene were observed in 26 patients. All these mutations are expected to lead either to aberrant splicing, to synthesis of a truncated APC protein because of the emergence of a stop codon, or to a change in the translation reading frame. Single-base-pair substitutions were observed on 21 occasions. The most frequent mutation (eight cases) was a C-to-T change which exclusively occurred on the nontranscribed strand within a CG dinucleotide.

Adenomatous Polyposis Coli↗
PubMed1993

A breast-ovarian cancer susceptibility gene maps to chromosome 17q21.

Nineteen North American Caucasian families that contain a minimum of four confirmed cases of breast or ovarian cancer have been studied. Four polymorphisms (cLB17.1, D17S579, D17S588, and D17S74), which span a region of approximately 15 cM on chromosome 17q12, were typed. Our data confirm the location of a dominant gene conferring susceptibility to breast and ovarian cancer (maximum lod = 9.78) and suggest that the breast-ovarian cancer syndrome is genetically heterogeneous. Two recombinants in one large family suggest that the breast-ovarian cancer locus lies between D17S588 and D17S579.

Adult↗
PubMed1993

Neurobehavioral study of borderline personality disorder.

The existence of an "organic" subgroup of borderline personality disorder (BPD) has been postulated. This report is of a case-controlled, chart-review study of BPD. The control sample consisted of patients with a variety of psychiatric diagnoses. The study found that 81% of the patients with BPD and 22% of the control patients had a history of brain injury, either developmental (44%), acquired (58%) or both. Furthermore, there was a positive correlation between the summed number of developmental and acquired brain injuries and the score on the retro-Diagnostic Interview for Borderline. A pilot neuropsychological study showed that seven of nine subjects with BPD had evidence of frontal system dysfunction. These results help to support the hypothesized existence of an organic BPD subgroup.

Adult↗