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T J White

Publications and source records attributed to T J White.

At least 55 records · Page 3Linked to original sources

A merR homologue at 74 minutes on the Escherichia coli genome.

The nucleotide sequence between the trkA gene and the alpha ribosomal protein operon of Escherichia coli was determined. This 1592-bp region contains four open reading frames, one of which shows striking similarity to the MerR family of transcriptional regulatory proteins.

Amino Acid Sequence↗

Is there a prognostic difference between functional and nonfunctional islet cell tumors?

BACKGROUND: Pancreatic islet cell tumors are categorized as either functioning or nonfunctioning. Functioning islet cell tumors (FIT) elaborate a variety of hormones, producing dramatic symptoms, while the initial presentation of non-functioning islet cell tumors (NIT) is commonly an abdominal mass or symptom complex related to invasion of adjacent structures. As a result, NIT are purported to present at a later stage, with lower resectability rates, and an overall poorer prognosis, when compared to FIT. In addition, a number of reports have indicated that the incidence of NIT has increased significantly in recent years. PATIENTS AND METHODS: Twenty-eight patients were studied retrospectively. All had islet cell tumors of the pancreas and were seen at the University of Nebraska Medical Center and affiliated Nebraska Methodist Hospital during a 19-year period. RESULTS: There were 9 patients (32%) in the NIT group and 19 (68%) in the FIT group. The mean ages at presentation were 61 years for the NIT and 52 years for the FIT group. In the NIT group, all presented with either abdominal pain (n = 7) or jaundice (n = 2). In contrast, over 90% of the patients with FIT had symptoms referable to the specific hormone elaborated by the tumor. Primary tumor size for NIT was 4.1 +/- 0.7 cm versus 5.0 +/- 0.6 cm for the FIT group. No significant difference was found for NIT versus FIT with respect to the incidence of metastatic disease at presentation (44% versus 53%), resectability rate with curative intent (44% versus 53%), or disease-free survival at 2 years (67% versus 40%). CONCLUSIONS: This series, in contrast to earlier reports, suggests that nonfunctioning islet cell tumors do not present at a more advanced stage, have lower resectability rates, or an overall poorer long-term prognosis when compared to functioning tumors.

Adenoma, Islet Cell↗

Unique oligonucleotide primers in PCR for identification of Cryptococcus neoformans.

On the basis of a comparison of rRNA sequences coding the internal transcribed spacer (ITS) and 5.8S regions of Filobasidiella neoformans, the teleomorph of Cryptococcus neoformans, and members of its most closely related taxa, unique oligonucleotides were designed for the specific amplification of DNA only from C. neoformans. Various combinations of these primers, designated CN4, CN5, and CN6, and the previously described fungal primers ITS1 and ITS2 were tested in PCR for their ability to amplify DNA from 37 strains of C. neoformans and 31 other isolates representing 18 species of yeasts. The combination of primers CN4 and CN5 amplified DNA from both varieties of C. neoformans but from none of the other species tested. Other pairs of primers (namely, CN5-CN6, CN4-ITS1, and CN6-ITS1) amplified DNA only from C. neoformans and from the saprophyte Filobasidiella depauperata, which is the only other member of the genus Filobasidiella. With appropriate controls, these specific oligonucleotides may be used as primers in PCR to identify C. neoformans.

Base Sequence↗

The origin of HIV-1 isolate HTLV-IIIB.

The striking similarity between the first two human immunodeficiency virus type 1 (HIV-1) isolates Lai/LAV (formerly LAV, isolated at the Pasteur Institute) and Lai/IIIB (formerly HTLV-IIIB, reported to be isolated from a pooled culture at the Laboratory of Tumor Cell Biology (LTCB) of the National Cancer Institute) provoked considerable controversy in light of the high level of variability found among subsequent HIV-1 isolates. In November 1990, the Office of Scientific Integrity at the National Institutes of Health commissioned our group to analyse archival samples established at the Pasteur Institute and LTCB between 1983 and 1985. Retrospective analyses have shown that contamination of a culture derived from patient BRU by one from patient LAI was responsible for the provenance of HIV-1 Lai/LAV; the contaminated culture (M2T-/B) was sent to LTCB in September 1983. Our goals were to determine which HIV-1 variants were present in the samples and the sequence diversity among HIV-1 isolates from the earliest stages of the AIDS epidemic. We examined archival specimens and report here the detection of six novel HIV-1 sequences in the cultures used to establish the pool: none is closely related to HIV-1 Lai/IIIB. A sample derived from patient LAI contained variants of both HIV-1 Lai/IIIB and HIV-1 Lai/LAV, and a sequence identical to a variant of HIV-1 Lai/IIIB was detected in the contaminated M2T-/B culture. We conclude that the pool, and probably another LTCB culture, MoV, were contaminated between October 1983 and early 1984 by variants of HIV-1 Lai from the M2T-/B culture. Therefore, the origin of the HIV-1 Lai/IIIB isolate also was patient LAI.

Acquired Immunodeficiency Syndrome↗

Molecular evolution of the fungi: relationship of the Basidiomycetes, Ascomycetes, and Chytridiomycetes.

Establishing the phylogeny of fungi and protists often has proved difficult owing to the simple morphologies and convergent characters in these organisms. We used DNA sequences of nuclear small-subunit ribosomal RNA genes to determine phylogenetic relationships among three major classes of organisms considered to be fungi--Basidiomycetes, Ascomycetes and Chytridiomycetes--and to assess the taxonomic position of Neocallimastix, an economically important anaerobic rumen microorganism whose classification is controversial. The Basidiomycetes and Ascomycetes, two classes of nonflagellated fungi, are the most closely related taxa. Chytridiomycetes, though bearing flagella, group with these higher fungi rather than with the protists. Neocallimastix, a eukaryote lacking mitochondria and variously classified as a protist or as a fungus, shows closest molecular affinities with the Chytridiomycete fungi in the order Spizellomycetales.

Ascomycota↗

Molecular evolution of the fungi: human pathogens.

The morphological, ecological, and clinical diversity among ascomycete fungi that are pathogenic to humans suggest that the potential for pathogenicity may have arisen multiple times within these higher fungi. We have obtained 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi in order to determine their evolutionary origins. The fungi studied include a skin pathogen that is confined to humans (Trichophyton rubrum) and three systemic, facultative parasites that cause histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis) and coccidioidomycosis (Coccidioides immitis) in humans and other higher animals. Also included in our analysis are representatives of non-pathogenic fungi, as well as two opportunistic pathogens, Pneumocystis carinii and Candida albicans, that cause severe disease in immunocompromised individuals, especially those with AIDS. Two of the fungi we sequenced, T. rubrum and C. immitis, are limited to asexual modes of reproduction and therefore lack the sexual structures that are most useful for evolutionary comparison as well as being essential for classification among the higher fungi. Coccidioides immitis is particularly problematic owing to its contradictory and confusing asexual morphologies, which have caused it to be placed in three fungal classes and the protista. Our analysis shows that the specialized, superficial parasite and the systemic, facultative parasites, including C. immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology. Analysis also shows that the opportunistic pathogens are more distantly related, with the likely explanation that pathogenicity has arisen more than once within the Ascomycetes.

Base Sequence↗

Thioethers as urinary metabolites of thiophene and monobromothiophenes.

1. Thiophene and its two monobromo derivatives were administered to rats and the amounts of thioether excreted in urine were measured by an assay based on Ellman's reagent. This assay, which involves extraction and hydrolysis, was validated by determining extraction and hydrolysis efficiencies for several authentic thioethers including N-acetyl-S-(2-thienyl)-L-cysteine, a previously reported metabolite of thiophene and 2-bromothiophene. 2. The thioethers present in urine of animals dosed with thiophenes have been examined chromatographically. Contrary to previous reports, the present work indicates that S-substituted, N-acetyl-L-cysteines (mercapturic acids) are not important thioether metabolites of thiophene in rats, and the small quantity of such compounds formed does not include either of the two simple S-thienyl derivatives. 3. The two monobromo thiophenes form higher proportions of thioethers than does thiophene, and one of these thioethers, arising from 3-bromothiophene, was identified, chromatographically, as N-acetyl-S-(3-thienyl)-L-cysteine.

Acetylcysteine↗

Comparison of 5.8S ribosomal DNA sequences among the basidiomycetous yeast genera Cystofilobasidium, Filobasidium and Filobasidiella.

Nucleotide sequences obtained from regions of the ribosomal DNA repeat were compared by phylogenetic methods and combined with a statistical evaluation to clarify the relationships among the genera Cystofilobasidium, Filobasidium (F.) and Filobasidiella (Fl.), to assess the affinity of Filobasidiella neoformans and Filobasidiella depauperata, and to compare the varieties of Fl. neoformans. With appropriate primers, the nuclear 18S, 5.8S and internal transcribed spacer (ITS) regions of the ribosomal RNA genes (rDNA) of 10 strains were amplified with the polymerase chain reaction. The resulting DNA products were compared by digestion with endonucleases and analysis of restriction fragments. Single strands of the 5.8S rDNA and ITS regions were subsequently sequenced by the dideoxy method. Statistical support for the phylogeny inferred from parsimony analysis of aligned 5.8S rDNA sequences was determined by bootstrapping. There were no nucleotide substitutions in this region, nor in the ITS, among strains of Fl. neoformans that differ in variety and serotype. There was strong support for retaining Fl. depauperata and Fl. neoformans in the same genus, but nucleotide substitutions can be used to distinguish the two species. There was no support for combining the genera Filobasidium, Filobasidiella or Cystofilobasidium.

Base Sequence↗

Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs cooperative study. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

In a double-blind randomized study, we evaluated the effects of 25 mg vs 50 mg of hydrochlorothiazide in 51 elderly patients (aged 68.9 +/- 7.0 years) with isolated systolic hypertension (blood pressure, 160 to 239 mm Hg systolic and less than 90 mm Hg diastolic). Dose levels could be increased to twice daily to control blood pressure. The reductions in blood pressure (25.4/6.8 mm Hg and 28.9/7.4 mm Hg) and proportion of patients in whom blood pressure was controlled (78% and 89%) were similar in the lower- and higher-dose groups during the titration phase. However, serum potassium level was reduced more in the higher-dosage (0.57 mmol/L) than the lower-dosage (0.17 mmol/L) group. There were no significant changes in blood pressure during a 24-week maintenance phase. No patient required withdrawal from the study because of adverse effects, and cognitive-behavioral function was well preserved. We conclude that hydrochlorothiazide is effective and well tolerated in older patients with isolated systolic hypertension, many of whom may be effectively treated with 25 mg of hydrochlorothiazide once daily.

Aged↗

Detection of Borrelia burgdorferi DNA in museum specimens of Ixodes dammini ticks.

In order to investigate the potential for Borrelia burgdorferi infection before the recognition of Lyme disease as a clinical entity, the polymerase chain reaction (PCR) was used to examine museum specimens of Ixodes dammini (deer ticks) for the presence of spirochete-specific DNA sequences. One hundred and thirty-six archival tick specimens were obtained representing various continental U.S. locations; DNA sequences characteristic of modern day isolates of B. burgdorferi were detected in 13 1940s specimens from Montauk Point and Hither Hills, Long Island, New York. Five archival specimens of Dermacentor variabilis (dog tick) from the same collection and 118 Ixodes specimens from other endemic and nonendemic sites were negative. These data suggest that the appearance of the Lyme disease spirochete in suitable arthropod vectors preceded, by at least a generation, the formal recognition of this disease as a clinical entity in the United States.

Animals↗

The human lung fibroblast cell line, MRC-5, produces multiple factors involved with megakaryocytopoiesis.

The human lung fibroblast cell line MRC-5 constitutively produces a megakaryocyte potentiator activity, identified in murine bone marrow liquid culture assays for acetylcholinesterase and megakaryocyte colony assays in the presence of low concentrations of IL-3. The production levels of this activity were increased after stimulation with the phorbol ester analog, mezerein, and the calcium ionophore, A23187. Complete purification of a protein having this activity from conditioned media of induced MRC-5 cells was achieved using gel filtration and ion exchange chromatography. The first 14 residues of the purified protein identified by amino-terminal sequencing were identical to the first 14 residues of IL-6. Recombinant human IL-6 was tested and found to promote megakaryocyte growth. IL-1 beta, another component detected in MRC-5 conditioned media, was unable to promote megakaryocyte colony formation but did reduce the concentration of IL-6 necessary to support megakaryocyte colony formation. Immunoprecipitation using rabbit antiserum prepared against IL-6 removed the megakaryocyte growth activity found in MRC-5 conditioned media. Thus, connective tissue cells such as fibroblasts in the bone marrow may co-stimulate thrombocytopoiesis via IL-6 and, possibly, via IL-1 production.

Acetylcholinesterase↗