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Biomedical subjects

T Johnson

Publications and source records attributed to T Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1995

Improved survival of patients with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation.

A total of 28 patients with chronic myelogenous leukemia (CML) in chronic phase (CP) received bone marrow allografts from HLA-matched siblings at the University of Florida between August 1984-July 1992. The present study compares the disease-free survival (DFS) for those patients who were transplanted before or after August 1988 using the same conditioning regimen. The analysis shows significant difference in 3-year DFS for those patients transplanted post- vs. pre-August 1988 (69.6% vs. 20%, respectively; P = 0.006). A decrease in pneumonitis due to different etiologies from pre-August 1988 (6/13, 46%) to post-August 1988 (1/15, 7%) was statistically significant (P = 0.029). A decrease, although statistically insignificant, in the overall incidence and severity of acute and chronic graft vs. host disease (GVHD) after August 1988 was also noticed. This study indicates significantly improved outcome for patients with CML in CP who have been treated in the University of Florida after August 1988. Better supportive care and prophylaxis for GVHD most likely contributed to such improvement.

Adult↗
PubMed1995

Spectroscopic diagnosis of bladder cancer with elastic light scattering.

BACKGROUND AND OBJECTIVES: Recently, significant progress has been made toward the development of optical, noninvasive medical diagnostics. The goal of this study was to evaluate elastic scatter measurements as a tool for diagnosing bladder cancer. STUDY DESIGN/MATERIALS AND METHODS: In vivo measurements on 10 patients with suspected bladder cancer were made with the optical biopsy system (OBS) developed at Los Alamos National Laboratory. Elastic-scatter spectra over the wavelength range 250-800 nm were obtained using a fiber-optic probe through one of the lumens of a urological cystoscope. Measurements were made on putatively normal areas and areas of uncertain abnormality, as well as those suspected to be cancerous. After measurements were made with the OBS, biopsy samples were taken at the measurement sites. Comparisons of the histopathology and the optical spectra were then made. RESULTS AND CONCLUSIONS: A diagnostic algorithm for distinguishing malignant from nonmalignant tissue based on the values of the slopes over the wavelength range 330-370 nm has a sensitivity of 100% and specificity of 97% for the limited number of patients in this study.

Absorption↗
PubMed1995

Expression of serum albumin and of alphafetoprotein in murine normal and neoplastic primitive embryonic structures.

Alphafetoprotein (AFP), a major serum protein synthesized during the embryo-fetal and postnatal period (in the yolk sac, then in the liver), is also an oncoprotein. The intracellular presence of AFP and of serum albumin (SA) in normal and neoplastic neural crest and neural tube derivatives was previously demonstrated. In this work we have studied the comparative expression of AFP and SA in primitive neuroectoblastic structures of mouse embryos (6 and 7 days "post coitum") and mouse teratocarcinomas (derived from the PCC4 cell line). Using immunofluorescence technique, antibodies to SA gave a positive reaction in embryos of 7 days, while AFP was not detected during this period. By mRNA in situ hybridization, SA mRNA gave a strong signal in both 6 and 7 day embryos, whereas AFP mRNA gave a weak signal only in 7-day embryos. The distribution of SA and AFP and their mRNAs was investigated in primitive neuroectoblastic structures of the teratocarcinomas by in situ hybridization and immunostaining. Only SA protein was detectable by immunostaining. SA mRNA gave a strong signal in differentiating structures as well as in undifferentiated cell clusters. AFP mRNA was observed only in differentiating structure. Dot-blot hybridization indicated that the level of SA transcripts was at least 6-fold higher than that of AFP transcripts in the teratocarcinomas investigated. In teratocarcinoma-bearing mice injected intraperitoneally with 125I-radiolabeled SA and AFP, significant accumulations of both SA and AFP were demonstrated in the tumors, SA being about 3-fold higher than that of AFP after normalization to quantity of uptake in liver. External in vivo photoscanning confirmed this relationship of accumulated radiolabeled proteins. The last observation could be useful in vivo for diagnosis of teratocarcinoma. We conclude that the expression of SA relative to AFP and the external cellular uptake of SA relative to AFP are similar in normal embryonic developing tissues and in the corresponding morphologically neoplastic tissues of the teratocarcinomas. The same SA:AFP relationship constitutes an oncofetal marker of primitive neuroectoblastic structures.

Animals↗
PubMed1995

The C. elegans sex-determining gene fem-2 encodes a putative protein phosphatase.

The genetic and molecular analysis of genes involved in the regulation of sex determination in Caenorhabditis elegans suggests that the gene fem-2 plays an important role in regulating a pathway transducing a non-cell-autonomous signal to a nuclear transcription factor. The wild-type fem-2 gene was cloned by identifying sequences from the C. elegans physical map that could restore normal Fem-2 function to homozygous mutant fem-2 transgenic animals. cDNA sequences mapping to the minimal rescuing region correspond to an open reading frame with a sequence similar to protein phosphatase 2C enzymes from systems as diverse as yeast, humans, and plants, but the alignments suggest that FEM-2 falls into a separate class of proteins than the canonical homologues. Several fem-2 mutant alleles were sequenced, and the mutations are predicted to cause protein changes consistent with their observed phenotypes, such as missense mutations in conditional alleles, and a nonsense mutation in a predicted null allele. This is the first evidence implicating phosphorylation and/or dephosphorylation as a control mechanism in C. elegans sex determination.

Alleles↗
PubMed1995

The pancreatic islet factor STF-1 binds cooperatively with Pbx to a regulatory element in the somatostatin promoter: importance of the FPWMK motif and of the homeodomain.

A number of homeodomain proteins have been shown to regulate cellular development by stimulating the transcription of specific target genes. In contrast to their distinct activities in vivo, however, most homeodomain proteins bind indiscriminately to potential target sites in vitro, suggesting the involvement of cofactors which specify target site selection. One such cofactor, termed extradenticle, has been shown to influence segmental morphogenesis in Drosophila melanogaster by binding cooperatively with certain homeodomain proteins to target regulatory elements. Here we demonstrate that STF-1, an orphan homeodomain protein required for pancreatic development in mammals, binds cooperatively to DNA with Pbx, the mammalian homolog of extradenticle. Cooperative binding with Pbx requires a pentapeptide motif (FPWMK) which is well conserved among a large subset of homeodomain proteins. The FPMWK motif is not sufficient to confer Pbx cooperativity on other homeodomain proteins, however; the N-terminal arm of the STF-1 homeodomain is also essential. As cooperative binding with Pbx occurs on only a subset of potential STF-1 target sites, our results suggest that Pbx may specify target gene selection in the developing pancreas by forming heterodimeric complexes with STF-1.

Amino Acid Sequence↗
PubMed1995

The thermal acclimation of burst escape performance in fish: an integrated study of molecular and cellular physiology and organismal performance

Goldfish (Family Cyprinidae, Carassius auratus) and killifish (Family Cyprinodontidae, Fundulus heteroclitus) were acclimated to 10, 20 and 35 °C for 4 weeks. The thermal acclimation of C-start (escape swimming) performance and the physiological properties of fast twitch muscle fibres that underlie it were investigated in these species at the molecular (myosin isoform expression), biochemical (myofibrillar ATPase activity), cellular (contractile kinetics) and organismal levels of organisation. Peptide maps were obtained for fast muscle myosin heavy chains, isolated from 10 °C- and 35 °C-acclimated fish. Different myosin heavy chain isoforms were expressed in response to a change in acclimation temperature in goldfish, but myosin heavy chain isoform expression was unaffected by acclimation temperature in killifish. Compared with fish acclimated to 35 °C, acclimation to 10 °C increased the activity of fast muscle myofibrillar ATPase assayed at 10 °C fivefold in goldfish and only 50 % in killifish. Muscle twitch contraction time at 10 °C decreased significantly in response to acclimation to 10 °C in both species; however, the magnitude of this response was much greater in goldfish (100 %) than in killifish (30 % or less). In goldfish, these changes in the physiological properties of fast twitch fibres during 10 °C acclimation resulted in a six- to eightfold increase in the speed and turning velocity of fish performing C-starts at 10 °C. By comparison, the somewhat smaller acclimatory response of killifish fast muscle properties was accompanied by only a minor (50 % or less) adjustment in locomotor performance. Thermal acclimatory responses of fast muscle at the molecular, biochemical and cellular levels of organisation are clearly reflected in alterations in organismal escape performance.

Journal Article↗
PubMed1995

Replacing residents with midlevel practitioners: a New York City-area analysis.

Reducing the number of residency positions in U.S. teaching hospitals poses special problems for New York City-area hospitals, which rely heavily on residents to deliver patient care services. This study analyzes the costs of replacing residents with midlevel practitioners under proposals considered in 1994 by Congress to limit the number of first-year training positions and alter the configuration of primary care physicians and specialists produced. The study found that, depending on the replacement strategy used, the proposals could require New York City-area hospitals to hire thousands of midlevel practitioners and other staff, costing a minimum of $242 million annually, to cover patient care services.

Allied Health Personnel↗
PubMed1995

Effects of reduced exposure on computed radiography: comparison of nodule detection accuracy with conventional and asymmetric screen-film radiographs of a chest phantom.

OBJECTIVE: Radiographic exposure has been thought to have little impact on the diagnostic quality of chest computed radiography because of automatic digital control of global optical density. The objectives of this study were to compare images obtained with two different exposures in computed radiography with conventional and asymmetric screen-film images of the chest for the detection of simulated lung nodules by use of receiver operating characteristic analysis and to relate differences in observer performance to parameters of image noise measured for each receptor condition. MATERIALS AND METHODS: At 110 kVp (fixed), exposures for the two screen-film systems were those necessary to achieve adequate optical densities over the lung and mediastinal regions of an anthropomorphic phantom. The two exposures used for the computed radiographs corresponded to the exposure used for the conventional chest screen-film system and an exposure 22% lower. An anthropomorphic phantom constructed of materials matched to the muscle, lung, and bone attenuation of a muscular adult man was used. Soft-tissue-equivalent plastic nodules of various sizes were secured at multiple sites on the phantom to simulate lung nodules. The chest phantom was imaged in 50 configurations with a total of 70 superimposed nodules. The perceptual performances of five radiologists were compared by use of receiver operating characteristic analysis. The signal-to-noise ratio in the mediastinum and the coefficient of variation of noise were measured for all four image conditions by use of a step wedge technique to provide an explanation for differences in diagnostic accuracy. RESULTS: We found no significant differences in the detection of lung nodules between the two screen-film systems or between the conventional screen-film images and the standard-exposure computed radiographs. However, there was a significant decrease in nodule detection on computed radiographs obtained at a reduced exposure; this result was associated with a 21% decrease in the signal-to-noise ratio. CONCLUSION: Our results show that underexposure of computed radiographs decreases the detection of low-contrast objects such as lung nodules. Although consistent global optical density on computed radiographs is achieved over a wide range of exposures, the alterations in signal-to-noise ratio that result from underexposure can reduce the diagnostic quality of computed radiographs.

Adult↗
PubMed1995

Multi-dimensional adolescent treatment with American Indians.

The purpose of this study was to determine the effectiveness of an American Indian adolescent treatment program. A two-year follow-up study was conducted measuring school performance and antisocial behavior. It was found that American Indian adolescents who completed the program tended to have improved school performance and less involvement with the criminal justice system.

Adolescent↗
PubMed1995

Accident experience and notification rates in people with recent seizures, epilepsy or undiagnosed episodes of loss of consciousness.

Collaborating neurologists provided a central office with clinical information, driving experience and accident rates in all drivers they counselled after diagnosing seizures or other unexplained episodes of loss of consciousness. Each patient received and was asked to return a notification slip to DVLA. Of 638 patients counselled, 11% had been involved as a driver in a road traffic accident in the previous year. Six patients had been involved in an accident producing serious injury. These estimates do not differ from those expected in a population of non-epileptic drivers with the same age and sex distribution. Of patients counselled, 27.1% returned a reply slip to the DVLA. Notification was more likely if the patient was aged 50 or over at the time of counselling, if the counselling was undertaken by a consultant, if an accident had occurred in the previous year and if the subject had also been advised to start or was already taking anti-epileptic drugs. Patients counselled after a single seizure were more likely to notify than those with a diagnosis of epilepsy.

Accidents, Traffic↗
PubMed1995

Discordant expression of Bcl-x and Bcl-2 by keratinocytes in vitro and psoriatic keratinocytes in vivo.

Apoptosis is a required event in maintaining kinetic homeostasis within continually renewing tissues such as skin. However, no systematic study of the apoptotic process in epidermal keratinocytes of the skin has been performed. In this report, we examined the expression of proteins associated with promoting (Fas) or preventing (Bcl-2, Bcl-x, CD40) apoptosis in the normal, psoriatic, and malignant keratinocyte. Immunohistochemical staining and flow cytometry analysis revealed that normal cultured keratinocytes express low levels of Fas, CD40, and Bcl-x that was enhanced by cytokines including gamma-interferon (IFN-gamma) and a phorbol ester tumor promoter, TPA. Only faint Bcl-2 staining was detected in cultured keratinocytes exposed to IFN-gamma and TPA compared with the prominent expression of Bcl-x. Biopsies of normal skin, psoriatic plaques, and basal cell carcinomas were examined to extend the in vitro observations. Immunohistochemical staining revealed that while keratinocytes in normal epithelium express low to absent levels of Fas and Bcl-x, psoriatic keratinocytes expressed significantly higher levels of Fas and Bcl-x. In contrast, malignant keratinocytes in basal cell carcinomas expressed high levels of Bcl-2, but minimal Bcl-x, and no Fas. Immunoblot analysis revealed that the long form of Bcl-x (Bcl-xI), which prevents apoptosis in lymphocytes, is expressed by cultured keratinocytes and psoriatic plaque keratinocytes. We conclude that normal cytokine-activated keratinocytes can express an apoptotic (Fas) and an anti-apoptotic protein (Bcl-x). The overexpression of Bcl-x in psoriasis, or Bcl-2 in basal cell carcinomas, may contribute to the longevity of these cells by blocking the normal apoptotic process involved in the terminal differentiation program of epidermal keratinocytes.

Adult↗
PubMed1995

Disposition of the opioid antagonist, LY255582, in rats and dogs.

LY255582 is a phenylpiperidine opioid antagonist under development as an appetite suppressant and for the treatment of obesity. Female beagles were administered [14C]LY255582 at dosages of 0.72 mg/kg intravenously or 7.2 mg/kg orally. The majority (54-58%) of the radioactivity was eliminated in the urine over 8 days after both oral and intravenous drug administration, primarily as polar metabolites. Peak plasma levels of parent drug in the dog were 11.5 and 311 ng/ml after oral and intravenous administration, respectively, and declined with a half-life of 3.2 hr. Peak plasma levels of LY255582 in the rat were 7.9 and 160 ng/ml after administration of [14C]LY255582 at dosages of 35 mg/kg orally and 1 mg/kg intravenously, respectively. The half-life of parent drug in rats was 1.5 hr; however, the terminal half-lives of radioactivity equivalents were 7.9 and 31.7 hr after intravenous and oral administration, respectively. The bioavailability of parent LY255582 was < 1% in both the rat and the dog, primarily because of extensive first-pass metabolism. Whole-body autoradiographic studies in rats after administration of a single oral 35 mg/kg dose of [14C]LY255582 indicated that radioactivity was rapidly absorbed and distributed throughout the body. Radioactivity concentrated in the liver and was eliminated slowly. Little or no parent drug was eliminated in the urine of either species. As in the urine, the major residues present in the liver and bile of rats orally administered [14C]LY255582 were uncharacterized polar metabolites with little parent drug present.

Administration, Oral↗
PubMed1995

Chemical synthesis of polar zipper peptides: motifs for potential protein association in inherited neurodegenerative diseases.

Syntheses of peptides containing contiguous repeats of glutamine or asparagine, related to sequences derived from proteins associated with neurodegenerative diseases, are described. Such homo-polymeric peptides are notoriously difficult to prepare due to the formation of aggregated structures during their solid phase synthesis. A novel approach using a randomized array of side chain protected and unprotected residues proved to be an effective strategy for preventing intermolecular peptide-chain association.

Amino Acid Sequence↗
PubMed1994

Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases.

Four inherited neurodegenerative diseases are linked to abnormally expanded repeats of glutamine residues in the affected proteins. Molecular modeling followed by optical, electron, and x-ray diffraction studies of a synthetic poly(L-glutamine) shows that it forms beta-sheets strongly held together by hydrogen bonds. Glutamine repeats may function as polar zippers, for example, by joining specific transcription factors bound to separate DNA segments. Their extension may cause disease either by increased, nonspecific affinity between such factors or by gradual precipitation of the affected proteins in neurons.

Amino Acid Sequence↗
PubMed1994

The use of low-energy collisionally activated dissociation negative-ion tandem mass spectrometry for the characterization of dog and human urinary metabolites of the drug BW 1370U87.

Liquid chromatography (LC) combined with atmospheric pressure chemical ionization mass spectrometry was used to identify phase I and II metabolites of the drug BW 1370U87 in dog and human urine. Additional analysis of individual high-performance liquid chromatograph fractions collected from dog urine by combined gas chromatography/mass spectrometry identified one metabolite which was not detected by LC/MS methods. Using negative-ion LC/MS, the majority of BW 1370U87 metabolites in human urine were identified as glucuronic acid conjugates of phase I oxidative metabolites. The negative-ion fragmentation produced by low-energy collisionally activated decomposition (CAD), studied by tandem mass spectrometry experiments, confirmed that these compounds were drug-related and allowed metabolite structures to be assigned. Product-ion spectra of the metabolites were dominated by the loss of neutral molecules from even-electron deprotonated [M-H]- ions.

Animals↗
PubMed1994

The effect of personality disorder on clinical outcome, social networks and adjustment: a controlled clinical trial of psychiatric emergencies.

One hundred psychiatric emergencies presenting to an inner London teaching hospital had formal assessments of psychopathology, personality disorder (using both ICD-10 and the Personality Assessment Schedule), social networks and social functioning before being randomly assigned to a multidisciplinary community-based team (Early Intervention Service (N = 48) or conventional hospital-based psychiatric services (N = 52) and treated for a period of 12 weeks. The ICD-10 classification yielded a higher proportion (50%) of personality disordered patients than the Personality Assessment Schedule (34%) and those from ethnic minorities (mainly Afro-Caribbean) and upper social classes had a lower incidence of personality disorder. Social networks were smaller in personality disordered patients and there were fewer attachment figures. Improvement in social function, and to a lesser extent with depressive symptomatology, was better in patients with no differences were found between the numbers and duration of social contacts in the two services and it is concluded that the better outcome in the community-treated patients was independent of changes in social networks.

Community Mental Health Services↗