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Biomedical subjects

N Martin

Publications and source records attributed to N Martin.

At least 127 records · Page 7Linked to original sources

Desmosomes are regulated by protein kinase C in primary rat epithelial cells.

In the present study, we addressed the possible relevance of protein kinase C (PKC) in the regulation of intracytoplasmic desmosome assembly. Treatment of cultured rat lingual and epidermal keratinocytes with a potent and highly selective PKC inhibitor (GF109203X) induced an increase in granular labelling for major desmosomal proteins, desmoplakins, desmoglein and plakoglobin, both intracellularly and at the cell surface. This was associated with the formation of ultrastructurally recognizable desmosomes deep in the cytoplasm and increase in intercellular desmosome number. In contrast, PKC activation upon short exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in altered cell morphology, loss of intercellular contact and accumulation of desmosomal proteins in the juxtanuclear zone. On the other hand, PKC depletion by long term TPA treatment re-established cell-cell contact, where desmosomal markers were exclusively redistributed. Taken together, these results suggest that inhibition of PKC is required for intracytoplasmic as well as intercellular desmosome assembly, whereas its activation may regulate disassembly process.

Animals↗

The origins of formal paraphasias in aphasics' picture naming.

Accounts of spoken word production differ on whether aphasics' formal paraphasias derive solely from segmental distortion or whether some derive instead from whole word substitution. Form-related paraphasias produced by nine aphasics during picture naming were examined for evidence of lexical effects (word, frequency, and grammatical class biases) and for the manner in which target phonemes and word shape were preserved. Preservation patterns were consistent with previous descriptions of aphasic and nonaphasic form-related speech errors. Evidence for word and frequency biases was found, as well as a grammatical class bias sensitive to the degree of target-response segmental overlap. In conjunction, the results indicate that formal paraphasias arise, at least in part, via word substitution. The findings are supportive of interactive models with phonological-to-lemma feedback and/or modular models with a grammatically organized lexeme level.

Adult↗

Early detection of vasospasm after acute subarachnoid hemorrhage using continuous EEG ICU monitoring.

The neurologic morbidity of delayed ischemic deficits from vasospasm following aneurysmal subarachnoid hemorrhage (SAH) continues to be the most debilitating complication from this devastating illness. Neurologic critical care is focused on recognition and treatment of these secondary insults but often the treatment is withheld until an irreversible deficit becomes manifest. Continuous EEG (cEEG) monitoring provides a unique potential to recognize early secondary insults and offers an opportunity for early intervention. We studied 32 SAH patients using cEEG and trending of the quantitative measure, relative alpha (RA), to determine if reductions in RA variability occurred with documented vasospasm. In 19/19 patients with angiographically documented vasospasm, we found that RA variability was decreased by a mean of two grades and improved with resolution of vasospasm. In 10/19 this reduction in RA variability preceded the diagnosis of vasospasm by a mean of 2.9 days (SD 1.73). The positive predictive and negative predictive values are 76% and 100%, respectively. Non-diagnostic clinical signs at the time of RA variability reduction and vasospasm were present in 12/19 patients. Thus decreased RA variability is able to provide early detection of neurologic complications such as vasospasm in patients before clear clinical symptoms and signs occur.

Adult↗

Influence of HLA alleles on the rate of progression of vertically transmitted HIV infection in children: association of several HLA-DR13 alleles with long-term survivorship and the potential association of HLA-A*2301 with rapid progression to AIDS. Long-Term Survivor Study.

The influence of host immunogenetics on the outcome of vertically transmitted HIV infection in children was examined in a multicenter cross sectional study of long term survivors and rapid progressors. Sequence-based typing was performed for the DRB1, DQB1 and HLA-A loci. 36.7% of 30 children surviving more than 8 years had one or more of the HLA-DR13 alleles, versus none of 14 rapidly progressing children who died within 2 years of age, p = 0.009, Haldane RR = 17.1. The alleles variably associated with this beneficial response to HIV were: DRB1*1301, DRB1*1302, DRB1*1303 and DRB1*1310, suggesting that the DR13 effect acted as a dominant trait. An additional 6 children were typed only by the SSOP method resulting in 44.4% of 36 long term surviving children with a DR13 allele and none of 14 rapid progressors, p = 0.002, Haldane RR = 23.3. No single DQB1 allele accounted for the HLA-DR13 allele association. In contrast, the presence of HLA A*2301 was associated with rapid progression to AIDS, 4% of long term survivors vs. 57.1% of 7 rapid progressors, p = 0.0006, RR = 0.031. Although the sample size is small, the marked differences in allele frequency along with differences between the peptide binding pockets of the HLA-A9 group of alleles including HLA A*2301 and the remainder of the HLA-A alleles suggest a structural basis for the dominant disadvantageous immune response to HIV conferred by A*2301.

Acquired Immunodeficiency Syndrome↗

Age changes in the causes of individual differences in conservatism.

Age-related changes are analyzed in the correlation of 3416 monozygotic and 3780 dizygotic U.S. twin pairs aged between 9 and 75+ years for conservatism scores derived from a 28-item social attitude inventory. The effects of the shared environment are overwhelming in twins aged 20 years or younger. In older twins, genetic effects appear to play a larger role. A more dynamic conception of the interaction between genes and environment in the development of complex human differences is needed.

Adolescent↗

Lexical access in aphasic and nonaphasic speakers.

An interactive 2-step theory of lexical retrieval was applied to the picture-naming error patterns of aphasic and nonaphasic speakers. The theory uses spreading activation in a lexical network to accomplish the mapping between the conceptual representation of an object and the phonological form of the word naming the object. A model developed from the theory was parameterized to fit normal error patterns. It was then "lesioned" by globally altering its connection weight, decay rates, or both to provide fits to the error patterns of 21 fluent aphasic patients. These fits were then used to derive predictions about the influence of syntactic categories on patient errors, the effect of phonology on semantic errors, error patterns after recovery, and patient performance on a single-word repetition task. The predictions were confirmed. It is argued that simple quantitative alterations to a normal processing model can explain much of the variety among patient patterns in naming.

Adult↗

A twin-pronged attack on complex traits.

Before one starts the hunt for quantitative trait loci (QTLs) for a complex trait, it is necessary to show that the trait is genetically influenced. This evidence is most likely to come from the classical twin study--the demonstration that monozygotic twins are more similar for the trait than dizygotic twins. The strengths and weaknesses of twin studies are discussed, and it is suggested that, far from becoming irrelevant with advances in molecular biology, they can improve the efficiency of QTL detection and play an important role in unravelling developmental genetic mechanisms.

Diseases in Twins↗

Post-traumatic stress disorder symptoms and the Clapham rail accident.

BACKGROUND: Post-traumatic stress disorder is a well recognised condition which can have long-term consequences. A rail accident to commuter trains in south London provided an opportunity, within the context of a Psychological Therapies Service, to study the prevalence and associations of the condition in a follow-up study. METHOD: Postal questionnaires were completed by 187 survivors (52% response rate) 10 to 22 months after the accident, and their symptoms were compared with a commuter control group. RESULTS: The accident group scored significantly higher on the Impact of Events scale (IES) than the control group. Severity of physical injury was significantly associated with high IES scores. Thirty per cent of those moderately or severely injured showed high levels of intrusion or avoidance symptoms (sub-scores of 20 or more). Thirty per cent of those nearest the accident focus had high sub-scores, associated variables being the accident experience of risk of death, feeling trapped and seeing death. For those less directly involved the proportions with symptoms were similar to those of controls. CONCLUSIONS: It is recommended that disaster services should provide for long-term psychological effects, particularly for those survivors who are injured, who experience risk of death, feeling trapped or who witness death.

Accidents↗

A descriptive survey of pediatric human immunodeficiency virus-infected long-term survivors.

OBJECTIVE: To identify the population of human immunodeficiency virus-infected pediatric long- term survivors (LTS) followed in major medical institutions in California, Florida and New Jersey. METHODS: A cross-sectional survey was performed with data collection forms sent to all investigators. Demographic, clinical, and laboratory data were obtained on all living patients >/=8 years infected in the perinatal period with human immunodeficiency virus. RESULTS: A total of 143 perinatally infected and 54 children infected by neonatal transfusion were identified. Fifty-four children (27%) had absolute CD4 counts >/=500 cells/mm (group 1: mean age 9.8 years), 54 children (27%) had CD4 counts between 200 and 500 cells/mm (group 2: mean age 10.1 years), and 89 children (45%) had CD4 counts <200 cells/mm (group 3: mean age 10.4 years). Ninety-five (48%) patients had developed AIDS defining conditions; 14 (26%) in group 1, 26 (48%) in group 2, and 55 (62%) in group 3. Ninety-two percent of patients had received antiretrovirals. Perinatally human immunodeficiency virus-infected children tended to be younger (mean age 9.8 years) than children infected via a blood transfusion (mean age 11 years). Generalized lymphadenopathy was the most prevalent clinical finding. Lymphoid interstitial pneumonia and recurrent bacterial infections were the most prevalent acquired immune deficiency syndrome-defining conditions. Twenty percent of LTS had CD4 counts >/=500 cells/mm and no immune deficiency syndrome-defining conditions. CONCLUSIONS: Pediatric LTS were in variable stages of disease progression. The proportion of children within each CD4 strata did not differ by mode of acquisition of infection. Increased CD4 counts were inversely proportional to age. Only 20% of pediatric LTS had minimal to no disease progression.

Acquired Immunodeficiency Syndrome↗

A comparison of the Eating Disorder Examination and a general psychiatric schedule.

OBJECTIVE: The aim of this study is to investigate the adequacy of a general interview schedule for the purpose of assessing bulimia nervosa. METHOD: In two waves of data collection 18-24 months apart, 250 women were assessed for disordered eating. The first interview was typical of that included in many psychiatric interview schedules and was used to screen women for selection in a subsequent interview. This latter interview, using the Eating Disorder Examination, represents the 'gold standard' for the assessment of disordered eating. RESULTS: While the psychiatric interview satisfactorily assessed disturbed eating in general, it seemed less capable of accurately assessing cases of bulimia nervosa in particular, the major weakness being the overestimation of binge-eating. CONCLUSIONS: Structured psychiatric interviews are suitable for screening purposes to identify women with disordered eating, but identification of bulimia nervosa requires further assessment with a suitable instrument.

Bulimia↗

Donor or recipient origin of post-transplantation lymphoproliferative disorders: evaluation by in situ hybridization.

Post-transplantation lymphoproliferative disorders (PTLDs) have been reported after bone marrow and solid-organ transplantation. It might be of interest to know the origin of PTLDs, because it has been suggested that a donor origin could be related to a better prognosis. We studied five cases of PTLD in sex-mismatched allografted recipients by in situ hybridization technique for chromosome Y on isolated cells as well as on frozen and on routinely fixed and paraffin-embedded material. Two proved to be of donor origin, including the only case of PTLD arising in the graft, and three of recipient origin. The best results were obtained on isolated cells, but it must be emphasized that hybridization on tissue sections from frozen material or from material fixed in formalin or in formalin-acetic acid-alcohol and then paraffin embedded also gave good results. Hybridization after fixation in Bouin's liquid was not reliable. These results suggest that evaluation of the origin of PTLDs can easily be performed on routinely processed cytologic and histologic material.

Adult↗

[Clinical pilot study on repeated use of heparin, vancomycin, colimycine locked flush solution for central intravenous implanted catheter in oncology].

With an anti-infectious and an antithrombotic prophylaxis aims, a locked flush solution including heparin and vancomycin, was used systematically for implantable venous access system for each patient, from january to april 1995. Since the 6th of april 1995, in order to widen the antibiotic spectrum on Gram negative bacteriae, we added colimycin at the flush solution. In 1995, 342 hospitalised patients held this type of venous access and received chemotherapy and/or radiochemotherapy for cancer. Two thousand six hundred thirty three manipulations were done, 575 with the first flush solution, 2058 with the second. During the year, 15 implantable access system (4.4%) were considered as infected, only 3 (0.9%) were removed, in the first period. THe infectious rate seemed to be stable, but the bacterial assessment to be modified between the two periods. The Gram negative bacterial infections seemed to decrease with colimycin addition (33% versus 50%). These results must be confirmed by a long term and/or randomized study.

Anti-Bacterial Agents↗

An in vivo pathway for disulfide bond isomerization in Escherichia coli.

Biochemical studies have shown that the periplasmic protein disulfide oxidoreductase DsbC can isomerize aberrant disulfide bonds. Here we present the first evidence for an in vivo role of DsbC in disulfide bond isomerization. Furthermore, our data suggest that the enzymes DsbA and DsbC play distinct roles in the cell in disulfide bond formation and isomerization, respectively. We have shown that mutants in dsbC display a defect in disulfide bond formation specific for proteins with multiple disulfide bonds. The defect can be complemented by the addition of reduced dithiothreitol to the medium, suggesting that absence of DsbC results in accumulation of misoxidized proteins. Mutations in the dipZ and trxA genes have similar phenotypes. We propose that DipZ, a cytoplasmic membrane protein with a thioredoxin-like domain, and thioredoxin, the product of the trxA gene, are components of a pathway for maintaining DsbC active as a protein disulfide bond isomerase.

Alkaline Phosphatase↗

Characterization of lymphocyte fibronectin.

In vitro cultured "activated" peripheral blood lymphocytes and T-cell lines synthesized a high-molecular-weight gelatin binding molecule (MW 500 kDa), whereas resting lymphocytes showed poor or negligible synthesis of the same component. Concanavalin A-mediated anchorage of the lymphocytes to a substratum potentiated synthesis of the high-molecular-weight molecule. Western blotting of the gelatin-binding lymphocyte molecule demonstrated reactivity with antibodies specific for human fibronectin. Furthermore, immunocytochemistry showed reactivity of anti-fibronectin antibodies with T-lymphocytes at the single-cell level. The lymphocyte-derived fibronectin was preferentially cell associated and relatively small amounts were present in the culture medium. RT-PCR of total RNA from CD4+ T-cells and the lymphoid T-cell line MOLT-4 showed that the most abundant species of fibronectin mRNA lacked the entire III CS exon encoding the alpha 4 beta 1 binding region LDV. Amplification of the III CS region from other T-cell lines revealed that these cells expressed several fibronectin mRNA isoforms most of which were lacking the LDV coding sequence. In conclusion, synthesis of fibronectin is demonstrated to occur in T-lymphocytes and to be regulated by signals which activate the cells.

Adult↗