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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 577 records · Page 32Linked to original sources
PubMed1992

Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study.

BACKGROUND: Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. METHODS: We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. RESULTS: As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus-amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]). The volume of the left posterior superior temporal gyrus correlated with the score on the thought-disorder index in the 13 patients evaluated (r = -0.81, P = 0.001). None of these regional volume decreases was accompanied by a decrease in the volume of the overall brain or temporal lobe. The volume of gray matter in a control region (the superior frontal gyrus) was essentially the same in the patients and controls. CONCLUSIONS: Schizophrenia involves localized reductions in the gray matter of the left temporal lobe. The degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.

Adult↗
PubMed1992

Effect of MHC class-I transfection on local tumor growth and metastasis in an H-2-negative clone derived from a chemically induced fibrosarcoma.

GR9 is a chemically induced fibrosarcoma composed of clones with different H-2 class-I expression. These clones differ with respect to local growth and spontaneous metastasis. The B9 clone (H-2 negative) is highly tumorigenic (local growth) but of low metastatic potential (spontaneous metastasis assay). We have analyzed the effect that transfection of H-2Dd and H-2Kd genes on this clone have upon local growth, lung colonization after i.v. injection and ability to form spontaneous metastases. The results showed that the effect on local growth of transfection of the Kd-gene was stronger than that of the Dd gene. In addition, B9 co-transfected with H-2Kd and Dd genes showed the highest immunogenic properties in syngeneic BALB/c mice. Interestingly, the pSV2-neo transfected clone gave almost the same result as that obtained with Dd transfection. Lung colonization after i.v. injection of the different clones (experimental metastasis), paralleled the results obtained for local growth: the number of lung nodules followed the cadence KdDd less than Kd less than Dd less than pSV2. Survival of mice was always inversely correlated with local growth, e.g., all mice injected with 5 x 10(5) B9 H-2KdDd transfected cells survived. In contrast, no mice injected with the B9 control did. These differences were abrogated in irradiated and nude BALB/c mice. Finally, all transfected clones remained non-metastatic in a spontaneous metastasis assay, behaving as the control, non-transfected B9 cells.

Animals↗
PubMed1992

Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic lateral sclerosis with dementia.

Amyotrophic lateral sclerosis (ALS) patients with dementia were found to have ubiquitin-immunoreactive (IR) inclusions in the dentate granule cells of the hippocampus. These inclusions were also present in some patients with minor cognitive changes but otherwise typical ALS. Ubiquitin-IR inclusions were also found in neurons of superficial layers of the frontal and temporal cortex and in the entorhinal cortex in patients with ALS and dementia. These ubiquitin-IR inclusions were non-argyrophilic, and were not labelled by antibodies which identify Alzheimer's neurofibrillary tangles and Pick bodies, nor were they typical of cortical Lewy bodies. Our findings indicate that ubiquitin-IR inclusions in small neurons of the hippocampus, entorhinal area and neocortex are a characteristic feature of degeneration of non-motor cortex in ALS, and are particularly associated with cognitive impairment and dementia of frontal lobe type.

Adult↗
PubMed1992

Characterization of ATP11 and detection of the encoded protein in mitochondria of Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, expression of functional F1-ATPase requires two proteins encoded by the ATP11 and ATP12 genes. Mutations in either gene block some crucial late step in assembly of F1, causing the alpha and beta subunits to accumulate in mitochondria as inactive aggregates (Ackerman, S. H., and Tzagoloff, A. (1991) Proc. Natl. Acad. Sci. U.S.A. 87, 4986-4990). In the present study we have cloned and determined the sequence of ATP11. The encoded product is protein of 37 kDa with no obvious homology to any known protein. In vitro import assays of ATP11 precursor and immunochemical evidence indicate that the protein is located in mitochondria. A fusion was made between ATP11 and a short sequence coding for 78 amino acids with the biotination signal of bacterial transcarboxylase. The protein expressed from this construct complements atp11 mutants, indicating that the addition of the extra 78 amino acids at the carboxyl terminus of the ATP11 protein does not compromise its function. The hybrid protein is detected in mitochondria with antibodies and with peroxidase-conjugated avidin. Biotinated ATP11 protein can be partially purified by affinity chromatography on monomeric or tetrameric avidin coupled to Sepharose. A fraction eluted from the avidin column and enriched for the biotinated ATP11 protein also contains the alpha and beta subunits of F1-ATPase.

Amino Acid Sequence↗
PubMed1992

Subclinical injuries in lacerations to the forearm and hand.

This report describes the incidence and severity of subclinical injuries to underlying structures in lacerations to the hand and forearm. One hundred consecutive hand and forearm lacerations that penetrated the full thickness of subcutaneous tissue were studied prospectively. Lacerations were explored under either biceps or forearm tourniquets. Injuries, treatment, tourniquet time, causative agent and complications were recorded. In all, 97 patients sustained 100 lacerations. A total of 49 deep injuries were discovered, none of which was detected clinically before exploration. Of these, 33 were tendon lacerations; 21 tendons, including three flexor tendons, were repaired. Nineteen patients required treatment in a volar slab for at least 3 weeks. Five patients of 49 returning for review developed wound infection. No patient developed significant problems related to the tourniquet, which was inflated for a mean time of 4.9 min. There is a high incidence of subclinical injury in full-thickness lacerations of the forearm and hand. These should be explored under tourniquet, which should minimize complications such as wound infection and delayed tendon rupture.

Forearm↗
PubMed1992

A comprehensive scanning method for rapid detection of beta-globin gene mutations and polymorphisms.

We describe a scanning procedure for the detection of beta-globin gene mutations and the prenatal diagnosis of beta-thalassemias. The method is based on the combined use of PCR and denaturing gradient gel electrophoresis (DGGE) of six amplified fragments encompassing the whole beta-globin coding region and splice junctions, as well as the promoter and 3' untranslated regions. The whole beta-globin gene can be rapidly scanned for the presence of deleterious mutations. The proposed diagnostic strategy provides a major improvement over current approaches to beta-globin gene analysis in both research and clinical laboratories, especially those which analyse DNA samples from individuals belonging to various ethnic or population groups. The use of this procedure has enabled us to detect six novel sequence changes in the beta-globin gene, including two deleterious mutations and four polymorphisms.

Base Sequence↗
PubMed1992

Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity.

The mechanism of GroEL (chaperonin)-mediated protein folding is only partially understood. We have analysed structural and functional properties of the interaction between GroEL and the co-chaperonin GroES. The stoichiometry of the GroEL 14mer and the GroES 7mer in the functional holo-chaperonin is 1:1. GroES protects half of the GroEL subunits from proteolytic truncation of the approximately 50 C-terminal residues. Removal of this region results in an inhibition of the GroEL ATPase, mimicking the effect of GroES on full-length GroEL. Image analysis of electron micrographs revealed that GroES binding triggers conspicuous conformational changes both in the GroES adjacent end and at the opposite end of the GroEL cylinder. This apparently prohibits the association of a second GroES oligomer. Addition of denatured polypeptide leads to the appearance of irregularly shaped, stain-excluding masses within the GroEL double-ring, which are larger with bound alcohol oxidase (75 kDa) than with rhodanese (35 kDa). We conclude that the functional complex of GroEL and GroES is characterized by asymmetrical binding of GroES to one end of the GroEL cylinder and suggest that binding of the substrate protein occurs within the central cavity of GroEL.

Bacterial Proteins↗
PubMed1992

Muscle excitation in elderly adults: the effects of training.

Muscle membrane excitability is thought to decline with aging; the extent of this decline may be noninvasively assessed by measurement of the electrically evoked compound muscle action potential (M-wave). The intent of this study was two-fold: (1) to compare the M-wave in the brachioradialis (BR), tibialis anterior (TA), and thenar (TH) muscles of elderly (mean age = 66.3 +/- 3.7 years) and young (mean age = 31.2 +/- 4.9 years) adults, and (2) to determine the effects of 12 weeks of resistance training on M-wave characteristics in elderly adults. Prior to training, the elderly subjects had significantly smaller (P less than 0.05) resting M-waves than the young adults in the BR (4.8 mV vs. 8.7 mV), TA (8.8 mV vs. 11.0 mV), and TH (5.2 mV vs. 10.2 mV) muscles. During a 2-minute voluntary fatigue paradigm (3 seconds MVC per 2 seconds rest for 2 minutes), there was no evidence of excitability failure in either group. Following training, there was a significant increase (P less than 0.05) in the size of the M-wave of the TH (pretraining: 5.2 mV; posttraining: 8.96 mV) and BR (pretraining: 4.8 mV; posttraining: 6.1 mV), and a nonsignificant increase in the M-wave of the TA, but there was no change in the relative behavior of the M-wave during the 2-minute voluntary fatigue paradigm. It is suggested that the decline in muscle membrane excitation with aging may be due, at least in part, to the effects of a decreased membrane potential on the muscle fiber action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Relationships between Lewy bodies and pale bodies in Parkinson's disease.

The prevalence of pale bodies and Lewy bodies was studied in the substantia nigra of 12 patients with typical Parkinson's disease (PD), in 5 patients with diffuse Lewy body disease (DLBD), and in a group of neurologically normal controls. Anti-ubiquitin antibodies labelled pale bodies and Lewy bodies in typical PD and DLBD, and there was a strong positive correlation between numbers of ubiquitin-immunoreactive pale bodies and Lewy bodies. BF10, a monoclonal antibody against a phosphate-dependent epitope of neurofilament 155-kDa polypeptide subunit, immunolabelled 57% of Lewy bodies and 15% of pale bodies in typical PD. Some pale bodies and Lewy bodies were seen in the substantia nigra of 2 of 5 neurologically normal, aged controls, probably representing "incidental PD". We conclude that there is a close relationship between pale bodies and typical Lewy bodies in the substantia nigra in clinical varieties of PD, and that these inclusions share antigenic determinants. If pale bodies and Lewy bodies reflect separate aspects of the cellular pathology in PD, their formation probably occurs in parallel. Alternatively, these observations may suggest that pale bodies represent a stage in the formation of Lewy bodies.

Aged↗
PubMed1992

Neuromuscular fatigue during repetitive stimulation in elderly and young adults.

The purpose of this investigation was to examine the integrity of neuromuscular transmission and impulse propagation during fatigue by examining the muscle compound action potential (M wave) in elderly and young adults. The tibialis anterior muscle of nine elderly [mean = 67.7 (SE 1.7) years] and nine young [mean = 26.7 (SE 1.2) years] adults was maximally stimulated repetitively at frequencies of 20, 30 or 40 Hz for 60 s on separate occasions. There was a significantly smaller resting M wave amplitude [7.9 (SE 0.4) mV versus 9.9 (SE 0.6) mV] and M wave area [0.038 (SE 0.005) mV s versus 0.06 (SE 0.004) mV.s] in the elderly versus the young adults respectively. Measurement of the evoked muscle contractile properties revealed significantly (P < 0.05) longer twitch durations and a significantly (P < 0.05) greater peak twitch torque [4.6 (SE 0.4) Nm versus 3.2 (SE 0.5) Nm] in the elderly versus the young adults, respectively. The elderly adults had a significantly greater torque decline during the 20-Hz trial; however, the decline in torque during the 30-Hz and 40-Hz trials was similar in the elderly and the young adults (30 Hz: 40%; 40 Hz: 56%). Throughout each of the stimulation trials, the decline in torque was accompanied by a significant reduction in M wave amplitude (20 Hz: 14%; 30 Hz: 53%; 40 Hz: 67%); M wave area also declined significantly during the 30-Hz (31%) and 40-Hz (53%) trials. There was no significant difference between the elderly and the young adults in the reduction in the M wave amplitude or area during each trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of isolated and combined exposures to whole-body vibration and noise on auditory-event related brain potentials and psychophysical assessment.

Auditory event-related brain potentials (ERP) in response to two different tone stimuli (1.1 kHz or 1 kHz, 80 dB, 50 ms; given by headphones at a regular interstimulus interval of 5 s with a probability distribution of 70:30) were recorded from 12 healthy male subjects (Ss) during four different conditions with two repetitions: A-60 dBA white noise (wN), no whole-body vibration (WBV); B-60 dBA wN plus sinusoidal WBV in the az-direction with a frequency of 2.01 Hz and acceleration of 2 m.s-2 root mean square; C-80 dBA wN, no WBV; D-80 dBA wN plus WBV. Each condition consisted of two runs of about 11 min interrupted by a break of 4 min. During the break with continuing exposure, but without auditory stimuli, Ss judged the difficulty of the tone-detection task and intensity of noise by means of cross-modality matching (CMM). Vibration-synchronous activity in the electrocardiogram was eliminated by a subtraction-technique. Noise caused an attenuation of the N1 and P2 amplitudes and prolongation of P3 latencies. The WBV did not cause systematic ERP effects. Condition B was associated with higher N1 and smaller P3 amplitudes. The factor "condition" had a significant effect on the peak latencies of P3 to target stimuli and the task difficulty judged by CMM. Both effects exhibited significant linear increases in the sequence of conditions A, B, C, D. For the evaluation of exposure conditions at work, it can be suggested that noise has a strong systematic effect which can be enhanced by WBV.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1992

Rapid molecular characterization of mutations leading to unstable hemoglobin beta-chain variants.

Characterization of unstable hemoglobins by protein analysis is often difficult. However, it is facilitated by DNA analysis, especially in the case of hyperunstable beta-chain variants, which produce a beta-thalassemia phenotype. We have applied an efficient strategy to the detection of such variants at the DNA level, based on computer-designed denaturing gradient gel electrophoresis (DGGE) of amplified DNA fragments. This approach makes it possible to detect any anomaly in the beta-globin gene. We describe the use of the DGGE method for rapid characterization of beta-chain variants and report a new missense mutation in the beta-globin gene third exon, beta 127 CAG-CGG/Gln-Arg, which is responsible for the synthesis of a highly unstable hemoglobin.

Adolescent↗
PubMed1992

Hemolytic-uremic syndrome associated with pancreatitis in an HIV-positive patient.

Hemolytic-uremic syndrome (HUS) is a newly recognized hematologic manifestation of HIV infection that may be triggered by local or systemic infections as well as by immunological disorders. We report the case of a 36-year-old HIV-positive man, an intravenous drug abuser who developed HUS during an episode of acute pancreatitis. Hematologic and clinical improvement occurred following 2 weeks of nonaggressive therapy including vitamin E and fresh-frozen plasma.

Acute Disease↗
PubMed1992

Purification and characterization of O-acetylserine (thiol) lyase from spinach chloroplasts.

O-Acetylserine (thiol) lyase, the last enzyme in the cysteine biosynthetic pathway, was purified to homogeneity from spinach leaf chloroplasts. The enzyme has a molecular mass of 68,000 and consists of two identical subunits of Mr 35,000. The absorption spectrum obtained at pH 7.5 exhibited a peak at 407 nm due to pyridoxal phosphate, and addition of O-acetylserine induced a considerable modification of the spectrum. The pyridoxal phosphate content was found to be 1.1 per subunit of 35,000, and the chromophore was displaced from the enzyme by O-acetylserine, leading to a progressive inactivation of the holoenzyme. Upon gel filtration chromatography on Superdex 200, part of the chloroplastic O-acetylserine (thiol) lyase eluted in association with serine acetyltransferase at a position corresponding to a molecular mass of 310,000 (such a complex called cysteine synthase has been characterized in bacteria). The activity of O-acetylserine (thiol) lyase was optimum between pH 7.5 and 8.5. The apparent Km for O-acetylserine was 1.3 mM and for sulfide was 0.25 mM. The calculated activation energy was 12.6 kcal/mol at 10 mM O-acetylserine. The overall amino-acid composition of spinach chloroplast O-acetylserine (thiol) lyase was different than that determined for the same enzyme (cytosolic?) obtained from a crude extract of spinach leaves. A polyclonal antibody prepared against the chloroplastic O-acetylserine (thiol) lyase exhibited a very low cross-reactivity with a preparation of mitochondrial matrix and cytosolic proteins suggesting that the chloroplastic isoform was distinct from the mitochondrial and cytosolic counterparts.

Acetyltransferases↗
PubMed1992

Experimental pathology of intravenous polyurethane cannulae containing disinfectant.

Cannula tubing (1.6 mm external, 1 mm internal diameter) manufactured from medical grade polyurethane containing 2%, 2,4,4'-tri-chloro-2'-hydroxydiphenylether ('Irgasan', Ciba-Geigy) was found to have no effect other than that seen with control ('Irgasan'-free) tubing in the following test systems: (i) haemolysis, (ii) endothelial cell cultures, (iii) paravertebral muscle of rabbits, (iv) jugular vein of rabbits, (v) cannulation of baboons and (vi) clotting times of human platelet-rich plasma. However, the results from (iv) showed a significant amount of damage from both inpregnated and control cannulae and (v) showed that all detectable 'Irgasan' had been eluted from the portions of tubing retained within the animal before the end of the experiment, more rapidly than predicted from in-vitro studies. The rate of elution of 'Irgasan' in vivo needs to be further investigated, and consideration should be given to developing a plastic-disinfectant combination with a slower rate of loss of disinfectant.

Animals↗
PubMed1992

Molecular characterization of cystic fibrosis: 16 novel mutations identified by analysis of the whole cystic fibrosis conductance transmembrane regulator (CFTR) coding regions and splice site junctions.

The spectrum of cystic fibrosis (CF) mutations was determined in 105 patients by using denaturing gradient gel electrophoresis to screen the entire coding regions and adjacent cystic fibrosis transmembrane conductance regulator (CFTR) gene sequences. The nucleotide substitutions detected included 16 novel mutations, 11 previously described defects, and 11 nucleotide sequence polymorphisms. Among the novel mutations, 6 were of the missense type, 4 were nonsense mutations, 4 were frameshift defects, and 2 affected mRNA splicing. The mutations involved all the CFTR domains, including the R domain. Of the 61 non-delta F508 CF chromosomes studied, mutations were found on 36 (59%), raising the proportion of CF alleles characterized in our patient cohort to 88%. Given the efficacy of the screening method used, the remaining uncharacterized mutations probably lie in DNA sequences outside the regions studied, e.g., upstream-promoter sequences, the large introns, or putative regulatory regions. Our results further document the highly heterogeneous nature of CF mutations and provide the information required for DNA-based genetic testing.

Base Sequence↗
PubMed1992

Exhaustive screening of exon 10 CFTR gene mutations and polymorphisms by denaturing gradient gel electrophoresis: applications to genetic counselling in cystic fibrosis.

Several mutations in the cystic fibrosis (CF) gene have been reported. Ten, including the most prevalent mutation in Caucasians, delta F508, are located in exon 10 of the gene, in addition to five sequence polymorphisms. We have previously presented a strategy based on denaturing gradient gel analysis for the rapid detection of any nucleotide variation in all the exons and their immediate flanking regions. We now report the application of this method to the simultaneous detection of all mutations and polymorphisms located in exon 10, together with the use of exon 10 polymorphisms, especially the most frequent one (M470V), as intragenic markers for prenatal diagnosis of cystic fibrosis in families with at least one affected child and unknown disease-causing mutations.

Base Sequence↗