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Biomedical subjects

J J Martin

Publications and source records attributed to J J Martin.

At least 73 records · Page 4Linked to original sources
PubMed1998

ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families.

The apolipoprotein E (ApoE) genotype is a significant risk factor and modulator of age of onset of Alzheimer's disease (AD). We analyzed the effect of the ApoE genotype in two distinct early-onset familial AD groups: families with a mutation in the presenilin-1 gene (PS-1) on chromosome 14, and families without a mutation detectable in the PS-1, presenilin-2 (PS-2), and the amyloid precursor protein (APP) gene (non-PS early-onset familial AD). The ApoE genotype is clearly shown not to modulate age of onset in families with a mutation in the PS-1 gene and families with no lesion detectable in either the presenilin or APP gene. The effects of a double dose of ApoE4 on age of onset were not assessed in the PS-1 AD families due to the lack of any affected ApoE4 homozygotes in the sample set; this insufficiency will need to be assessed in further studies. There was no association between the ApoE4 allele and AD in the PS-1 families. Non-PS early-onset AD families were shown to have a significantly higher frequency of ApoE4 compared to controls and the PS-1 AD group. These observations are important and suggest that 1) other genetic and environmental factors modify the AD phenotype in PS-1 and non-PS early-onset families; and 2) the ApoE4 allele is a significant risk factor in the etiology of non-PS early-onset AD and will be a useful adjunct in the diagnosis of unaffected family members.

Alleles↗
PubMed1998

Gly341Arg mutation indicating malignant hyperthermia susceptibility: specific cause of chronically elevated serum creatine kinase activity.

We report on three families with the Gly341Arg ryanodine receptor gene (RYR1) mutation. Thirteen individuals were heterozygote carriers of the Gly341Arg mutation and had clearly positive in vitro contracture tests, indicating malignant hyperthermia susceptibility. Nine Gly341Arg mutation positive individuals from two families had elevated serum creatine kinase (CK) activity at rest (up to six times the normal upper limit). Their clinical and neurological examinations as well as detailed muscle histology were normal. The third family did not show increased CK activity. These findings indicate that the Gly341Arg mutation can be a specific cause of chronically elevated serum CK activity in asymptomatic individuals.

Adult↗
PubMed1998

Chemotherapy as a part of each treatment fraction in a twice-a-day hyperfractionated schedule: a new chemoradiotherapy approach for advanced head and neck cancer.

BACKGROUND: Using chemotherapy as a part of each treatment fraction remains unexplored. This study integrates the concomitant administration of carboplatin with hyperfractionated irradiation by optimizing chemopotentiation through carboplatin administration with each irradiation fraction. METHODS: From February 1993 to August 1996, 52 patients with advanced head and neck cancer were treated on a twice-a-day chemoradiotherapy schedule. Each fraction consisted of 115 cGy preceded by 5 mg/m2 of carboplatin. Treatment was given 5 days a week up to total doses of 350 mg/m2 of carboplatin + 8050 cGy in 7 weeks. RESULTS: All (100%) of patients tolerated the treatment (83% as scheduled). Acute and late toxicities were moderate. Rates of 96% complete response (CR) and 4% partial response (PR) were achieved. At 52 months, local control and cause-specific survival rates are 72% and 59%, respectively. Nodal control rate is 95%. CONCLUSION: These results show potential for improvement upon hyperfractionated radiotherapy alone and compare favorably with those of most reported trials.

Adult↗
PubMed1998

Glutathione protects metastatic melanoma cells against oxidative stress in the murine hepatic microvasculature.

Calcein-labeled B16 melanoma (B16M) cells were injected intraportally, and in vivo video microscopy was used to study the distribution and damage of cancer cells arrested in the liver microvasculature over a period of 4 hours. The contribution of glutathione (GSH)-dependent antioxidant machinery to the possible oxidative stress-resistance mechanism of B16M cell was determined by in vitro incubation with the selective inhibitor of GSH synthesis L-buthionine (S,R)-sulphoximine (BSO) before B16M cell injection in untreated and 0.5-mg/kg lipopolysaccharide (LPS)-treated mice. In addition, untreated and LPS-treated isolated syngeneic hepatic sinusoidal endothelial cells (HSE) were used to determine in vitro their specific contribution to B16M cell damage. Trauma inherent to intrasinusoidal lodgement damaged 35% of B16M cells in both normal and LPS-treated mouse liver. The rest of the arrested B16M cells remained intact in normal liver for at least 4 hours, although their damaged cell percentage significantly (P < .05) increased since the second hour in normal mice injected with BSO-treated cells and since the first hour in LPS-treated mice given untreated cells. Recombinant human interleukin-1 receptor antagonist (rHuIL-1-Ra) given to mice 15 minutes before LPS significantly (P < .05) abrogated B16M cell damage. On the other hand, 40% of the B16M cells co-cultured with unstimulated HSE and 70% of the co-cultured with LPS-treated HSE became sensitive to endothelial cell-mediated damage after BSO treatment. These results demonstrate that a high intracellular level of GSH protects B16M cells from possible in vivo and in vitro sinusoidal cell-mediated oxidative stress, contributing to the mechanism of metastatic cell survival within the hepatic microvasculature.

Animals↗
PubMed1998

Immunoreactivity of presenilin-1 and tau in Alzheimer's disease brain.

Mutations in the presenilin-1 gene (PS-1) on chromosome 14 are causative for early-onset familial Alzheimer's disease (AD). In order to study the localization of PS-1 in human brain, a polyclonal antibody, SB63, against a N-terminal epitope of PS-1 (25VRSQNDNRERQEHND40), was raised in rabbits and characterized. Immunolabeling with SB63 of formalin-fixed sections of hippocampus from cases of PS-1-linked AD (PS-1 I143T (AD/A), G384A (AD/B)), sporadic AD, and controls showed a predominant neuronal staining pattern with a stronger immunoreactivity in pyramidal neurons. Staining was mainly granular and localized in the neuronal cell body as well as in neuronal processes. In AD some dystrophic neurites surrounding the amyloid plaques were stained, but no immunoreactivity was observed in the amyloid core. Although PS-1 was present in tangle bearing neurons, colocalization of PS-1 and tau could not be detected using immunofluorescence double labeling. Our data indicate that the pattern of PS-1 immunoreactivity in the hippocampus does not substantially differ between PS-1-linked AD, sporadic AD, and controls.

Alzheimer Disease↗
PubMed1998

Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation.

Mutations at codons 717 and 670/671 in the amyloid precursor protein (APP) are rare genetic causes of familial Alzheimer's disease (AD). A mutation at codon 693 of APP has also been described as the genetic defect in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). We have reported a APP692Ala-->Gly (Flemish) mutation as a cause of intracerebral hemorrhage and presenile dementia diagnosed as probable AD in a Dutch family. We now describe the post-mortem examination of two demented patients with the APP692 mutation. The neuropathological findings support the diagnosis of AD. Leptomeningial and parenchymal vessels showed extensive deposition of Abeta amyloid protein. Numerous senile plaques consisted of large Abeta amyloid cores, often measuring more than 30 microm in diameter and were surrounded by a fine meshwork of dystrophic neurites. In addition, there were a large number of paired helical filaments in pyramidal neurons and dystrophic neurites. Our findings show that the APP692 mutation leads to morphological abnormalities that are similar to AD, but the morphology of senile plaques is clearly distinct from that described in sporadic and chromosome 14-linked AD patients, in patients with APP717 mutations causing familial, presenile AD and in patients with the APP693 mutation causing HCHWA-D.

Alzheimer Disease↗
PubMed1998

Mucolipidosis type II with evidence of a novel storage site.

In a case of infantile mucolipidosis type II (I-cell disease), storage was identified at autopsy in serous-type secretory cells in exocrine pancreas, in the tracheal and sublingual salivary glands and in the chief (zymogenic) cells of the gastric oxyntic glands, suggesting a systemic involvement of this type of secretory cells. The content of specific secretory granules was inversely proportional to the intensity of the storage process. The mucus-producing cells were not affected. The serous glandular system is a novel storage site in I-cell disease. Review of archival material in three further cases confirmed the findings.

Biopsy↗
PubMed1998

Determination of growth fraction and cell density to evaluate the potential growth of human oligodendroglial and astrocytic tumours.

UNLABELLED: The object of this work was PURPOSE: to develop a methodology that enables net tumour growth, a balance between actual tumour growth and tumour cell loss, to be approximately evaluated. METHODS: The methodology proposed relies on detecting the growth fraction immunohistochemically by means of MIB-1 antibody labelling combined with cell density determination, carried out on 5-microm-thick Feulgen-stained histological sections with computer-assisted microscopy. The series investigated included 25 oligodendrogliomas (OLG-II), 9 anaplastic oligodendrogliomas (OLG-III). 13 astrocytomas (AST), 14 anaplastic astrocytomas (ANA) and 8 mixed oligoastrocytomas (OLG-AST). RESULTS: The results show that the biological characteristics of some cases were in total accordance with their histopathological diagnoses. This was the case for the "weakly proliferating weakly dense" OLG-II and AST-II tumours, and for the "highly proliferating highly dense" OLG-III and AST-III ones. In contrast, the biological characteristics of some cases seemed to contradict the histopathological case labels. This was the case for the "highly proliferating highly dense" OLG-II and AST-II tumours, the biological aggressiveness of which would be undervalued on the basis of the morphology-based grading system alone, and also for the "weakly proliferating weakly dense" OLG-III and AST-III tumours, the aggressiveness of which would be overvalued. CONCLUSIONS: Combining the determinations of the MIB-1 and the cell density variables appears to be satisfactory in terms of the cell kinetic characterization of glial tumours as a complement to the prognostic information given by a morphology-based grading system alone.

Adult↗
PubMed1998

Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP-linked and sporadic Alzheimer disease.

To determine whether similar abnormalities of various soluble full-length and N-terminal truncated Abeta peptides occur in postmortem cerebral cortex of affected PS1 mutation carriers, we examined the amounts of two amyloid species ending at residue 40 or at residues 42(43) using sandwich ELISA systems. Our results indicate that PS1 mutations effect a dramatic accumulation in brain of the highly insoluble potentially neurotoxic long-tailed isoforms of the Abeta peptide such as Abeta1-42(43) and Abetax-42(43). This enhancing effect of PS1 mutation on Abetax-42(43) deposition was highly similar to that of a betaAPP mutation (Val717Ile) but the effects on Abetax-40 production were significantly different between these two causal genes. In contrast to previous studies of soluble Abeta in plasma and in supernatants from cultured fibroblasts of subjects with PS1 mutations, our studies also show that there is an increase in insoluble Abetax-40 peptides in brain of subjects with PS1 mutations.

Adult↗
PubMed1998

Molecular genetic analysis of autosomal dominant cerebellar ataxia with retinal degeneration (ADCA type II) caused by CAG triplet repeat expansion.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCAII) was previously mapped by linkage analysis studies to chromosome 3p12-p21.1 (SCA7). Positional cloning efforts have recently identified a novel gene, SCA7 , containing a translated CAG repeat, expanded in SCA7 patients. We cloned the SCA7 gene from a yeast artificial chromosome (YAC) clone contig spanning the SCA7 candidate region. Using a combination of genomic sequencing and cosmid-based exon trapping, two expressed sequence tags were identified. Sequencing of the corresponding cDNA clones and RT-PCR analysis identified the full-length SCA7 cDNA. Together, our sequence data defined the intron/exon boundaries of the first two coding exons of the SCA7 gene, with the first exon containing the expanded CAG repeat. Further, sequence comparison with the published SCA7 cDNA identified one additional putative exon in the 5'-UTR region of the SCA7 gene. The SCA7 gene was mapped on the YAC contig in the 2.5 cM interval between D3S1600 and D3S1287. In one extended Belgian SCA7 pedigree the expanded alleles ranged from 38 to at least 55 repeats with allele lengths being inversely correlated with onset age of ADCAII symptoms. The SCA7 repeats increased in length in successive generations. Normal alleles had from four to 18 repeats, with 10 repeats being the most common allele.

Alleles↗
PubMed1998

Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits.

A subtype of neuronal ceroid lipofuscinosis (NCL) is well recognized which has a clinical course consistent with juvenile NCL (JNCL) but the ultrastructural characteristics of infantile NCL (INCL): granular osmiophilic deposits (GROD). Evidence supporting linkage of this phenotype, designated vJNCL/GROD, to the INCL region of chromosome 1p32 was demonstrated (pairwise lod score with D1S211 , Z max = 2.63, straight theta = 0.00). The INCL gene, palmitoyl-protein thioesterase (PPT ; CLN1), was therefore screened for mutations in 11 vJNCL/GROD families. Five mutations in the PPT gene were identified: three missense mutations, Thr75Pro, Asp79Gly, Leu219Gln, and two nonsense mutations, Leu10STOP and Arg151STOP. The missense mutation Thr75Pro accounted for nine of the 22 disease chromosomes analysed and the nonsense mutation Arg151STOP for seven. Nine out of 11 patients were shown to combine a missense mutation on one disease chromosome with a nonsense mutation on the other. Mutations previously identified in INCL were not observed in vJNCL/GROD families. Thioesterase activity in peripheral blood lymphoblast cells was found to be markedly reduced in vJNCL/GROD patients compared with controls. These results demonstrate that this subtype of JNCL is allelic to INCL and further emphasize the correlation which exists between genetic basis and ultrastructural changes in the NCLs.

Age of Onset↗
PubMed1998

Characterization of astroglial versus oligodendroglial phenotypes in glioblastomas by means of quantitative morphonuclear variables generated by computer-assisted microscopy.

The current WHO classification places glioblastomas in the astrocytoma category. However, whether or not glioblastomas also show oligodendroglial differentiation remains a matter of controversy. This study investigates, at the morphonuclear level, the hypothesis that some glioblastomas (GBMs) may also represent the ultimate level of malignancy in the oligodendroglial lineage. Using a series of 164 GBMs, we sought to ascertain whether any of these GBMs exhibited phenotypical characteristics that were more closely related to oligodendroglial lineages than astrocytic lineages. Phenotypical features were quantitatively determined by means of the computer-assisted microscope analysis of Feulgen-stained nuclei, a process that made it possible to quantitatively describe the patterns of the cell nuclei (and, more specifically, of their chromatin) through 16 variables, and the distribution of the nuclear DNA content (DNA ploidy) through 8 variables. The phenotypical characteristics typical of astrocytic and oligodendroglial tumors were analyzed by means of Discriminant Analysis, a statistical multivariate analysis, performed on a series of 65 astrocytic and oligodendroglial tumors. This series consisted of 14 WHO grade II and 19 grade III astrocytomas and 24 WHO grade II and 8 grade III oligodendrogliomas. This multivariate analysis enabled an accurate model to be produced that distinguished between astrocytomas and oligodendrogliomas on the basis of 5 cytometry-generated variables. This model was used to characterize the phenotype of each of the 164 glioblastomas. The results show that of these 164 glioblastomas, 6 (about 3.5%) displayed phenotypes that were very similar to oligodendrogliomas, and 141 displayed phenotypes that were very similar to astrocytomas. The phenotypes of the 17 remaining GBMs were too ambiguous to be categorized as having a pure astrocytic or oligodendroglial lineage.

Adolescent↗
PubMed1998

Extracerebral biopsy in lysosomal and peroxisomal disorders. Ultrastructural findings.

The lysosomal and peroxisomal disorders are characterized by specific storage affecting mainly the central nervous system with involvement of the peripheral nervous system and visceral organs. Most of these disorders can now be diagnosed by using biochemical and enzymatical assays and by molecular biology techniques, without the need for a brain biopsy used previously. Extraneural tissue biopsies have also been investigated at the ultrastructural level. The study of such tissues is still necessary when the enzymatic or biochemical defect remains unknown and when DNA studies are not informative. The choice of tissue is important. Skin and conjunctival biopsies are less traumatic and are cost-effective diagnostic tools allowing the examination of a great diversity of structures. Skeletal muscle and peripheral nerves are more frequently used for patients with a late-onset or slower course of disease. Rectal biopsy is helpful when neurons require examination in lysosomal diseases, whereas liver is more usually investigated than adrenal or testis in peroxisomal diseases. Bone marrow is most useful for Gaucher's disease while lymphocytes may be examined for all lysosomal disorders as a first diagnostic approach. Chorionic villi still have a diagnostic role in combination of electron microscopy with DNA studies in early pregnancies at-risk for neuronal ceroid lipofuscinosis. Cultured fibroblasts are less informative than other biopsy samples for the morphological evaluation of lysosomal and peroxisomal disorders.

Biopsy↗
PubMed1998

Mutation analysis of the nerve specific promoter of the peripheral myelin protein 22 gene in CMT1 disease and HNPP.

We analysed the nerve specific promoter of the peripheral myelin protein 22 gene (PMP22) in a set of 15 unrelated patients with Charcot-Marie-Tooth type 1 disease (CMT1) and 16 unrelated patients with hereditary neuropathy with liability to pressure palsies (HNPP). In these patients no duplication/deletion nor a mutation in the coding region of the CMT1/ HNPP genes was detected. In one autosomal dominant CMT1 patient, we identified a base change in the non-coding exon 1A of PMP22 which, however, did not cosegregate with the disease in the family. This study indicates that mutations in the nerve specific PMP22 promoter and 5' untranslated exon will not be a common genetic cause of CMT1A and HNPP.

Base Sequence↗
PubMed1998

Preliminary development of a scale to measure attitudes regarding the importance of role modeling in physical activity and fitness behaviors among Health, Physical Education, Recreation, and Dance professionals.

This paper presents a new 16-item scale designed to measure attitudes regarding the importance of role modeling in physical activity and fitness behaviors among Health, Physical Education, Recreation, and Dance professionals. The measure was reviewed for face validity by a panel of experts and preliminary analyses gave as Cronbach alpha of .95 and split-half reliability of .97 for 22 graduate students.

Attitude↗
PubMed1998

Creutzfeldt-Jakob disease and blood transfusion.

Experimental data suggest that blood components from patients with CJD may carry infectivity. However, most of the studies have been made on the classic form of CJD. Further studies are needed to discern whether infectivity levels in blood from patients with the nvCJD differ from those with the classic form. Possibility of transmission of CJD by blood or blood products can not be excluded and therefore adequate surveillance should be implemented. People who have been exposed to contaminated blood should be followed, while recommendations are being adapted according to new scientific data on infectivity.

Creutzfeldt-Jakob Syndrome↗
PubMed1998

Functional anatomy, vascularisation and pathology of the human thalamus.

The thalamus is a nuclear complex situated in the diencephalon. Besides a neuro-anatomical description of the thalamus, this article reviews the current knowledge on the functional anatomy of the three functional classes of thalamic nuclei: specific, non-specific and association nuclei. As the majority of the pathology affecting the thalamus is of cerebrovascular origin, the vascularisation of the human thalamus will be reviewed as well. Finally, the knowledge of the functional anatomy and the vascularisation of the human thalamus will be integrated in the review of the semeiology of thalamic syndromes. Besides its function as a relay centre in subserving sensory and motor mechanisms, the thalamus participates in various neurocognitive processes such as memory and language. The current knowledge on these topics will be reviewed as well.

Cerebrovascular Disorders↗