Biomedical subjects

J J Martin

Publications and source records attributed to J J Martin.

At least 163 records · Page 9Linked to original sources

PubMed1993

Duchenne muscular dystrophy immunohistochemistry of foetal muscles.

Between 1989 and 1991, we realized 36 prenatal DNA diagnoses in 23 families at risk for Duchenne muscular dystrophy (DMD). The families were previously analyzed using multiplex polymerase chain reaction (PCR) analysis, Southern blot hybridization with cDNA markers, pulse field gel electrophoresis (PFGE) and linkage studies with polymorphic DNA markers. Eighteen male foetuses were examined and seven were found to be affected. Immunohistochemistry (IHC) of muscle tissue was realized after abortion in four foetuses aged 12 to 22 weeks. Three age-matched controls were used. Poly- and monoclonal antibodies against different epitopes of dystrophin were used. A polyclonal spectrin antibody was utilized to check for membrane integrity. DNA analysis of chorion villi had demonstrated an out of frame deletion in all four foetuses, later confirmed on abortion material. The different epitopes of dystrophin were absent on immunohistochemical sections while they were present in control cases. Spectrin was present in patients as well as in controls. IHC can be used to confirm the results of DNA diagnosis of DMD in foetuses.

Antibodies, Monoclonal↗

PubMed1993

Interleukin-1 beta converting enzyme. Synthesis of hydroxyethyl dipeptide surrogate-containing compounds as potential ICE inhibitors.

A series of compounds containing a hydroxyethyl-based dipeptide surrogate have been prepared as probes to evaluate the possibility of ICE being an aspartic protease. The aldehyde t-BocAsp(beta-t-butyl)H reacted with the organochromium species derived from phenethyl bromide and CrCl2 to give the expected addition product. Lactonization, reprotection of the amine and oxidation with RuCl3 gave the two protected dipeptide surrogates 7a and 7b. These were incorporated into tetra-, penta- and hexapeptide-like molecules and evaluated as inhibitors of the enzyme. The failure of these compounds to inhibit ICE indicated that this enzyme was very unlikely to be an aspartic protease.

Caspase 1↗

PubMed1993

Steinert's disease.

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Diagnosis, Differential↗

PubMed1992

De-novo mutation in hereditary motor and sensory neuropathy type I.

Isolated cases of hereditary motor and sensory neuropathy type I (HMSN I, Charcot-Marie-Tooth disease type 1) have been thought to be most frequently autosomal recessive. We have found that a recently discovered duplication in chromosome 17, responsible for most cases of autosomal dominant HMSN I, is present as a de-novo mutation in 9 out of 10 sporadic patients. This finding has important implications for genetic counselling of isolated patients with HMSN I.

Adolescent↗

PubMed1992

Monoclonal antibodies with selective specificity for Alzheimer Tau are directed against phosphatase-sensitive epitopes.

A modified form of the microtubule-associated protein Tau is the major component of the paired helical filaments (PHF) found in Alzheimer's disease. The characterization of these posttranslational Tau modifications is hindered by the lack of sufficient PHF-Tau-specific markers. Here we describe several monoclonal antibodies, prepared by immunization with PHF, two of which showed a selective specificity for PHF-Tau without cross-reactivity with normal Tau. Epitope recognition by these two monoclonals was sensitive to alkaline phosphatase treatment. In Western blotting these monoclonal antibodies reacted specifically with the abnormally phosphorylated epitopes on Alzheimer's disease-associated PHF-Tau. One of the new antibodies can be used for the construction of a sandwich enzyme-linked immunosorbent assay for the specific detection of PHF-Tau without cross-reactivity to normal Tau proteins.

Animals↗

PubMed1992

Loss of constitutional heterozygosity in human astrocytomas.

Inactivation of tumour suppressor genes or anti-oncogenes as well as activation of dominant acting oncogenes seem to be important mechanisms in the pathogenesis of gliomas. We compared constitutional and tumoural genotypes at different restriction fragment length polymorphism loci (RFLP) on chromosomes 10 and 17 in 15 unrelated individuals. Loss of heterozygosity (LOH) pointing to chromosomal loss or deletions was detected for at least one chromosome 17 marker in 11 gliomas (astrocytomas grades I-III and glioblastoma multiforme), whereas LOH for chromosome 10 loci was only detected in 3 out of 9 cases of glioblastoma multiforme and was not detected in low grade gliomas. Since LOH for chromosome 10 loci seems to be restricted only to glioblastoma multiforme, it is possible that recessive mutations on chromosome 10 are engaged in tumour progression from astrocytomas to glioblastoma multiforme. As LOH of chromosome 17 markers occurs in astrocytomas as in glioblastoma multiforme, chromosome 17 loci probably are involved in early tumour development.

Astrocytoma↗

PubMed1992

Persistent hypermethioninaemia with dominant inheritance.

A clinically benign form of persistent hypermethioninaemia with probable dominant inheritance was demonstrated in three generations of one family. Plasma methionine concentrations were between 87 and 475 mumol/L (normal mean 26 mumol/L; range 10-40 mumol/L); urinary methionine and homocystine concentrations were normal. Plasma homocystine, cystathionine, cystine and tyrosine were virtually normal. The concentrations in serum and urine of metabolites formed by the methionine transamination pathway were normal or moderately elevated. Methionine loading of two affected family members revealed a diminished ability to catabolize methionine, but the activities of methionine adenosyltransferase and cystathionine beta-synthase were not decreased in fibroblasts from four affected family members. Fibroblast methylenetetrahydrofolate reductase activity and its inhibition by S-adenosylmethionine were also normal, indicating normal regulation of N5-methyltetrahydrofolate-dependent homocysteine remethylation. Serum folate concentrations were not increased. The findings in this family differ from those previously described for known defects of methionine degradation. Since the hepatic and fibroblast isoenzymes of methionine adenosyltransferase differ in their genetic control, this family's biochemical findings appear consistent with a mutation in the structural gene for the hepatic methionine adenosyltransferase isoenzyme.

Amino Acid Metabolism, Inborn Errors↗

PubMed1992

Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree.

We describe a six generation family affected with the autosomal dominant form of distal hereditary motor neuropathy type II (distal HMN II). The distal HMN shows similarities with the hereditary motor and sensory neuropathies type I and II (HMSN I and HMSN II) or Charcot-Marie-Tooth disease type 1 and 2 (CMT 1 and CMT 2) and with some proximal HMN or spinal muscular atrophies (SMA). Gene loci have been assigned to chromosomes 1q, 17p, and 19q for CMT 1 and to chromosome 5q for recessive SMA. In this study we excluded all four regions for the presence of distal HMN II, indicating that this neuropathy is genetically different from CMT 1 and recessive SMA.

Charcot-Marie-Tooth Disease↗

PubMed1992

Electron microscopic features of skin in neurometabolic disorders.

Skin biopsy may contribute to the clinical diagnosis of neurometabolic disorders. It is an easy and much less traumatic procedure than brain, rectal, peripheral nerve and skeletal muscle biopsies. The method is informative and not too time-consuming for an experienced examiner. Differential diagnosis is possible in most storage disorders since the ultrastructure of the storage is virtually typical in lysosomal and in nonlysosomal diseases. The storage has a particular distribution with characteristic ultrastructural patterns in the various cell types. Skin biopsy plays a major diagnostic role when clinical features are atypical for a storage disorder, to discover new phenotypic variants of known enzymatic deficiencies or when the biochemical defect has not yet been determined. It can be used as a screening procedure to orientate the investigations, to suggest specific biochemical assays on cultured fibroblasts or other tissues or body fluids. It can be applied to detect "presymptomatic" patients in affected families. Other disorders of the nervous system should be investigated in the future to ascertain whether skin biopsies could possibly be used for diagnostic purposes. Thorough knowledge of the morphological features of these disorders may also improve the understanding of their pathogenesis, shed some light on the underlying basic defects and control the results of therapy.

Animals↗

PubMed1992

The association of astrocytoma and pituitary adenoma in a patient with alcaptonuria.

A female patient with a juvenile pilocytic astrocytoma and a pituitary adenoma is described. The patient also has alcaptonuria, a rare inborn error of metabolism with autosomal recessive mode of inheritance. The association of these three disorders has never been reported previously. The possible existence of a common genetic factor in the development of both tumors and alcaptonuria is discussed.

Adenoma↗

PubMed1992

Becker-type muscular dystrophy. Report of a family with one postmortem study.

Becker-type muscular dystrophy (BMD) is reported in two brothers. In one of the patients, the molecular demonstration of an in-frame deletion of exons 45, 46 and 47 has confirmed the clinical and pathological diagnosis of BMD. The autopsy of the other patient revealed mild neuronal losses in the anterior horns at C8, lumbar and sacral levels of the spinal cord. Mild neuronal losses in the spinal cord may explain the mixed type of neurogenic-myogenic features in the skeletal muscles of adult BMD patients.

Adult↗

PubMed1992

Samarium-153-labelled EDTMP for bone metastases from cancer of the prostate.

A Phase I dose-escalation trial of a bone seeking phosphonate labelled with Samarium-153 was conducted on heavily pretreated patients with widespread bony metastases from cancer of the prostate. The bone marrow dose was calculated initially on a 4:1 uptake of cortical to cancellous bone, but subsequent information suggested the distribution was approximately equal so that the marrow received about three times the dose that has been prescribed. As a result, what were at first thought to be doses of 0.5 Gy, 1.0 Gy and 1.5 Gy were probably 1.5 Gy, 3.0 Gy and 4.5 Gy respectively. Three patients were treated at each dose level. The dose was repeated in the first three. Pain relief was delayed for 2 weeks, and was maximal by 4 weeks. All but one patient gained some benefit but this was transitory, lasting only 4-6 weeks in most. A recalculated dose of 3 Gy proved the most effective. The major toxicity was to platelets. Thrombocytopenia was fatal in four cases (two with repeat doses). All patients died but three survived more than 6 months with the help of third line hormonal measures and local radiotherapy to maintain comfort. A second group of five patients, not previously irradiated, were given 153Sm-EDTMP to a marrow dose of 3 Gy and all have survived for more than 4 months and achieved minimal to excellent relief of pain. The technique is recommended as initial therapy in unirradiated patients with good bone marrow function and with significant pain above and below the diaphragm, making half-body irradiation less likely to be a useful palliative procedure.

Aged↗

PubMed1992

Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene.

Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with presenile dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, presenile dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.

Adult↗

PubMed1992

Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24.3.

Genetic linkage studies with chromosome 21 DNA markers and mutation analysis of the beta-amyloid protein precursor gene located in 21q21.3 have indicated that early-onset Alzheimer's disease (EOAD) is a heterogeneous disorder for which at least one other chromosomal locus exists. We examined two extended histopathologically confirmed EOAD pedigrees, AD/A and AD/B, with highly informative short tandem repeat (STR) polymorphisms and found complete linkage of the disease to a (CA)n dinucleotide repeat polymorphism at locus D14S43 in 14q24.3 (Zmax = 13.25 at theta = 0.0). Using additional chromosome 14 STR polymorphisms we were able to delineate the region containing the EOAD gene to an area of, at most, 8.9 centiMorgans between D14S42 and D14S53, flanking D14S43 on both sides.

Adult↗

PubMed1992

In vitro contracture tests in patients with various neuromuscular diseases.

In order to investigate the relationship between neuromuscular disease and malignant hyperthermia (MH) susceptibility, the caffeine and halothane in vitro contracture test (European Malignant Hyperthermia Group Protocol) were performed in 60 patients who underwent muscle biopsy for investigation of a clinically suspected neuromuscular disorder. Two test results were classified as MH susceptible, 10 as MH equivocal and 48 MH negative. The large number of equivocal results is thought to indicate the lack of specificity of the individual components of this test in patients with clinical or histological evidence of neuromuscular disease. The increased in vitro sensitivity to the drugs tested may nevertheless provide some explanation for several in vivo "MH-like reactions" reported frequently in these patients. These reactions, however, are likely to be based on pathophysiological mechanisms different from those responsible for a true MH crisis.

Adolescent↗

PubMed1992

In vitro diagnosis of malignant hyperthermia: influence of electrical stimulation on the contracture response to caffeine.

We have examined the influence of electrical stimulation on caffeine-induced tension generation during contracture testing used to diagnose malignant hyperthermia. The cumulative contracture response to caffeine was compared in pairs of morphologically comparable muscle bundles obtained from the same patient. Only one of the two bundles was stimulated electrically during the test. Statistically significant differences in tension were found at caffeine concentrations greater than or equal to 4 mmol litre-1, the tension developed being invariably larger in the unstimulated fascicles. These results suggest that electrical stimulation results in suppression of the dose-dependent, caffeine-induced contracture. This effect could be a result of the potentiation of twitch tension by caffeine, muscle fatigue, or both. Overall, the observed differences did not alter the in vitro diagnosis of malignant hyperthermia.

Caffeine↗

PubMed1992

Estimation of the size of the chromosome 17p11.2 duplication in Charcot-Marie-Tooth neuropathy type 1a (CMT1a). HMSN Collaborative Research Group.

We have previously shown a duplication in 17p11.2 with probe pVAW409R3 (D17S122) in 12 families with hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1). In this study we aimed to estimate the size of the duplication using additional polymorphic DNA markers located in 17p11.2-p12. Two other 17p11.2 markers, pVAW412R3 (D17S125) and pEW401 (D17S61), were found to be duplicated in all HMSN I patients tested. Furthermore, all HMSN I patients showed the same duplication junction fragment with probe pVAW409R3. On the genetic map the duplicated markers span a minimal distance of 10 cM while on the physical map they are present in the same NotI restriction fragment of 1150 kb. The discrepancy between the genetic and physical map distances suggests that the 17p11.2 region is extremely prone to recombinational events. The high recombination rate may be a contributing factor to the genetic instability of this chromosomal region.

Charcot-Marie-Tooth Disease↗

PubMed1992

Transient musical hallucinosis of central origin: a review and clinical study.

A 52 year old, right handed, hearing impaired woman was admitted with headache and neck stiffness. The only neuropsychological symptom was transient auditory perceptions in the left ear, which were musical, seemed familiar and were not influenced by verbal communication. CT and MRI showed a right subarachnoid haemorrhage, while brainstem auditory evoked potentials failed to reveal a brainstem lesion. In patients with organic cerebral disease, unilateral auditory hallucinations (AHs) may indicate a lesion in the contralateral hemisphere. However, according to this review the type of AHs (verbal versus musical) is not consistently associated with a cerebral lesion on either side.

Auditory Perception↗