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Biomedical subjects

J J Martin

Publications and source records attributed to J J Martin.

At least 127 records · Page 7Linked to original sources
PubMed1995

Phenotype plasticity and immunocytochemical evidence for ChAT and D beta H co-localization in fetal pig superior cervical ganglion cells.

The early expression of the cholinergic phenotype in sympathetic neurons was already studied in superior cervical ganglion cells derived from rat, quail and chicken embryo. In the present work, we set up a neuron culture derived from the superior cervical ganglia of fetal pigs. The yield is 1000 times of that of a neonatal rat [17], 100 times of a 10- to 13-day-old chick embryo [26] and 20 times of a 10-day-old quail embryo [3]. This high yield will greatly facilitate further biochemical studies concerning neuronal differentiation. Using these cells as a model, the phenotype plasticity was studied by both biochemical and immunocytochemical methods in normal physiological medium, in a high KCl (30 mM) medium and in a splenocyte co-culture. The phenotype shift occurs in the normal physiological medium and in the splenocyte co-culture, but not in the high KCl medium. Taking into account the species difference, the fetal pig superior cervical ganglion neurons behave in a comparable manner as reported in earlier studies for other animal models. Moreover, for the first time, using immunocytochemical methods, direct evidence for a co-localization of choline-acetyl-transferase and dopamine-beta-hydroxylase in mammalian fetal sympathetic neurons, at least during a certain period, is given.

Animals↗
PubMed1995

Instability of microsatellites in human gliomas.

We have analyzed DNA obtained from 10 glioblastomas multiforme and 6 astrocytomas for microsatellite instability, using 17 different microsatellite loci dispersed over 7 different chromosomes. Six of 16 gliomas showed 1 or more microsatellite alterations in tumor DNA as compared to constitutional DNA. We observed microsatellite instability resulting in allelic shifts in 5 of 10 glioblastomas multiforme but not in any of the astrocytomas. Loss of an allele was observed in 3 glioblastomas multiforme. An imbalance in the intensity of alleles was noticed in 1 astrocytoma and in 1 glioblastoma multiforme. In 1 glioblastoma multiforme, an extra allele was present at two distinct loci. Overall, 5.3% of microsatellite analyses showed an abnormality. We conclude that microsatellite instability is present at a low grade in glioblastomas multiforme but to a lesser extent in astrocytomas. Genomic instability in human gliomas, therefore, should not be regarded as a mechanism for tumor initiation but as an evolution in tumor progression.

Alleles↗
PubMed1995

Postmortem MRI of the brain with neuropathological correlation.

We prospectively correlated in vitro MRI of the brain with the neuropathological findings in patients with suspected intracranial disease. In vitro MRI was performed on 91 consecutive formalin-fixed whole-brain specimens. In 60 cases, the images were correlated with the neuropathological findings (number of lesions, lesion boundaries, spread of oedema and type of lesions). As compared with neuropathology, MRI showed an equal number of lesions in 50 cases, more in 5, and less in 5 specimens, resulting in a sensitivity of 83.3%. The extent of perilesional oedema was better seen on in vitro MRI than on gross pathology. Microscopic extent of glial tumours was underestimated on both T2-weighted images and macroscopic examination. Neuropathology remains the reference study, since on in vitro MRI primary brain tumours, metastatic deposits and non-neoplastic space-occupying lesions cannot be differentiated. However, in our study MRI had a specificity of 76.6%. MRI of postmortem specimens is sensitive to focal brain lesions, and can focus the attention of the neuropathologist to abnormal regions.

Adolescent↗
PubMed1995

Neuropathology of peroxisomal diseases.

This paper gives a description of the essential neuropathological techniques applied to the study of metabolic disorders affecting the nervous system. Subsequently, the neuropathological features of a series of peroxisomal disorders are described with special attention being paid to adrenoleukodystrophy.

Humans↗
PubMed1995

The gene for autosomal dominant cerebellar ataxia with pigmentary macular dystrophy maps to chromosome 3p12-p21.1.

Autosomal dominant cerebellar ataxia with pigmentary macular dystrophy (ADCA type II) is a rare neurodegenerative disorder with marked anticipation. We have mapped the ADCA type II locus to chromosome 3 by linkage analysis in a genome-wide search and found no evidence for genetic heterogeneity among four families of different geographic origins. Haplotype reconstruction initially restricted the locus to the 33 cM interval flanked by D3S1300 and D3S1276 located at 3p12-p21.1. Combined multipoint analysis, using the Zmax-1 method, further reduced the candidate interval to an 8 cM region around D3S1285. Our results show that ADCA type II is a genetically homogenous disorder, independent of the heterogeneous group of type I cerebellar ataxias.

Adolescent↗
PubMed1995

The relationships of anxiety and self-attention to running economy in competitive male distance runners.

Although running economy (RE) is an important physiological characteristic associated with superior distance running performance, little is known about the potential psychological correlates of RE. Therefore, the current study examined the relationship of anxiety and self-attention to RE. Anxiety was measured with the Sport Competition Anxiety Test (SCAT; Martens, 1977) and the Trait Anxiety Inventory (TAI; Spielberger et al., 1970). Self-attention was assessed with the Private Self-Consciousness (PSC) subscale of the Self-Consciousness Scale Revised (SCSR; Scheier and Carver, 1985). Running economy was determined by the oxygen cost of running at a submaximal velocity of 4.13 m s-1 (< 80% of maximal aerobic capacity). The subjects were 18 competitive male distance runners (mean 10-km race time 34.17 min). No relationship was found between anxiety (SCAT: r = -0.18, N.S.; TAI: r = -0.17, N.S.) and RE. However, PSC and RE were related (r = 0.50, P < 0.05), suggesting that runners who habitually directed attention inwards were also the most economical. Runners high in PSC may have been more economical because they were sensitive to muscle tension interfering with performance and subsequently employed relaxation techniques to reduce tension. Additionally, they may have employed cognitive techniques aimed at increasing RE such as positive self-talk and associative strategies. Despite the tenability of these explanations, the association between PSC and RE should be interpreted cautiously due to the small sample size.

Adult↗
PubMed1995

Genetic and physical characterization of the early-onset Alzheimer's disease AD3 locus on chromosome 14q24.3.

Genetic linkage studies have provided significant evidence that a major gene defect, AD3, for familial early-onset Alzheimer's disease (EOAD) is located at chromosome 14q24.3, between the short tandem repeat (STR) markers D14S52 and D14S53 defining a genetic size of 22.7 cM for the AD3 candidate region. We constructed a physical map of the AD3 region using yeast artificial chromosomes (YACs) selected from both the CEPH and megaCEPH YAC libraries using the AD3 linked STR markers as well as new sequence-tagged sites (STSs) designed based on YAC terminal sequences. The YAC map is contiguous in the region between D14S258 and D14S53, a region of 8.2 cM, and has an estimated physical size of 4-8 Mb. The YAC contig map was used as a framework to localize three known genes, a pseudogene and two brain expressed sequence tags (ESTs). Linkage analysis studies in two Belgian chromosome 14 EOAD families AD/A and AD/B, identified obligate recombinants in family AD/A with D14S289 and D14S61 reducing the genetic size of the candidate AD3 region substantially. The minimal AD3 candidate region measured 6.4 cM on the genetic map and is contained within six overlapping megaCEPH YACs that covered a physical distance estimated between 2 and 6 Mb. These YACs as well as other YACs in the YAC contig map are valuable resources in gene cloning efforts or genomic sequencing experiments aiming at isolating the AD3 gene.

Age of Onset↗
PubMed1995

Neurological disorders in members of families with Leber's hereditary optic neuropathy (LHON) caused by different mitochondrial mutations.

Neurological abnormalities have been occasionally associated with Leber's hereditary optic neuropathy (LHON). We describe four patients with spastic dystonia from two of our 35 LHON families. Magnetic resonance imaging revealed signal alterations of globus pallidus, putamen, internal capsula, and substantia nigra. Neuropathological findings in one of the patients with dystonia are described. Each of the dystonia families carries a different mtDNA mutation; one at np 3460 and one at np 11778. Periventricular multiple sclerosis-like white matter lesions were observed in one individual from a third family with the mtDNA 3460 mutation. Neurological disorders are probably underestimated in association with LHON.

Adolescent↗
PubMed1995

Surgical treatment of myogenic blepharoptosis.

We describe the surgical approach of two patients with myogenic blepharoptosis. The ptosis is caused by a glycogenosis type II (Pompe disease) in the first case and is due to a juvenile, chronic progressive external ophthalmoplegia (Kearns-Sayre syndrome) in the second case. The first patient presented a unilateral ptosis. The ptosis in the second patient was bilateral and manifest. The eyelids could only be opened manually. A resection of the palpebral levator muscle was carried out under local anesthesia. The choice of the technique will be explained. The amount of levator resection was calculated considering the residual eyelid motility and Bell's phenomenon. Electronmicroscopy of the resected levator muscle will be discussed.

Adult↗
PubMed1995

Chronic colchicine-induced myopathy and neuropathy.

The presented case concerns a 77-year old man who had been chronically taking colchicine for treatment of gout. He was admitted because of a transient ischemic cerebrovascular attack with motor aphasia and complained of preexisting paraesthesias in the lower extremities. Neurological examination revealed a global muscular weakness, absent myotatic reflexes and a diminished sensation. Serum creatine kinase (CK) levels were increased and electromyography showed spontaneous fibrillations in deltoid muscles, positive spikewaves in deltoids and anterior tibial muscles. Motor and sensory conduction velocities were mildly reduced. Nerve biopsy findings were compatible with a chronic axonal neuropathy having produced a significant loss of myelinated axons and also denervation features of unmyelinated axons. In muscle, combined neurogenic and myogenic features were found. The former result from the axonal neuropathy. The latter were mainly characterized by focal myofibrillar disorganisation and accumulation of autophagic vacuoles in muscle fibres. The presented neuromuscular symptoms and signs, the increased CK values, the electromyographic and nerve conduction velocity findings as well as nerve and muscle biopsy observations, are consistent with the diagnosis of colchicine-induced myopathy and neuropathy. Furthermore, the disappearance of paraesthesias, normalisation of CK values, and disappearance of fibrillations and positive spike waves in deltoid and anterior tibial muscles on electromyography, after stopping of the colchicine therapy, supported the diagnosis.

Aged↗
PubMed1994

Genetic analysis of the cellular oncogene fos in patients with chromosome 14 encoded Alzheimer's disease.

A major gene for familial early-onset Alzheimer's disease (AD) has been localised to chromosome 14q24.3. The c-fos gene (FOS), localised to 14q24.3-q31, is a candidate for the AD gene since it may be involved in the transcription regulation of the amyloid precursor protein gene (APP). Part of APP codes for the beta A4 amyloid present in AD brain lesions. We analyzed linkage of AD in the 2 early-onset AD families. AD/A and AD/B, using a polymerase chain reaction (PCR) based assay for a restriction fragment length polymorphism (RFLP). The RFLP is detected in BstNI digested DNA and is located near the 3' end of FOS. No obligate recombinants were detected. The 4 exons of FOS were sequenced in one pathologically confirmed AD patient in each family. No exonic mutations were found. Two intronic sequence variations were observed, one in intron 2 and one in intron 3. The intron 2 variation did not segregate with AD. The intron 3 variation which is a single G insertion was used in linkage studies in families AD/A and AD/B and showed conclusive linkage in both families in the absence of recombinants. Therefore, FOS cannot yet be excluded as a candidate gene for AD in these families since mutations may be present in regulatory sequences.

Alzheimer Disease↗
PubMed1994

Peripheral myelin protein-22 expression in Charcot-Marie-Tooth disease type 1a sural nerve biopsies.

Peripheral myelin protein-22 (PMP22) is expressed in myelinating Schwann cells and shows significant homology to murine growth arrest-specific gene gas3. Charcot-Marie-Tooth disease type 1a (CMT1a) is a common hereditary demyelinating neuropathy. Recently it was demonstrated that the gene for PMP22 is duplicated in CMT1a patients. A gene dosage mechanism has been postulated to cause CMT1a. According to this hypothesis, the increase in copy number of PMP22 gene would lead to an elevated expression of PMP22 and thereby cause the demyelinating phenotype of CMT1a. In the present communication we analyzed PMP22 mRNA and protein expression in sural nerve biopsies from CMT1a patients and normal controls. We show that PMP22 mRNA expression in CMT1a is not uniform. We found both elevated as well as normal PMP22 mRNA levels in patients. Interestingly, the highest PMP22 mRNA level was found in the least affected patient. In contrast to the mRNA levels, PMP22 was clearly reduced in all CMT1a patients as shown by immunohistochemistry. Thus the CMT1a phenotype may not be strictly correlated with increased PMP22 mRNA and protein expression. Possible roles of PMP22 in the pathogenesis of CMT1a are discussed.

Biopsy↗
PubMed1994

APOE genotype does not modulate age of onset in families with chromosome 14 encoded Alzheimer's disease.

A recent study has demonstrated an association of the apolipoprotein E allele epsilon 4 (APOE*4) to familial and sporadic late-onset Alzheimer's disease (AD). Also, in late-onset AD families linked to chromosome 19, the onset age decreased when the number of APOE*4 alleles increased. A similar effect of the APOE*4 genotype was observed in early-onset AD families linked to mutations in the APP gene located on chromosome 21. We assessed whether the APOE genotype had an influence on the age of onset of AD in chromosome 14 linked early-onset AD families. No significant effect of the APOE genotype on onset age could be detected.

Age of Onset↗
PubMed1994

Rapid screening of myelin genes in CMT1 patients by SSCP analysis: identification of new mutations and polymorphisms in the P0 gene.

Charcot-Marie-Tooth type 1 (CMT1) disease or hereditary motor and sensory neuropathy type I (HMSNI) is an autosomal dominant peripheral neuropathy. In most CMT1 families, the disease cosegregates with a 1.5-Mb duplication on chromosome 17p11.2 (CMT1A). A few patients have been found with mutations in the peripheral myelin protein 22 (PMP-22) gene located in the CMT1A region. In other families mutations have been identified in the major peripheral myelin protein P0 gene localized on chromosome 1q21-q23 (CMT1B). We performed a rapid mutation screening of the PMP-22 and P0 genes in non-duplicated CMT1 patients by single-strand conformation polymorphism analysis followed by direct polymerase chain reaction sequencing of genomic DNA. Six new single base changes in the P0 gene were observed: two missense mutations in, respectively, exons 2 and 3, two nonsense mutations in exon 4, and two silent mutations or polymorphisms in, respectively, exons 3 and 6.

Base Sequence↗
PubMed1994

Sensitivity and specificity of thallium-201 single-photon emission tomography in the functional detection and differential diagnosis of brain tumours.

The aim of this retrospective study was to assess the contribution of thallium-201 single-photon emission tomography (SPET) in the detection and differential diagnosis of brain tumours. In 90 patients 201Tl SPET was performed because of clinical or radiological suspicion of tumoral invasion, completed by technetium-99m hexamethylpropylene amine oxime and 99mTc-sestamibi SPET in some patients. For all tumours, diagnosis was based on biopsy or autopsy. Other diagnoses were made only after clinical and radiological follow-up for at least 6 months. Histologically tumours consisted of astrocytoma stage I or II (number of patients, n = 6), astrocytoma stage III (n = 8), glioblastoma multiforme (n = 14) and oligodendroglioma (n = 3), brain metastasis (n = 14), lymphoma (n = 3), meningioma (n = 3), pituitary adenoma (n = 2), pineal tumour (n = 1), colloid cyst (n = 1) and craniopharyngioma (n = 1). False-negative studies included pineal tumour (n = 1), colloid cyst (n = 1), craniopharyngioma (n = 1), astrocytomas stage I or II (n = 6) and stage III (n = 3), oligodendroglioma (n = 2) and metastasis in the brain stem (n = 1). Additional metastases approximately < 1.5 cm were not detected in two patients and 201Tl SPET underestimated tumoral extent in one patient suffering from glioblastoma multiforme (n = 1). A false-positive study was obtained in a patient with skull metastasis (n = 1). All 15 patients who were finally shown to suffer from ischaemic infarction had a normal SPET study 9-28 days after the onset of symptomatology. Of five patients with haemorrhagic infarction, studied within 2 weeks, four were false-positive. Of six patients with intracranial haemorrhage, studied 9-39 days later, one showed focal 201Tl accumulation. Two further false-positive studies consisted of angioma and epidural haematoma. Finally, SPET studies were normal in six patients with definite diagnosis of (reactive) gliosis (n = 3), Binswanger's encephalopathy (n = 1), postinfectious encephalopathy (n = 1) and multiple sclerosis (n = 1). In the patient population presented, sensitivity of 201Tl SPET for supratentorial brain tumours was 71.7% and specificity was 80.9%. Clinical information and control SPET studies in combination with early, 30-min and 3- to 4-h delayed imaging may be expected to improve on these figures. On the other hand it seems that, in addition to tumoral histology, the presence of tumours in the fossa posterior and small volumes contribute to the occurrence of false-negative 201Tl SPET studies.

Adult↗
PubMed1994

On an autosomal dominant form of retinal-cerebellar degeneration: an autopsy study of five patients in one family.

We describe a family with an autosomal dominant form of retinal-cerebellar atrophy. There is an extreme variability in age of onset and severity of the clinical symptoms: some patients remain nearly asymptomatic throughout their entire life; others develop severe retinal and cerebellar symptoms after the age of 35 years; others suffer from a severe disorder with onset in adolescence and death during the third decade of life; in others the onset is in early childhood with prevalence of cerebellar symptoms. There is neither dementia nor epilepsy in any of the patients. Four out of five autopsies showed a severe retinal atrophy, and all five autopsies were also characterized by (1) a cerebellar atrophy affecting the spinocerebellar and olivocerebellar tracts, the cerebellar cortex and the efferent cerebellar pathways, (2) an involvement of the pyramidal pathways and of the motor neurons of brain stem and spinal cord, and (3) an atrophy of the subthalamic nucleus and to a much lesser extent of the pallidum, with also some damage to the substantia nigra. The posterior columns are much less affected except in one patient. In this family, we have excluded linkage with the two loci for spinocerebellar ataxia, i.e., SCA1 on chromosome 6p and SCA2 on chromosome 12q as well as with the locus for Machado-Joseph disease (MJD) on chromosome 14q. A genome-wide search is currently being performed to detect the disease locus responsible.

Adolescent↗