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Biomedical subjects

J D Glass

Publications and source records attributed to J D Glass.

At least 109 records · Page 6Linked to original sources
PubMed1992

Macrophage responses and myelin clearance during Wallerian degeneration: relevance to immune-mediated demyelination.

Macrophages are important effector cells in immune-mediated demyelination. Current concepts regarding their entry and activation focus on the effects of T-cell-derived cytokines. This presentation describes the responses of macrophages and microglia to a non-inflammatory, non-immune injury, Wallerian degeneration. During Wallerian degeneration in the peripheral nervous system (PNS), macrophages are promptly and abundantly recruited from the circulation, and myelin clearance is prompt. In the central nervous system (CNS), the appearance of macrophages is markedly slower, and entry from the circulation is modest or absent. Myelin clearance is similarly delayed. The nature of the factors promoting macrophage entry and activation in Wallerian degeneration, and the bases for the differences between PNS and CNS, are relevant to current issues in immune-mediated demyelination.

Animals↗
PubMed1992

Chronic demyelinating polyneuropathy associated with eosinophilia-myalgia syndrome.

Eosinophilia-myalgia syndrome (EMS) is a newly described syndrome associated with use of L-tryptophan. A neuropathy with features of axonal degeneration has also been described in conjunction with EMS. Demyelinating polyneuropathy is not a well recognised association of the syndrome. The two patients with EMS reported presented with profound weakness and sensory loss and were found to have clinical, electrophysiological and pathological evidence of a chronic demyelinating polyneuropathy. The concurrence of this neuropathy with EMS, as well as several other features of their illness, is suggestive of an immune mediated mechanism in the pathophysiology of EMS.

Aged↗
PubMed1992

Diurnal variation in 5-hydroxyindole-acetic acid output in the suprachiasmatic region of the Siberian hamster assessed by in vivo microdialysis: evidence for nocturnal activation of serotonin release.

In vivo brain microdialysis was used to characterize the daily pattern of 5-hydroxyindole-acetic acid (5-HIAA) release in the region of the suprachiasmatic nuclei (SCN) in freely behaving male Siberian hamsters housed under 16L:8D. A marked diurnal variation in the concentration of extracellular 5-HIAA was apparent, with peak levels (147 +/- 5% of the daily mean; p < 0.05) occurring 2-3 h after lights-off. Smaller nocturnal rises in extracellular 5-HIAA were observed in the posterior hypothalamus and preoptic area (128 +/- 4 and 123 +/- 8% of the daily mean, respectively; both p < 0.05 vs. average daytime levels). Tryptophan loading increased 5-HIAA in SCN microdialysates by 44 +/- 6%, and this response was enhanced by localized perfusion with tetrodotoxin (TTX; 5 microM). Localized applications of KCl (150 mM) or veratridine (100 microM) decreased 5-HIAA by 62 +/- 5 or 49 +/- 11%, respectively. The effect of KCl was not significantly affected by specific calcium channel blockers. Perfusion with TTX markedly decreased SCN 5-HIAA during the dark phase, but had little effect during the light phase (42 +/- 8 vs. 12 +/- 5% suppression, respectively; p < 0.01). Addition of serotonin (3 microM) to the perfusate significantly stimulated 5-HIAA output. This treatment increased the release of 5-HIAA more during the dark than during the light phase (61 +/- 8 vs. 25 +/- 5%, respectively; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Wallerian degeneration in peripheral nerve disease.

This article first reviews the different classes of nerve injury. The temporal evolution of electrophysiologic changes occurring during Wallerian degeneration in humans is then described, followed by a description of sequential structural changes and cellular responses that occur after nerve transection. The final section focuses on the basis for resurgent research interest in Wallerian degeneration and the different research approaches being taken to answer basic science and clinical questions.

Animals↗
PubMed1991

Epstein-Barr virus in AIDS-related primary central nervous system lymphoma.

Primary central nervous system lymphoma occurs more often in patients with AIDS. Epstein-Barr virus (EBV) has been detected in these tumours, but the degree of association has not been defined because of both the highly restricted expression of EBV in malignant tissue and the lack of a technique that is reliable in formalin-fixed paraffin-embedded specimens. EBV-transformed lymphocytes contain short non-protein coding EBV transcripts (EBERs), which are expressed in much higher quantity than other EBV-latency transcripts. We describe a new strategy for detection of latent EBV with these transcripts as targets for in-situ hybridisation. 18 cases of AIDS-related primary CNS lymphoma from a consecutive necropsy series together with specimens from 3 further cases were studied. In each case, a strong positive signal over tumour cells indicated abundant expression of the EBV-EBER1 transcript. This 100% association suggests that the pathogenesis of these AIDS-associated lymphomas may differ from the systemic disease in which only 30-50% of tumours are associated with EBV. A pathogenetic role for EBV was further supported by showing expression of a viral protein (the latent membrane protein) that is implicated as an effector for EBV-associated lymphomagenesis. EBV might have a role as a tumour marker in the diagnosis and management of AIDS-related primary CNS lymphoma.

Central Nervous System Neoplasms↗
PubMed1991

A sequence related to the human gonadoliberin precursor near the N-termini of HIV and SIV gag polyproteins.

A highly conserved sequence near the N-terminus of all human (HIV) and simian (SIV) immunodeficiency virus gag polyproteins appears to be a precursor for a viral mimic of the amidated C-terminus of human gonadoliberin. The gag polyproteins are known to be myristylated; processing of the amidation site would yield myristylated 23-residue peptides whose C-terminal sequences mimic gonadoliberin and presumably behave as ligands for the gonadoliberin receptor. This paper describes the discovery of conserved gonadoliberin-precursor-related sequences in HIV and SIV gag polyproteins and in the p-17 core proteins derived from them. Arguments are presented that the conserved precursor structure requires post-translational processing to a peptide amide derivative which is a ligand for the gonadoliberin receptor. A model has been developed for entry of the viral genomic RNA into host cells through the gonadoliberin receptor and experiments are suggested to confirm or refute the model. This proposed mechanism for entry of HIV genomic RNA into host cells, if it proves to be substantially correct, suggests several new approaches to prevention and treatment of acquired immunodeficiency syndrome (AIDS).

Amino Acid Sequence↗
PubMed1991

Inter- and intra-examiner reliability of nerve conduction measurements in normal subjects.

Nerve conduction studies are widely employed in evaluating patients with peripheral nerve disease and are often used serially to measure disease progression or to assess a therapeutic intervention. We determined the inter- and intra-examiner reliability of electrophysiological data by performing serial nerve conduction studies on 7 normal subjects. A high degree of intra-examiner reliability was present, but significant inter-examiner differences were found. Our results suggest that if nerve conduction studies are to be used longitudinally, they should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.

Electromyography↗
PubMed1991

Conduction block in diabetic neuropathy.

Symmetric sensorimotor polyneuropathy is a common complication of diabetes. Sensory and motor evoked amplitudes and conduction velocities are reduced. Both demyelination and axon loss have been reported in pathologic studies. Conduction block (CB), a manifestation of segmental demyelination, has not been previously studied in diabetic neuropathy. We determined the prevalence of conduction block in patients with diabetes by analyzing electrodiagnostic data from 24 diabetics. Conduction block was defined as a greater than 20% drop in peak-to-peak amplitude, and a less than 15% change in negative-peak duration between proximal and distal stimulation sites. A total of 76 nerve segments were studied. The criteria for conduction block were met in only 6 segments in 6 patients. The mean decrease in peak-to-peak amplitude between stimulation sites was 28% (range 21% to 40%). We conclude that conduction block over long nerve segments is uncommon in diabetic neuropathy, and, if present, suggests that other causes for neuropathy in diabetic patients should be sought.

Demyelinating Diseases↗
PubMed1991

Neurophysin-neurohypophyseal hormone interactions: studies using a dansylated vasotocin analogue.

We have synthesized a neurohypophyseal hormone analogue containing an extrinsic fluorescence probe by linking a dansyl (DNS) group to the epsilon-amino group of the lysine at residue 8 of vasotocin. The fluorescence properties of this analogue have been characterized by steady-state and time-resolved spectroscopic methods and compared with those of epsilon-DNS-lysine and the dansylated carboxyl terminal tripeptide Pro-Lys(DNS)-GlyNH2. The binding of this hormone analogue to purified isoforms of bovine neurophysins, the natural carrier proteins of the neurohypophyseal hormones, results in changes in several fluorescence parameters of the dansyl probe. These changes include an increase in intensity and average lifetime, a shift of the emission band to higher energies, and an increase in the emission anisotropy. Anisotropy changes have been used to determine dissociation constants for binding to these neurophysin isoforms. Based on the changes in the fluorescence properties of the dansyl probe, the dansyl group itself interacts with the protein. The degree of the dansyl-neurophysin interaction, however, appears to be different for the full sequence isoform of neurophysin I and the Val89 isoform of neurophysin II.

Amino Acid Sequence↗
PubMed1991

Neurofilament redistribution in transected nerves: evidence for bidirectional transport of neurofilaments.

Nerve fibers of the C57BL/6/Ola mouse exhibit very slow Wallerian degeneration following axotomy, thus allowing prolonged observation of mammalian axons separated from their cell bodies. The present study utilized teased-fiber preparations, silver histochemistry, immunocytochemistry, and electron microscopy to examine the distribution of axonal components in the distal stumps of axotomized sciatic nerves in C57BL/6/Ola mice. In examining nerve segments at varying intervals after nerve transection, we found no evidence of proximal-to-distal "emptying out" of the cytoskeleton, as would be predicted if the cytoskeleton in these transected nerves were undergoing anterograde transport as an assembled structure. Instead, we observed a gradual redistribution of cytoskeletal constituents over time, dominated by the progressive accumulation of neurofilaments at the severed ends of axons. In particular, there were massive accumulations at the proximal ends of the distal stumps. These results strongly suggest that, at least in transected nerve fibers, neurofilaments can be transported bidirectionally.

Animals↗
PubMed1990

Selective delivery of boron by the melanin precursor analogue p-boronophenylalanine to tumors other than melanoma.

The melanin precursor analogue p-boronophenylalanine (BPA) has been used to deliver 10B to melanoma tissue for boron neuron capture therapy. Uptake studies in tumor models other than melanoma now indicate that BPA is capable of delivering therapeutic amounts of boron to tumors other than melanoma. The KHJJ murine mammary tumor carried s.c. in BALB/c mice, the GS-9L rat glioma carried both s.c. and intracranially in F-344 rats, and the human U-87 MG glioma xenograft carried s.c. in nude mice have all shown significant accumulation of boron in tumor tissue following single p.o. (intragastric) doses of BPA. In this KHJJ mammary tumor, the L isomer of BPA was preferentially accumulated compared to the D isomer, indicative of a carrier-mediated transport process. Double-label, whole-body autoradiographic studies in a pigmented murine melanoma have shown that the boron distribution (from BPA) differs from the distribution of a tritiated melanin precursor (tyrosine). Boron accumulated only in the tumor; labeled tyrosine accumulated in tumor, liver, intestinal epithelium, bone-marrow, and secretory glands. Toxicity studies in mice and rabbits indicate that, even at very high doses, BPA p.o. caused no adverse effect in tissues, on blood chemistry, or on differential leukocyte counts. These data indicate that BPA may be generally useful as a boron delivery agent for boron neutron capture therapy of tumors.

Animals↗
PubMed1990

Wilson's disease. Development of neurological disease after beginning penicillamine therapy.

Patients with neurological symptoms and signs of Wilson's disease have been frequently noted to have a worsening of their condition after beginning chelation therapy with D-penicillamine. Presymptomatic patients, however, are not expected to develop neurological manifestations once appropriate therapy is begun. We describe a patient who was seen with hepatic disease and no neurological symptoms who became neurologically incapacitated soon after beginning penicillamine therapy. This case identifies an unexpected complication of penicillamine therapy that should be watched for in the presymptomatic patient who is beginning therapy.

Adult↗
PubMed1990

The dysarthria-clumsy hand syndrome: a distinct clinical entity related to pontine infarction.

Using magnetic resonance imaging, we studied 6 patients with the dysarthria-clumsy hand syndrome. All were found to have pontine infarctions contralateral to the symptomatic side. Clinically, these patients exhibited dysarthria; "clumsiness," characterized by dysmetria, dysrhythmia, dysdiadochokinesia and sometimes truncal and gait ataxia; and mild ipsilateral weakness. Previous clinical-anatomical correlations for this syndrome are limited by inconsistencies in clinical diagnostic criteria and low-resolution imaging methods. In our patients, and in a review of the literature, the overwhelming majority of patients with the dysarthria-clumsy hand syndrome had pontine infarcts. We conclude that if rigid clinical criteria are used, the label of the dysarthria-clumsy hand syndrome predicts a lesion in the contralateral basis pontis.

Adult↗
PubMed1990

Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma.

The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. We have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of that observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma.

Animals↗
PubMed1989

Evidence that short photoperiod-induced gonadal regression in the Mongolian gerbil is mediated by the action of melatonin in the medial hypothalamus.

The present study was undertaken to examine the effects of exposure to short photoperiod (SD) and treatment with subcutaneous (s.c.) or intrahypothalamic melatonin-containing beeswax implants on reproduction in the Mongolian gerbil Meriones unguiculatus. Exposure of adult female gerbils to SD (8 h light: 16 h dark) caused a significant decrease in weight of the reproductive tract (ovaries, oviducts, uterus and vagina; RTW) compared to animals maintained under stimulatory photoperiod (12 h light: 12 h dark; 81.4 +/- 8.0 mg vs 151.8 +/- 16.0 mg, respectively (P less than 0.01]. Treatment with two large s.c. implants, each containing 3 mg melatonin, mimicked the antigonadal effect of SD (68.7 +/- 3.9 mg vs 118.1 +/- 19.5 mg for the blank (melatonin-free) implant controls; P less than 0.05). Gerbils with a small melatonin-beeswax pellet (containing 0.2 mg melatonin) in the anterior hypothalamus (AH) underwent a significant reduction in RTW compared to gerbils with a blank intrahypothalamic implant (73.0 +/- 5.7 mg vs 134.6 +/- 14.5 mg, respectively; P less than 0.01). Melatonin pellets in the mediobasal hypothalamus (MBH) also induced gonadal regression, but to a lesser degree (88.7 +/- 12.6 mg; P less than 0.05 vs blank controls). Small melatonin pellets placed elsewhere in the hypothalamus or s.c. had little effect on RTW (143.4 +/- 20.9 mg and 129.2 +/- 19.7 mg, respectively). Only 25% of the gerbils with melatonin pellet in the AH or MBH had a corpus luteum compared to 73% of the blank controls (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Dural scrofula.

A middle-aged woman presenting with multiple cranial neuropathies, hemiparesis, and CSF pleocytosis had tuberculous infection of the cranial dura mater at autopsy. This is the first description of dural scrofula in modern medical literature.

Autopsy↗