Biomedical subjects

H D Chung

Publications and source records attributed to H D Chung.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effect of pre- and postmortem variables on specific mRNA levels in human brain.

The method of polymerase chain reaction was used to investigate the pre- and postmortem factors which affect the stability of specific mRNAs in the C1 region of human autopsy brain. Eight premortem and 4 postmortem factors were correlated to levels of phenylethanolamine N-methyltransferase (PNMT), three splice forms of amyloid precursor protein (APP) and actin mRNAs in 10 control brains using Pearson's correlation coefficient. Significant negative correlations were found between hypoxia and PNMT mRNA, and between postmortem and storage intervals and APP751 and beta-actin mRNAs. A positive correlation was found between death-refrigeration interval and total APP and APP695 mRNAs. There was also a positive correlation between seizure activity and APP770 mRNA. The results indicate that a variety of pre- and postmortem factors can affect mRNA levels. The possible effect of pre- and postmortem factors on specific mRNA levels should be investigated prior to comparing mRNA levels in different disease states.

Adult↗

PubMed1991

Analysis and quantitation of the beta-amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients with a monoclonal antibody-based immunoassay.

One of the major clinical findings in Alzheimer's disease (AD) is the formation of deposits of beta-amyloid protein in amyloid plaques, derived from the beta-amyloid precursor protein (beta-APP). To determine the possible use of beta-APP as a diagnostic marker for AD in CSF, a monoclonal antibody-based immunoassay specific for this protein was developed. The assay does not differentiate between beta-APP695 and beta-APP751 forms but does preferentially recognize beta-APP751 complexed with a protease. Of the two sets of CSF samples tested, one set, obtained from living patients, gave a slightly lower level of beta-APP in AD and Parkinson's disease patients relative to controls, whereas the other set, composed of postmortem samples, showed no significant differences between the AD and control groups.

Alzheimer Disease↗

PubMed1990

Evidence for decreased transport of tryptophan hydroxylase in Alzheimer's disease.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin and a specific marker for serotonergic neurons. These neurons are affected in Alzheimer's disease (AD) in several ways: serotonin is decreased in axon terminals, serotonin neurons accumulate neurofibrillary protein, and these neurons are lost in AD brains. One subcellular mechanism which may underlie degeneration of neurons in AD is decreased axonal transport with accumulation of enzymes and their potentially toxic metabolites in the cell body. To determine whether there is a defect in axonal transport in serotonin neurons in AD we measured TPH activity, serotonin and its oxidative metabolite 5-hydroxyindoleacetic acid (5-HIAA) in dorsal raphe cell bodies from Alzheimer and control cases. TPH activity is increased 4.7-fold in raphe neuron cell bodies in Alzheimer brains. Serotonin and 5-HIAA are increased by 4.0- and 2.0-fold, respectively in Alzheimer compared to control raphe cell bodies. In contrast, in synaptic terminals of the amygdala 5-HT and 5-HIAA were decreased by 41% and 50%, respectively in the same AD cases. We propose that the accumulation of TPH and its products in the raphe perikarya in AD results from a diminished transport of TPH to axon terminals. The accumulation of oxidative metabolites of serotonin may contribute to the degeneration of serotonergic neurons in AD.

Aged↗

PubMed1990

Evidence for decreased transport of PNMT protein in advanced Alzheimer's disease.

Phenylethanolamine N-methyltransferase (PNMT) is the rate-limiting enzyme in the synthesis of epinephrine and a specific marker for adrenergic neurons. PNMT protein is decreased in axon terminals in brains from patients with Alzheimer's disease due to retrograde degeneration of epinephrine neurons. To determine the subcellular mechanism underlying retrograde degeneration, the distribution of PNMT between axon terminal and cell body was calculated in early and advanced Alzheimer cases compared with age-matched controls. In early Alzheimer's disease there is a decrease in PNMT in axon terminals and in total PNMT in epinephrine cell bodies and terminals compared with control values. There is no difference in the ratio of PNMT in cell body/axon terminal compared with controls. In contrast, in advanced Alzheimer's disease, PNMT activity increases by 124% in epinephrine neuronal cell bodies compared with controls. Immunochemical titration shows that this increased enzyme activity is due to an increase in PNMT protein. The cell body/axon terminal ratio of PNMT is increased 2.5-fold in advanced Alzheimer's disease compared with controls. These findings are consistent with the hypothesis that in early Alzheimer's disease there is a decreased synthesis or increased degradation of PNMT. However, in advanced Alzheimer's disease we propose that the accumulation of this enzyme in the perikarya results from a diminished transport of PNMT to axon terminals. We further postulate that epinephrine, the product of PNMT, and its further metabolites are endogenous neurotoxins. Therefore, the accumulation of PNMT in epinephrine cell bodies may contribute to the degeneration of these neurons in Alzheimer's disease.

Aged↗

PubMed1990

Homonymous quadrantic visual field defect resulting from vertebrobasilar insufficiency: report of a case.

A patient showing a congruous homonymous superior quadrantanopsia was found at autopsy to have infarction of the striate cortex. The lesion involved the inferior bank of the calcarine fissure almost entirely and approximately one fifth of the superior bank. Additionally, infarctions of the visual association cortex and the pontine tegmentum were found. No lesions in the corresponding temporal lobe were present. Two types of visual field defects have been described in association with occipital lobe lesions: a monocular temporal crescentic defect if the lesion is anterior and a congruous homonymous hemianopsia if it is posterior. This patient seems to represent a variant of the latter. The most prominent difference with respect to quadrantanopsias resulting from lesions of the optic radiation is the high degree of congruity, especially in the central portion of the field. Association with nonocclusive vascular events related to vertebrobasilar hypoperfusion rather than embolization is also more common.

Cerebral Infarction↗

PubMed1988

Mycobacterial meningomyelitis associated with human immunodeficiency virus infection.

A homosexual man, seropositive for human immunodeficiency virus, developed back and leg pain that evolved, over three weeks, into a T-10 anesthetic, areflexic paraplegia. Spinal fluid examination showed lymphocytosis, markedly elevated spinal fluid protein, and hypoglycorrhachia. A spinal cord biopsy specimen disclosed an intramedullary granuloma containing acid-fast bacilli. The patient was treated with antituberculous drugs and had no progression of neurologic deficit. He died, eight months after first becoming ill, of Klebsiella pyelonephritis and septicemia. Mycobacterial meningomyelitis is presently the only known acquired immunodeficiency syndrome-related myelopathy responsive to specific treatment.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Evidence for retrograde degeneration of epinephrine neurons in Alzheimer's disease.

Alzheimer's disease (AD) is associated with a progressive loss of locus ceruleus neurons. These noradrenergic neurons receive a major afferent projection from epinephrine neurons in epinephrine cell groups in the brainstem. The epinephrine neurons have a specific enzymatic marker, phenylethanolamine N-methyltransferase (PNMT), which allows them to be identified chemically and immunohistochemically. We have previously reported a decrease in PNMT in brains of patients with AD. We now report that the decrease in PNMT activity in projections to the locus ceruleus is not due to the loss of epinephrine neurons, although up to 33% of these neurons are atrophic. The decrease in presynaptic PNMT does, however, correlate with the loss of postsynaptic locus ceruleus neurons in brains from AD patients. The percentage of degenerating neurons in the epinephrine nuclei also correlates significantly with the amount of loss of locus ceruleus neurons in AD. In addition, there is a 55% decrease in mitogen activity, a nonspecific measure of growth or maintenance factors, in dialysed locus ceruleus extracts from the AD patients compared to those from control subjects. The mitogen activity in the locus ceruleus was significantly correlated with PNMT activity and with the density of locus ceruleus neurons in all cases examined. These findings provide evidence for the hypothesis that retrograde degeneration is a mechanism of neuronal degeneration in AD and suggest that trophic factors may play a role in this process.

Aged↗

PubMed1987

Phenylethanolamine N-methyltransferase activity is decreased in Alzheimer's disease brains.

Phenylethanolamine N-methyltransferase (PNMT) is the rate-limiting enzyme involved in the synthesis of epinephrine and a specific marker for epinephrine neurons. We have previously described the stability of this enzyme in a variety of pre- and postmortem conditions in human brain autopsy specimens and demonstrated its presence in areas of the human brain that are associated with memory and attention. We now report on 5 patients with Alzheimer's disease (AD) who had a decrease in PNMT activity of 37 to 48% in areas of the brain affected by the disease but not in the cerebellum, an area of the brain unaffected by the disease. The degree of decrease in PNMT activity in the hippocampus correlated significantly with the degree of dementia. We have provided direct immunochemical evidence that the decrease in PNMT activity in AD is due to the loss of this specific enzyme protein.

Aged↗

PubMed1986

A highly sensitive assay for phenylethanolamine N-methyltransferase in human brain.

A rapid, highly sensitive assay for phenylethanolamine N-methyltransferase in brain using the natural substrate, norepinephrine, is described. The method is based on the selective adsorption and elution of the reaction product, epinephrine, from alumina. A small but important further lowering of blanks and increase in sensitivity is attained by removal of the radiolabeled substrate, [methyl-3H]-S-adenosylmethionine by precipitation as the reineckate prior to adsorption of norepinephrine to alumina. The assay has a sensitivity of 30 fmole and the PNMT activity could be measured in as little as 1 mg (wet wt) of human locus coeruleus tissue. The sensitivity is enhanced by homogenizing tissue in small volumes and removing potential inhibitors by dialysis. We report for the first time PNMT activity in specific regions of the human cerebral and cerebellar cortex.

Brain↗

PubMed1985

Retrograde crossed cerebellar atrophy.

Retrograde crossed cerebellar atrophy was present in 4 autopsied cases of severe unilateral destruction of the frontal lobe and thalamus. The thalamus, including the ventrolateral and ventromedial nuclei, had been severely damaged. Degeneration of thalamic afferent fibres with neuronal loss in the ipsilateral red nucleus, atrophy of the contralateral superior cerebellar peduncle and neuronal loss and atrophy of the contralateral dentate nucleus are described. These pathological changes are interpreted as the result of retrograde transsynaptic degeneration within the cerebellorubrothalamic tract following the unilateral thalamic and frontal cerebral, or thalamic lesions.

Adult↗

PubMed1982

Periodic EEG discharges and status spongiosus of the cerebral cortex in anoxic encephalopathy: a necropsy case report.

A periodic EEG pattern very similar to the changes in Creutzfeldt-Jakob disease was seen in a case of anoxic encephalopathy. Necropsy revealed status spongiosus of the cerebral cortex. Generalised repetitive sharp transients in anoxic encephalopathy occur when the patient is comatose and carry a poor prognosis. They are not specific for Creutzfeldt-Jakob disease.

Alpha Rhythm↗

PubMed1982

Infantile hypoventilation syndrome, neurenteric cyst, and syringobulbia.

Hypoventilation syndrome was observed in an infant with a neurenteric cyst. She died at 9 months of age following episodic bradycardia and the loss of voluntary as well as autonomic respiratory control. There was a mediastinal neurenteric cyst with anterior spina bifida and extension into the upper thoracic spinal cord. Secondary syringomyelobulbia was present at necropsy. The syringobulbia involved the hypoglossal nuclei, the dorsal motor nuclei of the vagus in the lower medulla, the right nucleus ambiguus, the right fasciculus and nucleus solitarius, the right mediolateral reticular formation, and the right dorsal motor nucleus of the vagus at the level of the obex. This morphologic distribution is attributed to the intraspinal rupture and upward extension of the mucinous contents of the cyst, and appears to be responsible for the hypoventilation syndrome.

Brain↗

PubMed1981

Hyperphagia and obesity. Relationship to medial hypothalamic lesions.

Progressive left hemiparesis followed by face and trunk cutaneous vasodilation and hyperphagia developed in a 28-year-old man. He began eating five to six meals a day and gained 16 kg in 60 days. Computed tomography disclosed a neoplastic lesion involving the midline via the hypothalamus and reaching the contralateral lenticular nucleus. Findings from endocrine studies, including thyroid-stimulating hormone, growth hormone, prolactin, and cortisol serum levels, were normal. Hyperphagia and consequent obesity were associated with bilateral destruction of the ventromedial hypothalamic area; cutaneous vasodilation was related to involvement of the preoptic area.

Body Weight↗

PubMed1980

Hydrolytic enzyme activities of the nervous system.

The activities of five hydrolytic enzymes (acid and alkaline phosphatase, hexosaminidase [N-acetyl-beta-D-glucosaminidase], beta-galactosidase, and beta-glucorinidase) were measured in reconstituted homogenates of lyophilized human brain tissue and primary and metastatic tumors. The linearity of reaction, with respect to incubation time, and optimal pH of each enzyme and in tumor tissues were comparable to those in normal brain tissue. Total enzyme activities of hexosaminidase, beta-glucuronidase, and beta-galactosidase were significantly higher in tumors than in normal cerebral white matter. The ratio of hexosaminidase activity to beta-glucuronidase activity was significantly lower for metastatic than for primary tumors or normal white matter. When histological observations do not clearly establish if a brain tumor is primary or metastatic, this ratio may help. Alteration of hydrolytic enzyme activities as demonstrated here may be indicative of "ket enzymes" that are essential for maintaining the metabolic advantages of tumors.

Acetylglucosaminidase↗

PubMed1980

Hydrolytic enzymes in meningiomal subtypes.

Estimation of activity of five hydrolytic enzymes was made in foru histologically different types of human meningiomas derived from surgery. The hydrolytic enzymes examined in 13 tumors included four lysosomal enzymes: beta-glucuronidase, N-acetyl-beta-D-glucosaminidase (hexosaminidase), beta-galactosidase, and acid phosphatase. The fifth enzyme studied was alkaline phosphatase. The one papillary-type meningioma examined appeared to contain generally greater activities of the lysosomal enzymes than the other tumor types. Alkaline phosphatase was decidedly greater in transitional type meningiomas. The correlation of histological types with alkaline phosphatase activity is discussed with regard to previous observations.

Acid Phosphatase↗

PubMed1979

Fatal basilar artery occlusion following cervical spine injury.

A patient rendered acutely quadriplegic in an automobile accident was shown by angiography to have occlusion of the left vertebral artery. One month later, he abruptly became unconscious, apneic and died. Autopsy showed an organised thrombus in the left vertebral artery and a fresh thrombus occluding the entire basilar artery. This case differs from previously reported cases of traumatic vertebral artery thrombosis wherein symptoms of brain stem infarction were more immediately evident.

Adult↗

PubMed1975

Fine structure of a cerebellar "fibroma".

The fine structure of an intracerebellar "fibroma" has been examined. The tumor consists of irregularly-shaped cells connected by well developed junctional complexes. Unusual, fenestrated capillaries with extremely narrow and irregular lumens are frequent. Collagen fibers are not common but the wide extracellular spaces contain large amounts of dense, granular or fibrillar material. The dense material coats the tumor cells and is a apparently secreted from small vesicles found within these cells.

Adult↗

PubMed1975

Some new observations in an intracranial germinoma.

A case of an intracranial germinoma from the suprasellar region of a 9-year-old girl was examined in the electron microscope. The tumor consists, for the most part, of both large polygonal and small lymphocyte-like elements. Annulate lamellae are common in the epithelial cells. The small blood vessels are fenestrated, and the endothelial cells contain tubular bodies, membrane-bounded vacuoles containing dense fluid and occasional tubules, arrays of tubules within the nuclear envelope and rough endoplasmic reticulum, and a markedly irregular luminal surface. Dense, lamellated structures are present in the widened, collagen-containing perivascular spaces.

Brain Neoplasms↗