Biomedical subjects

J Z Wang

Publications and source records attributed to J Z Wang.

At least 19 recordsLinked to original sources

PubMed1992

Antitumor activity of polysaccharide from a Chinese medicinal herb, Acanthopanax giraldii Harms.

The results of experiments with Acanthopanax giraldii polysaccharide (AGP) demonstrated that it inhibited the growth of solid Sarcoma 180 and prolonged the survival time significantly. In tumor-bearing mice, AGP enhanced the phagocytosis and chemiluminescence of macrophages. By the immunofluorescent method, binding of the third component of complement (C3) cleavage product to macrophages and proportion of C3 positive cells were increased. In crossed immunoelectrophoresis, human serum C3 was converted by AGP and appeared as the 3rd peak. The height of the 3rd peak was directly proportional to doses of AGP. The residual CH50 units of human serum decreased dose-dependently. These results suggest that the antitumor activity of AGP is related to the enhancement of immune responses.

Animals↗

PubMed1992

Risk of lung cancer among cigarette and pipe smokers in southern China.

Studies in Shanghai and in north-east China indicate that cigarette smoking is a major contributor to the high rates of lung cancer in those areas, but doubts persist regarding the influence of cigarette use on lung cancer rates in other areas of China. In addition, the risk of lung cancer associated with other methods of tobacco consumption--in particular, the use of bamboo water-pipes and long-stem pipes--is uncertain. A population-based case-control study of 427 male lung cancer patients residing in a mining area of Southern China and 1,011 controls was carried out to address this and other issues. Of these patients, 63% smoked cigarettes and (water and long-stem) pipes; 17% and 14% smoked only cigarettes or pipes, respectively; and 6% did not smoke. Compared to non-smokers, smokers of cigarettes only, smokers of pipes only and mixed smokers were at increased risk; OR = 2.6 (95% CI 1.1-6.2), 1.8 (95% CI 0.8-4.2) and 4.1 (95% CI 2.3-9.2), respectively. Risk increased with duration of tobacco use; however, the rate of increase with years of cigarette use was significantly greater than for years of pipe use (p = 0.03). In addition, risks increased 8-fold in the highest quartile of number of cigarettes per day compared to non-cigarette smokers vs. 2.3-fold for the highest quartile of number of liang (50 g) smoked per month compared to non-pipe-smokers; the trends in the ORs differed significantly (p less than 0.001). Results suggest that, in this area of China, tobacco use is an important cause of lung cancer, and that smoking cigarettes may be more deleterious than smoking pipes (primarily water pipes).

Adult↗

PubMed1992

Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype.

OBJECTIVE: To define the clinical spectrum of glucocorticoid-remediable aldosteronism (GRA) in a large kindred. DESIGN: Screening all at-risk relatives of a proband for GRA using a specific biochemical phenotype and collecting of medical histories of kindred members from five generations. SETTING: Outpatient General Clinical Research Centers and patients' homes. MEASUREMENTS: Screening was done while patients were on a self-selected diet and included blood pressure determinations; serum potassium and plasma renin activity and aldosterone measurements; and 24-hour urinary tetrahydroaldosterone, 18-oxotetrahydrocortisol, and 18-hydroxycortisol measurements. RESULTS: Diagnosis of GRA was established on the basis of a previously described specific biochemical abnormality, overproduction of the cortisol C-18 oxidation products (18-oxotetrahydrocortisol and 18-hydroxycortisol) in urine and their ratio relative to tetrahydroaldosterone. Glucocorticoid-remediable aldosteronism was diagnosed in 11 additional patients spanning three generations; this group included the youngest patient (3 months old) ever diagnosed with GRA. Complete penetrance of the biochemical abnormality is likely, with 11 of 18 at-risk patients displaying the phenotype. All patients with GRA had elevated blood pressure. Affected adult patients had been diagnosed as hypertensive before reaching 21 years of age (n = 7 mean, 16.1 +/- 3.4 years). All affected patients were normokalemic (4.3 +/- 0.3 mmol/L). CONCLUSION: Hypertension is a characteristic feature of GRA. Elevated blood pressure in this kindred developed at an early age and often was severe. Because a normal potassium level does not exclude the diagnosis of GRA, the disorder may be underdiagnosed. The value of a specific cortisol C-18 oxidation phenotype in the diagnosis of GRA has been confirmed.

Adolescent↗

PubMed1992

Dietary determinants of lung-cancer risk: results from a case-control study in Yunnan Province, China.

The relation between diet and lung cancer was studied among male residents of a mining community in Yunnan Province. After obtaining food frequency data from subjects or proxies, we compared diets of 428 cases, aged 35-74 years, and 1,011 age-matched controls. Cases tended to consume slightly more rice, but less protein-rich foods (i.e., bean curd, meat, eggs) and vegetables than did controls. The relative risks of lung cancer across increasing quartiles of meat (i.e., pork) consumption, for example, were 1.00, 0.67, 0.72 and 0.46 (p for trend less than 0.01). The relative risks of lung cancer across increasing quartiles of consumption of dark-green, leafy vegetables were 1.00, 0.62, 0.52 and 0.41 (p for trend less than 0.01). Although specific dietary constituent(s) responsible for the protective effect of vegetable consumption could not be identified, carotenoids other than beta-carotene, or compounds in cruciferous or Allium vegetables, are possibilities.

Animals↗

PubMed1992

Sequence and genomic structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q.

The amino acid sequence of the sodium channel alpha subunit from adult human skeletal muscle has been deduced by cross-species PCR-mediated cloning and sequencing of the cDNA. The protein consists of 1836 amino acid residues. The amino acid sequence shows 93% identity to the alpha subunit from rat adult skeletal muscle and 70% identity to the alpha subunit from other mammalian tissues. A 500 kb YAC clone containing the complete coding sequence and two overlapping lambda clones covering 68% of the cDNA were used to estimate the gene size at 35 kb. The YAC clone proved crucial for gene structure studies as the high conservation between ion channel genes made hybridization studies with total genomic DNA difficult. Our results provide valuable information for the study of periodic paralysis and paramyotonia congenita, two inherited neurological disorders which are caused by point mutations within this gene.

Adult↗

PubMed1992

Changes in cortical activity when subjects scan memory for tones.

The magnetoencephalogram (MEG) was used to detect regional changes in spontaneous cortical activity accompanying short-term memory search. This method was chosen because magnetic fields are detectable only within a few centimeters of the projections of their sources onto the scalp. The specific hypothesis that auditory cortex is involved in scanning memory for tones was tested by sensing the field of the magnetic counterpart to N100 (N100m) which is known to originate in auditory cortex. N100m was measured at many different positions and the spontaneous cortical rhythms in the alpha bandwidth (8-12 Hz) were measured at the same places. These rhythms were found to be suppressed while subjects scanned memory for musical tones in a Sternberg paradigm. For 3 subjects, both the MEG suppression time (ST) and reaction time (RT) increased linearly with memory set size. The correlation between ST measured over the left hemisphere and set size was significant for two subjects but not significant for the third, and the slopes of the regression lines relating ST to set size were too shallow to be related to the time required to scan memory. However, the correlation between ST of the right hemisphere and set size was highly significant for all subjects, and the slopes of the regression lines were comparable to those relating RT to set size. The electroencephalogram (EEG) recorded with midline electrodes failed to reveal a significant relationship between suppression time and set size for 2 of the subjects, thus ruling out global alpha blockage and generalized arousal as the basis for the task-related suppression duration. The electric N100, measured at Cz, decreased significantly in amplitude with set size for 2 subjects, but it increased significantly in amplitude for the third subject. In contrast, RT increased with set size for all subjects. N100m measured over the right hemisphere was similar to the behavior of N100, while N100m measured over the left hemisphere showed little change in amplitude with set size, thus establishing an asymmetry in N100 between the hemispheres. Since N100 amplitude is normally larger when attention is paid to auditory stimuli, differential attention alone cannot account for the relation between ST and set size. Furthermore, the processing negativity, which may be superimposed on N100 in selective attention tasks, was not discernible for any set size. It was also found that ST prior to the button press was not correlated with RT. Hence, the covariation of set size with ST is not attributable to preparation for a motor response.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

PubMed1992

Magnetic source images determined by a lead-field analysis: the unique minimum-norm least-squares estimation.

The minimum norm least-squares approach based on lead field theory provides a unique inverse solution for a magnetic source image that is the best estimate in the least-squares sense. This has been applied to determine the source current distribution when the primary current is confined to a surface or set of surfaces. In model simulations of cortical activity of the human brain, the magnetic field pattern across the scalp is interpreted with prior knowledge of anatomy to yield a unique magnetic source image across a portion of cerebral cortex, without resort to an explicit source model.

Artifacts↗

PubMed1992

Defective ring A reduction of cortisol as the major metabolic error in the syndrome of apparent mineralocorticoid excess.

Impaired peripheral metabolism of cortisol in the syndrome of apparent mineralocorticoid excess is currently understood to be causally related to the severe but otherwise unexplained manifestations of mineralocorticoid excess. A normally ambivalent mineralocorticoid receptor responding equally well to glucocorticoids and mineralocorticoids requires prereceptor inactivation of glucocorticoids to elicit a specific mineralocorticoid effect. The failed inactivation step in the form of the syndrome of apparent mineralocorticoid excess first described (type 1) involves the 11 beta-hydroxydehydrogenation of cortisol to cortisone. In another form of the syndrome (type 2) this conversion occurs normally in the face of otherwise similar clinical and biochemical features. Markedly decreased cortisol metabolic clearance in the type 2 form suggested impairment of a major component of that clearance, ring A reduction. A noninvasive method was developed for measuring the conversion of cortisol to tetrahydrocortisol and allotetrahydrocortisol, and this step was found to be profoundly decreased in both type 1 and type 2 forms. Thus, the major abnormality in the peripheral metabolism of cortisol common to both forms involved ring A reduction, not 11 beta-hydroxydehydrogenation. Since ring A reduction was better correlated with the manifestation of mineralocorticoid excess in both forms of the syndrome, this step might also be a normal major prereceptor mechanism conferring mineralocorticoid specificity.

Adult↗

PubMed1992

Cortisol inactivation overload: a mechanism of mineralocorticoid hypertension in the ectopic adrenocorticotropin syndrome.

The more severe mineralocorticoid manifestations in the ectopic ACTH syndrome compared to pituitary Cushing's disease have been attributed to hypersecretion of 11-deoxycorticosterone. Another difference between the two forms of ACTH-excess, however, is a more severe degree of hypercortisolism in the ectopic syndrome. Cortisol can become a potent mineralocorticoid if its peripheral metabolism is interfered with as occurs in the syndrome of apparent mineralocorticoid excess. This mechanism also occurs in an experimental model of the apparent mineralocorticoid excess syndrome induced by licorice derivatives. We have tested the hypothesis that cortisol is a major mineralocorticoid in the ectopic ACTH syndrome because of two factors, marked hypersecretion and incomplete peripheral metabolism of cortisol as a result of an overload of metabolizing enzymes. Two measures of the peripheral metabolism of cortisol were found to be markedly decreased in two patients with the ectopic ACTH syndrome. The cortisol turnover quotients were 17.2 and 19.6 (normal = 215 +/- 98) and the ring A reduction constants were 11.8 and 13.8 (normal = 101 +/- 23). These values were comparable to that found in the syndrome of apparent mineralocorticoid excess and consistent with the hypothesis that cortisol is a significant functioning mineralocorticoid in the ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗

PubMed1992

The biochemical phenotypes of two inborn errors in the biosynthesis of aldosterone.

Two inborn errors in the methyl oxidation of corticosterone to form aldosterone correspond to the two oxygenation-hydroxylation reactions required for this transformation. Both defects are characterized by overproduction of corticosterone of glomerulosa zone origin and deficient synthesis of aldosterone. In the type 1 corticosterone methyl oxidase defect (CMO I) impairment in the first step is reflected in decreased production of 18-hydroxycorticosterone while in CMO II an impaired second step is characterized by overproduction of 18-hydroxycorticosterone leading to an increased 18-hydroxycorticosterone:aldosterone metabolite ratio as a diagnostic index. This metabolite ratio may be increased somewhat in CMO I but not as much as in CMO II. The absolute value of 18-hydroxycorticosterone is a more reliable discriminator as is the corticosterone:18-hydroxycorticosterone metabolite ratio which is increased in CMO I and decreased in CMO II. On the basis of these findings, a North American kindred is reclassified as CMO I making this defect the more prevalent form in the Western Hemisphere. The two biochemical phenotypes will very likely describe different mutations in the gene encoding cytochrome P-450 CMO.

18-Hydroxycorticosterone↗

PubMed1992

[Neurological manifestation of Takayasu's arteritis].

38 cases of Takayasu's arteritis were reported. The mean age of onset was 23.3 years with a female: male ratio of 1:1.7. The median delay between first symptom and time of diagnosis was 12.2 years. Headache was the most common symptom of neurologic manifestations (55%). Major neurologic events occurred in 52.7% patients in this group, including TIA, cerebral infarction, hypertensive encephalopathy, lacunar infarct, seizure, paraplegia, watershed infarct, cerebral hemorrhage, Moyamoya phenomenon, and confusion in the order of frequency. A variety of mechanisms that must be taken into account in explaining this neurologic events were proposed. The secondary hypertension and cardiac complications play an important role in causing neurologic symptoms. The formation of anastomotic networks has "Jekyll and Hyde" effect on brain both in preventing or limiting the ischemic injury and in producing some special symptoms and signs, that further widen the clinical spectrum of brain involvement.

Adolescent↗

PubMed1991

A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis.

HYPERKALAEMIC periodic paralysis (HYPP) is an autosomal dominant disease that results in episodic electrical inexcitability and paralysis of skeletal muscle. Electrophysiological data indicate that tetrodotoxin-sensitive sodium channels from muscle cells of HYPP-affected individuals show abnormal inactivation. Genetic analysis of nine HYPP families has shown tight linkage between the adult skeletal muscle sodium channel alpha-subunit gene on chromosome 17q and the disease (lod score, z = 24; recombination frequency 0 = 0), strongly suggesting that mutations of the alpha-subunit gene cause HYPP. We sequenced the alpha-subunit coding region isolated from muscle biopsies from affected (familial HYPP) and control individuals by cross-species polymerase chain reaction-mediated complementary DNA cloning. We have identified an A----G substitution in the patient's messenger RNA that causes a Met----Val change in a highly conserved region of the alpha-subunit, predicted to be in a transmembrane domain. This same change was found in a sporadic case of HYPP as a new mutation. We have therefore discovered a voltage-gated channel mutation responsible for a human genetic disease.

Amino Acid Sequence↗

PubMed1991

Sputum occult blood screening for lung cancer. Stage II screening of 14,431 subjects.

Sputum occult blood screening (SOBS) for lung cancer was performed in outpatients with suspected lung cancer. A total of 1011 patients were seen. Among them, 604 patients were found to be negative for SOBS, and 407 were found to be positive. The false-negative rate was 3.97% (24 of 604), and the opposite positive rate was 19.65% (80 of 407). A total of 14,431 normal subjects over 40 years of age were screened by SOBS. In the series, 1942 specimens were found to be positive. Among the 1942 patients, 31 were found to have definite cancer cells.

Adult↗

PubMed1991

Magnetic resonance imaging reflects cartilage proteoglycan degradation in the rabbit knee.

Cartilage degeneration in osteoarthritis is initiated by a loss of proteoglycan. Intra-articular injection of papain causes a reversible loss of proteoglycan in rabbit knees. Rabbits were scanned with magnetic resonance imaging (MRI), using a 1.5T Signa superconducting magnet with 3 inch surface coil. Spin echo sequences were performed in the coronal and sagittal planes at 0, 24, 48, and 72 h after intra-articular injection of papain to obtain T1, proton density, and T2-weighted images. Cartilage proteoglycan content was measured biochemically and histochemically. Reduced articular cartilage thickness in the MR images of papain-treated knees corresponded to changes in cartilage proteoglycan content.

Animals↗

PubMed1991

Magnetic resonance imaging of the rabbit knee: detection of cartilage proteoglycan degradation.

Intra-articular (i.a.) injection of papain causes a reversible loss of proteoglycan in intact rabbit knees. Twelve rabbits were scanned with magnetic resonance imaging (MRI) at 0, 24, 48 and 72 hours after 5 units of papain i.a. in a 1.5 Tesla Signa with a three inch surface coil using spin echo sequence. Total cartilage thickness in proton density images was 1.08 +/- 0.09 mm prior to papain injection. The magnetic resonance images showed a reduction in articular cartilage thickness in papain-treated rabbit femurs at 24 hours to 0.69 +/- 0.18 mm and partial restoration by 72 hours to 0.77 +/- 0.21 mm.

Animals↗

PubMed1991

On cortical folds and neuromagnetic fields.

A folded cortical source of neuromagnetic fields, similar in configuration to the visual cortex, was simulated. Cortical activity was modelled by different distributions of independent current dipoles. The map of the summed fields of the dipoles of this cruciform model changed, depending upon the statistical distribution of the electrical activity of the dipoles and its geometry. Arrays of dipoles of random orientations and strengths produced field patterns that could be interpreted as due to moving neural currents, although the geometry of the neural tissue remained unchanged and the average activity remained approximately constant. The field topography at any instant was apparently unrelated to the depth or orientation of the underlying structure, thus raising questions about how to interpret topographic MEG and EEG displays. Furthermore, asynchronous activity (defined as independent directions and magnitudes of activity of the dipoles) did not result in less field power than when the dipoles were synchronized, i.e., when the direction of current flow was correlated across all of the dipoles within the cruciform structure. Therefore, in this model 'alpha blockage' cannot be mimicked by desynchronization. More generally, for the cruciform or any other symmetrically folded and active cortical sheet, 'blockage' cannot be attributed to desynchronization. The same is true for the EEG except that smooth unfolded sheets of radially oriented dipoles would result in enhancement of voltage due to synchronization. Such radial dipoles do not contribute to the MEG. Blockage was simulated by reducing the amount of activity within different portions of the synchronized cruciform model. This resulted in a dramatic increase in the net field because attenuation broke the symmetry of the synchronized cruciform structure. With asynchronous dipoles populating the structure, the attenuation of the same portion of the structure had no easily discerned effect on the net field. However, maps of average field power were consistently related to the position of the region of attenuated activity. The locations of regions of attenuated activity were determined by taking the difference between the mean square field pattern obtained when all portions of the cruciform structure were active and the pattern obtained when a portion of the structure was relatively inactive. When activity of the same portions were incremented rather than attenuated, the resulting plot of average power was essentially the same as that of the attenuated portion derived by taking these differences between power distributions. The major conclusions are that the concepts of synchronization and desynchronization have no explanatory power unless the physical conditions under which they occur are specified precisely.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

PubMed1991

Synthesis of a deuterium-labeled cortisol for the study of its rate of 11 beta-hydroxy dehydrogenation in man.

11 beta-Hydroxy dehydrogenation of cortisol to cortisone is specifically impaired in the syndrome of apparent mineralocorticoid excess. This defect bears on the pathogenesis of the disorder by unmasking the potential mineralocorticoid agonism of unmetabolized cortisol at or near mineralocorticoid target tissues. A specific index of this defect is provided by measurement of the formation of tritiated water following the administration of [3H]11 alpha-cortisol. We have explored the use of a non-radioactive tracer to follow this unidirectional dehydrogenation reaction but because of the relatively lower sensitivity of measurement of 2H2O compared to 3H2O in body fluids, use of the corresponding [2H]11 alpha-cortisol was not feasible. We have devised instead a method incorporating additional deuterium atoms into cortisol to measure unidirectional 11 beta-hydroxy dehydrogenation not by the formation of labeled water but by the determination of the dehydrogenated cortisol product from its residual deuterium content. Cortisol-d4 metabolized to cortisone-d3 is conveniently measured by the techniques of organic mass spectrometry. The synthesis of cortisol-9 alpha, 11 alpha, 12 alpha 12 beta-d4 and the validation of its isotopic distribution by mass spectrometry and nuclear magnetic resonance is described.

Cortisone↗

PubMed1991

Measurement of 4 urinary C-18 oxygenated corticosteroids by stable isotope dilution mass fragmentography.

The cortisol C-18 oxidation pathway leading to the production of 18-hydroxy- and 18-oxocortisol is expressed in adenomatous primary aldosteronism and glucocorticoid remediable aldosteronism. In order to better define the significance of the pathway and its usefulness in differential diagnosis, we have developed a stable isotope dilution mass fragmentographic method for the determination of the tetrahydro metabolites of aldosterone, 18-hydroxycorticosterone and 18-oxocortisol and of unmetabolized 18-hydroxycortisol in urine. Stereochemically correct tetrahydro steroids containing 3 deuterium atoms were synthesized from the available 3-keto-4-pregnenes in 2 steps and 1,2-deuterium-labeled 18-hydroxycortisol was prepared by selective deuteration of the 1,2-double bond of a dienone precursor. Simultaneous measurement of the 4 steroids permitted a comparison of the abnormal products of the C-18 oxidation of cortisol with the normal C-18 oxidation products of corticosterone, 18-hydroxycorticosterone and aldosterone. Application of the method to the definition of the normal range is described.

Adrenal Cortex Hormones↗