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Biomedical subjects

H Weiner

Publications and source records attributed to H Weiner.

At least 145 records · Page 8Linked to original sources

Premature maternal separation and lymphocyte function.

Premature separation of rat pups from their mothers, on postnatal Day 15, produced a decreased response of peripheral blood lymphocytes to phytohemagglutinin (PHA) at 40 days of age. A significant lymphopenia was also found in the early weaned animals at 40 days of age although this was accounted for statistically by their lower body weight. These consequences of early maternal separation may have been mediated through the effects of early separation on nutritional state, hypothalamic function, or maturation of the immune system.

Animals↗

Metabolite diffusion into bundle sheath cells from c(4) plants: relation to c(4) photosynthesis and plasmodesmatal function.

The present studies provide the first measurements of the resistance to diffusive flux of metabolites between mesophyll and bundle sheath cells of C(4) plants. Species examined were Panicum miliaceum, Urochloa panicoides, Atriplex spongiosa, and Zea mays. Diffusive flux of metabolites into isolated bundle sheath cells was monitored by following their metabolic transformation. Evidence was obtained that the observed rapid fluxes occurred via functional plasmodesmata. Diffusion constants were determined from the rate of transformation of limiting concentrations of metabolites via cytosolic enzymes with high potential velocities and favorable equilibrium constants. Values on a leaf chlorophyll basis ranged between 1 and 5 micromoles per minute per milligram of chlorophyll per millimolar gradient depending on the molecular weight of the metabolite and the source of bundle sheath cells. Diffusion of metabolites into these cells was unaffected by a wide variety of compounds including respiratory inhibitors, monovalent and divalent cations, and plant hormones, but it was interrupted by treatments inducing cell plasmolysis. The molecular weight exclusion limit for permeation of compounds into bundle sheath cells was in the range of 850 to 900. These cells provide an ideal system for the quantitative study of plasmodesmatal function.

Journal Article↗

Purification and characterization of beef and pig liver aldehyde dehydrogenases.

Beef liver cytosolic, mitochondrial, and pig liver mitochondrial aldehyde dehydrogenases (ALDH) had been purified to homogeneity. The two mitochondrial enzymes as with other mammalian mitochondrial enzymes had properties very similar to that of the corresponding human enzyme. These include immunological as well as basic kinetic properties such as low Km for aldehyde, activation by Mg2+ ions, and lack of inhibition by disulfiram. A major difference between these two enzymes and the human mitochondrial enzyme was that they contained an N-terminal-blocked amino acid. Cytosolic ALDHs from human and horse liver have been shown to possess an N-acetyl serine as the N-terminal residue; beef cytosolic ALDH was also found to be blocked. Tissue preparations and subcellular fractions from beef or pig liver could be used to study acetaldehyde oxidation. This is the subject of the accompanying paper (Cao Q-N, Tu G-C, Weiner H, Alcohol Clin Exp Res 12:xxx-xxx, 1988).

Aldehyde Dehydrogenase↗

Mitochondria as the primary site of acetaldehyde metabolism in beef and pig liver slices.

Aldehyde dehydrogenase (ALDH) is the major enzyme involved in the oxidation of acetaldehyde. It has been shown that the liver enzyme is located in both cytosol and mitochondria. It has not been established where the subcellular oxidation of acetaldehyde occurs in species other than rat. Using slices isolated from beef and pig livers and selectively inhibiting the mitochondria enzyme with cyanamide or the cytosolic enzyme with disulfiram, it was possible to address this question. It was found that with both beef and pig liver slices 60% of the oxidation was catalyzed by the mitochondrial ALDH and 20% by the higher Km cytosolic enzyme. The remainder of the metabolism was the result of non-ALDH involvement. Furthermore, any decrease in the level of the low Km mitochondrial aldehyde dehydrogenase activity resulted in a decreased rate of acetaldehyde oxidation showing that its activity governed the rate of acetaldehyde oxidation. These were the same conclusions previously reached using rat liver tissue slices. Thus, it appears that for all mammalian tissue, mitochondria is the primary location of acetaldehyde oxidation.

Acetaldehyde↗

TRH analogue, RX 77368, injected into dorsal vagal complex stimulates gastric secretion in rats.

Medullary sites inducing gastric acid secretion in response to microinjection of the stable analogue of thyrotropin-releasing hormone (TRH; RX 77368, pGlu-His-[3,3'-dimethyl]-Pro-NH2) were investigated in urethan-anesthetized rats. Gastric acid output was recorded every 2 min through a double gastric cannula constantly perfused with 0.9% saline solution maintained at pH 5.5 using an automatic titrator. Unilateral microinjection of RX 77368 (10-100 ng in 50-nl volume) into the dorsal vagal complex (DVC), the dorsal vagal nucleus and nucleus tractus solitarius, induced a significant dose-dependent stimulation of gastric acid secretion. The peak response occurred within 50 min and lasted over 1 h. Other medullary sites, including the lateral, dorsal, and parvocellular reticular nuclei; the medial longitudinal fasciculus; and the medial cuneate nucleus injected with RX 77368 (10-100 ng), were inactive. The TRH metabolites, TRH-OH and His-Pro diketopiperazine (100 ng), injected into the DVC did not influence gastric acid secretion. The stimulation of gastric acid secretion induced by DVC injection of TRH was abolished by vagotomy. These results demonstrate that 1) the DVC is an important site of action for TRH-induced stimulation of gastric acid secretion, 2) TRH action in the DVC is not secondary to the formation of TRH metabolites, and 3) the effect is expressed by vagal efferent pathways. These findings added to the high concentration of TRH-immunoreactivity and receptors in the DVC suggest a role for endogenous TRH in the regulation of vagal outflow to the stomach.

Animals↗

Inactivation of horse liver mitochondrial aldehyde dehydrogenase by disulfiram. Evidence that disulfiram is not an active-site-directed reagent.

The inhibition of mitochondrial (pI 5) horse liver aldehyde dehydrogenase by disulfiram (tetraethylthiuram disulphide) was investigated to determine if the drug was an active-site-directed inhibitor. Stoichiometry of inhibition was determined by using an analogue, [35S]tetramethylthiuram disulphide. A 50% loss of the dehydrogenase activity was observed when only one site per tetrameric enzyme was modified, and complete inactivation was not obtained even after seven sites per tetramer were modified. Modification of only two sites accounted for a loss of 75% of the initial catalytic activity. The number of functioning active sites per tetrameric enzyme, as determined by the magnitude of the pre-steady-state burst of NADH formation, did not decrease until approx. 75% of the catalytic activity was lost. These data indicate that disulfiram does not modify the essential nucleophilic amino acid at the active site of the enzyme. The data support an inactivation mechanism involving the formation of a mixed disulphide with a non-essential cysteine residue, resulting in a lowered specific activity of the enzyme.

Aldehyde Dehydrogenase↗

Electroencephalographic spectra and coherence in the diagnosis of Alzheimer's-type and multi-infarct dementia. A pilot study.

The accurate diagnosis of dementia is difficult because there are no specific physiologic tests. Computer-analyzed electroencephalography (EEG) has shown promise as a tool for the differential diagnosis of dementia, but topographic methods for data collection and analysis have seldom been used. We used these methods to investigate EEG differences among three groups of elderly subjects: those with mild to moderate dementia of the Alzheimer's type (DAT), those with mild to moderate multi-infarct dementia (MID), and age- and sex-matched normal controls. The two groups of demented subjects were distinguished from the control group by a new criterion, the ratio of high-frequency to low-frequency electrical activity in the left temporal region, which was greatly diminished in demented subjects. Using this single variable, all control subjects and 15 of 18 demented subjects were correctly classified (sensitivity 83%, specificity 100%). The three misclassified subjects were among the least impaired subjects with DAT. Examination of coherence, or synchronization of the EEG signal, enabled us to distinguish subjects with DAT from those with MID. Using discriminant analysis of both EEG frequency and coherence, 92% (22/24) of subjects were accurately classified. These results justify further evaluation of topographic, computer-based EEG analysis as a test for the differential diagnosis of dementia.

Alzheimer Disease↗

Impaired natural killer cell activity during bereavement.

Natural killer (NK) cell activity, a component of the immune surveillance system, was compared in women whose husbands had recently died with that found in age-matched women who had not experienced recent adverse life events. Bereaved women had significantly lower NK activity than women whose husbands were healthy. In a second study, depressive symptoms and NK activity were measured longitudinally in women before and after the death of their husbands. Our results suggest that depressive symptoms, not merely the death of the spouse, are related to a reduction in NK activity during bereavement.

Bereavement↗

Effects of a single administration of morphine or footshock stress on natural killer cell cytotoxicity.

We previously reported that daily exposure for 4 days to an inescapable form of footshock stress, known to cause opioid-mediated analgesia, suppressed the cytotoxic activity of splenic natural killer (NK) cells in rats. Similarly, daily injection of high doses of morphine (greater than or equal to 30 mg/kg) for 4 days also suppressed splenic NK cell activity. We now report that a single exposure to the opioid form of footshock stress or a single high dose of morphine induces suppression of splenic NK cell cytotoxicity. This effect is evident 3 h after treatment, returning to normal by 24 h. Morphine-induced NK suppression is evident in both male and female rats, is blocked by the opiate antagonist naltrexone, and develops tolerance. Morphine-induced NK suppression is seen in cells derived simultaneously from the spleen, bone marrow, and peripheral blood, suggesting that this suppression does not result from a selective egress of NK cells from the spleen.

Animals↗

Some unexplored regions of psychosomatic medicine.

The history of psychosomatic medicine in the 20th century is predominantly marked by a concern with studies of major diseases (e.g., angina pectoris, bronchial asthma, diabetes mellitus, essential hypertension, neurodermatitis, rheumatoid arthritis, etc.). Traditional physicians also narrowly focus on disease--a trend that began with Morgagni in the 18th century. But disease (defined by structural alterations) is not the only cause of illness and disability. In fact, most persons seeking health care are ill without having a disease. It is only recently that this distinction has been fully made. The various manifestations of ill-health go by a variety of descriptive names--the functional or irritable bowel and hyperventilation syndromes, fibromyositis, psychophysiological, functional and somatoform or somatization disorders. They lead to loss of productivity, cost the health care system excessively, produce negative reactions in physicians, and are fertile ground for iatrogenic disease. They do not constitute discrete syndromes but overlap, each also being closely associated with anxiety and depression, sleep disturbances or marital disruption. They are the manifestations of sick persons not only of disturbances of bodily systems. They may be precipitated by unemployment, marital discord, bereavement, and job dissatisfaction. Curiously, ill-health has not been the major area of investigative interest of psychosomatic medicine. This presentation will emphasize why it should be, and why proper interventions may radically reduce the cost of medical care, prevent iatrogenic disease, and reduce the use of ill-advised procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Corticotropin-releasing factor acts on the brain to reduce gastric contractility.

Various stressors (cold restraint, electric shock, etc.) applied to rats increase gastric contractility and are associated with gastric erosions. Intracisternal (i.c.) thyrotropin-releasing hormone (TRH) increases contractility, gastric acid secretion and the incidence of erosion formation. Corticotropin-releasing hormone (CRF) is released by stress, and acting centrally produces autonomic and endocrine changes. We have studied the role of i.c. CRF on gastric contractility in anesthetized rats (n = 6). Contractility was measured by extraluminal force transducers sutured to the gastric corpus. Frequency, amplitude of contractions and a motility index were analyzed by computer. Baseline measures, after recovery from surgery were obtained in 24-hour fasted rats. Contractility was stimulated by intravenous carbachol (100 mg/kg/h) or i.c. injection of the TRH analog, RX 77368. Contractility thus induced was inhibited by intravenous atropine (1 mg/kg). CRF (30-1,000 ng i.c.) produced a dose-dependent suppression of RX 77368 (p less than 0.05) but had no effect on that induced by intravenous carbachol; saline i.c. had none either. Intravenous CRF was 1/10th as potent in suppressing contractions produced by i.c. RX 77368. Diminution of gastric contractions after i.c. CRF (1 mg) occurred within 5 min of administration, and lasted for at least 60 min. These data show that i.c. CRF injection acts centrally to inhibit gastric contractions stimulated centrally (i.e. by i.c. RX 77368) but not peripherally (i.e. by carbachol), and by inference reduces the risk of erosion formation induced by some stressors.

Animals↗

Life events, depressive symptoms, and immune function.

Because both bereavement and depression have been associated with impaired immune responses, the authors studied two indicators of immune function, natural killer (NK) cell activity and measures of T cell subpopulations, in 37 women who differed in the magnitude of recent life events. Women who had experienced major life changes had lower NK cell activity than women who had few changes. Severity of depressive symptoms in these women was associated with an impairment of NK cell activity, an absolute loss of suppressor/cytotoxic cells, and an increase in the ratio of T helper to T suppressor/cytotoxic cells.

Adult↗

Immune and neuroendocrine changes during bereavement.

Several studies document an association between bereavement and both suppressed lymphocyte responses to mitogen stimulation and impaired NK activity. In addition, women who are bereaved and have depressive symptoms show alterations in T cell subpopulations including a loss of T suppressor-cytotoxic cells and an increase in the ratio of T helper to T suppressor-cytotoxic cells. Although depressive symptoms may possibly mediate the immunologic changes during bereavement, the processes that modulate the immune system and link bereavement, changes in CNS activity, and immune function remain unknown. The increased secretion of cortisol in bereaved persons does not appear to mediate the suppression of NK activity, and further studies are necessary to explore the potential role of neuropeptides or catecholamines in altering immune function during bereavement.

Adrenal Cortex Hormones↗

Use of polyclonal antibodies to study properties of mammalian aldehyde dehydrogenases.

Polyclonal antibodies prepared against horse liver mitochondrial aldehyde dehydrogenase (ALDH) crossreact with both cytoplasmic and mitochondrial ALDH. Antibodies prepared against the cytosolic enzymes were more specific in that they only precipitated enzymes derived from cytosol. These polyclonal antibodies were used to determine the subcellular localization of aldehyde dehydrogenase isozymes isolated from other species and other tissues. A sequential precipitation technique was developed which allowed for the determination if samples contain both antigens. The polyclonal antibodies contained antibodies which recognize peptide fragments of mitochondrial ALDH. These antibodies can be used to probe for structural homology between similar regions in different forms of ADLH.

Aldehyde Dehydrogenase↗