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Biomedical subjects

S H Ackerman

Publications and source records attributed to S H Ackerman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Identification of two nuclear genes (ATP11, ATP12) required for assembly of the yeast F1-ATPase.

Nuclear respiratory-deficient mutants of Saccharomyces cerevisiae (pet mutants) have been screened for defects in the mitochondrial ATPase. Mutants in two complementation groups were found to have 10% or less of wild-type ATPase activity. The two wild-type nuclear genes defined by the mutants have been designated ATP11 and ATP12. The proteins encoded by the two genes are not subunits of the ATPase but rather appear to exercise an important function at a late stage in the synthesis of F1 after transport of the subunits into the internal compartment of mitochondria. Mitochondria of atp11 and atp12 mutants have only marginally reduced levels of the alpha and beta subunits of F1. Both proteins are processed to their mature size but are not part of a native F1 structure or associated with the mitochondrial membrane. The most reasonable explanation for the mutant phenotype is a block in the assembly of the F1 oligomer.

Cell Nucleus↗
PubMed1989

Energy expenditure during stress ulcer formation in vulnerable rats.

Rat pups separated early from their mothers at day 15 become vulnerable to hypothermia and gastric erosion formation when food deprived and physically restrained on postnatal day 30 (S.H. Ackerman, M. A. Hofer, and H. Weiner, Science Wash. DC. 201: 373-376, 1978, and Gastroenterology 75: 649-654, 1978). We tested the hypothesis that this hypothermia is associated with a decrease in oxidative metabolism. We measured O2 consumption of 30-day-old rat pups that had been previously separated at either day 15 (15w) or day 21 (21w). When food was available, 15w rats used as much O2 as 21w rats. When rats were food deprived or food deprived and restrained, 15w rats used significantly less O2 than 21w rats, implying less heat production. We hypothesized that this decrease in heat production during food deprivation and/or restraint was due to impaired thermogenesis resulting from inadequate release of endogenous norepinephrine (NE), which is a stimulant of brown adipose tissue- (BAT) mediated thermogenesis. To test this hypothesis we administered exogenous NE to 15w to 21w rats. Exogenous NE failed to increase O2 consumption in 21w or 15w rats when injected during either food deprivation or restraint. We concluded that 30-day-old 15w rats have decreased oxidative metabolism during food deprivation and restraint and therefore become hypothermic. This decreased oxidative metabolism does not appear to be attributable to insufficient endogenous NE, since it is not reversed by the addition of exogenous NE. We suggest that a decrease in oxidative metabolism may explain susceptibility to stress ulcers in a number of previously reported experimental models.

Adipose Tissue, Brown↗
PubMed1988

Antidepressants and weight gain.

Weight gain is an often reported, but incompletely understood, side effect of many antidepressant medications. We will discuss the literature with respect to the following issues: weight gain as a pharmacological effect of antidepressants or as an effect of recovery from depression; the incidence of antidepressant-induced weight gain and possible reasons for individual variability in its occurrence; possible mechanisms of antidepressant-induced weight gain; and options for clinical management. Further elucidation of these issues may contribute to our understanding of the neurobiology of affective disorders and appetitive mechanisms.

Antidepressive Agents↗
PubMed1988

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↗
PubMed1987

Evidence for catalytic cooperativity during ATP hydrolysis by beef heart F1-ATPase. Kinetics and binding studies with the photoaffinity label BzATP.

The photoaffinity analog of ATP, 3'-O-(4-benzoyl) benzoyl ATP (BzATP), was used to covalently modify the catalytic sites on the beef heart mitochondrial F1-ATPase. In the absence of actinic illumination, BzATP was a slow substrate for the enzyme (Vmax = 0.19 mumol min-1 mg-1; kcat/Km = 2.2 X 10(6) M-1s-1) and behaved as a classical competitive inhibitor versus ATP (Ki = 0.85 microM). Under photolytic conditions, BzATP inactivated F1 with pseudo first-order kinetics, and the photoinactivation reaction showed rate saturation suggesting specific, reversible binding of BzATP to F1 prior to covalent bond formation. ATP protected against F1 photoinactivation (Kprotect = 0.3 microM) and partially covalently modified F1 yielded the same Km for ATP as unmodified enzyme. These results strongly suggested that BzATP was bound to catalytic sites on the enzyme. In the absence of photolysis, BzATP saturated two binding sites on the F1 (KD = 1.6 microM), and under photolytic conditions, 1 mol of BzATP was shown to be covalently liganded to the beta subunit of the enzyme coincident with 100% loss in ATPase activity. Previous studies with the mitochondrial F1-ATPase have suggested a mechanism involving catalytic cooperativity during ATP hydrolysis. Our demonstration of a molar stoichiometry of 1 for photoinactivation is in accord with this mechanism. It is suggested that either F1 is unable to hydrolyze covalently bound BzATP, or that subsequent to hydrolysis, the BzADP product can not be released from the catalytic site. It is therefore inferred that F1 hydrolytic activity requires cooperativity between multiple, viable catalytic sites and that covalent modification of a single catalytic site is sufficient for complete enzyme inactivation.

Adenosine Diphosphate↗
PubMed1987

Salivation and depression: a role for appetitive factors.

A decrease in salivary flow rate (SFR) is associated with depressive illness although the mechanisms underlying this association are unknown. Appetitive factors are known to influence SFR, but are not adequately considered in the studies of salivation and depression. Diminished SFR in depressive illness may be more closely related to the appetite disturbances commonly associated with depressive illness than to mood disorder or depressive illness per se. The implications for considering SFR as a physiological correlate of depressive illness are discussed in light of this possibility.

Appetite↗
PubMed1987

Chronobiologic factors in experimental stress ulcer.

The available literature on chronobiologic factors in experimental stress ulcer is extremely small and thematically limited. It focuses almost exclusively on circadian rhythms and, within that, on rhythms related to light-dark cycles, activity and body temperature. Among these, only differences in ulcer induction related to circadian activity patterns have been adequately demonstrated. Other circadian patterns and other temporal phase relationships might be profitably explored, including those related to postnatal development. It is also likely that the important relationships between biorhythms and stress ulcer are not limited to ulcer induction. Future studies should address chronobiologic factors in predisposition, severity of illness, the probability of recovery and response to various therapeutic interventions.

Age Factors↗
PubMed1986

Ontogeny of gastric secretion in the rat. Ultrastructural changes in relation to secretory changes.

Basal and stimulated gastric acid secretion are three to four times greater in the juvenile (30-day-old) rat than in the adult (100-day-old) rat, even though the parietal cell mass is greater in the adult. In this study we examined the possibility that the H+ secretory activity of individual parietal cells is greater in juvenile rats. To do this we used quantitative measures of secretory canaliculi and tubulovesicles as indirect measures of parietal cell H+ secretory activity. We determined that, under the experimental conditions used, the morphologic measures bear a sufficiently close linear relationship to total gastric H+ output to justify their use. We then found that when individual parietal cells from 30-day-old rats are compared quantitatively with those from 100-day-old rats, each cell from the younger rats has, on average, significantly more of the morphologic characteristics associated with higher H+ output. We inferred that individual parietal cells of 30-day-old rats, on average, may be secreting more H+ than corresponding cells of 100-day-old rats under comparable stimulation conditions.

Aging↗
PubMed1986

Reduced fat stores after early weaning: a correlate of vulnerability of stress ulcers.

Rats prematurely weaned at day 15 (15w) are more susceptible to restraint-induced gastric erosions (RGEs) than rats weaned normally at day 21 (21w). Increased RGE susceptibility is linked to nutritional changes occurring during premature weaning and to a disturbance of temperature regulation during restraint. Here we examine the hypotheses that: premature weaning leads to decreases in fat stores, a decrease in fat stores is associated with the occurrence of RGEs and hypothermia. Wet weights of white and brown adipose tissue deposits were determined in 30 day old 15w and 21w rats before or subsequent to food deprivation and restraint. In additional 21w animals we excised bilateral inguinal fat depots or interscapular brown adipose tissue (BAT) prior to food deprivation and restraint. Stomachs were examined for the presence of RGEs. Early weaned (15w), but not 21w rats became hypothermic and developed RGEs. White and brown adipose tissue weighed significantly less in 15w rats than in 21w rats, and 15w rats used a larger percentage of white adipose tissue. Excision of BAT, but not white adipose tissue increased RGE susceptibility of 21w rats. We conclude that the occurrence of RGEs in 15w rats is associated with decreased fat stores. Furthermore, the results suggest that BAT protects against RGE formation.

Adipose Tissue↗
PubMed1986

Verbal expression of affect in rheumatoid arthritis patients. A blind, controlled test for alexithymia.

The claim that alexithymia is associated with specific disease categories is subjected to empirical testing. We report results from a controlled, single blind study in which Thematic Aperception Test (TAT) protocols from 64 arthritis patients attending an outpatient clinic were examined for operationally defined characteristics of alexithymia. We studied two groups of rheumatoid arthritis patients, one with the combination of rheumatoid factor and erosive joint changes and the other without and a third group with other forms of arthritis. Controlling for all variables that may confound alexithymia, we were unable to find any relationship between alexithymia and diagnostic subgroup, duration of illness or functional impairment.

Adult↗
PubMed1984

Genetically obese (ob/ob) mice are predisposed to gastric stress ulcers.

Genetically obese (ob/ob) mice and lean littermate controls were food deprived and subsequently physically restrained at normal room temperatures. Obese mice became hypothermic and developed gastric stress ulcers. Lean mice maintained normal body temperatures and did not form gastric ulcers. Oxygen consumption was measured during food deprivation and restraint. Obese and lean mice had parallel metabolic responses, with obese animals using significantly less oxygen at all times. The predisposition to formation of gastric ulcers is a new phenotypic expression of the ob/ob genotype. The pathogenesis of this susceptibility appears to be related to a genetic disturbance in heat production.

Animals↗
PubMed1984

Maturational increases and decreases in acid secretion in the rat.

We compared basal acid output (BAO) and maximally stimulated acid output (MAO) in 15-, 30-, and 100-day-old anesthetized rats. At each age we measured BAO and MAO in response to six different stimuli, pentagastrin (120 micrograms X kg-1 X h-1), bethanechol (1 mg X kg-1 X h-1), histamine (8 mg X kg-1 X h-1), the H2-receptor agonist impromidine (0.9 mumol X kg-1 X h-1), hypothermia (30 +/- 2 degrees C core temperature), and pyloric ligation, and we determined H+ output by continuous perfusion of the gastric lumen of anesthetized rats. Both weight-adjusted and absolute BAO were significantly greater in 30-day-old rats than in 15- or 100-day-old rats. Although 30-day-old rats had only one-fourth the fundic mass of 100-day-old rats, they could secrete two to three times more H+ per hour. These differences in MAO persisted even after subtracting BAO. Anatomic data indicate that these age-related changes do not correspond to changes in mucosal mass or parietal cell mass.

Acids↗
PubMed1984

Differential growth rate of rat gastric mucosal cells during postnatal ontogeny.

The growth rate of surface epithelial, chief, and parietal cells of the base and neck of oxyntic glands was studied in the albino rat by comparing morphometric measures at days 15, 21, 30, and 100 postnatally. All cells increased in size. The number of cells per micrometer squared increased rapidly for chief cells and base parietal cells, while neck parietal cells remained constant and surface epithelial cells decreased. There was a net increase in the volume density of parietal and chief cells and a slight net decrease in surface epithelial cells during postnatal development. In a second experiment, the effects of early weaning on these variables was studied. Early-weaned rats gained less body weight than normally weaned counterparts. The change in surface epithelial cell size was not affected by early weaning. However, parietal and chief cells grew more quickly, initially, in early-weaned rats than in normally weaned rats. Cell numbers were unaffected except for an initial decrease in relative number of neck parietal cells. One long-term effect of early weaning was noted. The size and volume density of neck parietal cells in early-weaned rats was smaller, in the adult animal, then in normally weaned rats.

Animals↗
PubMed1984

The developmental physiology of the stomach: possible contributions to the regulatory disturbances of duodenal ulcer disease.

Several different disturbances in the regulation of acid secretion have been found in persons with duodenal ulcer disease (DU). This paper examines the possibility that some of these regulatory disturbances might arise during postnatal development. The regulation of acid secretion is not fixed in adult form at birth, in either animals or humans. Instead, these regulatory processes continue to change during postnatal development. Examples are developmental changes in the responsiveness of the stomach to parietal cell stimulants and developmental increases and decreases in basal and maximal acid output. The unfolding of these developmental changes requires complex regulatory adjustments. It is possible that untoward environmental circumstances could induce "errors" in these regulated changes or adjustments. Some errors might persist as disturbances in the regulation of acid secretion seen in patients with DU.

Adult↗