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Biomedical subjects

M J Smith

Publications and source records attributed to M J Smith.

At least 217 records · Page 12Linked to original sources
PubMed1992

Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and kappa B regulatory elements.

Human immunodeficiency virus type 2 (HIV-2) displays several features which distinguish it from HIV-1. Among the differences in these two viruses are the responses of their enhancer regions to T-cell activation. For example, stimulation of HIV-1 transcription is largely dependent on two kappa B regulatory elements. In contrast, the HIV-2 enhancer has a single kappa B site and contains additional cis-acting sequences responsive to induction. One of these sites, previously termed CD3R, is a purine-rich site, also called PuB1, which is responsive to stimulation of the CD3 component of the T-cell receptor complex and binds Elf-1, a member of the ets proto-oncogene family. In this report, we examine the interaction of the PuB1 site with other sites in the HIV-2 enhancer. We demonstrate that the PuB1 site confers responsiveness to T-cell activators only in cooperation with additional enhancer elements. Induction of the HIV-2 enhancer is dependent on at least two other cis-acting regulatory elements in addition to PuB1 and kappa B. One of these elements is another purine-rich site (PuB2), which also binds recombinant Elf-1. An adjacent region, proximal to the PuB2 ets (pets) site, shows protection in DNase footprinting experiments with extracts from Jurkat T cells. Mutation of either the kappa B, PuB1, PuB2, or pets site significantly reduces the response of the HIV-2 enhancer to T-cell stimulation, an effect which is mediated at the RNA level. Therefore, activation of the HIV-2 enhancer is dependent on at least four cis-acting elements, only one of which is found in HIV-1, which act in synergy with one another. Despite their sequence similarity, the organization and function of the HIV-2 enhancer have diverged considerably from those of HIV-1.

Base Sequence↗
PubMed1992

Development of hypertension in animals with reduced total peripheral resistance.

The object of the present study was to determine whether deoxycorticosterone acetate (DOCA)-salt hypertension can be produced in rats in the presence of low total peripheral resistance (TPR) induced by long-term administration of minoxidil, a vasodilator. The rats were divided into four groups: sham-control, DOCA-salt, minoxidil, and DOCA-salt with minoxidil. The rats in both DOCA groups had DOCA pellets implanted subcutaneously and were given saline to drink. The rats in both minoxidil groups were given minoxidil (3 mg/day) in the drinking water throughout the experiment. Final measurements, including mean arterial blood pressure, cardiac index, and renal blood flow were made after 4-6 weeks. Flow measurements were made using radioactive microspheres. Cardiac index (ml.min-1.100 g-1) in sham-control rats averaged 18 +/- 2 and was higher in the other groups: 23 +/- 4 (DOCA-salt), 25 +/- 2 (minoxidil), and 30 +/- 2 (DOCA-salt plus minoxidil). Mean arterial pressure (mm Hg) was increased in both DOCA-salt rats (160 +/- 8) and DOCA-salt plus minoxidil rats (153 +/- 5) as compared with sham-control (116 +/- 2) and minoxidil (113 +/- 3) rats. There was no significant difference in TPR between the sham-control and DOCA-salt rats, but TPR in minoxidil and DOCA-salt plus minoxidil rats was 30% and 28% lower than that in untreated sham-control and DOCA-salt hypertensive rats, respectively. In contrast, renal vascular resistance was significantly increased in both DOCA-salt groups as compared with non-DOCA-salt groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Evidence from the oestrous cycle for male-induced ovulation in Bettongia penicillata (Marsupialia).

Female brush-tailed bettongs (Bettongia penicillata) housed in a breeding group of one male and one to three females had an average gestation period of 21.2 days (n = 58) and parturition was followed within 24 h by oestrus and mating. If a young was not born as a result of the mating, oestrus recurred after about 21.7 days (n = 12). From removal of pouch young to birth was 17.5 days, on average (n = 85), in females that had mated post partum, but most females that were isolated from a male before parturition returned to oestrus about 6.6 days after simultaneous removal of pouch young and return to the male (n = 9). Females housed in female-only groups appeared not to come into oestrus or to do so irregularly. These females, when returned to the male, usually came into oestrus within 10 days. These data provide evidence that, in most females of B. penicillata, ovulation does not occur in the absence of a male and that previously isolated females return to oestrus within 10 days of return to the male.

Animals↗
PubMed1992

Evidence from plasma progesterone concentrations for male-induced ovulation in the brush-tailed bettong, Bettongia penicillata.

Female brush-tailed bettongs, Bettongia penicillata, were housed with either an intact or vasectomized male or isolated from males in the peripartum period. Development of the quiescent corpus luteum formed at the post partum oestrus was initiated by removing the pouch young. Blood samples for analysis of plasma progesterone were collected from the females 2 days before removal of pouch young, daily for 5 or 6 days and then 2-3 times each week until 19 days after removal of pouch young. Plasma progesterone profiles were similar in pregnant and nonpregnant cycles. There was an early progesterone peak (1206 +/- 121 pg ml-1, mean +/- SEM; n = 16) between days 2 and 5 after removal of pouch young, and a second period of high concentrations (greater than 800 pg ml-1) before birth on day 17.4 +/- 0.2 (n = 16). The interval between the early peak and birth was 14 or 15 days. On five of 34 occasions, no increases in plasma progesterone concentrations occurred after removal of pouch young. On 12 of 15 occasions for 13 females that had been isolated from males post partum, plasma progesterone concentrations also remained low (less than 100 pg ml-1) and did not change after removal of pouch young. Females that showed no increases in plasma progesterone concentration after removal of pouch young had significantly lower (P less than 0.001) plasma progesterone concentrations while lactating than those females that did undergo a cycle after removal of pouch young (60 +/- 4 pg ml-1, n = 17 and 225 +/- 23 pg ml-1, n = 30, respectively). Females isolated from males post partum, and monitored until day 12 after removal of the pouch young, and that showed no increases in progesterone in this period, had ovaries that contained no corpus luteum, only corpora albicantia and numerous atretic or developing follicles. We conclude that brush-tailed bettongs are induced ovulators, a characteristic described for only one other marsupial, Monodelphis domestica, from South America.

Animals↗
PubMed1992

A C. elegans gene encodes a protein homologous to mammalian calreticulin.

The gene encoding a C. elegans homologue of the mammalian reticuloplasmin, calreticulin, was cloned and sequenced and the amino-acid sequence of its product deduced. The coding region of the gene comprises three exons separated by introns of 95 and 55 nucleotides, followed by either 158 or 279 bases of 3' non-coding sequence before putative polyadenylation signals. The precursor protein of 395 residues includes an N-terminal signal sequence of 13 residues. The C-terminus has the ER retention signal HDEL preceded by a polyacidic zone similar to known mammalian calreticulins. The sequence shows a 61% identity with mouse calreticulin, increasing to 82% in the proline-rich region of the molecule. Comparison of the C. elegans sequence with the calreticulin-related antigen RAL-1 of Oncocerca volvulus shows 73% identity, excluding the calreticulin C-terminal region. The sequence of this region differs markedly from RAL-1 where the parasite protein has a polybasic stretch and no ER retention signal. The C. elegans gene described here and designated crt-1 was mapped to a region towards the left-hand end of Chromosome V on the physical map of the genome. Southern blotting of genomic DNA indicates that in C. elegans the calreticulin homologue exists in only one form as the product of a single gene.

Amino Acid Sequence↗
PubMed1992

Nucleotide sequence of a Drosophila melanogaster gene encoding a calreticulin homologue.

A Drosophila melanogaster gene encoding a homologue of the mammalian ER calcium binding protein, calreticulin, was cloned and the nucleotide sequence determined. Four exons can be identified, contained within 1700 bp of sequence, separated by introns of 124, 266 and 92 bases. The exons encode a 389 amino acid protein which may be a precursor form as it includes an N-terminal signal region of 17 residues that could potentially be cleaved to form a mature protein. The C-terminal region of the protein contains the established pattern of polyacidic clusters, common to calreticulins of other species and ends in the ER retention signal HDEL. Excluding the N-terminal signal region, the Drosophila protein amino acid sequence has a 67% identity to mammalian calreticulins and the length and acidity of the C-terminal zone in the insect protein are intermediate between higher mammalian and lower nematode values.

Amino Acid Sequence↗
PubMed1992

An evaluation of single-room maternity care.

Patients appreciated the opportunity to give feedback. Nurses felt they were doing a good job and also that the decision to move into SRMC had been the right one. This project also highlighted for the nursing community the benefits for nursing practice that can result when representatives from education and service collaborate in research and evaluation.

Attitude of Health Personnel↗
PubMed1991

Dependence of subcellular damage on various laser beam parameters.

A cw argon laser operating at the multiline UV TEM00 mode was used to create lesions in the nucleoli of fibroblast cells. Laser powers emitted through the objective were varied from 5-8 mW and laser pulse durations ranged from 50 to 600 ms. Our study showed lesion diameters ranging from 0.7 microns to 2.9 microns and an average lesion diameter of 1.77 microns. All cells were exposed to at most a laser spotsize of 2.2 microns diameter and for a laser spotsize of this diameter, we calculated that the central 18.3% of the total energy was in the central area of 0.7 microns diameter. We also found that as little as 0.3 mJ of energy could produce a lesion. No absolute threshold correlation was found between the size or type of lesion and the laser parameters used.

Animals↗
PubMed1991

Effect of an oral alpha 2-adrenergic blocker (MK-912) on pancreatic islet function in non-insulin-dependent diabetes mellitus.

We used MK-912, a potent new selective alpha 2-adrenergic receptor antagonist that is active orally, to study the effect of short-term, selective alpha 2-blockade on fasting plasma glucose (FPG) and pancreatic islet function in non-insulin-dependent diabetes (NIDDM). Ten asymptomatic patients with NIDDM received either a single oral dose of MK-912 (2 mg) or placebo in a double-blind, cross-over study. B-cell function was measured by the acute insulin response (AIR) to glucose (1.66 mmol/kg intravenously [IV]) and by the AIR to arginine (5 g IV) during a hyperglycemic glucose clamp at a mean glucose level of 32.1 mmol/L to provide an estimation of maximal B-cell secretory capacity. A-cell function was estimated by the acute glucagon response (AGR) to arginine during the glucose clamp. Effective alpha 2-adrenergic blockade was apparently achieved, as there were substantial increases of plasma norepinephrine (NE) (P less than .01) and both systolic blood pressure (SBP) (P less than .01) and diastolic blood pressure (DBP) (P less than .05) after treatment with MK-912, but not after placebo. MK-912 caused a significant (P less than .05) although modest decrease of FPG that was associated with a small increase of fasting plasma insulin (P less than 0.01), C-peptide (P less than .05), and glucagon (P less than .01). FPG and hormone levels remained unchanged after placebo. MK-912 tended to increase the AIR (P = .06) and the C-peptide response (P = .07) to glucose compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Time course of renal responses to greater splanchnic nerve stimulation.

The objective of the present study was to describe the time courses of renal responses during renal sympathetic stimulation and to determine whether the kidney can provide a sustained response to sympathetic stimulation for 3 h. In four pentobarbital sodium-anesthetized dogs, stimulation (3.3 Hz) of a greater splanchnic nerve (GSN) on one side caused reductions in renal blood flow (RBF) and sodium excretion (UNaV) of both stimulated and contralateral-denervated kidneys, plus an increase in plasma renin activity (PRA). During continued stimulation, RBF partially recovered, but UNaV fell to less than 5% of control and PRA rose and remained at least eight times above control. In nine dogs, a single GSN was stimulated after ipsilateral adrenal medullectomy and ligation of the splanchnic circulation. The acute response to GSN stimulation was now confined to the ipsilateral kidney. Ipsilateral RBF fell by 32 +/- 10% but returned to 85 +/- 5% of control values by the end of the stimulation period. Contralateral RBF fell slowly by approximately 10%. Ipsilateral and contralateral UNaV fell to 34 +/- 10 and 43 +/- 11% of control values, respectively. PRA increased rapidly at the onset of GSN stimulation and remained at least 2.8 times control levels. After stimulation, RBF, UNaV, and PRA returned toward control levels. These results confirm the findings of others that the response of the renal vasculature to sympathetic stimulation is mainly transient. However, they additionally demonstrate a strong and sustained decrease in UNaV lasting for the total 3-h period of sympathetic stimulation.

Adrenal Medulla↗
PubMed1991

Hormonal and circulatory responses to chronically controlled increments in right atrial pressure.

To study the time-dependent changes in the secretion of atrial natriuretic peptide (ANP) in response to chronic stimulation by controlled increments in atrial pressure, we developed methodology for precise control of right atrial pressure (RAP) in dogs by employing an externally adjustable occluder around the pulmonary artery and a servo-control system. During 7 days of servo-control of RAP at 6.3 +/- 0.1 mmHg above control levels (1.3 +/- 0.1 mmHg), the 24-h coefficient of variation in RAP was 1/45 the variation that occurred under control conditions. After 30 min of increased RAP, mean arterial pressure (MAP) was reduced from 101 +/- 4 to 84 +/- 3 mmHg in association with increments in plasma renin activity (PRA) from 0.6 +/- 0.1 to 2.5 +/- 0.9 ng angiotensin I (ANG I).ml-1.h-1 and in the plasma concentrations of ANP, arginine vasopressin (AVP), and epinephrine from 93 +/- 18 to 484 +/- 61 pg/ml, from 0.5 +/- 0.1 to 9.2 +/- 2.4 pg/ml, and from 82 +/- 27 to 585 +/- 133 pg/ml, respectively. In comparison, on day 7 of servo-control of RAP, sodium balance was achieved and MAP remained depressed (82 +/- 4 mmHg) along with sustained increments in both plasma ANP concentration (482 +/- 67 pg/ml) and PRA (1.7 +/- 0.6 ng ANG I.ml-1.h-1); on the other hand, the plasma concentrations of AVP and epinephrine returned to control levels. This quantitative study indicates that ANP secretion does not chronically adapt to stimulation by increased atrial pressure and suggests that the plasma levels of ANP achieved in heart failure markedly increase renal excretory capability and allow fluid balance to be achieved at a substantial fall in renal perfusion pressure.

Angiotensin I↗
PubMed1991

Effect of desipramine on norepinephrine metabolism in humans: interaction with aging.

To determine whether differences in neuronal reuptake contribute to age-related changes of sympathetic nervous system activity, we compared norepinephrine (NE) release and metabolism during [3H]NE infusion and decay in six young (age 19-26 yr) and seven older (age 61-73 yr) healthy nonobese subjects. Subjects were studied on a control day and on a separate day after desipramine (DMI; 125 mg orally), a neuronal reuptake blocker. Compartmental analysis of plasma NE specific activity was used to determine several NE kinetic parameters. Plasma NE levels and NE spillover rates were higher in the elderly. Although plasma NE was unaffected by DMI in both age groups, both the metabolic clearance rate of NE from plasma and the rate of NE spillover into plasma fell in young and older groups during DMI. Furthermore, DMI dramatically lowered the mass of NE in the extravascular compartment and the rate of NE entry into the extravascular compartment. Thus neuronal uptake blockade has major effects on NE release as well as NE metabolism in humans. However, age-related differences in NE kinetics cannot be explained by differences in neuronal uptake.

Adult↗
PubMed1991

Stimulation of renin release by hyperkalemia in the nonfiltering kidney.

This study was designed to analyze the acute effects of hyperkalemia on renin release in the normal filtering kidney and the nonfiltering kidney. Plasma K was increased by acute intravenous KCl infusion. In the normal filtering kidney experiment plasma K was 5.7 vs. 3.5 meq/l. Hyperkalemia resulted in a 45% increase in renal blood flow (RBF) and a 35% increase in glomerular filtration rate (GFR) at the 120-mmHg pressure level. Renin release was significantly greater in the hyperkalemic group than in the control group (P less than 0.01) with the greatest effect over the lower pressure range. In the nonfiltering kidney experiment plasma K was 6.09 vs. 3.5 meq/l. RBF was 33% greater in the hyperkalemic than in the normokalemic group at the 130-mmHg pressure level. Renin release was also greater in the hyperkalemic group than in the normokalemic group (P less than 0.01). However, unlike the normal filtering kidney experiments, in the nonfiltering kidneys the difference in renin release was most prominent at the highest level of renal perfusion pressure. These experiments demonstrate that acute hyperkalemia can cause renal vasodilation and stimulate renin release in both filtering and nonfiltering kidney preparations and that potassium may affect renin release both through a direct effect on the juxtaglomerular cells and indirectly by affecting delivery of fluid and/or NaCl to the macula densa.

Animals↗
PubMed1991

Effect of epinephrine on pancreatic beta-cell and alpha-cell function in patients with NIDDM.

The purposes of this study were to determine whether patients with non-insulin-dependent diabetes mellitus (NIDDM) have an enhanced glycemic response to epinephrine (EPI) and to quantitate the effect of physiological elevations of EPI on pancreatic islet function in these patients. The increment of plasma glucose (PG) in response to 45 min of EPI infusion (mean plasma EPI 2490 pM) was more than twofold greater in nine NIDDM patients than in 20 nondiabetic control subjects (mean +/- SE delta PG 3.9 +/- 0.3 vs. 1.7 +/- 0.1 mM, P less than 0.0001). The effects of EPI on beta-cell and alpha-cell function were compared in nine NIDDM patients and 9 age- and weight-matched control subjects during infusions of saline or two doses of EPI on separate days (mean plasma EPI 270, 1120, and 2490 pM). On each day, the acute insulin response (AIR) and acute glucagon response (AGR) to 5 g i.v. arginine were measured at three matched steady-state PG levels (means of 9, 14, and 29 mM). Beta-Cell sensitivity to glucose (slope of glucose potentiation) and beta-cell secretory capacity, or AIRmax (AIR at the highest clamped PG level), were calculated. In control subjects, EPI inhibited the AIR at PG concentrations of 9 and 14 mM (both P less than 0.05) but had no effect on the AIRmax, resulting in a rightward shift of the curve relating the AIR and PG and a decrease in the slope of glucose potentiation (P less than 0.01). In contrast in NIDDM patients, EPI inhibited the AIR at all PG levels, including the AIRmax (all P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Effects of extended hospitalization: a one-year follow-up study.

The C. F. Menninger Memorial Hospital is conducting an ongoing follow-up study of the effects of extended hospitalization. The authors report key indicators of outcome at one year postdischarge for 110 patients hospitalized on extended care units for at least 180 days. Outcome is determined by postdischarge rates of rehospitalization, postdischarge suicide attempts, and occupational functioning at the time of the one-year follow-up interview. After comparing these areas with preadmission levels of symptomatology and functioning, the authors report significant improvement in each category at the time of follow-up.

Adaptation, Psychological↗