PubMed Health⌕ Search

Biomedical subjects

M Manning

Publications and source records attributed to M Manning.

At least 145 records · Page 8Linked to original sources
PubMed1981

Light-dependent pupation site preferences in Drosophila. II. Drosophila melanogaster and Drosophila simulans.

Drosophila melanogaster prefers to pupate in the dark, while its sibling species, D. simulans, prefers the light when the species are tested in isolation and when cultured and tested together. Reciprocal interspecific hybridizations were carried out and the F1 individuals were tested. Progeny from the cross of D. melanogaster females with D. simulans males chose pupations sites exactly intermediate between those of the two parental species, while the reciprocal-cross offspring preferred light pupation sites. The pupation site preferences (PSPs) of the hybrids are compatible with a sex-linked locus or loci influencing light-dependent PSP in this pair of species. Examination of light preferences of larvae prior to the late third instar demonstrates that these preferences are highly specific, being restricted to the time just before pupation. During the first two larval instars D. melanogaster is quite photopositive while D. simulans is comparatively photoneutral. These differences in light-dependent behaviour could aid in reducing competition between the two species.

Animals↗
PubMed1981

Filamentous bacteriophage contract into hollow spherical particles upon exposure to a chloroform-water interface.

The bacteriophage M13 is a 1 micrometer long filament consisting of a circular single-stranded DNA loop firmly held within a tubular protein and capsid. We report here that exposure to a chloroform-water interface initiates a 20 fold contraction of each filament into a hollow protein sphere. In these 0.04 micrometer diameter particles, termed M13 "spheroids," two thirds of the DNA is apparently extruded through a hole in the wall of the spheroid; the portion of DNA remaining inside the shell centers about the origins of M13 DNA replication. These results suggest that the filament, upon exposure to a membrane environment, undergoes an ordered change whereby the DNA is released into the cell and the coat protein is changed to a form more easily solubilized by the membrane lipids.

Binding Sites↗
PubMed1981

Arginine vasopressin and a vasopressin antagonist peptide: opposite effects on extinction of active avoidance in rats.

Systemic injection or arginine vasopressin (AVP) (1 micrograms/rat) significantly prolonged extinction of a pole-jump, active avoidance response in rats; lateral ventricular injection of 1000-fold less AVP (1 ng/rat) produced similar results. A new AVP analogue, [1-deaminopenicillamine-2-(O-methyl)tyrosine]arginine vasopressin (dPTyr-(Me)AVP), is known to antagonize behavioral and vascular effects of exogenous AVP at molar ratios of 5 : 1. At a dose of 100 micrograms/rat (subcutaneously) dPTyr-(Me)AVP produces, by itself, a behavioral effect opposite to that of exogenous AVP, namely a facilitation of extinction. Injections of dPTyr-(Me)AVP into the lateral ventricle were ineffective except at a dose of 10 micrograms/rat. These results confirm previous reports of the effect of vasopressin on delaying extinction of avoidance behavior, but suggest a site of action distant from the lateral ventricle.

Animals↗
PubMed1981

Synthetic antagonists of in vivo antidiuretic and vasopressor responses to arginine-vasopressin.

Four analogues of [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),4-valine,8-D-arginine]vasopressin [d-(CH2)5 VDAVP] and four analogues of its L-arginine isomer d(CH2)5 VAVP with O-methyl-, O-ethyl, O-isopropyl, and O-n-propyltyrosine substituents at position 2 were prepared by the solid-phase method using a slightly modified reoxidation procedure following deblocking with sodium in liquid ammonia to overcome losses due to insolubility. These analogues are the following: 1, d(CH2)5Tyr(Me)VDAVP;2, d(CH2)5Tyr(Et)VDAVP; 3, d(CH2)5Tyr(i-Pr)VDAVP; 4, d(CH2)5Tyr(n-Pr)VDAVP; 5, d(CH2)5Tyr(Me)VAVP; 6, d(CH2)5Tyr(Et)VAVP; 7, d(CH2)5Tyr(i-Pr)VAVP; 8, d(CH2)5Tyr(n-Pr)VAVP. These analogues were tested for agonistic and antagonistic activities in rat antidiuretic and rat vasopressor assay systems. All eight analogues cause a transient antidiuresis when injected intravenously and effectively antagonize antidiuretic responses to subsequent injections of arginine-vasopressin (AVP). They exhibit the following antiantidiuretic pA2 values: 1, 6.68 +/- 0.11; 2, 7.10 +/- 0.08; 3, 6.88 +/- 0.07; 4, 6.67 +/0 0.05; 5, 7.35 +/- 0.06; 6, 7.57 +/- 0.06; 7, 7.32 +/- 0.10; 8, 7.29 +/- 0.07. They are also highly effective antagonists of the vasopressor responses to AVP, with antivasopressor pA2 values in the range of 7.86 to 8.44. These findings indicate tht in this series O-ethyl substitution on the tyrosine at position 2 is optimal for antiantidiuretic potency and that L-arginine is far superior to D-arginine in this regard also. Thus, d(CH2)5Tyr(Et)VAVP with an antiantidiuretic pA2 of 7.57 +/- 0.06 is the most potent of these eight antidiuretic antagonists. These are the first known effective antagonists of in vivo antidiuretic responses to AVP. They are, thus, potentially useful pharmacological tools for studies on the roles of AVP in regulating water balance in normal and pathophysiological states in animals and in humans. They also serve as excellent lead compounds for the design of even more potent antagonists for potential therapeutic use for the treatment of hyponatremia secondary to inappropriate secretion of the antidiuretic hormone (SIADH or the Schwartz-Barter syndrome).

Animals↗
PubMed1981

Mechanism of coliphage M13 contraction: intermediate structures trapped at low temperatures.

The filamentous coliphage M13 can be transformed into a spherical particle (termed spheroid) by exposure to an interface of water and slightly polar but hydrophobic solvent such as chloroform-water at 24 degrees C. We report here that exposure of M13 filaments to a chloroform-water interface at 2 degrees C trapped the phage particles in forms morphologically intermediate to filaments and spheroids. These structures were rods 250 nm long and 15 nm wide, and each had a closed, slightly pointed end, an open flaired end, and a hollow central channel. The final contraction of these intermediates (termed I-forms) into spheroids was dependent upon both temperature and the presence of the solvent-water interface but was apparently independent of both the minor phage coat proteins and the virion DNA. Although stable in an aqueous environment, I-forms, in contrast to filaments, were readily disrupted by detergents, suggesting that the phage structure had been altered to a form more easily solubilized by membrane lipids. These solvent-induced changes might be related to the initial steps of phage penetration in vivo.

Chloroform↗
PubMed1981

Vascular effects of arginine vasopressin during fluid deprivation in the rat.

The vascular effects of arginine vasopressin (AVP) were examined in conscious Sprague-Dawley rats. In six control rats, synthetic AVP at a dose of 40 ng/kg, injected as an intravenous bolus, resulted in a rise in mean arterial blood pressure (BP) from 127 to 149 mm Hg (P < 0.005). No tachyphylaxis was observed after a second AVP bolus administered 30 min later, as BP increased from 125 to 150 mm Hg, P < 0.005. In a second group of six rats, 1-deamino penicillamine, 2-(O-methyl) tyrosine AVP ([dPTyr (Me)]AVP), was administered intravenously at a dose of 10 mug/kg, just before the second AVP bolus. In this group of studies BP rose from 124 to 150 mm Hg (P < 0.01) after the first AVP bolus, but not after the second AVP bolus, which was administered after [dPTyr (Me)]AVP (129 vs. 129 mm Hg, NS). To assess the effect of this AVP pressor antagonist on BP in rats with suppressed endogenous vasopressin, six water-diuresing rats (mean urinary osmolality, 99 mosmol/kg H(2)O) were administered the analogue at the same dose as the first group of rats. The analogue exerted no demonstrable effect on mean BP (128 before vs. 129 mm Hg after [dPTyr (Me)]AVP, NS). In these rats, mean radioimmunoassayable levels of AVP were at or below the detectable limits of our assay (0.5 pg/ml). In contrast, six rats in which endogenous AVP was stimulated by fluid deprivation for 24 h (mean urinary osmolality, 2,489 mosmol/kg H(2)O and mean AVP level of 21.6 pg/ml) had a marked fall in BP when administered the AVP analogue. In these animals [dPTyr (Me)]AVP caused a fall in BP from 124 to 110 mm Hg (P < 0.005). This fall in blood pressure was due to a fall in peripheral vascular resistance (0.35 vs. 0.30 mm Hg/ml per min per kg, P < 0.02) after [dPTyr (Me)]AVP, as cardiac index remained unchanged. To eliminate the possibility that this AVP analogue was antagonistic to endogenous pressor substances other than AVP, additional studies were performed. In homozygous Brattleboro (diabetes insipidus) rats receiving exogenous AVP, the vasopressin analogue lowered BP (133 to 112 mm Hg, P < 0.001), but failed to lower BP (112 vs. 112 mm Hg) in rats not receiving AVP. BP in a group of bilaterally nephrectomized Sprague-Dawley rats, after 24 h of fluid deprivation, fell from 130 to 118 mm Hg (P < 0.02) after the AVP analogue, precluding an effect of the analogue on lowering BP by inhibiting the renin-angiotensin system. Finally, the AVP analogue failed to alter the pressor response to exogenous infusions of either norepinephrine or angiotensin II. These results demonstrate that (a) the AVP analogue [dPTyr (Me)]AVP abolishes the pressor effect of large exogenous doses of AVP; (b) the analogue has no effect on BP in rats with suppressed or absent endogenous AVP; (c) the depressor effect of the analogue does not involve antagonism of the vasoconstrictors, norepinephrine or angiotensin; and (d) most importantly, BP fell significantly after AVP antagonist administration in intact, conscious, fluid-deprived rats with elevated endogenous AVP levels. This effect of the AVP antagonist to block endogenous AVP and lower BP was primarily due to a fall in peripheral vascular resistance.

Angiotensin II↗
PubMed1981

Diabetes induced with multiple subdiabetogenic doses of streptozotocin: lack of protection by exogenous superoxide dismutase.

The addition of exogenous superoxide dismutase (SOD) was examined as a possible means of protecting B-cells of mice against either the immediate or delayed toxicity caused by multiple injections of low doses of streptozotocin (Sz). Three different routes of SOD administration (i.p. and i.v. injection and continuous s.c. infusion) and several different doses and schedules were tried. In addition, a long-acting derivative of SOD was synthesized and tested. Despite the observation of a modest delay in the onset of diabetes in one experiment, no protective effect of SOD on the progressive elevation of blood glucose concentrations was evident in the majority of studies. Moreover, a loss in pancreatic insulin content and a tripling of pancreatic glucagon content occurred in all mice treated with low dosages of Sz, irrespective of whether or not either SOD or a long-acting derivative of SOD was administered. Finally, in parallel experiments in vitro, this enzyme was ineffective in protecting isolated rat islets from the acute toxicity of exposure to Sz on glucose-stimulated insulin release.

Animals↗
PubMed1981

Vasopressin in the rat with partial nephrectomy-salt hypertension.

The role of vasopressin in the pathogenesis of partial nephrectomy (PN)-salt hypertension was examined in the rat. Hypertension was produced by reducing renal mass 70% and substituting 1% saline for drinking water 2 to 4 days after surgery. PN alone resulted in an increase in systolic blood pressure. Subsequent salt loading led to a further large increase in arterial pressure. On the second to third day after substitution of saline for drinking water, urinary vasopressin excretion (UADHV) was increased six-fold and the plasma vasopressin concentration was increased two and one-half-fold. UADHV then fell to a level that was three-fold greater than control values 5 days later. Although there was a marked stimulation of vasopressin release during the period of salt loading, a vasopressin pressor antagonist had only a small effect on arterial pressure. This suggests vasopressin is not a major pressor agent in PN-salt hypertension.

Animals↗
PubMed1981

Combination chemotherapy with cisplatin, bleomycin, and methotrexate in patients with advanced head and neck cancer.

Twenty-six patients with advanced head and neck cancer, 22 of whom had failed prior surgery and/or radiotherapy, were treated with a combination regimen of cis-diamminedichloroplatinum II, bleomycin, and methotrexate. There were no complete responses. Nine patients achieved a partial response (35%). Three of the four (75%) patients without prior therapy achieved a partial response while only 6 of the 22 patients (27%) with prior surgery and/or radiation therapy obtained a partial response. The median response duration was 3 months. Patients with a partial response did not live significantly longer than those who did not live significantly longer than those who did not respond. Toxic reactions were frequent: there were three episodes of sepsis secondary to leukopenia and two cases of bleomycin pulmonary toxicity. Mucositis was noted in 40% and nausea and vomiting in 60% of patients. We conclude that this triple-drug regimen has little value in the treatment of patients with advanced squamous cell carcinoma of the head and neck who have failed prior surgery and radiotherapy.

Adult↗