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Biomedical subjects

M Hay

Publications and source records attributed to M Hay.

At least 73 records · Page 4Linked to original sources

Epithelial differentiation and intercellular junction formation in the mouse early embryo.

Trophectoderm differentiation during blastocyst formation provides a model for investigating how an epithelium develops in vivo. This paper briefly reviews our current understanding of the stages of differentiation and possible control mechanisms. The maturation of structural intercellular junctions is considered in more detail. Tight junction formation, essential for blastocoele cavitation and vectorial transport activity, begins at compaction (8-cell stage) and appears complete before fluid accumulation begins a day later (approx 32-cell stage). During this period, initial focal junction sites gradually extend laterally to become zonular and acquire the peripheral tight junction proteins ZO-1 and cingulin. Our studies indicate that junction components assemble in a temporal sequence with ZO-1 assembly preceding that of cingulin, suggesting that the junction forms progressively and in the 'membrane to cytoplasm' direction. The protein expression characteristics of ZO-1 and cingulin support this model. In contrast to ZO-1, cingulin expression is also detectable during oogenesis where the protein is localised in the cytocortex and in adjacent cumulus cells. However, maternal cingulin is metabolically unstable and does not appear to contribute to later tight junction formation in trophectoderm. Cell-cell interactions are important regulators of the level of synthesis and state of assembly of tight junction proteins, and also control the tissue-specificity of expression. In contrast to the progressive nature of tight junction formation, nascent desmosomes (formed from cavitation) appear mature in terms of their substructure and composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Real-time sector compression ultrasonography v. contrast venography in femoropopliteal thrombosis.

Compression ultrasonography with a 5 MHz sector transducer was compared prospectively with contrast venography in 61 patients for the diagnosis of deep-vein thrombosis (DVT) in the femoropopliteal segment (63 legs). The ultrasonographic procedure was found to be sensitive (84%) and specific (100%) in diagnosing femoropopliteal thrombosis. The results using a sector transducer are comparable with results obtained from the use of linear transducers. The wide availability of 5 MHz sector transducers in radiology departments makes compression ultrasonography a widely applicable alternative to contrast venography for diagnosis of DVT of the femoropopliteal segment. The procedure is less costly, less invasive and less time-consuming than contrast venography.

Adult↗

Entry of human immunodeficiency virus infection into a population of injecting drug users, Victoria, 1990.

OBJECTIVE: To investigate the pathway by which the human immunodeficiency virus (HIV) is entering populations of injecting drug users (IDUs) in Victoria. DESIGN: A retrospective case-control study comparing the prevalence of self reported risk behaviour in HIV-infected and uninfected Victorian IDUs. SETTING: Subjects were recruited by trained peer outreach workers from their personal networks, community agencies and Fairfield Hospital outpatients, and by a research worker from the major metropolitan prison. PARTICIPANTS: People who had been resident in Victoria for the past 12 months and had injected an illicit drug more than once in the previous three years were eligible to participate. Sixty-two such people (28 HIV-infected, 34 not infected) were included in the study. MAIN OUTCOME MEASURES: The two main hypothesised portals of entry were from the non-IDU homosexual population in Victoria, and from HIV-infected IDUs elsewhere. RESULTS: male homosexual contact was the most consistent risk factor identified by this study (odds ratio [OR], 6.2; 95% confidence interval [CI], 1.7-23.8). Having lived in or visited Sydney before 1986 was also associated with being infected with HIV (OR, 13.2; 95% CI, 1.5-603), and this was associated with homosexuality. Infected IDUs reported more sharing of injecting equipment than controls (OR, 9.0; 95% CI, 1.5-92.5), particularly with sexual partners; when this was the case, they were more likely to always use the injecting equipment after their partner (61% of cases, 0% of controls; OR, greater than or equal to 4.1; P = 0.0006). CONCLUSION: Men who have a history of both homosexual contact and injecting drug use represent the group of IDUs at highest risk of HIV infection in Victoria. Although heterosexual and homosexual IDUs may have limited contact only, a larger epidemic of HIV infection in heterosexual IDUs could spread from homosexual IDUs through the sharing of injecting equipment.

Adult↗

Chromatin motion in neuronal interphase nuclei: changes induced by disruption of intermediate filaments.

Motion of nucleoli within interphase nuclei, known as nuclear rotation, may be used as a measure of motion of chromatin domains within the global confines of the nucleus. Mechanisms by which chromatin domains are transposed remain enigmatic. It has been established that nuclei are anchored by a network of intermediate filaments, structural proteins which share epitopes with nuclear lamins and possibly representing a constraint on nuclear rotation. It is postulated that selective removal of this constraint, by acrylamide, would result in increased chromatin motion. Mean rates of nucleolar displacement were quantified in neurons, in vitro. Nuclear rotation increased from a mean control rate of 0.102 +/- 0.002 micron/min (n = 52) to a maximum mean rate of 0.207 +/- 0.026 micron/min (n = 11), after 23 hr of exposure to 4 mM acrylamide. Despite this significant increase in motion of intranuclear domains, cytoplasmic structures in the immediate juxtanuclear area did not exhibit increases in rates of motion. Immunocytochemistry was used to visualize cytoskeletal structures and to assay selective disruption of neurofilaments by acrylamide. Increased rates of chromatin motion coincided with breakdown of the intermediate filament network. Ultrastructural analyses showed that the increase in chromatin motion induced by acrylamide was also associated with a significant (P less than 0.005) change in the thickness of the nuclear lamina, decreasing from 20.9 +/- 5.10 nm (n = 159) in controls to 18.9 +/- 3.1 nm (n = 148), to 19.5 +/- 3.6 nm (n = 240) and to 16.1 +/- 4.4 nm (n = 103) at 4, 8 and 22 hr exposure, respectively. Moreover, the number of mitochondria per unit area changed significantly (P less than 0.0001) with exposure to acrylamide, increasing from 9.1 +/- 2.2 mitochondrial profiles in controls to 16.5 +/- 5.3 profiles after 22 hr exposure to acrylamide. Distribution of other cytoskeletal components, actin and microtubules, was not altered and does not appear to play a significant role in the observed increase in rates of nuclear rotation. We conclude that the removal of the damping effects on chromatin motion normally imposed by the nuclear lamina and by intermediate filaments results in increased chromatin motion.

Acrylamide↗

Strategic staircases: planning the capabilities required for success.

Creating an adequate supply of the requisite skills and competitive capabilities is a fundamental objective of strategy. Managing this process in an effective and systematic manner is difficult. Employing the strategic staircase is a proven way of overcoming this difficulty. The framework enables managers to break the strategic agenda into bit-sized pieces, it guides the selection of priorities and provides a powerful device for communicating strategy throughout the organization, thereby bridging the gap between strategy and action.

Decision Making, Organizational↗

Ligand affinity of the 67-kD elastin/laminin binding protein is modulated by the protein's lectin domain: visualization of elastin/laminin-receptor complexes with gold-tagged ligands.

Video-enhanced microscopy was used to examine the interaction of elastin- or laminin-coated gold particles with elastin binding proteins on the surface of live cells. By visualizing the binding events in real time, it was possible to determine the specificity and avidity of ligand binding as well as to analyze the motion of the receptor-ligand complex in the plane of the plasma membrane. Although it was difficult to interpret the rates of binding and release rigorously because of the possibility for multiple interactions between particles and the cell surface, relative changes in binding have revealed important aspects of the regulation of affinity of ligand-receptor interaction in situ. Both elastin and laminin were found to compete for binding to the cell surface and lactose dramatically decreased the affinity of the receptor(s) for both elastin and laminin. These findings were supported by in vitro studies of the detergent-solubilized receptor. Further, immobilization of the ligand-receptor complexes through binding to the cytoskeleton dramatically decreased the ability of bound particles to leave the receptor. The changes in the kinetics of ligand-coated gold binding to living cells suggest that both laminin and elastin binding is inhibited by lactose and that attachment of receptor to the cytoskeleton increases its affinity for the ligand.

Actin Cytoskeleton↗

Nuclear maturation of domestic cat ovarian oocytes in vitro.

Using the domestic cat as a model for salvaging genetic material from rare Felidae, we collected oocytes from ovarian tissue and placed them in 1 of 3 treatments to observe time-related, meiotic changes of in vitro oocyte maturation. Oocytes obtained from ovaries collected at ovario-hysterectomy were assigned to 1 of 3 treatment groups: 1) modified Krebs-Ringer bicarbonate buffer (mKRB) + 4% BSA and 5 micrograms/ml FSH (+FSH, n = 499); 2) mKRB + 4% BSA (-FSH, n = 502); or 3) mKRB + 5% natural estrus cat serum (NE, n = 873). They were placed in the respective media in a 5% CO2 humidified environment at 38 degrees C. Beginning at 16 h, oocytes were removed at 4-h intervals through 48 h, and the meiotic status was evaluated by means of cytogenetic analysis. On the basis of chromosomal analysis, each cell was placed into one of the following categories: metaphase II (MII); metaphase I (MI); pre-MI (germinal vesicle [GV], GV breakdown, or diakinesis); degenerate or unidentifiable. The percentage of oocytes with degenerate chromatin increased over time in all culture treatments, but was always greatest (p less than 0.05) in the NE group. In the +FSH and -FSH treatments, the proportion of oocytes with nuclear material reaching MII increased with time in culture to 32 h and was equal to or greater than the proportion of oocytes with pre-MI + MI chromatin at this time interval (-FSH, 55%; +FSH, 38%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of baroreceptor afferents on area postrema-induced inhibition of sympathetic activity.

Activation of the area postrema by either electrical stimulation or chemical application of L-glutamate has been shown to result in an enhancement of cardiovascular baroreflexes similar to that seen with systemic infusions of arginine vasopressin (AVP). In addition, it has been found that the effects of AVP on baroreflex inhibition of renal sympathetic nerve activity (RSNA) are similar to those observed with phenylephrine following lesions of the area postrema or after partial denervation of baroreceptor afferents. The present study was undertaken to determine the role of baroreceptor afferent input on area postrema stimulation-induced decreases in sympathetic activity. In anesthetized rabbits, the responses of arterial pressure, heart rate, and RSNA to area postrema electrical stimulation were obtained before and after progressive sinoaortic denervation and vagotomy. Stimulation of the area postrema in carotid sinus-denervated animals consistently decreased RSNA in a frequency-dependent manner. However, following bilateral removal of both the aortic nerves and the vagi, electrical stimulation of the area postrema had no effect on RSNA. These results suggest that the ability of area postrema stimulation to inhibit RSNA is dependent on the presence of baroreceptor afferent input.

Afferent Pathways↗

Effects of area postrema stimulation on neurons of the nucleus of the solitary tract.

Previous studies have suggested that neurons of the area postrema may modulate cardiovascular function through an interaction at the level of the nucleus of the solitary tract (NTS). Using an in vitro brain slice preparation of the rabbit medulla, the present study investigated the electrophysiological and pharmacological effects of area postrema stimulation on NTS neuronal activity. In the majority of neurons tested (85.7%), electrical stimulation of the area postrema consistently produced either single or multiple action potentials in NTS neurons. Latency values for neurons showing single spike responses to area postrema stimulation ranged from 3.0 to 17.0 ms with an average latency of 9.3 +/- 4.3 ms. The average threshold for area postrema activation of these nonspontaneously active NTS neurons was 99.8 +/- 12 microA with a stimulus threshold range between 15 and 200 microA (n = 53). Perfusion of the slice with phentolamine (1.0 microM) or yohimbine (200 nM) blocked the area postrema-evoked action potentials, whereas perfusion of the slice with prazosin (200 nM) had no effect. These findings suggest that area postrema neurons do modulate NTS neuronal activity and that this modulation results in an increase in NTS neuronal activation.

Afferent Pathways↗

Interactions of area postrema and solitary tract in the nucleus tractus solitarius.

The nucleus tractus solitarius (NTS) receives information from both area postrema (AP) and peripheral afferents. It is, therefore, one likely site of interaction between AP and peripheral afferent fibers. The present study's purpose was to determine the influence of AP stimulation on solitary tract-induced modulation of NTS neuronal activity. With the use of an in vitro rabbit brain slice preparation, extracellular recordings were made from 58 NTS neurons in which action potentials were evoked by both solitary tract and AP stimulation. In the majority of the cells tested, simultaneous stimulation of solitary tract and AP, at voltage levels that evoked no action potentials when stimulated separately, resulted in production of either single or multiple action potentials. In 27 units, stimulation levels to the solitary tract and to the AP were adjusted such that their respective separate stimulations produced an NTS action potential less than 30% of the time. When the two inputs were stimulated together, simultaneous stimulations produced an NTS action potential 100% of the time, suggesting a facilitatory interaction between the AP and the solitary tract on NTS neuronal activity. In nine cells, perfusion of the slice with clonidine induced a facilitation of solitary tract-evoked NTS response to a level similar to that seen during simultaneous stimulation of the solitary tract with the AP. Application of the alpha 2-adrenergic receptor antagonist yohimbine blocked the ability of both clonidine and AP to facilitate the solitary tract-evoked response. These results support a possible interaction between AP and peripheral afferents and suggest that AP stimulation facilitates effects of solitary tract activation at the level of the NTS.

Action Potentials↗

Superficial microwave-induced hyperthermia in the treatment of chest wall recurrences in breast cancer.

Our study concerns 42 patients with chest wall recurrences from breast cancer: 17 Stage 1 (less than 4 cm in diameter), 11 Stage 2 (more than 4 cm), seven Stage 3 (skin ulceration whatever tumor size), and seven Stage 4 (neoplastic lymphangitis and/or skin nodules covering chest wall beyond midline). All the patients were treated with 2450 MHz microwaves by means of a generator with 4 magnetrons (250 to 300 W) and arterial applicators delivering 5 to 10 W/cm2. Each applicator is coupled with an infrared thermometer allowing an atraumatic temperature control processed by a PC-compatible computer using a Turbo Pascal program. A temperature of 41.5 degrees C to 42.5 degrees C was maintained for 45 minutes from the skin surface to a 2.5-cm depth within tissues. Hyperthermia alone was done in four patients; hyperthermia was combined with chemotherapy in four patients, and with electrontherapy (2 X 450 cGy or 3 X 350 cGy/week) in 34 patients: tumor dose under 3000 cGy in seven patients and over 3000 cGy in 27 patients. We observed a complete response in 22 patients (52.3%), a partial response (greater than 50%) in 11 patients (26.1%), and no response in nine patients (21.4%). No complete response was observed in patients treated with hyperthermia alone or in conjunction with chemotherapy. The local control was demonstrated to be improved only in patients treated with hyperthermia and radiotherapy. The results were correlated with tumor stage: ten complete responses out of 12 Stage 1, and one complete response out of four Stage 4. We noted nine side effects completely reversible within a month with no late skin reaction. Our results show that hyperthermia can give improved local control without any morbidity in treating chest wall recurrences of breast cancer.

Adult↗

Anticipatory wheel-running in behaviorally anosmic rats.

Rats rendered behaviorally anosmic by the intranasal infusion of zinc sulfate were placed on a single daily meal, 2 hr in duration. Anosmic rats and controls showed a similar degree of wheel-running anticipatory to the meal. It was concluded that the stimulus for entrainment of meal-associated rhythmicity is not olfaction and that other characteristics of food intake need to be systematically investigated.

Animals↗

Renal excretion of enteral gastrografin in the absence of free intestinal perforation.

The renal excretion of orally administered water-soluble contrast medium has been described in intestinal perforation (Mori and Barret, 1962). We present a case in which orally administered Diatrizoate methylglucamine (Gastrografin, Schering) was detected in the renal collecting system on computed tomography in a man with an ischaemic segment of small bowel associated with abscess formation but no evidence of intra-peritoneal perforation.

Adult↗

Neurons in area postrema mediate vasopressin-induced enhancement of the baroreflex.

Intravenous infusion of arginine vasopressin (AVP) has been shown to enhance baroreflex sensitivity, and this enhancement is dependent on the integrity of the area postrema. However, previous studies did not differentiate a role for cell bodies in the area postrema vs. the dense network of fibers located in and around the lateral and ventral margins of this circumventricular organ. In the present study, baroreflex function was assessed in conscious rabbits by examining heart rate after ramp infusions of phenylephrine (PE) and AVP. The subsequent day, the excitotoxin kainic acid was injected (30 nl initially, with five 15-nl supplemental injections of a 1 ng/nl solution over 1 h) into the area postrema, thus selectively destroying cell bodies. After an 8-day recovery period, baroreflex function was again assessed. The bradycardic response to graded infusion of PE (slope = -2.29 +/- 0.30) was not significantly different after selective lesions of area postrema neurons (slope = -1.88 +/- 0.49). In contrast, the previously enhanced bradycardic response to infusion of AVP (slope = -5.76 +/- 1.02) was significantly attenuated (slope = -2.31 +/- 0.21) to levels similar to that seen with infusion of PE. Thus selective chemical lesions of area postrema neurons block vasopressin-induced enhancement of the baroreflex.

Animals↗

Membrane plasma fractionation: effect of the surface area.

The influence of the surface area on the performance of plasma filters for dead-end mode of filtration is presented in this paper. Theoretical analysis of the dead-end filtration was performed and verified experimentally (using ENKA cellulose-diacetate PF-100 membranes) in respect to beta-lipoprotein. The theoretical model allows to optimize the course of the transmembrane pressure during plasma fractionation procedure in dependence of the surface area, initial concentration of macromolecules, total volume of the feed and membrane structure. The results indicate that the surface area effect is an important factor in the operation of membrane plasma fractionation and should be considered in the design of the plasma fractionation filter.

Blood Volume↗

Modulation of cerebellar granule cell activity by iontophoretic application of serotonergic agents.

Serotonergic fibers have been identified within the granule cell layer of the cerebellar cortex; however, their functional significance has not been identified. In this study the effect of serotonin on granule cell spontaneous activity was determined in the rat cerebellum. Of the 136 granule cells tested, 44.8% displayed a decrease in firing rate, 21.3% increased firing rate and 33.8% were not affected. The serotonin-induced changes in activity were not blocked by bicuculline or methysergide. The serotonin agonist 1,3 (trifluoromethylphenyl) piperazine mimicked the serotonin-induced suppressive response. Iontophoretically applied serotonin was also found to modulate GABA-induced suppression of granule cell activity. The variable effects of serotonin on spontaneous activity suggests the presence of more than one type of serotonergic receptor in the cerebellar granule cell layer.

Animals↗