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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 307 records · Page 17Linked to original sources

Factors related to the nocturnal worsening of asthma.

The nocturnal worsening of asthma is a very common problem, yet little is known about the relationships between the nocturnal worsening and daytime lung function, methacholine bronchial responsiveness, the degree of the circadian variability in bronchial responsivity, and the nocturnal sleep pattern. This study demonstrates in 20 asthmatic patients that the overnight fall in the peak expiratory flow rates (PEFR) is related to the severity of daytime airflow limitation (r = 0.73, p less than 0.001) and daytime bronchial responsiveness (r = 0.48, p less than 0.05). In individuals with larger overnight decrements in PEFR, bronchial responsivity at 0400 h is so great that normal saline inhalation alone can produce a greater than 20% fall in the FEV1. Sleep quality and sleep staging are not correlated to the change in the PEFR. Thus, the overnight decrement in asthmatic lung function is related to the daytime severity of asthma as determined by daytime measurements of airflow limitation and bronchial responsiveness as well as the circadian variation in bronchial responsivity.

Adult↗

Effects of spontaneous and simulated gastroesophageal reflux on sleeping asthmatics.

We examined the effect of intraesophageal acid (either spontaneous gastroesophageal reflux or infused) on airflow resistance in 15 sleeping asthmatic subjects. We observed no significant acute or sustained changes in airflow resistance relative to periods of intraesophageal acid. Overnight changes in spirometry and lower airway resistance also demonstrated similar nocturnal worsening of bronchoconstriction despite the occurrence of spontaneous or simulated gastroesophageal reflux. The presence or absence of clinical evidence of esophagitis (Bernstein test response) did not alter the observed lack of response to intraesophageal acid. We conclude that gastroesophageal reflux contributes little to the nocturnal worsening of asthma.

Adult↗

Circadian basis of the late asthmatic response.

The late asthmatic response (LAR) to an allergen challenge has a marked impact on lung function in the patient with asthma. Virtually all studies on the LAR have been done during the daytime. This study evaluated the LAR as a function of the time of day an inhaled allergen challenge was performed. An allergen challenge given in the morning produced a LAR in 4 of 10 subjects, while the same challenge in the evening caused a LAR in 9 of 10 (p less than 0.05). The time to onset of the LAR following the morning and evening challenges was 9.4 +/- 2.0 h versus 3.1 +/- 0.3 h, respectively (p less than 0.05). The maximal decrease in FEV1 for the LAR was 32.8 +/- 5.6% for the morning challenge versus 43.0 +/- 3.1% in the evening (p less than 0.05). Additionally, the bronchial responsiveness to methacholine was significantly greater at 24 h following evening allergen challenge than after the morning (p less than 0.05) challenge. Thus, it is important to take into account the time of day a patient is exposed to an allergen in regard to the development of the LAR.

Adult↗

Psychiatric symptoms associated with Alzheimer's disease.

A retrospective chart review was undertaken to assess the prevalence of specifically defined psychiatric symptoms in 217 outpatients with clinically probable Alzheimer's disease. A weak but significant correlation was found between Alzheimer's disease and suspiciousness and paranoia (reported by 35.5% of patients), delusions (30%), and formed visual hallucinations (18.4%). Mild depressive symptoms, such as sad affect, hopelessness, and helplessness were reported by 40.6% of patients, anxiety and fearfulness by 30.9%, and aggressive acts by 24.9%. Psychotropic medications used to manage these symptoms included antipsychotics, in 11.5% of patients, anxiolytics, in 9.2%, and antidepressants, in 7.4%.

Activities of Daily Living↗

A patch-clamp study of acetylcholine-activated ion channels in Ascaris suum muscle.

Acetylcholine-activated single-channel currents were recorded from cell-attached and inside-out patches of isolated muscle vesicles from Ascaris suum. Acetylcholine (1-10 mumols l-1) activated cation-selective channels of two amplitudes: 40-50 pS and 25-35 pS. Both channels had linear I/V relationships and mean open durations independent of voltage. The larger conductance was analysed in detail to determine its open-, closed- and burst-time kinetics; the open and burst durations were composed of two components (short and long), while closed durations had at least three components (short, intermediate and long). The data were then corrected to allow for missing short events in order to estimate various parameters including corrected mean open time (1.26 + 0.11 ms, mean +/- S.E.). Values were also derived for the efficacy (beta/alpha = 4.9) and affinity [1/KD = 147 x 10(3) (mol l-1) -1] of acetylcholine at this receptor. Larger concentrations of acetylcholine (25-100 mumols l-1) were shown to produce desensitization and caused single-channel currents to occur in clusters with long closed times (mean 171 s) between clusters. It was concluded that the extrasynaptic muscle of Ascaris suum contains two types of acetylcholine-activated ion channel and these are possible sites of action of various anthelmintic drugs. This paper is the first to describe acetylcholine-activated single-channel currents in invertebrate muscle.

Acetylcholine↗

The present and the future of AIDS and tuberculosis in Illinois.

The relation between the acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) was examined by matching the Illinois AIDS and TB registries. The match group was examined and compared with patients with only one disease by race, method of human immunodeficiency virus (HIV) transmission, site of tuberculous disease, radiographic findings, and results of Mantoux tests. The time of TB diagnosis was centrally distributed around the time of AIDS diagnosis; from this, it was determined that 4.1 percent of AIDS patients develop active TB. Projections for future AIDS cases were made by fitting a polynomial model to historical data. These projections were then used to predict the future impact of AIDS-related TB upon state TB rates. The rise in TB rates call for special efforts to minimize this impact.

Acquired Immunodeficiency Syndrome↗

Recombinant tumor necrosis factor-alpha chronically administered in rats: lack of cachectic effect.

Recombinant human tumor necrosis factor-alpha (rHuTNF) was injected into rats to test its reported cachectic effects. Rats were subcutaneously injected daily at 1730 hr with either saline or rHuTNF (0.25 mg/kg body wt) for either 5 or 14 days. Daily food intakes were significantly depressed only for the first day and first two days of rHuTNF injection in animals treated for 5 days and 14 days, respectively. There were no significant differences in daily body weights among the groups. Analysis of carcass composition revealed no significant differences in percentage of lipid or protein. Liver and inguinal pad weights were not significantly different. In vitro determination of lipogenesis showed it was enhanced in the inguinal pad and depressed in the liver only after 14 days of treatment. These results demonstrate that although in vivo rHuTNF may specifically alter tissue metabolism, it does not, by itself, result in a sustained cachectic effect.

Adipose Tissue↗

Surface properties of membrane vesicles prepared from muscle cells of Ascaris suum.

To facilitate biochemical, pharmacological, and biophysical studies on the membrane of the body muscle of Ascaris suum, a method for preparing intact vesicles was developed. Vesicles were prepared by incubating a muscle flap preparation with 1 mg/ml collagenase in a saline solution and then washing in saline without enzyme. The vesicles then formed gradually over the next hour as outgrowths of the original surface membrane from the bag region of the muscle. The vesicles were harvested readily by suction using a Pasteur pipette. The structure of the vesicles was examined with the transmission electron microscope. The whole-cell patch-clamp technique showed that the vesicles had a high input resistance and that the membrane was complete. The vesicle membrane was shown to contain Ca-activated Cl channels and gamma-aminobutyric acid-activated Cl channels. The vesicles also were shown to be suitable for fluorescence recovery after photobleaching studies designed to examine lateral and vertical movement of a lipid probe (5-N [octadecanoyl]-aminofluorescein) in the membrane. This probe had a mean lateral diffusion coefficient (DL) of 8.1 x 10(-9) cm2/sec, but only a proportion (68.4%) of the probe was mobile. The latter observation illustrated the nonuniform nature of the membrane. Ivermectin (10(-7) M) had no effect on DL or percent recovery. Trypan blue quenching experiments showed that the lipid probe remained in the outer monolayer of the membrane. These observations illustrate the experimental value of the vesicles; they are potentially useful in discerning anthelmintic mode of action and in drug screening.

Animals↗

Microassay for N-acetyltransferase activity using high-performance liquid chromatography with electrochemical detection.

A rapid, sensitive procedure has been developed for determination of N-acetyltransferase activity against octopamine, dopamine and 5-hydroxytryptamine. The assay, which is performed in a volume of 10 microliters, is based upon the separation and detection of monoamine substrates and their N-acetylated derivatives using high-performance liquid chromatography with electrochemical detection. The method has been used to measure N-acetyltransferase activity against octopamine, dopamine and 5-hydroxytryptamine in the cerebral ganglion of the American cockroach, Periplaneta americana and to study bi-substrate kinetics of the enzyme.

5-Hydroxytryptophan↗

High-frequency jet ventilation in neonatal pulmonary hypertension.

To determine if high-frequency jet ventilation is beneficial in neonates with persistent pulmonary hypertension, we compared the ventilator settings, blood gas concentrations, and outcome of infants who met established criteria for a high predictive mortality. During a six-year period, 14 neonates who had severe respiratory failure and hypoxemia while receiving conventional ventilation were treated with high-frequency jet ventilation. Twenty-three comparable infants meeting the same criteria were treated exclusively with conventional ventilation. After initiation of high-frequency jet ventilation there was a significant reduction in mean airway pressure and partial pressure of arterial carbon dioxide (PaCO2). In contrast, neonates treated exclusively with conventional ventilation continued to have higher airway pressures and PaCO2. However, there was no difference in the alveolar-to-arterial oxygen gradient, air leakage, incidence of bronchopulmonary dysplasia, or duration of assisted ventilation or oxygen supplementation. Furthermore, mortality was comparable in both groups of infants. These preliminary observations suggest that high-frequency jet ventilation can reduce airway pressure and PaCO2 in neonates with persistent pulmonary hypertension but does not appear to improve outcome.

Carbon Dioxide↗

The effect of increased adiposity on food intake of juvenile rats.

The regulation of feeding by body adiposity, as proposed by the lipostatic theory, has been well demonstrated in adult animals. However, mechanisms controlling long-term feeding in juvenile animals have not been well defined. In this study, increased adiposity was induced in young rats through oral gavage. Four-week-old rats were divided into three groups; ad lib feeding (100%-AL), tubefed 100% (100%-TF) or 150% (150%-TF) of ad lib intake. Animals were tube-fed these levels for one week. At the end of this period, one third of each group were killed and all remaining animals were returned to ad lib feeding for either 4 or 29 days later. During this recovery period, the 150%-TF group had significantly depressed food intakes for the first 4 days in comparison to the 100%-TF group. Afterwards, there were no significant differences between these two groups for the remainder of study. Overfeeding induced significant increases in total body fat in the 150%-TF group (24.8 grams) in comparison to the 100%-AL group (11.0 grams) and the 100%-TF group (14.0 grams). By day five of recovery, only the 150% group exhibited a significant loss of body fat. Total carcass protein and ash were not different between groups at any period. At day 29 of recovery, there were no treatment differences in carcass weight or fat content. Loss of body fat from the 150%-TF rats was associated with the decline in caloric intake. It appears that food intake is affected by relative adiposity during the dynamic phase of growth.

Adipose Tissue↗

Relationships between sustained sucrose-feeding and opioid tolerance and withdrawal.

This study examines the effect of sustained sucrose consumption on the development of tolerance to morphine analgesia (20 mg/kg IP injections) and subsequent, naloxone-precipitated withdrawal (2 mg/kg IP). Food intakes are also measured. Sprague-Dawley rats were allowed ad lib access to a 20% sucrose solution in addition to their normal diet. Pain thresholds and intakes were monitored for two weeks, then morphine tolerance was induced, followed by precipitated withdrawal. Tolerance was assayed by the tailflick method, and withdrawal was gauged by weight loss. The animals given access to sucrose developed lowered pain thresholds prior to tolerance induction relative to those of control animals, but they failed to exhibit any differences from controls in tolerance development of severity of withdrawal. The induction of tolerance first decreased, then increased sucrose consumption and steadily decreased chow consumption. Naloxone-precipitated withdrawal decreased chow consumption, but failed to affect the ingestion of the sucrose solution. It is concluded that changes in opioid function caused by sustained sucrose-feeding are insufficient to affect the development of tolerance to morphine analgesia; however, tolerance induction biphasically alters sucrose consumption.

Analgesia↗

A cryogenic device for reversibly blocking transmission through small regions of the spinal cord white matter.

A simple cryogenic device is described. This device is capable of cooling neural tissue in contact with the probe and maintaining the tissue at the desired temperature for extended periods of time. The cold probe can thereby reversibly block neural transmission through small portions of the spinal cord white matter. Interruption of axonal transmission is achieved by placing the tip of the device in contact with the exposed surface of the spinal cord and cooling the tip of the probe to -1 to +2 degrees C. The investigator monitors the tip temperature and adjusts the pump rate to maintain a constant tip temperature. The cross-sectional area under the probe where effective transmission block is achieved is about 1.5 mm2 which approximates the size of a single funiculus in the cat thoracic spinal cord. The cryogenic device was constructed for less than $700. The properties of this device were studied in physiologic experiments in cats. This device reversibly, selectively and repeatedly blocked the ascending mass action potential in the dorsolateral funiculus, transmission through ascending spinal axons in the dorsal columns, transmission through axons of spinal dorsal horn cells, the descending inhibitory input to the dorsal horn and the activity of thalamic nociceptive neurons. The reversible cold block effects on single units were observed for the duration of the experiments (up to 18 h) with no detectable damage to the underlying tissue. The physiologic effects of the cold block were usually reversed a few minutes after rewarming, although in some cases it took up to 40 min for the complete reversal of the cold block. This cryogenic device is useful for studying spinal cord pathways.

Animals↗

The influence of human growth hormone on preadipocyte development in serum-supplemented and serum-free cultures of stromal-vascular cells from pig adipose tissue.

The influence of human growth hormone (hGH) on the differentiation of preadipocytes was examined in primary cultures of stromal-vascular (s-v) cells from porcine adipose tissue. In these experiments, cells were exposed to test media for 7-8 days after seeding and plating for two days in fetal bovine serum. In serum-free (insulin, transferrin and selenium) cultures hGH (1 and 10 nM) reduced the number and size of fat cell clusters (P less than .05) by 50% relative to controls (no hGH). Differentiation of preadipocytes was assayed by labelling dividing cells with tritiated thymidine under identical conditions and then exposing cultures to test media for seven days. Fat cells were then separated from the other cells and radioactivity was determined in each fraction. In serum containing (2% pig serum) cultures hGH (10 nM) inhibited (P less than .05) the differentiation of labelled preadipocytes. In cultures with serum and with 1 microM insulin and in serum-free cultures, 1 and 10 nM hGH reduced (P less than .05) the levels of glycerol phosphate dehydrogenase (GPDH) specific activity by approximately 50%. However, hGH (1 and 10 nM) had no affect on GPDH activity in cultures with serum but without insulin. These studies indicate that hGH significantly impedes porcine preadipocyte development in vitro. Therefore, the decreased rate of adipose tissue growth observed in pigs chronically treated with GH could be due in part to impaired preadipocyte growth.

Adipose Tissue↗

Evidence for abnormal prostaglandin synthesis in obese Zucker rat adipose cell cultures.

Prostaglandin E2 (PGE2) is synthesized in adipose tissue and acts locally to inhibit lipolysis. This study examined PGE2 synthesis by presumptive and mature adipocytes isolated from lean and obese Zucker rats. Isoproterenol-stimulated lipolysis was greater in short-term incubations of mature adipocytes isolated from lean rats than in those from obese rats in terms of both sensitivity (lean 10(-7) M vs. obese 10(-6) M) and magnitude of response (five-fold greater in lean at 10(-6) M). Prostaglandin E2 synthesis was dose-dependent in isoproterenol-stimulated adipocytes from lean rats, while PGE2 synthesis in adipocytes from obese rats was not altered, regardless of treatment. Primary cell cultures of presumptive adipocytes from both phenotypes released PGE2 in response to lipolytic compounds, however, cultures from obese rats had lower PGE2 release rates than cultures from lean rats. In addition, compared to cultures derived from lean rats, a greater degree of adipocyte differentiation in cultures from obese rats was associated with lower basal PGE2 synthesis. These results suggest that an impairment in the ability of adipocytes isolated from obese Zucker rats to enzymatically synthesize PGE2 accompanies maturation.

Adenosine Deaminase↗

A patch-clamp study of effects of dihydroavermectin on Ascaris muscle.

1. Effects of bath-application of the anti-parasitic agent 22,23-dihydroavermectin B1a (DHAVM 20 fM to 0.2 microM) on outside-out and inside-out patches from collagenase-treated muscle membranes of Ascaris suum were examined. 2. DHAVM was tested as a gamma-aminobutyric acid (GABA) agonist by application to outside-out patches. DHAVM failed to open characteristic GABA channels even when high concentrations (20 nM to 0.2 microM) were used. These high concentrations of DHAVM also failed to potentiate opening of channels activated by application of 3-4 microM GABA; instead they acted to depress GABA-activated channel currents by reducing mean conductances and P open. 3. In outside-out patches, low concentrations of DHAVM (1 pM to 100 pM) produced opening of 0-13 channels, the number depending on the patch. The progressive opening of channels gave rise to a 'Staircase' effect. The conductance of these channels was 9-15 pS and open times were long (greater than 100 mS). Ion substitution experiments showed these channels to be permeable to Cl. The channels were not blocked by 20 microM picrotoxin. There was a long delay (greater than 15 s) between DHAVM application and channel opening; this delay and lipophilic nature of DHAVM suggested a site of action in the lipid phase of the membrane. 4. The effect of bath-application of low concentrations of DHAVM on inside-out patches was investigated under low-Ca conditions (to avoid Ca-activated Cl channels). DHAVM (20 fM to 1 nM) did not produce opening of Cl channels but produced opening after a long delay (mean 2.5 minutes) of noisy cation-selective channels which had conductances of 5-30 pS. 5. The actions of DHAVM are discussed.

Animals↗

Increased GABA shunt activity in VMN of three hyperphagic rat models.

Metabolic signals have been proposed as controls of energy balance. Glucose utilization for gamma-aminobutyric acid (GABA) synthesis was evaluated in diet-restricted and streptozotocin-diabetic rats. Rates for glucose flux through the GABA shunt and glutamate decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis, were measured in ventro-medial nucleus (VMN) and lateral hypothalamic (LHA) homogenates. Rates of GAD activity were elevated in the VMN of both restricted and diabetic rats but did not change in the LHA of either model. The rate of glucose flux through the GABA shunt in the VMN was increased in restricted rats but were decreased in the VMN of diabetic rats. Restricted rats allowed to feed ad libitum initially ate 160% of the amount the control rats ate. GAD activity rates in the VMN returned to near control levels after 2 days of refeeding. Obese Zucker rats (fa/fa) also had higher rates of GAD activity and glucose flux through the GABA shunt in the VMN but not in the LHA. The increased rate of GABA synthesis may represent increased GABAergic activity in the VMN and may possibly be involved in feeding behavior and energy balance.

Animals↗

Site of action of putative lipostatic factor: hypothalamic metabolism of parabiotic rats.

Studies were conducted to determine whether metabolic adaptation occurred in the hypothalamus of overfed parabiotic rats and their partners to distinguish between the adaptations caused by increased caloric intake and those caused by the production of a "lipostatic factor." The induction of overfed obesity in one parabiotic partner was employed to test the hypothesis that a putative lipostatic factor produced in the obese parabiotic elicited the hypophagic-lipid-mobilizing effect observed in the lean parabiotic via alterations in hypothalamic fatty acid and glucose metabolism. Fatty acid oxidation in the ventrolateral hypothalamus (VLH) of overfed parabiotic rats and their partners was lower than in ad libitum parabiotic rats. Net flux of glucose through the VLH gamma-aminobutyric acid (GABA) shunt was elevated in overfed parabiotic rats compared with the net flux observed in their partners and ad libitum parabiotic rats, the levels being similar in these last two groups. Net flux of glucose through the ventromedial hypothalamic (VMH) pentose shunt in overfed parabiotic rats and their partners was elevated relative to ad libitum parabiotic rats. The putative lipostatic factor may act to regulate energy balance through modification of VLH fatty acid oxidation and/or glucose flux via the VMH pentose shunt.

Animals↗