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Biomedical subjects

T M Kelly

Publications and source records attributed to T M Kelly.

At least 55 records · Page 3Linked to original sources

Classical conditioning of the eyeblink reflex in the decerebrate-decerebellate rabbit.

The purpose of these experiments was to test the hypothesis that a conditioned nictitating membrane reflex can be acquired in decerebrate rabbits in the absence of the cerebellum. Experiments examining the effects of large cerebellar lesions on the acquisition and performance of the conditioned reflex were performed in acutely prepared decerebrate rabbits. Most lesions encompassed all of the cerebellar nuclear regions ipsilateral to the eye receiving the unconditioned stimulus. In all rabbits included in this study the continuity between the cerebellar nuclei and the brainstem was interrupted, even in those preparations in which small regions of the nuclei were present in the lateral hemisphere. The findings demonstrate that these animals could acquire the conditioned reflex independent of whether conditioning had occurred prior to the cerebellectomy. Strong associativity was found between the latency of the conditioned response and the interstimulus interval between the conditioned and unconditioned stimuli. The behavior of the conditioned reflex observed in the decerebrate-decerebellate animals differed from that reported for awake intact rabbits in two ways. Once the conditioned behavior had been acquired, the percent of trials showing conditioned responses was somewhat less in decerebrate-decerebellate rabbits and was also more variable in these animals. The data demonstrate that the nictitating membrane reflex can be classically conditioned in the absence of the cerebellum, indicating that this structure is neither necessary nor sufficient for the acquisition of this type of conditioned behavior. In addition, an hypothesis is presented which addresses the difference between the data reported here and those previously reported by other laboratories based on observations in awake intact animals.

Animals↗

Predicting microbial growth: graphical methods for comparing models.

Some simple computer-based graphics were used to compare different models predicting microbial growth responses of salmonellae to three factors (pH, sodium chloride concentration and incubation temperature). Simple linear regression, contour and three-dimensional surface plots all revealed gross differences between the predicted growth parameters from different growth models. Regression and contour plots were found to be more sensitive to small differences in surface topography, but three-dimensional surface plots provided a good overview.

Computer Graphics↗

Kinematic analysis of the defense response in crayfish.

1. A threatening visual stimulus frequently elicits the defense response (DR) in crayfish, a behavior that comprises orienting the body to face the stimulus, raising the thorax, and extending and opening the claws. Although this behavior has been reported previously, its kinematics have not been characterized. This work employs kinematic analysis to provide a quantitative description of the claw (cheliped) as it is moved during the DR. 2. The cheliped was modeled as an open kinematic chain with three segments and 4 df. Simulations employing the model were compared with actual cheliped trajectories during the DR to ascertain the applicability of the model. The model was then employed to demonstrate the effects of individual joint rotations on the overall trajectory of the claw. 3. The individual segments of the cheliped were monitored during the DR, and spatial trajectories, tangential velocities, and intersegmental joint angles were calculated. 4. The joint angles assumed at the final position of the DR were highly stereotyped. This constancy in joint angle at the endpoint of the movement stands in contrast to the variability in both the angular and spatial trajectories of the cheliped as it was moved towards the final position. 5. Movement time was relatively constant. Larger amplitude movements were performed with a proportional increase in velocity similar to arm movements in primates. 6. The DR positions the cheliped in a fixed location in the workspace. Unlike the primate arm during reaching, the cheliped does not proceed towards the endpoint with a smooth controlled trajectory characteristic of a system with fine interjoint coordination. Instead, it appears that individual joint rotations are performed independently, thus precluding trajectory control although permitting an accurate specification of the endpoint.

Animals↗

Predicting microbial growth: the consequences of quantity of data.

Having developed a mathematical model of the growth responses in a laboratory medium of salmonellae (mixed inoculum of Salmonella thompson, S stanley and S. infantis) as affected by pH level, NaCl concentration and storage temperature, the consequences of systematic removal of data has been examined. Three-dimensional plots of fitted response surfaces for the whole data set and the data reduced by three strategies highlighted differences between models and illustrated the consequences of using insufficient data. The risk of an erroneous model was demonstrated.

Culture Media↗

Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal.

Activated charcoal usually provides effective and safe treatment for drug overdose. We describe a patient who developed bronchiolitis obliterans and respiratory failure following aspiration of activated charcoal. This patient had a markedly reduced vital capacity with roentgenographic evidence of airtrapping. Chest roentgenograms did not demonstrate the large amount of charcoal identified at postmortem examination.

Adolescent↗

Corticosteroids stimulate an increase in phospholipase A2 inhibitor in human serum.

A corticosteroid induced increase in a circulating inhibitor of serum phospholipase A2 activity is described. Inhibitor activity was found to be normally present in serum in agreement with the findings of other workers, and this activity was significantly increased by either acute or chronic administration of corticosteroids. The possible relation of this inhibitor to the known inhibitory effects of lipocortin and sphingomyelin on phospholipase A2 activity is briefly discussed.

Enzyme Inhibitors↗

An inexpensive, microcomputer-based system for recording movements in real time.

An inexpensive, microcomputer-based system was developed for recording movements in real time. The positions of 5 serially illuminated, infrared emitting diodes fixed on the object of interest were tracked by a remote, position-sensing photodiode. Positional information from the photodetector was digitized by an LSI 11/23+ microcomputer (sampling rate = 50/s/channel) and stored for subsequent analysis. Any microcomputer equipped to perform analog-digital conversion is compatible for use with this system. The small size of the components that are mounted on the animal allows movement to occur virtually unimpeded and makes this recording system especially suited for small animal observation.

Animals↗

Maximum respiratory pressures in morbidly obese subjects.

Maximum inspiratory and expiratory pressures were measured at residual volume, total lung capacity, and functional residual capacity in 45 morbidly obese patients who on average weighed 183% of their predicted weights. The pressures were compared to determinations made in 25 subjects of similar age whose mean weight was 99% of predicted. For both men and women, pressures generated by control subjects tended to be higher than those produced by obese patients but the differences were not statistically significant. The mean vital capacity and total lung capacity were also similar in the 2 subject groups. The results indicate that despite working constantly against a less compliant chest wall, obese patients do not increase their capacity to generate maximal respiratory pressures.

Adult↗

A self-controlled study of the effect of continuous subcutaneous insulin infusion on diabetic neuropathy.

Ten patients with poorly controlled type I diabetes mellitus and a documented complication of their disease were observed during 6 months of conventional diabetic management followed by 6 months of insulin infusion pump treatment and home blood glucose monitoring. Median nerve conduction velocity (NCV) was inversely correlated with the glycosylated hemoglobin (HbA1c) level at entry into the study (r = 0.71; P less than 0.05). The mean HbA1c value at the end of the conventional treatment period was 14.3% and fell to 10.1% by completion of the pump treatment period (P less than 0.0001). The median NCV was significantly greater at the completion of the infusion treatment period than it was at the end of the conventional management portion of the study. However, the rate of increase in NCV during the infusion period was not greater than the rate established during the prior treatment period. In addition, change in HbA1c levels during the pump treatment period did not correlate with change in conduction velocity for any of the nerves studies. These results from a self-controlled study of continuous subcutaneous insulin infusion indicate that improved blood glucose control without normalization of metabolic parameters is not sufficient to reverse the functional deterioration of large, fast-conducting nerve fibers that occurs in type I diabetes.

Adult↗

Sodium excretion and atrial natriuretic peptide levels during mineralocorticoid administration. A mechanism for the escape from hyperaldosteronism.

Urinary sodium excretion initially decreases when mineralocorticoid levels are increased, but if high plasma levels of hormone are maintained, sodium excretion rises to again equal sodium intake. To ascertain if atrial natriuretic peptide (ANP) plays a role in reestablishing sodium balance during mineralocorticoid ingestion, 0.3 to 0.5 mg per day of fludrocortisone were administered for 18 days to four healthy male subjects. The average daily intake of sodium was regulated at 180 +/- 2 meq. ANP levels rose from a mean of 91.7 +/- 13.0 pg/ml during the control week to 179.7 +/- 39.2 pg/ml during the final week on fludrocortisone (p less than 0.05). Urinary sodium excretion fell 27% immediately after fludrocortisone administration was initiated but returned to baseline levels in an average of 5 days. Levels of ANP, normalized for each subject to the mean of his control week values, correlated with the amount of sodium excreted in the subsequent 24 hours (p less than 0.05). Simultaneous with the rise in ANP values, levels of plasma renin activity (PRA) and aldosterone decreased. ANP concentrations throughout the study were inversely correlated with PRA and aldosterone levels (p less than 0.001 for both correlations). Values of serum osmolality and plasma arginine vasopressin did not change significantly during the study. The results obtained demonstrate that increased secretion of ANP is associated with escape from the sodium retaining effect of chronically high mineralocorticoid levels in man and suggest that ANP plays a prominent role in the mechanism of this escape.

Adult↗

Membrane association of soluble protein activators of rat liver adenylate cyclase. Evidence for distinctness from the guanine nucleotide-binding stimulating protein (Ns).

Sonication of a crude rat liver membrane preparation and centrifugation at 100,000 X g yielded a supernatant which activated basal and hormone-sensitive adenylate cyclases [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. The membrane origin of the stimulatory activity was confirmed by the use of lactate dehydrogenase as a marker for contamination by cytosol. The solubility of the activating factors was verified by their passage through 0.05 micron diameter pores of Millipore filters. The membrane-derived activators were nondialyzable and destroyed by heat and trypsin in the same manner as adenylate cyclase activators detectable in cytosol. Stimulation by factors from membranes and cytosol was not additive. The amount of the activators which could be freed from membranes by sonication was 12-15% of that contained in cytosol previously separated from the membranes. Soluble activators from the two sources had limited ability to restore adenylate cyclase activity to membranes from the cyclone of S49 mouse lymphoma cells which are deficient in the enzyme's guanine nucleotide-binding stimulatory protein, Ns. Cytosol did not contain a substrate for ADP-ribosylation by cholera toxin that corresponded electrophoretically to Ns. Furthermore, purified Ns did not affect adenylate cyclase activity in preparations stimulated by the soluble activators. These findings suggest that the activating factors found in cytosol may be released from membranes during tissue homogenization. Because these protein activators can be obtained from membranes without use of detergents and can neither substitute for nor be substituted for by Ns in functional assays, they are distinct from Ns.

Adenylyl Cyclases↗

Spirometry as a preoperative screening test in morbidly obese patients.

We performed spirometry on 114 morbidly obese patients considered for gastric bypass surgery to assess its efficacy as a preoperative screening test. One hundred eight subjects underwent surgery, and 61 patients returned for repeat spirometry 1 year later. The average preoperative forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and mid flow (FEF25-75%) were 100% of predicted. Spirometry identified no more of our obese subjects as abnormal than would have been identified in a group of healthy, nonobese individuals. Each surgical case was reviewed. An abnormal preoperative spirogram did not identify the patients who experienced postoperative complications. Weight loss was associated with very small increases in FVC (300 ml) and FEV1 (245 ml). Preoperative spirometric testing is not indicated in morbidly obese patients with no other identifiable risk factors for postoperative respiratory complications.

Adult↗

Changes in serum lipids after gastric bypass surgery. Lack of a relationship to weight loss.

Serum lipid levels were measured in 65 obese patients before and a mean of 13.4 +/- 0.2 months after gastric bypass surgery performed to facilitate weight reduction. The 58 women studied lost an average of 39.8 +/- 1.2 kg thereby reducing their mean body mass index from 41.9 +/- 0.7 to 26.8 +/- 0.6. Postoperatively, total cholesterol, LDL cholesterol, and triglyceride levels were significantly lower and HDL cholesterol levels significantly higher than preoperative values (for each of the four comparisons P less than 0.0001). Whereas before surgery 83 percent of the women had levels of total, LDL, or HDL cholesterol indicative of an increased risk of coronary heart disease, after surgery only 24 percent did so. Preoperative cholesterol abnormalities in the seven men were not as severe as were those in the women, and the men's postoperative cholesterol changes were not as marked. Correlations of the difference between pre- and post-operative weight and the difference between pre- and post-operative lipid levels showed that weight loss accounted at most for just 8 percent of the simultaneous lipid change. The data indicate that gastric bypass surgery for morbid obesity produces a favorable change in serum lipid profiles and suggest that the change is due primarily to factors other than the associated weight reduction.

Adult↗

Hypoxemia after gastric bypass surgery for morbid obesity.

Fifty-six patients who underwent Roux-en-Y gastrojejunostomy for morbid obesity had arterial blood gas analysis before surgery and during the first five postoperative days. Preoperatively, seven subjects were hypoxemic and three were hypercapneic. Twenty-four hours after gastric bypass, 75% of the patients had an arterial oxygen pressure (Pao2) less than 60 mm Hg. Compared with preoperative measurements, blood gas values on the first postoperative day showed a 13.7-mm Hg decrease in the mean arterial Pao2 and a 5.0-mm Hg increase in the mean arterial carbon dioxide pressure. Arterial Pao2 determinations on the third, fourth, and fifth postoperative days returned toward, but remained significantly less than, paired values obtained before surgery. Patients with hypoxemia after gastrojejunostomy were significantly older and had significantly lower preoperative arterial Pao2 measurements than patients who were not hypoxemic after surgery. Weight, body mass index, and preoperative spirometric measurements did not distinguish between those patients who did and did not become hypoxemic postoperatively. We conclude that hypoxemia commonly follows gastric bypass for morbid obesity, and thus we recommend that all patients undergoing this procedure be treated with supplemental oxygen for at least the first three postoperative days.

Adolescent↗

Ectopic beta-adrenergic receptors coupled to adenylate cyclase in human adrenocortical carcinomas.

The adenylate cyclase of an adrenocortical carcinoma of the rat is activated not only by ACTH but also by beta-adrenergic agonists, which bind to ectopic beta-adrenergic receptors not present in normal rat adrenal cortex. Previous reports examining possible beta-adrenergic control of adenylate cyclase in human adrenocortical carcinomas failed to demonstrate beta-adrenergic receptor-linked enzyme activity. We studied six human adrenal carcinomas and normal adrenal cortex from three subjects for beta-adrenergic agonist-sensitive adenylate cyclase and beta-adrenergic binding sites. Three of the six carcinomas had adenylate cyclase responses to both ACTH and beta-agonists. Two tumors were ACTH responsive but not beta-agonist responsive; one tumor responded to beta-agonists but not to ACTH. Adenylate cyclase activity of normal adrenal cortex from three subjects was stimulated by ACTH but not by beta-agonists. In membrane preparations from three tumors with beta-agonist-sensitive adenylate cyclase, the radiolabeled beta-adrenergic antagonist [125I]pindolol bound specifically and with high affinity (Kd = 38-83 pM) to a single class of binding sites which showed saturation with ligand concentration, reversibility of binding, pharmacological specificity, and stereospecificity. Normal cortex and one tumor without beta-adrenergic agonist-sensitive adenylate cyclase had no specific binding of [125I]pindolol. These results indicate that malignant transformation of adrenal cortex in man is frequently but not invariably associated with the appearance of ectopic beta-adrenergic receptors functionally linked to adenylate cyclase. Loss of ACTH-responsive adenylate cyclase may also occur simultaneously with the development of beta-adrenergic receptor-linked adenylate cyclase.

Adenylyl Cyclases↗

Effect of insulin infusion pump use on diabetic retinopathy.

Ten patients with insulin-dependent diabetes mellitus (IDDM) had fundus photographs and fluorescein angiograms obtained before and after a control period characterized by conventional insulin injections and a test period characterized by continuous subcutaneous insulin infusion (CSII). The mean glycosylated hemoglobin value at the end of the control period was 14.3% +/- 3.8% and decreased to 10.1% +/- 3.3% at the end of the test period. During the control period, none of the patients' eyes changed more than one grade in a modified Early Treatment Diabetic Retinopathy Study classification. All seven eyes without retinopathy at the start of the control period were still without retinopathy at its completion. One eye improved three grades during the test period, but four eyes, including two without retinopathy when CSII was initiated, progressed one grade. The data suggest that metabolic control that is improved but not normalized by CSII neither reverses retinopathy in IDDM nor prevents its development.

Adult↗

Thyrotoxic periodic paralysis in a black male.

The findings and course in a 55-year-old Black man with thyrotoxic periodic paralysis are described. This disorder appears to have a strong predilection for Orientals (approximately 90% of reported cases) with occasional reports in Caucasians and only one previous description in a Black. HLA phenotyping of the reported patient demonstrated neither of the two genetic markers previously noted among Chinese with thyrotoxic periodic paralysis, indicating that these haplotypes do not serve as markers for the disorder in Blacks.

HLA Antigens↗