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Biomedical subjects

D M Smith

Publications and source records attributed to D M Smith.

At least 361 records · Page 20Linked to original sources

A comparative study of generic stains for carcinoid secretory granules.

Generic stains for secretory granules in carcinoid tumors often yield inconsistent and unpredictable results. Consequently, these techniques have been modified and new ones devised; however, very few studies comparing the efficacy of the various methods have been published. To determine which method would most consistently demonstrate carcinoid granules, we applied a battery of six stains to 73 tumors, all morphologically identified as carcinoids, from various sites (17 pulmonary, 13 small intestinal, 20 appendiceal, 18 rectal, five miscellaneous). Stains employed included four argyrophil (Sevier-Munger, Grimelius, Pascual, Churukian-Schenk), one argentaffin (Fontana-Masson), and one non-silver technique (lead hematoxylin). Of the 73 carcinoids, 97% stained positively with the Churukian-Schenk, 82% with the Pascual, 79% with the Grimelius, 74% with the Sevier-Munger, 67% with lead hematoxylin, and 51% with the Fontana-Masson technique. The two cases negative by the Churukian-Schenk technique were also negative with all other stains; thus, this technique most consistently demonstrated secretory granules in carcinoids, including all 18 rectal tumors. The Churukian-Schenk method achieves its superior results by reducing background staining and nonspecific precipitation to a level that permits sparse, small granules to be readily identified. In control sections of normal mucosa and in some tumors, this stain revealed more than one population of argyrophil cells as identified by the size, color, and staining intensity of the granules.

Carcinoid Tumor↗

Influence of auriculotemporal nerve anaesthesia on the masseteric silent period.

Silent periods were evoked from the masseter muscles bilaterally in response to chin taps during a clench. Injection of 0.75 ml of 3% Mepivicaine posteromedial to each condyle led to a distribution of skin anaesthesia consistent with the distribution of the auriculotemporal nerve. Silent periods were evoked prior to and during anaesthesia in ten subjects. The silent period latencies (mean +/- standard deviation) prior to anaesthesia were 12.5 +/- 1.8 ms and 11.9 +/- 2.5 ms in the right and left masseters. During anaesthesia the latency decreased by 0.3 +/- 1.3 ms in the right masseter and by 0.3 +/- 2.1 ms on the left masseter. Neither change was statistically significant (P greater than 0.05). The silent period durations prior to anaesthesia were 20.3 +/- 4.0 ms and +/- 22.8 +/- 7.1 ms in the right and left masseters. During anaesthesia, these decreased by 2.74 +/- 5.8 ms on the right and 2.15 +/- 4.4 ms on the left. These decreases were not statistically significant (P greater than 0.05). These results failed to demonstrate an influence of the predominant nerve supply of the TMJ on either the latency or the duration of the masseteric silent period.

Anesthesia, Dental↗

Arachidonic acid metabolism in polymorphonuclear leukocytes from patients with chronic granulomatous disease.

The effect of the calcium ionophore A23187 on the release and metabolism of [3H]arachidonic acid was examined in normal polymorphonuclear leukocytes and those obtained from patients with chronic granulomatous disease. The ionophore A23187 which stimulates oxidative metabolism in normal polymorphonuclear leukocytes was ineffective in increasing oxidative metabolism (chemiluminescence) in polymorphonuclear leukocytes from patients with chronic granulomatous disease. However, the ionophore A23187 stimulated the release of [3H]arachidonic acid from chronic granulomatous disease neutrophil phospholipids and stimulated its metabolism into hydroxyeicosatetraenoic acids and leukotrienes.

Arachidonic Acid↗

Thyroid hormone binding to adult rat alveolar type II cells. An autoradiographic study.

Hypothyroid adult rats were injected intravenously with [3, 5, 3'-125I]triiodothyronine (T3) or [125I]thyroxine (T4). Others were similarly treated except for the addition of a 500-fold excess of the appropriate unlabeled hormone. Light microscopic autoradiography of semithin sections of lung from these animals demonstrated labeling localized over alveolar parenchymal tissue. Analysis of the labeling studies of type II cells revealed high affinity, low capacity binding of T3 and, to a much lesser extent, T4 to both the nuclear and cytoplasmic compartments. Adult lung in organ culture was also treated with 125I-T3 or 125I-T4 and electron microscopic autoradiography performed. These studies revealed that, when expressed as grains per square micrometer, there was substantially more labeling over the lamellar inclusion bodies and the mitochondria than over the nucleus. The results of this study provide morphologic evidence of specific uptake and binding of thyroid hormones by the nucleus and cytoplasm of alveolar type II cells, and suggest that the lamellar inclusion bodies and mitochondria may be the primary location of the cytoplasmic binding. These findings also substantiate the view of a direct effect of thyroid hormones on the lung and, in particular, on the type II alveolar cells.

Animals↗

Unexpected hospital admissions among patients with diabetes mellitus.

In a search for a new way to recognize the patients who are at higher risk of unexpected hospitalizations, the characteristics of patients with diabetes mellitus were examined after their last office visit prior to hospitalization. Six characteristics contributed significantly in distinguishing 256 patients who were subsequently hospitalized from 512 patients who were not. The six characteristics included the following: frequent emergency room visits, low serum albumin level, cardiomegaly, anemia, hypotension, and hyperglycemia. The sensitivity of prediction was 43.2%, specificity was 77.4%, and the relative risk by odds ratio was 2.60:1. The intensity of care, as estimated by the level of the provider, and the intended intensity of care, as measured by the scheduled return-visit interval, were not clinically consistent with the magnitude of risk. The characteristics of patients at higher risk of unexpected hospitalizations were identified and provide a direction for increased intensity of ambulatory care.

Aged↗

The effects of glucose, acetate, lactate and insulin on protein degradation in the perfused rat heart.

Rat hearts were perfused as working preparations by the method of Taegtmeyer, Hems & Krebs [(1980 Biochem. J. 186, 701--711]. In the presence of glucose, insulin significantly inhibited protein degradation at concentrations as low as 50 mu units/ml. Acetate or lactate, when present either as sole fuel for contraction or in combination with glucose, did not inhibit protein degradation. Insulin inhibition or protein degradation was decreased with either lactate as sole fuel. We suggest that the inhibition of protein degradation occurs over the normal range of plasma concentrations of insulin present in vivo and that the presence of glucose may be at least in part necessary for this effect of insulin.

Acetates↗

The effects of insulin on glucose uptake and lactate release in perfused working rat heart preparations.

The effects of insulin on glucose uptake and lactate release in the perfused working rat heart have been investigated in three types of preparation: (i) a control low-workload preparation; (ii) an increased-pressure-workload preparation, simulating conditions of aortic pressure encountered in vivo; (iii) an increased-volume-workload preparation, where pumping work done is approximately the same as (ii) but coronary flow is restricted because of the decreased aortic pressure. Insulin stimulated glucose uptake and lactate release in preparations (i) and (ii), but failed to do so in preparation (iii). It was considered possible that preparation (iii) was hypoxic, thus necessitating a maximal stimulation of glucose uptake. This was confirmed by improving cardiac oxygenation by addition of stroma-free haemoglobin to the perfusate in preparation (iii). Under these conditions in the absence of insulin, glucose uptake and lactate release were decreased compared with perfusions in the absence of haemoglobin. Insulin stimulation of both processes was restored. We conclude that the failure of other workers to observe insulin effects on glucose uptake and lactate release under physiological workloads [preparation (ii)] may be a consequence of intracellular hypoxia in their preparations.

Animals↗

The temporal relationship between the luteinizing hormone surge and human oocyte maturation.

The temporal relationship of oocyte maturation to endogenous luteinizing hormone (LH) in vivo throughout the preovulatory period has not been previously reported. In order to study in vivo oocyte maturation follicular aspiration was carried out from 4 to 38 hours after the onset of the LH surge. Oocytes were obtained in 72% of cases. If oocytes were harvested more than 18 hours after the onset of the LH surge, resumption of meiosis had occurred. Twenty-eight to thirty-eight hours after the onset of the LH surge preovulatory oocytes in metaphase II were obtained. A corpus luteum was found 38 hours after the onset of the LH surge.

Female↗

Ultrastructural stereologic analysis of fetal rabbit type II alveolar epithelial cells following maternal pilocarpine treatment or fasting.

We have previously reported that subcutaneous administration of 5 mg/kg pilocarpine HCl, a muscarinic agonist, to pregnant white rabbits on days 24 through 27 of gestation results in an acceleration of fetal lung maturation. In the present study the ultrastructural differences observed within alveolar type II cells of 28-day fetuses from the pilocarpine and control groups were quantified by stereologic analysis. In addition, maturational changes occurring within the lungs of 28-day fetuses obtained from pregnant rabbits which were fasted for 7 days (days 21-28) were similarly analyzed. Stereologic analysis revealed that the fetal type II cells in the pilocarpine-treated group possessed a significantly greater volume density of lamellar inclusion bodies and rough endoplasmic reticulum and a significantly smaller volume density of glycogen than did controls. The volume density values for fetal type II cells of the fasted group were, with the exception of the Golgi apparatus, found to be intermediate between those of control and the pilocarpine-treated groups. It was also noted that a high percentage of the lamellar inclusion bodies within type II cells of the fasted group appeared morphologically abnormal, being characterized by a highly irregular outline and tightly packed lipid membranes. The results of this study substantiate and quantify our previously reported observation of accelerated maturation in pilocarpine-treated fetuses. In addition, they suggest a similar, though not as pronounced, effect of maternal fasting prior to delivery. However, the abnormal morphology of the lamellar inclusion bodies in the fasted group may reflect a qualitative change in the pulmonary surfactant produced by these fetuses.

Animals↗

Analysis of results from a collaborative study of the dominant lethal assay.

A dominant lethal (DL) mutation is a genetic change that results in the death of the conceptus that inherits it. The assay is normally carried out in mice and the production of DL mutation by the test chemical is characterised by an increase in non-viable embryos. A distinct advantage of the DL assay is that it is an in vivo, mammalian, germ cell assay and is therefore pertinent to the fundamental question of chemical mutagenesis, i.e.: is a chemical likely to produce genetic changes that can be transferred to the offspring? The two principal criticisms of the assay are that the main type of genetic damage it detects is chromosomal breakage that leads to death of the conceptus, and that the assay is considered to be relatively insensitive. The Association of the British Pharmaceutical Industry (ABPI) Working Party on Mutagenicity was established in 1974. Its principal objective was to consider the problem of mutagenicity and associated matters in relation to the development of new medicines and to make recommendations and proposals for collaborative work if indicated. The dominant lethal assay is one of several tests for mutagenicity chosen for evaluation by collaborative study. The objective of the collaborative study was to gain more information about the validity and dependability of the dominant lethal assay. The present report concerns an analysis of the differences between compounds, laboratories and statistical methods utilising the data from the collaborative study.

Animals↗

Duration of pulmonary function adaptation to ozone in humans.

The duration of pulmonary function adaptation subsequent to cessation of a 5-day repeated ozone (O3) exposure was studied in 24 nonsmoking human subjects. A three-week, 3 hr/day study was conducted. The subjects received filtered air on Week 1 and 0.4 ppm O3 on Week 2. During Week 3, 13 subjects were re-exposed to O3 on Friday and 11 were re-exposed to O3 on Tuesday. Spirometric measurements (FVC and FEV1) and bronchial reactivity to methacholine showed adaptation within 2-3 days of the repeated daily exposures (Week 2). Although the duration of adaptation seen with bronchial reactivity appears longer than 7-days, the FVC and FEV1 clearly demonstrated complete loss of adaptation by 7 days, with a trend toward significance by 4 days. We conclude, therefore, the loss of ozone adaptation in pulmonary function is a gradual phenomenon lasting less than 7 days following cessation of repeated daily exposures.

Adaptation, Physiological↗

A study of diet, serum lipids, and fecal constituents in spouses.

The diet, serum cholesterol, and fecal constituents of 23 healthy spouses have been compared. The pattern of food intake between couples was similar, but of dietary constituents, only dietary fat and fiber intake showed a significant correlation. Of fecal constituents, only fecal fat correlated significantly between couples.

Adult↗

Aluminum-containing dense deposits of the glomerular basement membrane: identification by energy dispersive X-ray analysis.

Heavy metals, including gold, mercury, lead, bismuth, and cadmium, have the potential to cause renal disease. With the development of X-ray microanalysis, these heavy metals can now be identified in tissue deposits. This report describes a case of renal failure, probably related to dysproteinemia, in which granular, electron-opaque dense deposits were present in the glomerular basement membranes. Energy dispersive X-ray analysis demonstrated that these dense deposits contained aluminum. An analysis of this patient's history in relation to the current knowledge of aluminum metabolism suggests that the aluminum deposition occurred secondary to previous glomerular injury. This case emphasizes the need to utilize heavy metal identification technology whenever granular, electron-opaque dense deposits are identified and represents, to our knowledge, the first study to document aluminum deposits within the glomerular basement membrane of humans.

Acute Kidney Injury↗

Effects of maternal protein deficiency on synaptic plasma membranes in offspring.

This study examined the influence of maternal protein deficiency during lactation on the accretion and synthesis of synaptic plasma membrane (SPM) proteins in developing offspring. It also examined the activity of Mg2+-dependent, ouabain-sensitive (Na+-K+)-ATPase in SPMs. The results of this study demonstrated that early postnatal undernutrition produces a significant deficit of SPM proteins. Despite this deficit, 10- to 20-day-old undernourished rats incorporated more [3H]-leucine into SPM proteins than age-matched control rats. The specific activity of (Na+-K+)-ATPase was decreased in SPMs from undernourished rats early in development, but was increased at 20 and 34 days of age. Interestingly, 20- and 34-day-old undernourished rats also had an increased proportion of [3H]-leucine-derived radioactivity in the band on SDS gels which corresponded to (Na+-K+)-ATPase. In summary, it appears that maternal deficiency of protein during lactation affects the synaptic plasma membranes in offspring quantitatively and qualitatively.

Animal Population Groups↗

Autoradiographic demonstration of thyroid hormone binding to intact liver cells in vivo.

Adult rats were injected intravenously with [125I]-3,5,3'-triiodothyronine (T3) of [125I]-thyroxine (T4). Others were similarly treated, except for the addition of a 500-fold excess of the appropriate unlabeled hormone. Light microscopic autoradiography of semi-thin sections of liver from these animals demonstrated high affinity, low capacity binding of T3 and, to a much lesser extent, T4 to the nuclei of the liver cells. Labeling over the cytoplasmic portion of the cells was greater than that over the nucleus with either hormone, but was not decreased significantly with the addition of unlabelled hormone, suggesting the absence of specific binding sites in this location.

Animals↗