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Biomedical subjects

C L Martin

Publications and source records attributed to C L Martin.

At least 55 records · Page 3Linked to original sources

Cellular electrophysiological properties of a new aminosteroid antiarrhythmic agent, SC-35135.

SC-35135 is a structurally unique class I antiarrhythmic agent previously shown to suppress arrhythmias produced by a two-stage coronary artery ligation or by administration of ouabain, but to be arrhythmogenic at high doses. SC-35135 was evaluated in guinea pig papillary muscle using standard microelectrode techniques to record transmembrane action potentials. SC-35135 markedly blocked Vmax (maximum rate of membrane depolarization) as a function of pacing frequency in the concentration range of 3 x 10(-6) to 3 x 10(-5) M, and was without effect on action potential duration. The effective refractory period was significantly shortened only at the highest concentration tested (3 x 10(-5) M). Rate constants for the onset of Vmax block determined at two stimulation rates, 60 and 200 pulses/min, were 0.17 +/- 0.052 and 0.06 +/- 0.005 (action potentials)-1, respectively, in the presence of 10(-5) M SC-35135. The recovery from Vmax depression following a train of stimuli was very slow in the presence of SC-35135. The average time constant for the recovery from block of Vmax after addition of 10(-5) M SC-35135 was 10.2 +/- 0.94 s. SC-35135 caused both a concentration- and stimulation frequency-dependent hyperpolarizing shift in the half point of the relationship between Vmax and resting membrane potential. Slow response (Ca current-dependent) action potentials were not changed by SC-35135 at concentrations less than or equal to 3 x 10(-5) M, indicating a lack of class IV antiarrhythmic activity. The results of these experiments indicate that SC-35135 has electrophysiological properties similar to other previously studied aminosteroid antiarrhythmics such as amafolone and CCI 22277. Its onset and recovery kinetics also resemble the well known class IC antiarrhythmics flecainide, lorcainide, and encainide. The arrhythmogenic activity of SC-35135 has prevented further development of this compound.

Action Potentials↗

Topically applied cyclosporin for modulation of induced immunogenic uveitis in rabbits.

The experimental model of immunogenic uveitis induced by intraocular injection of human serum albumin in rabbits was inhibited by the topical application of cyclosporin A. The acute nonspecific inflammatory response that immediately follows intravitreous injection was not affected. However, the severe panuveitis that develops during the second week was markedly reduced. The safety and efficacy of topically applied cyclosporin A in this model of uveitis suggests that topical administration of this antigen-nonspecific immunosuppressor may be an effective route of therapy for certain immune-mediated forms of uveitis.

Administration, Topical↗

Normal ultrastructure and histochemical characteristics of canine lacrimal glands.

Lacrimal glands of 12 dogs free of ocular disease were examined to determine the normal structure of these glands. The glands consisted of tubuloacinar cells that ultrastructurally and histochemically were of a single type of secretory cell in the tubules and possibly 3 types of secretory cells in the acini. The tubular epithelium contained homogenous electron-dense granules that stained as neutral glycoconjugates (periodic acid-Schiff positive and Alcian blue and high iron diamine negative). The predominant acinar cells contained granules of lesser electron density than those of the tubules, and stained as sialomucin (Alcian blue [pH 2.5] and periodic acid-Schiff-positive, and high iron diamine-negative). A second type of acinar cell was in peripheral lobules that ultrastructurally and histochemically appeared like lipid granules (positive with oil red O and osmium tetroxide). Ultrastructurally, a third type of acinar granule was finely granular, electron-lucent, and frequently coalesced. It was not readily apparent whether the latter was an artifact, a stage in the maturation of the sialomucin granules, or a third type of acinar granule. Individual acinar cells usually had a predominance of 1 granule type, but greater than 1 granule type could be found in some cells. The basal surfaces of the acinar, tubular, and ductal cells were incompletely ensheathed by myoepithelial cells. Plasma cells, lymphocytes, mast cells, endothelial cells, fat cells, and Schwann cells composed the cellular elements of the interstitium. Lymphocytes, mast cells, and nerve endings also were found in the parenchyma.

Animals↗

Multiple hereditary ocular anomalies in a herd of cattle.

A Brahman x Santa Gertrudis herd of cows bred to a Hereford bull was evaluated because of a 3-year history of several calves born with congenital blindness. Multiple congenital ocular anomalies in 2 calves included microphthalmos, microcornea, microcoria, heterochromia iridis, microlentia, cataracts, retinal dysplasia, retinal detachment, anterior segment dysgenesis, acorea, and proliferation of the anterior neuroectoderm. On the basis of the lack of environmental factors and persistence of an intermittent problem when breeding to a single bull, a genetic defect was diagnosed as the probable cause. Dominant inheritance with varied expressivity may have best explained the lack of obvious signs in the bull, with emergence of various anterior and posterior segment defects in offspring from unrelated cows.

Abnormalities, Multiple↗

Blindness and convulsions associated with vitamin A deficiency in feedlot steers.

Blindness and convulsions were the predominant clinical signs in a group of feedlot steers inadvertently fed a vitamin-A deficient diet. Although vitamin A had been added to the feed at the time of preparation, it was believed that the vitamin A had been destroyed by heat, humidity, and minerals mixed in the feed. Feedlot heifers fed the same high-grain diet were clinically normal, and one heifer from which a blood sample was obtained had normal serum vitamin A content. The ingestion of sparse grasses and weeds found along the fence row of the heifers' pens was thought to have provided sufficient vitamin A to these animals. This episode demonstrated the importance of monitoring vitamin A and vitamin A precursor concentrations in stored feeds, especially those stored under adverse conditions and those fed to animals ingesting only a high-grain diet.

Animal Feed↗

Raman spectroscopy of oxidized and reduced nicotinamide adenine dinucleotides.

We have measured the Raman spectra of oxidized nicotinamide adenine dinucleotide, NAD+, and its reduced form, NADH, as well as a series of fragments and analogues of NAD+ and NADH. In addition, we have studied the effects of pH as well as deuteration of the exchangeable protons on the Raman spectra of these molecules. In comparing the positions and intensities of the peaks in the fragment and analogue spectra with those of NADH and NAD+, we find that it is useful to consider these large molecules as consisting of component parts, namely, adenine, two ribose groups, two phosphate groups, and nicotinamide, for the purpose of assigning their spectral features. The Raman bands of NADH and NAD+ are found generally to arise from molecular motions in one or another of these molecular moieties, although some peaks are not quite so easily identified in this way. This type of assignment is the first step in a detailed understanding of the Raman spectra of NAD+ and NADH. This is needed to understand the binding properties of NADH and NAD+ acting as coenzymes with the NAD-linked dehydrogenases as deduced recently by using Raman spectroscopy.

Molecular Conformation↗

Predicting adult temperament from minor physical anomalies.

It is known that in children, individual differences in temperament are linked to rates of minor physical anomalies (MPAs). These anomalies are a standard set of 17 nonobvious but measurable characteristics of the face, hands, and feet. We explored the relation between MPAs and temperament in adults. An intact sample of 88 undergraduates completed a battery of personality tests and lifestyle questions, and then were examined for MPAs. The index of MPAs for each subject was simply the total count out of 17. The results showed a pattern of correlates parallel to that found in children. Among male subjects, correlations with MPAs were significant for the Physical Activity and Clumsiness factors of the lifestyle inventory as well as for measures of emotionality, extraversion, masculinity, femininity, and Type A personality. The MPA index was also predictive of a behavioral index of temperament in male subjects. No correlations were significant among female subjects.

Adult↗

AVGs: framework for ambulatory care payment.

In preparation for an ambulatory care prospective payment system, the Health Care Financing Administration (HCFA), Office of Research and Demonstration, supported a two-year grant project at Yale University for further development of an ambulatory patient classification system based on Ambulatory Visit Groups (AVGs). This article explains the premises of the study and gives us insight into what we may ultimately expect in an ambulatory care prospective payment system.

Ambulatory Care↗

Effect of xylazine and ketamine on intraocular pressure in horses.

Intraocular pressure was measured with a MacKay-Marg tonometer in eight horses following auriculopalpebral nerve block and topical application of lignocaine. Measurements were recorded before and after xylazine, 1.1 mg/kg intravenously, every two minutes for 16 minutes after administration of ketamine, 2.2 mg/kg intravenously, and after recovery from anaesthesia. Before xylazine, intraocular pressure was 17.1 +/- 3.9 and 18.4 +/- 2.2 mm Hg in the left and right eyes, respectively. Intraocular pressure tended to decrease after administration of xylazine and ketamine, with a significant decrease in one eye six minutes after injection of ketamine.

Animals↗

Keratoconjunctivitis sicca: immunological evaluation of 62 canine cases.

The etiology of keratoconjunctivitis sicca (KCS) in 62 dogs was evaluated, using immunologic techniques. Using direct fluorescent antibody testing, autoantibodies within the lacrimal, salivary, or pancreatic glands were detected in 5 of 8 dogs tested. Circulating antibodies to the nictitating membrane gland, main lacrimal gland, parotid salivary gland, or mandibular salivary gland were detected using indirect fluorescent antibodies in 9 of 31, 3 of 31, 5 of 31, and 5 of 31 sera, respectively. Using radial immunodiffusion, hyper-gamma-globulinemia was detected in 21 of 30 dogs with KCS. Antinuclear antibodies, primarily in a nucleolar pattern, were demonstrated in 20 of 50 dogs with KCS. Lymphocytic infiltrates were evident in 5 of 9 labial salivary biopsies, 2 of 4 parotid gland specimens, 2 of 4 mandibular gland specimens, and 2 of 3 thyroid gland specimens taken from dogs with KCS. Autoimmune diseases had been previously documented in 4 of 62 dogs. Twenty-five of the 62 dogs (40%) had concurrent problems indicative of an underlying immunologic disorder.

Animals↗

Raman study of reduced nicotinamide adenine dinucleotide bound to liver alcohol dehydrogenase.

We report the first Raman spectra of reduced nicotinamide adenine dinucleotide (NADH) when bound to an enzymatic active site, that of liver alcohol dehydrogenase (LADH). This was obtained by subtracting the Raman spectrum of LADH from that of the binary LADH/NADH complex. There are significant changes in the spectrum of bound NADH as compared to that in solution. The data indicate that both the nicotinamide moiety and the adenine moiety are involved in the binding. At least one of the two NH2 moieties of NADH also participates.

Alcohol Dehydrogenase↗

Raman spectroscopy of liver alcohol dehydrogenase.

We report the Raman spectrum of liver alcohol dehydrogenase in solution. The enzyme's secondary structure as determined from an examination of the Raman bands is slightly different than that found in crystals by X-ray diffraction.

Alcohol Dehydrogenase↗

Leber's congenital amaurosis associated with familial juvenile nephronophthisis and cone-shaped epiphyses of the hands (the Saldino-Mainzer syndrome).

Three affected children (a 13-year-old girl and her 7- and 8-year-old brothers) in a sibship of eight had findings consistent with the Saldino-Mainzer syndrome (skeletal dysplasia associated with Leber's congenital amaurosis, familial juvenile nephronophthisis, and cone-shaped epiphyses of the hands). Two also had pigmented midline nevi. Although tapetoretinal degeneration and familial juvenile nephronophthisis are associated in the inherited Senior-Loken syndrome, the rare association of these abnormalities with cone-shaped epiphyses of the hands suggested an autosomal recessive syndrome with variable expression remarkably similar to the Saldino-Mainzer syndrome, which may or may not be distinct from the Senior-Loken syndrome. The association of tapetoretinal degeneration with skeletal dysplasia may indicate asymptomatic renal or hepatic disease.

Adolescent↗

Flow cytometric detection of histamine binding to lymphocytes.

Using flow cytofluorimetry histamine binding was demonstrated by 90-100% of human peripheral blood lymphocytes. Cells were labelled with fluorescein isothiocyanate-human albumin-histamine (FITC-HA-His) and analysed using a Fluorescence Activated Cell Sorter (FACS-II). A parallel control FITC-HA conjugate and blocking with both free histamine and histamine bound to albumin were used to establish specificity. The binding of histamine could be blocked with both H1 and H2 type histamine antagonists. Nylon wool separated T and B lymphocyte subpopulations showed the same high proportions of histamine binding cells.

Animals↗

Keratoconjunctivitis sicca: histopathologic study of nictitating membrane and lacrimal glands from 28 dogs.

Forty nictitating membrane glands and 9 main lacrimal glands were obtained for histologic evaluation from 28 dogs with keratoconjunctivitis sicca as the result of azosulfapyridine toxicity, canine distemper, multisystemic autoimmune disease (Sjögren's syndrome-like syndrome), congenital origin, and unilateral and bilateral idiopathic keratoconjunctivitis sicca. Similar glands from 6 control dogs were studied. The most prevalent (87%) histopathologic finding was variable degrees of multifocal chronic adenitis, characterized by acinar atrophy and replacement with increased numbers of plasma cells and lymphocytes within increased amounts of interacinar fibrous connective tissue stroma. Occasional tubular structures were dilated and filled with neutrophils and cellular debris.

Animals↗

Rheumatoid factor determination in 50 dogs with keratoconjunctivitis sicca.

Sera from 50 dogs with keratoconjunctivitis sicca were examined for rheumatoid factor. In 17 (34%) of dogs tested, rheumatoid factor was found at titers equal to or greater than 1:16. Fifteen dogs (30%) had probable concurrent immunologic disorders. Ten dogs (20%) had xerostomia, as indicated by dry oral mucosa, marked periodontitis, and loss of teeth.

Animals↗

Tuberculin anergy in clinically normal individuals. I. Lymphokine and lymphocyte transformation studies.

Tuberculin anergy was demonstrated in a number of clinically normal individuals who, on being immunized with Bacillus Calmette-Guérin (BCG), failed to demonstrate a positive Mantoux skin test. Lymphoid cells from these anergic subjects when stimulated with purified protein derivative (PPD) in vitro did not produce macrophage migration inhibition factor (MIF). Lymphocyte transformation studies demonstrated that while Mantoux-positive, non-BCG immunized Mantoux-negative and anergic individuals could all undergo blast cell transformation in the presence of PHA, only lymphoid cells from Mantoux-positive and a proportion of anergic people were capable of blast cell transformation when cultured with PPD. These results suggest that more than one mechanism may account for tuberculin anergy in clinically normal people operating at the level of lymphokine production and in some cases lymphocyte transformation.

Adult↗