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Biomedical subjects

A Saran

Publications and source records attributed to A Saran.

At least 73 records · Page 4Linked to original sources

Simultaneous measurement of tinnitus pitch and loudness.

OBJECTIVE: Simultaneous measures of the frequency and level of a pure tone matching the predominant pitch and loudness of tinnitus were obtained using four interleaved staircases. DESIGN: Two staircases in a forced-choice procedure tracked two frequencies, one higher and one lower than the predominant pitch of the tinnitus, while two staircases tracked two levels, one louder and one softer than the tinnitus. RESULTS: The standard deviation of the pitch matches to tinnitus using the forced-choice procedure with four staircases (4SFC) exceeded that from a double staircase (2SFC) task in which the level of the matching tone was fixed, whereas the 2SFC and 4SFC tasks had similar SDs for loudness matches to tinnitus when the frequency of the matching tone was fixed and for matches to the pitch or loudness of external tones. As the level of the tone matching the tinnitus pitch in the 4SFC task increased relative to that of the 2SFC task, so did its frequency. CONCLUSION: These data may be interpreted as indicating that tinnitus is a fluctuant signal, and that matches of pure tones to tinnitus are not single-valued.

Acoustic Stimulation↗

Neoplastic transformation of C3H 10T1/2 cells: a study with fractionated doses of monoenergetic neutrons.

As most occupational and environmental exposures to ionizing radiation are at low dose rates or in small dose fractions, risk estimation requires that the effects of the temporal distribution of dose are taken into account. Previous in vitro studies of oncogenic transformation, as well as in vivo studies of carcinogenesis induced by high-LET radiation, yielded controversial results concerning the presence of an inverse dose-rate effect. The present study tested the influence of one scheme of dose fractionation of monoenergetic neutrons on neoplastic transformation of C3H 10T1/2 cells. Neutrons of 0.5, 1.0 and 6.0 MeV were used. Cells were exposed to doses of 0.25 and 0.5 Gy, given acutely or in five fractions at 2-h intervals. The acute and fractionated irradiations with each energy were done on the same day. No significant difference between the two irradiation modes was found for both cell inactivation and neoplastic transformation at all energies. These results are in agreement with our data for fractionated fission-spectrum neutrons from the RSV-TAPIRO reactor.

Animals↗

Neutron-induced tumors in BC3F1 mice: effects of dose fractionation.

An experimental study of the biological effectiveness of multifractionated low doses of high-LET radiation was carried out using BC3F1 male mice. They were treated with whole-body irradiation with five equal daily fractions of fission neutrons to yield cumulative doses of 0.025, 0.05, 0.10, 0.17, 0.25, 0.36, 0.535 and 0.71 Gy at the RSV-TAPIRO reactor (mean neutron energy 0.4 MeV, in terms of kerma, y D = 51.5 keV/microns, dose rate 0.004 Gy/min) and were followed for their entire life span. The statistical method described by Peto et al. (IARC Monograph, Suppl. 2, 1980) to establish the existence of a carcinogenic effect in long-term animal experiments was applied to the data sets. This analysis was done for myeloid leukemia and for the presence of selected solid tumors. Myeloid leukemia was absent in the control group and was rarely found in irradiated animals. However, a positive significant trend was found in the dose ranges 0-0.17 Gy and higher. Epithelial tumors were induced at doses from 0.17 Gy on. Tumor occurrence was evaluated further as final incidences with age adjustment for the differences in mortality rates. Survival and incidence data for selected classes of tumors after 0.17, 0.36 and 0.71 Gy were compared with those from a previous experiment at corresponding doses given acutely (dose rate between 0.05 and 0.25 Gy/min). This indicated no marked overall influence of the time regimen of neutron irradiation on survival and tumor induction.

Aging↗

An outbreak of Corynebacterium pseudotuberculosis infection in an Israeli dairy herd.

An outbreak of Corynebacterium pseudotuberculosis infection in an Israeli dairy herd appeared in four clinical forms: cutaneous, mastitic, visceral and a mixed form. Only cows were affected and susceptibility increased with age. Most cases occurred during a short period in the summer months. The total morbidity rate was 13.7 per cent involving 41 cows. Thirty cows were affected by the cutaneous form, five by the mastitic form, four by the mastitic and cutaneous forms, one by the mastitic and visceral forms and one by the visceral form. The cutaneous form appeared as one or two pyogranulomatous lesions affecting the body or head. Subclinical to severe clinical mastitis was found in the mastitic form. In the visceral form the upper and lower respiratory system were affected by multiple purulent lymphadenitis. All the cutaneous lesions recovered irrespective of treatment. Mastitis did not respond to treatment and severely affected milk production in most cases. All the isolates of C pseudotuberculosis were nitrate reductase negative. Most isolates were sensitive to norfloxacin, cephalothin, methicillin, kanamycin and furazolidone and resistant to ampicillin, lincomycin and neomycin.

Age Factors↗

Clomipramine versus placebo in the treatment of premature ejaculation: a pilot study.

This study evaluated clomipramine as a possible treatment for premature ejaculation. Twenty patients with premature ejaculation were randomly allocated to treatment with clomipramine or placebo in a double-blind study. Average estimated time to ejaculation after vaginal penetration increased to 6.1 minutes on 25 mg. of clomipramine and to 8.4 minutes on 50 mg. of clomipramine. These estimated times were significantly different from estimated time to ejaculation while on placebo. These findings suggest that low dose clomipramine may be useful in the treatment of premature ejaculation.

Adult↗

Conformational structure variations in DNA: a PCILO study.

Perturbative configuration interaction using localized orbital (PCILO) computations have been carried out on conformational preference of d(GpC) and d(CpG) units of Z-II DNA. By keeping the sugar pucker fixed in the crystallographic conformation, PCILO energies have been calculated as a function of torsion angles alpha and zeta around two P-O ester bonds with preselected values of beta, gamma and epsilon. The results indicate that the d(GpC) unit is energetically more stable than the d(CpG) unit and prefers a g+ t conformation in (alpha-zeta) hyper-space observed in the crystal structure. The d(CpG) unit, on the other hand, shows intrinsic preference for g-g- conformation with other torsion angles close to DNA-B structure. The possibility of d(GpC) unit responsible for the stability of Z-helix has been discussed.

Base Sequence↗

Genetic and environmental relationships among somatic cell count, bacterial infection, and clinical mastitis.

Incidence of bacterial infection in 9784 lactations of 7763 cows in 31 herds, SCC in 32,448 lactations of 19,764 cows from 54 herds, and incidence of first parity mastitis recorded in the first lactations of 148,143 cows in 828 herds were analyzed. Bacterial infection was analyzed dichotomously by both threshold and linear models. The effects of parity, season, stage of lactation, and parity by stage of lactation interaction on SCC were estimated. Heritability of mean lactation log SCC--corrected for the effects of parity, season, and stage of lactation--varied from .13 to .27 for all parities in different data sets. Heritability of bacterial infection was .04 for the threshold model and .02 for the linear models. Heritability of field-recorded mastitis was .01. The genetic correlation between bacterial infection and SCC was near unity, but the genetic correlation between SCC and mastitis was .3. Selection for lowered SCC should reduce incidence of bacterial infection by 2% per unit of selection intensity.

Animals↗

Growth and behavior development in rural infants in relation to malnutrition and environment.

A group of 224 children from a rural cohort of 625 children registered from 1981 to 1983 in 10 villages of KV Block, Varanasi was assessed for morbidity, physical growth, and behavior development (Gesell's developmental schedule). By first birthday children of normal nutrition grade were reduced to one fourth and numbers in Grade II and III malnutrition doubled. This deterioration in nutritional status was probably due to high morbidity, i.e., gastrointestinal, respiratory infections, etc. The skull circumference was 43 cm at the age of one year, being lower by 3 cm than the average size. Children having Grades II and III malnutrition showed poor development in all the areas of behavior, i.e., motor, adaptive, language and personal social. Besides malnutrition, environmental factors like mother's involvement in teaching, encouraging the child, talking to him or being within the visual range; the parental education, their caste and the child's birth order contributed significantly to the development of the child during infancy.

Child Development↗

Conformational studies on cimetidine and ranitidine by PCILO calculations and NMR spectroscopy.

The conformational characteristics of two H2-receptor antagonists, cimetidine and ranitidine, have been investigated by quantum mechanical PCILO method and the results indicate a folded conformation for cimetidine stabilized by intramolecular hydrogen bonding and an extended backbone conformation for ranitidine. NMR investigations carried out on these two drugs in solution, however, indicate a predominance of an extended conformation for both the molecules. The significance of this result has been discussed in terms of the activity of these two drugs. Besides these studies, NMR experiments have also been carried out on the drugs incorporated into the lipid bilayers to investigate the drug-lipid interaction. The results from this study suggest that the hydrophobic portion of the drugs is buried in the hydrophobic hydrocarbon chains of the lipid bilayer, while the terminal hydrophilic end of the drug lies at the lipid-water interface.

Cimetidine↗

Desipramine lowers tritiated para-aminoclonidine binding in platelets of depressed patients.

Platelet adrenergic receptor binding has been studied by several groups of investigators as a possible marker for depression and other psychiatric conditions. Although some of the findings have been discrepant, the results of the majority of studies that have used imidazoline compounds as ligands have confirmed elevated alpha 2-adrenergic receptor binding in depression. We have emphasized the advantages of obtaining platelet-purified plasma membranes and using tritiated para-aminoclonidine as the ligand of choice. By using "site-selective" concentrations of tritiated para-aminoclonidine, we have identified two high-affinity-binding sites of the platelet alpha 2-adrenergic receptor that appear to be upregulated in depression before treatment. Depressed patients were treated with desipramine hydrochloride for 6 to 8 weeks, and platelet binding was reassessed. Desipramine reduced binding to nearly normal levels at both site-selective concentrations of tritiated para-aminoclonidine. The concentrations of plasma catecholamines could play a role in the downregulation of binding at posttreatment. We discuss these findings in the context of platelet imidazoline-binding sites being a possible state-dependent marker for depression.

Adrenergic alpha-Agonists↗

Relationship between membrane fluidity and adrenoceptor binding in depression.

Membrane fluidity and adrenergic receptor binding were studied in platelets of depressed patients before and during treatment with desmethylimipramine to investigate the relationship between the alpha 2-adrenergic receptor and its membrane environment in depression. Most samples came from a previous study in which we observed higher 3H-para-aminoclonidine (3H-PAC) binding in platelets from depressed patients compared to healthy subjects. Fluidity was measured by steady state diphenylhexatriene (DPH) anisotropy in both purified plasma membranes and in intracellular membrane preparations from platelets. No differences were observed in DPH membrane fluidity, per se, indicating that fluidity changes probably do not underlie either the increased alpha 2-adrenergic receptor binding in depression or the normalization of binding during treatment. However, lower intracellular membrane fluidity was correlated with higher binding to 3H-PAC site-1 in healthy subjects, but not in depressed patients. Thus, during depression there may be a disruption in the normal relationship between the adrenergic receptor and its membrane environment.

Adrenergic alpha-Agonists↗

Absence of a dose-fractionation effect on neoplastic transformation induced by fission-spectrum neutrons in C3H 10T1/2 cells.

We have investigated the effect of fission-spectrum neutron dose fractionation on neoplastic transformation of exponentially growing C3H 10T1/2 cells. Total doses of 10.8, 27, 54, and 108 cGy were given in single doses or in five equal fractions delivered at 24-h intervals in the biological channel of the RSV-TAPIRO reactor at CRE-Casaccia. Both cell inactivation and neoplastic transformation were more effectively induced by fission neutrons than by 250-kVp X rays. No significant effect on cell survival or neoplastic transformation was observed with split doses compared to single doses of fission-spectrum neutrons. Neutron RBE values relative to X rays determined from data for survival and neoplastic transformation were comparable.

Animals↗

Genetics of chemical carcinogenesis. 1. Bidirectional selective breeding of susceptible and resistant lines of mice to two-stage skin carcinogenesis.

Six generations of a bidirectional selective breeding model for producing lines of mice susceptible (Car-S) and resistant (Car-R) to two-stage skin carcinogenesis are described. Initiation was with 9,10-dimethyl-1,2-benzanthracene (DMBA single application), and promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA twice weekly). The selective breeding was initiated with a highly genetically polymorph foundation population, produced by the intercrossing of eight inbred mouse strains. The Car-S line was produced by assortative mating of the mice presenting the largest number of tumors induced by low DMBA and TPA doses, the Car-R line by mating tumorless mice or mice showing the smallest number of tumors induced by large DMBA and TPA doses. The character investigated was expressed as per cent tumor incidence and as tumor multiplicity per mouse. The mean heritability of the susceptibility character for the two first generations was 0.84 for tumor incidence and 1.3 for tumor multiplicity; these values decreased to 0.53 and 0.44 respectively for the two consecutive generations. The heritability of the resistance character maintained a constant value of 0.29 +/- 0.04 for tumor incidence, and 0.53 +/- 0.08 for tumor multiplicity. The progressive response to selection indicates that the characters investigated are subject to polygenic regulation, even though some genes may have a major effect on the susceptibility character. The interline separation in F5, challenged with the same initiation and promotion schedule, is very large. In the Car-S line, tumor incidence was 82.5% and tumor multiplicity 4.9/mouse on promotion day 49, whereas the corresponding values for the Car-R line were 4.5% and 0.1/mouse on promotion day 81.

9,10-Dimethyl-1,2-benzanthracene↗

Systemic dry cow therapy--a preliminary report.

Efficacy of three different treatment regimens in the elimination and prevention of Staphylococcus aureus intramammary infection was studied in 106 dry cow periods. At drying off, norfloxacin nicotinate was given subcutaneously to 44 cows at 10 mg/kg, oxytetracycline-HCl was administered intramuscularly to 18 cows at 20 mg/kg, 500 mg cephapirin benzathine were infused into each udder quarter of 21 cows, and a group of 23 cows served as an untreated control. Number of existing Staphylococcus aureus intramammary infections was reduced only in the norfloxacin nicotinate treatment group. New infection rate appeared lower in the two systemic treatment groups. The percentage of infected quarters remained the same throughout the dry period in the norfloxacin treatment group but number of infected quarters increased by 33 to 85% (significant in the cephapirin group) in the other groups. Minimal inhibitory concentration of the drugs for 57 S. aureus isolates was determined. Isolates were sensitive to norfloxacin and cephapirin and moderately sensitive to oxytetracycline. Results suggest that systemic dry cow therapy using norfloxacin nicotinate, which possesses large distribution volume, long half-life, and is highly active against the pathogen involved, was more effective than the other treatments.

Animals↗

Conformational preference of Leu side chain in melanostatin in DMSO.

The solution conformation of melanostatin (Pro-Leu-Gly-NH2) in the neutral and protonated forms of DMSO has been monitored by one and two dimensional NMR techniques at 500 MHz. The temperature coefficients of the amide proton chemical shifts in conjunction with the observed NOESY spectra suggest that melanostatin in neutral form in DMSO adopts a backbone conformation such that leucine amide proton is buried by the proline ring and the side chain of leucine. Similar observation is made for protonated form of melanostatin in DMSO. The results of the present study are at variance with the earlier NMR studies which proposed a beta-turn structure for both the forms of melanostatin. There is, however, no evidence for the presence of beta-turn structure for both the forms of melanostatin in DMSO. In CDCl3 also Leu NH appears to be buried as evident from the solvent titration with DMSO and NOESY spectra.

Dimethyl Sulfoxide↗

Elevated 3H-para-aminoclonidine binding to platelet purified plasma membranes from depressed patients.

Purified platelet plasma membranes were used to compare 3H-para-aminoclonidine binding in 18 depressed patients and 24 sex- and age-matched, healthy control subjects. Two site-selective concentrations of the radioligand were used (0.06 and 1.5 nmol/L) to investigate two high-affinity 3H-para-aminoclonidine binding sites. Radioligand binding was significantly elevated in platelets of depressed patients at both concentrations of 3H-para-aminoclonidine whether expressed per milligram protein, per platelet, or per square micrometer of platelet surface area (each p less than 0.02). These data agree with most previous studies, suggesting that a subset of platelet alpha 2 adrenoceptors, recognized by clonidine and its derivative para-aminoclonidine, is upregulated in depressed patients. By using purified plasma membranes, our data rule out the possibility that an inhibitor may have masked receptor binding in previous studies which used total platelet lysates. The present findings thus support the alpha 2 adrenoceptor hypersensitivity theory of depression.

Adrenergic alpha-Antagonists↗

Two gamma-bends in the backbone conformation of [D-Ala2]-leucine enkephalin in solution.

The solution conformation of [D-Ala2]-leucine enkephalin in its zwitterionic form in DMSO-d6 has been monitored by one- and two-dimensional proton magnetic resonance spectroscopy at 500 MHz. The resonances from the labile amide protons and the nonlabile protons have been assigned from the shift correlated spectroscopy. The chemical shift of the amide and C-alpha protons are found to vary with temperature but in opposite directions, except the C-alpha proton of the terminal tyrosine residue. This behavior has been explained by the shifting of equilibrium between the zwitterionic and neutral forms of the [D-Ala2]-leucine enkephalin and probably conformational changes accompanying temperature variation. The low values of the temperature coefficients of leucine and glycine amide protons indicate that these protons are either intramolecularly hydrogen bonded or solvent shielded. The observation of sequential cross peaks in the nuclear Overhauser effect spectra obtained at various mixing times, tau m (200-900 ms), indicate an extended backbone, which does not corroborate with the presence of a folded structure, i.e., beta-bend type structure. The estimate of interproton distances in conjunction with the low values of temperature coefficients of the leucine and glycine amide protons and vicinal coupling constants 3JHN-C alpha H have been rationalized by the predominance of two gamma-bends in the backbone conformation of [D-Ala2]-leucine enkephalin. The gamma-bend around the D-Ala residue has phi = 80 degrees and psi = 270 degrees, while the one around Phe it has phi = 285 degrees and psi = 90 degrees.

Enkephalin, Leucine↗