A freezing technique applicable to transformation studies of C3H10T1/2 cells.
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Animals↗
Biomedical subjects
A Saran
Publications and source records attributed to A Saran.
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↗
Electroencephalographic changes and other indices of neurotoxicity with haloperidol-lithium therapy.
This prospective study was undertaken in order to establish indices of possible neurotoxicity due to the combination of lithium with haloperidol and a combination of lithium with other neuroleptics. Twenty-one subjects who were receiving neuroleptic-lithium combination were studied. Of them, 14 had a primary affective disorder-manic phase, and 7 had schizophrenia as judged by Feighner criteria. The subjects were evaluated on clinical, neuropsychological measures and EEG at baseline and 10-14 days after addition of lithium to the neuroleptic regimen. Of 11 subjects receiving the haloperidol-lithium combination, 5 (45.4%) showed abnormal responses on EEG. Of these 5 subjects, 3 showed abnormal photic responses, and 2 showed slowing in posterior alpha activity. These photoparoxysmal and photomyoclonic responses are indicative of cerebral pathophysiology resulting from the interactive effect of the haloperidol-lithium combination. The photic and other associated EEG abnormalities reported may be the earliest indication of neurotoxicity. No significant changes were observed in the EEG in 10 subjects treated with other neuroleptic-lithium combinations. In a statistical comparison the haloperidol-lithium combination had significantly more frequent EEG changes than the combination of lithium with other neuroleptics. This study presents sufficient evidence from reported photic and other associated EEG changes to pursue further investigation of neurotoxicity due to haloperidol-lithium therapy. Such a study should employ a larger number of subjects, random assignment of subjects to treatment and control groups, and blind evaluation of data.
Adult↗
Panic attack precipitated by fluoxetine.
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Adult↗
Antidepressants not effective in headache associated with minor closed head injury.
The author compared the response to amitriptyline in headache associated with depression between twelve patients having primary depression (control group) and ten patients with depression after minor closed head injury. In the primary depression group, there was significant reduction in headache and improvement in depression. The minor closed head injury group did not show significant reduction in headache or improvement in depression. The latter group, upon further treatment with phenelzine also showed no reduction in headache or improvement in depression. Results of this study question the earlier reports of the usefulness of amitriptyline in chronic muscle contraction headache and depression associated with minor closed head injury.
Adult↗
Dose-response relationship of radiation-induced harderian gland tumors and myeloid leukemia of the CBA/Cne mouse.
Transplantation of harderian gland cells from CBA/-Cne mice into the fat pad of isogenic recipients was used for a quantitative in vivo study of cell survival and risk of transformation after x-ray irradiation (1-7 Gy). A survival curve for gland cells was generated in vivo with a D0 of 1.83 Gy and an extrapolation number of 7.23. Subsequently, the dose-response curve for lesions observed in nodules after cell transplantation was compared with that for lesions observed in glands irradiated in situ. A high incidence of epithelial hyperplasias with severe dysplasia was observed in transplantation nodules after x-irradiation. Gland tumors were significantly induced in whole-body irradiated animals; the tumors reached a maximum incidence after doses of 3 Gy. The risk of transformation per surviving cell was estimated both for dysplastic lesions and for tumors. These results approximated a dose-squared relationship in both cases, suggesting a common induction mechanism at the cellular level. Myeloid leukemia was observed at all doses in whole-body irradiated mice, and the maximum tumor incidence was reached at doses around 3 Gy.
Animals↗
Radiation-induced mouse liver neoplasms and hepatocyte survival.
Transplantation of hepatocytes from CBA/Cne mice into the fat pads of isogeneic recipients has been used for the quantitative in vivo study of cell survival and risk of transformation after x-ray irradiation (1-7 Gy). A survival curve for liver cells was generated in vivo with a D0 of 3.08 Gy and an extrapolation number not significantly different from 1. Data on liver tumor incidence in whole-body irradiated CBA/Cne and C57BL/Cne X C3H/HeCne (BC3F1) mice are also reported. A statistical analysis of trend in both cases proved a significant induction of tumors by x-rays mainly for doses above 2 Gy. The risk of transformation per surviving cell was estimated for both mouse strains. For CBA mice the data points suggested the presence of a linear component in the dose-effect curve at low doses, whereas for BC3F1 mice a quadratic expression appeared to provide a better description of the points from 1 to 6 Gy. The data of this study suggested that liver tumors can be induced by radiation in mouse strains with either a high or low spontaneous hepatoma incidence.
Animals↗
Molecular orbital studies on lipids: conformation of glycerol trivalerate by the PCILO method.
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Computers↗