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Biomedical subjects

L G Davis

Publications and source records attributed to L G Davis.

At least 73 records · Page 4Linked to original sources

A quantitative, immunochemical demonstration of the postnatal development of neurotensin in the medial preoptic area of the rat.

The postnatal ontogeny of neurotensin (NT) in the medial preoptic area (MPO) of the rat was quantitatively investigated using immunocytochemical and neurochemical techniques. On postpartum day 0, NT-like immunoreactive neurons could not be identified within the MPO by peroxidase-antiperoxidase histochemistry and, in fact, did not appear until 9 days postpartum. After this age, the number of NT cells in the MPO increased ontogenetically, as did concentrations of NT in MPO extracts measured by radioimmunoassay and enzyme-linked immunosorbent assay. In organotypic MPO explants derived from neonatal rats, NT-like immunoreactivity was detected only after the explants were maintained 14 days in vitro, after which, the number of NT-like immunoreactive somata increased as the time in vitro was extended. These findings indicate that a substantial amount of differentiation occurs postnatally in the MPO both in vivo and in vitro and, more specifically, that the ontogenetic expression of NT may be an intrinsic property of the MPO.

Age Factors↗

Topical acyclovir treatment of herpes zoster in immunocompromised patients.

Topical acyclovir favorably influences the healing of localized herpes zoster in immunocompromised patients. This therapy, or placebo, was applied to forty-three patients in a random access, double-blind trial, four times daily for 10 days, beginning within 72 hours after the onset of skin lesions. The mean time to pustulation is decreased from 12.4 to 6.7 days and the mean time to crusting is decreased from 16.0 to 11.4 days (p = 0.038 and 0.086, respectively) by topical treatment. The mean time to 50% healing is decreased from 24.5 to 15.2 days and the mean time to 100% healing is decreased from 34.9 to 25.8 days (p = 0.023 and 0.033, respectively). Favorable effects in treated patients are not associated with a more rapid decline in lesion virus titer, but do accrue without any toxicity.

Acyclovir↗

Benzodiazepine receptors and seizure susceptibility in epileptic fowl.

Benzodiazepine binding to brain membrane preparations obtained from epileptic and nonepileptic carrier fowl was compared. [3H]Flunitrazepam binding to whole brain homogenates from 2-day-old chicks and [3H]diazepam binding to synaptosomal membranes and homogenates from adult chickens were determined. Scatchard analysis revealed no differences in either the number of receptors or their affinity for the ligands when the epileptics were sacrificed in the interictal state. Evoked seizures in adult epileptics had no effect on the number or affinity of binding sites using [3H]diazepam as the ligand. Moreover, the ability of gamma-aminobutyric acid to facilitate benzodiazepine binding was not different in epileptic fowl when compared with carriers.

Animals↗

Benzodiazepine binding to cultured human pituitary cells.

Benzodiazepine receptors were investigated in a cell line of human pituitary cells (18-54,SF) grown in serum-free medium. Preparations of 18-54,SF whole cells and cell membranes were shown to possess saturable [3H]diazepam binding sites. Membrane sites were found to have a KD of 20 nM for diazepam while whole cells possessed a twofold higher value. The KD values determined from Rosenthal, Hill, and kinetic analyses were consistent for each preparation. Whole-cell binding of [3H]diazepam was observed to be more stable than binding to membranes at higher temperatures (37 degrees C) and when longer incubation times (60 min) were employed at 4 degrees C. The rank order potency of various benzodiazepines to inhibit [3H]diazepam binding to whole cells and membranes was Ro 5-4864, flunitrazepam, diazepam, and clonazepam. Representatives of other drug classes did not inhibit this benzodiazepine binding. When 18-54,SF cells were grown for 24 h with 100 nM diazepam and then extensively washed membranes prepared, the KD for diazepam increased to 38 nM whereas the Bmax was unchanged when compared with untreated controls. Overall, these findings indicate that pituitary cells possess a peripheral-type benzodiazepine receptor and that the whole cell receptor differs quantitatively when compared with the membrane receptor.

Benzodiazepines↗

Topically administered acyclovir in the treatment of recurrent herpes simplex genitalis: a controlled trial.

Eighty-eight patients with culture-proven recurrent herpes simplex genitalis were entered into a collaborative, randomized, placebo-controlled, double-blind trial to evaluate the efficacy and toxicity of a topical formulation of acyclovir. Patients entered the study within 48 hr of the onset of lesions, and the study medication was applied six times daily for five days. The duration of virus shedding from lesions present at the time of entry into the study was significantly reduced for men who received acyclovir compared with men who received placebo (P less than 0.05). There were no significant differences between the acyclovir- and placebo-treated groups of either sex in time to crusting of lesions, time required for lesions to heal, time to cessation of pain, or in frequency with which new lesions developed during the course of therapy. Mild, transient burning or pain associated with application of the study medication was a common complaint.

Acyclovir↗

Double-blind controlled trial of topical acyclovir in genital herpes simplex virus infections.

Sixty-nine patients with first episodes and 111 with recurrent episodes of genital herpes simplex virus (HSV) infection were enrolled in a double-blind trial comparing a 5 percent topical acyclovir ointment versus placebo, polyethylene glycol (PEG). Among acyclovir recipients with first episodes of genital herpes, the mean duration of viral shedding from genital lesions, 2.0 days, mean duration of local pain or itching, 3.6 days, and mean time to healing of lesions, 11.2 days, were less than in placebo recipients 4.6, 6.7, and 15.8 days, respectively (p less than 0.05 for each comparison). Among patients with recurrent genital herpes, the mean duration of viral shedding from genital lesions was 0.8 days in acyclovir recipients compared with 1.7 days in placebo recipients (p less than 0.001). Among men with recurrent genital herpes, the mean time to crusting and healing of lesions was 3.5 and 7.5 days in acyclovir recipients compared with 5.0 and 9.7 days in placebo recipients, p = 0.03 and 0.07, respectively. No significant differences in the duration of symptoms or healing times were noted between acyclovir- and placebo-treated women with recurrent genital herpes. Acyclovir therapy was not associated with a decrease in frequency of clinical recurrences or an increase in the time of the next recurrence in patients with either first or recurrent genital herpes. Topical acyclovir appears effective in shortening some of the clinical manifestations of genital HSV infections.

Acyclovir↗

The metabolism and structure of phosphoglycoproteins in rat brain.

Glycoproteins that contain phosphohexosyl groups were found to be present in the myelin- and synaptosomal-enriched fractions as well as in the microsomes of rat brain. The kinetics of flow of intraperitoneally injected [32P]phosphate suggests that the phosphate is enzymatically added in structures found in the microsomal fraction. The newly synthesized phosphoglycoproteins then appear in the soluble fraction of the synaptosomes and in the cytosol, prior to incorporation into the membranes of the synaptosomes and myelin. Phosphoglycopeptides recovered from the phosphoglycoprotein contain 3 Mannose units per N-acetylglucosamine residue; one of the mannose residues is phosphorylated. [13C]NMR studies indicate that the phosphoglycopeptides contain a chitobiose group and more than four sugar residues. Thus, the phosphomannoglycopeptides from rat brain contain an average of 2 N-acetylglucosamine, 6 mannose, and two phosphate moieties per oligosaccharide chain. Enzymatic treatment with alpha-mannosidase failed to remove the phosphomannose, although some mannose residues were released. Thus, the phosphorylated mannose is not removed by the glycosidase and terminal nonphosphorylated mannose residues are present in the oligosaccharide. The phosphate residues are removed by treatment with alkaline phosphatase.

Animals↗

Baseline exploratory activity predicts anxiolytic responsiveness to diazepam in five mouse strains.

Inbred mouse strains showing variability in spontaneous exploratory behaviors displayed differential responsiveness to diazepam in an anxiety-related exploration model. C57B1/6J, BALB/cJ, Swiss Webster/NIH, Swiss Webster/Harlan Sprague-Dawley, and CF-1 mice demonstrated a significant correlation between baseline exploratory activity and maximal percentage increase in exploratory behavior induced by diazepam. No correlation was seen between those behavioral responses and the characteristics of brain benzodiazepine binding sites in the different strains. Anti-anxiety responsiveness appears to be a function of some genetically-determined substrate for spontaneous exploratory behaviors which may have multiple neurochemical substrates.

Animals↗

Platelet MAO in children with attention deficit disorder and hyperactivity: a pilot study.

The authors examined platelet MAO activity in 8 hyperactive and 18 control children who were admitted to a clinical research center and placed on a low monoamine diet. After 5 days, their blood was analyzed; the hyperactive children were discharged on day 7, placed on d-amphetamine for 2 weeks, and readmitted for repeat blood analysis. The hyperactive children initially had significantly lower levels of platelet MAO than the controls. After the hyperactive children were treated with d-amphetamine for 2 weeks, their platelet MAO levels were comparable to those of the control children. The authors suggest an association between low platelet MAO activity and a behavioral state of overactivity, short attention span, and impulsivity.

Attention Deficit Disorder with Hyperactivity↗

An endogenous ligand to the benzodiazepine receptor: preliminary evaluation of its bioactivity.

Chromatographic separation of aqueous brain extracts yields a peptide containing fraction which competitively inhibits 3H-diazepam binding to its receptor. An intracerebral-ventricular injection of this isolated fraction results in altered responses in pharmacological and behavioral tests which are similar to those observed when diazepam is administered in the same fashion. The most pronounced effect was obtained in the conflict test. Changes observed in other tests, such as blocking pentylenetetrazole convulsions, altering motility or reducing hyperthermia, were also consistent with the actions of diazepam. At the dose used, neither diazepam nor the brain extract altered muscular co-ordination in two ataxia evaluations. Thus, the animals' performance in the other paradigms would not be adversely influenced by immobilization side-effects. The results reported here support the notion that an endogenous factor does exist in brain which can act like the benzodiazepine drugs when tested for bioactivity in animal studies.

Animals↗

Genital herpes simplex virus infection: clinical course and attempted therapy.

The epidemiology, clinical course, diagnosis, and attempted treatments of herpes genitalis are reviewed. Herpes genitalis is an increasingly common sexually transmitted disease for which there is no effective treatment. It can occur in either sex and is mot commonly first found in patients 14 to 29 years old. Initial exposure to the virus may result in prolonged local symptoms (pain, itching, discharge) and signs (ulcerative lesions) as well as fever, malaise, myalgias, and fatigue. After the initial exposure, the virus may be found in a latent stage in the dorsal nerve root ganglia in the sacral area, and recurrences of disease may ensue. The frequency and clinical course of recurrent genital herpes can be of varying duration and severity. Although antiviral substances, immune potentiators, topical surfactants, and photodynamic inactivation have been used to treat genital herpes infections, there is no proven effective therapy.

Adolescent↗

Urinary glycoconjugates in schizophrenic patients.

The level of glycoconjugates excreted in the urine of five schizophrenic patients was compared to that excreted by six controls. Urinary samples were fractionated by means of gel filtration and anion exchange chromatography to yield (i) fraction I consisting of basic, neutral, or slightly acidic glycopeptides and/or oligosaccharides, (ii) fraction II consisting of acidic glycopeptides and/or oligosaccharides, and (iii) fraction III consisting of glycosaminoglycans (acidic mucopolysaccharides). The hexose levels of fraction II (p less than 0.05) and uronate levels of fraction III (p less than 0.025) were significantly reduced in schizophrenic patients. The ratio of galactose/mannose in the glycoconjugates of fraction II was lower than normal in the urine from schizophrenic patients. Significantly (p less than 0.05) lower levels of rhamnose and higher levels of fucose were found in the glycoconjugates of fraction I from schizophrenic patients. Contrary to a previous report, we found no evidence for the presence of an abnormally elevated rhamnose-containing glycoprotein or glycoconjugate in fraction II. I appears that the pattern of metabolism of glycoproteins and glycosaminoglycans in schizophrenic patients deviates from the normal.

Adult↗