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Biomedical subjects

J Gilmore

Publications and source records attributed to J Gilmore.

At least 37 records · Page 2Linked to original sources

Serotonin transporter binding sites and mRNA levels in depressed persons committing suicide.

The serotonin transporter (5-HTT) has been found altered in postmortem brain samples from persons committing suicide, but the results of radioligand binding studies have been inconsistent. In the present series of experiments, autoradiographic radioligand binding and in situ hybridization techniques were utilized to examine 5-HTT function in the brains of 8 depressed subjects who had committed suicide, and matched controls. It was hypothesized that depressed subjects would demonstrate decreased numbers of 5-HTT binding sites and mRNA; however, [125I]RTI-55 binding to the 5-HTT was not different in the midbrain, hippocampus, or frontal cortex of depressed subjects. Also, 5-HTT mRNA levels in dorsal and median raphe nuclei were not different between controls and depressed subjects. The current results, although limited in scope because of the small number of subjects included, offer no evidence that alterations in the 5-HTT occur in pertinent brain regions of depressed individuals.

Adult↗

Discovery and analysis of inflammatory disease-related genes using cDNA microarrays.

cDNA microarray technology is used to profile complex diseases and discover novel disease-related genes. In inflammatory disease such as rheumatoid arthritis, expression patterns of diverse cell types contribute to the pathology. We have monitored gene expression in this disease state with a microarray of selected human genes of probable significance in inflammation as well as with genes expressed in peripheral human blood cells. Messenger RNA from cultured macrophages, chondrocyte cell lines, primary chondrocytes, and synoviocytes provided expression profiles for the selected cytokines, chemokines, DNA binding proteins, and matrix-degrading metalloproteinases. Comparisons between tissue samples of rheumatoid arthritis and inflammatory bowel disease verified the involvement of many genes and revealed novel participation of the cytokine interleukin 3, chemokine Gro alpha and the metalloproteinase matrix metallo-elastase in both diseases. From the peripheral blood library, tissue inhibitor of metalloproteinase 1, ferritin light chain, and manganese superoxide dismutase genes were identified as expressed differentially in rheumatoid arthritis compared with inflammatory bowel disease. These results successfully demonstrate the use of the cDNA microarray system as a general approach for dissecting human diseases.

Arthritis, Rheumatoid↗

Lack of pineal beta-adrenergic receptor alterations in suicide victims with major depression.

Noradrenergic function may be altered in depressive illness and thereby contribute to decreased pineal production of melatonin levels, as previously described in some depressed subjects. In the present study, the hypothesis was tested that pineal beta-adrenergic binding would be increased in persons committing suicide with evidence of depressive disorders, reflecting diminished noradrenergic input. Initially, post-mortem human pineal glands were obtained at autopsy. Diagnostic and symptomatic information was then systematically collected from family members using standardized interview techniques. Seven subjects who committed suicide and suffered from major depression, and without exposure to treatment for depressive symptoms were age- and sex-matched with control subjects. Pineal beta-adrenergic binding was assessed by quantitative autoradiography employing four concentrations of [125I]pindolol. Because of possibly complex adrenergic regulation of the pineal, beta-adrenergic receptor binding were subtyped using the selective blocker ICI 89406. No differences in beta-adrenergic receptors were detected between subjects with major depression compared to the matched controls.

Adult↗

The effects of ifenprodil and eliprodil on voltage-dependent Ca2+ channels and in gerbil global cerebral ischaemia.

Ifenprodil and eliprodil are both non-competitive NMDA receptor antagonists which have been shown to inhibit neuronal Ca2+ channel currents. We have examined the effects of these agents on two defined subtypes of voltage-dependent Ca2+ channels and in the gerbil model of global cerebral ischaemia. Recombinantly expressed human alpha 1B-1 alpha 2b beta 1-3 Ca2+ subunits in HEK293 cells, which results in an omega-conotoxin-sensitive neuronal N-type voltage-dependent Ca2+ channel and omega-Aga IVA sensitive Ca2+ channels (P-type) in acutely isolated cerebellar Purkinje neurones were reversibly inhibited by ifenprodil and eliprodil. Human N-type Ca2+ channel currents were inhibited by ifenprodil and eliprodil with IC50 values of 50 microM and 10 microM respectively whereas P-type Ca2+ channel currents were inhibited reversibly by ifenprodil and eliprodil with approximate IC50 values of 60 microM and 9 microM respectively. Maximum current block observed for both channel subtypes was approximately 80% for both ifenprodil and eliprodil. For neuroprotection studies, animals were subjected to 5 min bilateral carotid artery occlusion with or without administration of either ifenprodil or eliprodil (5, 10 or 20 mg/kg i.p.) immediately after surgery followed by two further doses (2.5, 5 or 10 mg/kg, respectively) at 3 and 6 h post-occlusion. Both compounds provided significant protective effects against ischaemia-induced neurodegeneration in the CA1 region of the hippocampus. These results indicate that both ifenprodil and eliprodil protect against ischaemia-induced neurodegeneration when administered post-occlusion and that they also block N and P-type voltage-dependent Ca2+ channels.

Animals↗

Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients.

Differential loss of neurons and terminals occurs in Huntington's disease. Neurons expressing preproenkephalin (PPE) appear to be more vulnerable than neurons expressing preprotachykinin and terminals in the lateral pallidum (containing enkephalin) are more affected than terminals in the medial pallidum (containing substance P). We used in situ hybridization histochemistry and emulsion autoradiography to quantify the number of PPE expressing neurons and the neuronal levels of PPE mRNA in striatum of individuals who died with Huntington's disease and normal controls. We found a grade-related decline in the number of PPE-labeled neurons per field in the striatum of individuals with Huntington's disease compared with controls. Three measures of the neuronal level of PPE mRNA, the mean number of silver grains per PPE neuron, the median number of grains per PPE neuron, and the percentage of PPE neurons with more than 30 grains, were all significantly reduced (41 to 80% of control) in Huntington's disease striatum. The magnitude of the reduction in levels of PPE mRNA per neuron was related to the grade of lesions. These data support the notion that decreased levels of PPE mRNA may account, in part, for the greater loss of enkephalin staining in lateral pallidal terminals compared with substance P staining in medial pallidal terminals. Decreased levels of PPE mRNA may result in clinical symptoms prior to the loss of neurons. The reduction in expression of PPE mRNA suggests that surviving striatal neurons may be affected by the expression of the Huntington's disease gene prior to their imminent cell death.

Adult↗

Distribution of plasminogen activator in different fractions of bovine milk.

The type and relative amounts of plasminogen activator (PA) in different fractions of bovine milk obtained from 15 Holstein cows were examined. Raw milk was centrifuged to separate skim milk and a somatic cell pellet. PA was mainly localized within the casein fraction, being 42 times that in the serum, and in association with somatic cells. The predominant form of PA in milk casein was isolated from SDS-PAGE gel extracts and had a molecular mass of approximately 75 kDa. Its activity was increased 4.1-fold (P < 0.01) in the presence of fibrin but was unaffected by the presence of amiloride, indicating that it was due to tissue-PA. The predominant forms of PA associated with milk somatic cells were isolated from SDS-PAGE gel extracts and had molecular masses of approximately 30 and approximately 50 kDa. The activity of both proteins was unaffected by the presence of fibrin but was dramatically reduced by the presence of amiloride, indicating that they represented urokinase-PA.

Amiloride↗

Reduction of interferon-gamma as a critical mechanism by which ultraviolet radiation prevents tumor rejection.

Mice irradiated with UVB, unlike nonirradiated mice, are highly susceptible to syngeneic, immunogenic tumors induced by UVB irradiation or by chemicals. We postulated that UV induced susceptibility to immunogenic tumors results from a reduction in host capacity to generate an interferon (IFN)-gamma immune response to tumor antigens. Shaved BALB/c mice were exposed to 6 x 10(5) J m-2 of UVB radiation delivered intermittently over 12 weeks. The UVB-irradiated and nonirradiated mice received intradermal injections of UVM12 or BP2 tumor cells. After 0, 1.5, 3, 7 or 21 days, draining lymph nodes were excised. Lymph node cells were incubated with UVM12 or BP2 cells that had received 2.5 Gy of gamma-radiation. After 48 h in culture, supernatants were analyzed for IFN-gamma content by enzyme-linked immunosorbent assay and cellular RNA was extracted for mRNA detection by reverse transcriptase-polymerase chain reaction analysis. At 7 days after tumor injection, draining lymph node cells from nonirradiated control mice secreted significant levels of IFN-gamma and contained at least 0.0729 amol of IFN-gamma mRNA/microgram cDNA upon in vitro exposure to gamma-irradiated tumor cells. Draining lymph node cells removed from UV-irradiated mice contained only 18% as much IFN-gamma mRNA and secreted little or no IFN-gamma when exposed to gamma-irradiated tumor cells. A single injection of antibody directed against murine IFN-gamma rendered normal mice as susceptible as UV-irradiated mice to BP2 tumor cells. Thus, chronic UV irradiation leads to an inability of host tumor draining lymph node cells to mount an IFN-gamma response to tumor antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of Staphylococcus aureus toxins on the growth of bovine mammary epithelial cells (MAC-T) in culture.

The effects of Staphylococcus aureus M60 culture supernatant on growth of mammary epithelial cells were tested in vitro. Exposure of MAC-T cells to S. aureus culture supernatant reduced cell proliferation and colony-forming ability because of reduced ability to adhere to plastic. Growth-inhibiting effects of S. aureus culture supernatant were abolished by pretreatment with trypsin. Lysis of S. aureus cells with lysostaphin demonstrated that the inhibition was also present in cell lysates. Treatment of MAC-T cells with culture supernatant from isogeneic mutants of S. aureus M60 that produced either alpha or beta toxins implicated alpha toxin as the main factor inhibiting cell proliferation.

Animals↗

Distribution of plasminogen activator forms in fractions of goat milk.

Distribution of plasminogen activator forms in fractions of goat milk was examined. Raw milk was centrifuged to separate skim milk, cream, and a somatic cell pellet. Somatic cell extracts were obtained by sonication. Skim milk was centrifuged to separate milk serum and casein micelles. Activity of plasminogen activator was detected in casein, serum fractions, and in association with somatic cells. Plasminogen activator forms in milk casein had approximate molecular weights of 75,000, 50,000, and 30,000. The predominant forms of plasminogen activator in milk serum and in association with milk somatic cells had molecular weights of 30,000 and 50,000. Based on fibrin dependency and inhibition of activity in the presence of amiloride, the forms at 30,000 and 50,000 represent urokinase-plasminogen activator, and the form at 75,000 represents tissue-plasminogen activator.

Amiloride↗

The pharmacology of LY290324 in the guinea-pig: an orally active, potent and selective cysteinyl leukotriene receptor antagonist.

This study describes the evaluation of LY290324 as a leukotriene D4 (LTD4) receptor antagonist in guinea-pigs. In vitro, LY290324 was a potent and persistent antagonist of the contractile responses to LTD4 and LTE4 with pA2 values of 9.1 +/- 0.2 and 8.9 +/- 0.17 respectively. The antagonism appeared competitive and selective for LTD4/E4, as LY290324 (10(-6) M) had no effects on contraction elicited by LTC4, prostaglandin F2 alpha (PGF2 alpha), histamine and acetylcholine. In vivo the compound was highly effective in a dose-dependent manner by the intravenous, oral and inhaled routes in preventing LTD4-induced bronchospasm. Administered i.v. LY290324 prevented the development (ED50 = 3.4 micrograms/kg) of an LTD4-induced bronchospasm and readily reversed an established bronchospasm, but failed to prevent the bronchospasm to either histamine or platelet activating factor (PAF). Oral studies demonstrated efficacy for at least 12 h. Administered orally 6 h previously, LY290324 reduced LTC4, LTD4 and LTE4-induced bronchospasm with ED50s of 0.3, 0.28 and 0.37 mg/kg respectively. Relatively low inhaled levels (2 micrograms/kg) also significantly reduced (72.5%, P < 0.001) LTD4-induced bronchospasm. Finally the compound administered orally was effective in reducing antigen-induced bronchospasm in immunologically sensitised animals.

Administration, Inhalation↗

Endogenously formed leukotriene C4 activates LTC4 receptors in guinea pig tracheal strips.

The bioconversion of leukotriene (LT) C4 to LTD4 via gamma-glutamyl transpeptidase is clearly defined in guinea pig trachea. Acivicin, an inhibitor of gamma-glutamyl transpeptidase, was used to study the contractile responses elicited by either endogenously released or exogenously administered LTC4 and the antagonistic nature of LY 171883 and ICI 204,219, LTD4/LTE4 receptor antagonists, on guinea pig tracheal strips. Pretreating tracheal strips with acivicin resulted in a concentration-related, selective leftward shift in the LTC4 concentration-response curves. Potency of LTC4 was increased 3-fold. Likewise, antigen concentration response curves were potentiated in acivicin-pretreated tissues. Antagonism of LTC4 and antigen contractile responses by LY 171883 and ICI 204,219 were reduced or abolished by acivicin-pretreatment. In contrast, these receptor antagonists effectively blocked LTD4 responses in control and acivicin-pretreated tissues. The results demonstrated that inhibition of gamma-glutamyl transpeptidase by acivicin blocked the bioconversion of LTC4 to LTD4 regardless of the source of LTC4. Data indicated that endogenously formed LTC4 was able to activate the LTC4 receptor in guinea pig tracheal strips.

Acetophenones↗

Behçet's disease in a patient with immunodeficiency virus infection.

A patient with human immunodeficiency virus (HIV) infection who developed Behçet's disease is described. As various vasculitis syndromes have been encountered recently in association with HIV infection it is suggested that Behçet's disease may be related to the HIV infection in this patient.

Adult↗

The rare presentation to the cosmetic and plastic surgeon of a patient with myxedema.

Myxedema results from hypofunction of the thyroid gland. Symptoms include dry skin, loss of and dryness of hair, mental apathy, drowsiness, and sensitivity to cold. Ocular complications associated with myxedema may be the symptoms that first prompt patients to seek a physician or cosmetic surgeon, however, though other symptoms may be present before eyelid myxedema occurs. The case reported here illustrates the value of a correct diagnosis and appropriate medical treatment, and demonstrates how surgical intervention to correct remaining eyelid problems can succeed when it is part of a comprehensive treatment plan.

Eyelids↗

Use of Vicryl mesh in prevention of postrhinoplasty dorsal irregularities.

Small, palpable, and visible dorsal irregularities may occur in as many as 5 to 10% of rhinoplasties. They can be unacceptable to both the surgeon and patient and can lead to unwanted secondary surgery. In 88 patients treated over an 18-month period, Vicryl mesh implants consisting of one to three layers of Vicryl were placed under direct vision over the dorsal cartilage; care was taken to avoid disturbing any cartilage implants. Early results were impressive; there was an absence of palpable dorsal irregularities. This report describes the surgical technique and impressions during the 18-month period.

Humans↗

Blood flow in diabetics with foot lesions due to 'small vessel disease'.

Blood flow was measured in the feet and toes of 23 diabetics, 7 controls and 6 non-diabetic neuropathic controls, using venous occlusion plethysmography. All of the diabetics showed a characteristic flow abnormality with mild hyperperfusion of the foot at rest but impaired peak flow following arterial occlusion. When the diabetics were subdivided into those with 'small vessel disease', those with neuropathic ulceration and those with neuropathy but no ulceration, the groups had remarkably comparable blood flows, except that peak great toe blood flow was rather lower in small vessel disease. In small vessel disease, the combination of high resting blood flow and elevated foot venous oxygen saturation suggests that the hyperperfusion is due to arteriovenous shunting. It seems likely that the toe lesions ascribed to small vessel disease were in fact manifestations of severe diabetic neuropathy. The term small vessel disease should be avoided in the context of diabetic foot lesions.

Adult↗

Clinical photography utilizing office staff: methods to achieve consistency and reproducibility.

This report describes solutions to common problems incurred in clinical photography for facial and cosmetic surgery and focuses on the physician who utilizes office staff to obtain photographs. Issues addressed include space and room requirements, camera and lens, lighting and shadows, pose, retrieval, and quality control. The methods and systems described are aimed at assisting the physician in obtaining consistent, reproducible, quality pre- and postoperative photographs.

Humans↗