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Biomedical subjects

J D Martin

Publications and source records attributed to J D Martin.

At least 19 recordsLinked to original sources
PubMed1998

Delayed obsessive-compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients.

Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder. However, such treatment may decrease serotonin receptor responsivity. We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients. Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterwards. Ten unmedicated patients underwent the same procedures. Symptoms improved 4 h after both metergoline and placebo. The day after metergoline but not placebo, fluoxetine-treated patients had significantly increased anxiety, obsessions and compulsions, abating over several days. Depression was unchanged. Metergoline had no similar delayed effects in unmedicated patients. Metergoline levels were higher in fluoxetine-treated patients. These results, consistent with less conclusive earlier findings, suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder.

Adult↗
PubMed1998

Attacking poverty and improving health: a report on the WHO/State of Maryland International Health Congress, Baltimore, September 1997.

An international meeting, 'Investment Strategies for Healthy Urban Communities', in Baltimore in September 1997 called on the the business community, city authorities and the health professions to reduce poverty and its adverse health consequences, especially in urban areas, in both the industrialized and developing world. In addition to issuing the Baltimore Charter on partnership for a healthy urban future, the meeting had two main outcomes: the innovative concept of Business for Health, championed by progressive business leaders from Australia, Europe and the United States, to promote business principles to reduce poverty, create enterprises and improve people's health, especially in developing countries; and the establishment by health professionals of an information network between cities and countries on poverty and ill-health. Two follow-up meetings in London in December 1997 resulted in an action plan to create networks of health professional groups and representatives of the business community.

Baltimore↗
PubMed1998

Health systems for the 21st century.

Health systems for the 21st century will have to respond to many challenges. This article indicates, against the background of health for all, which factors, both from within and outside, will influence health systems and what approaches and strategies are needed to address them. A strong emphasis will be placed on the government and its ministry of health. By improving the impact of its activities and interventions, by influencing the policies of other sectors and by creating partnerships for health, governments and the ministries of health should become real leaders for health.

Delivery of Health Care↗
PubMed1997

Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study.

OBJECTIVE: Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms. METHOD: Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward. RESULTS: Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation. CONCLUSIONS: These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.

Adult↗
PubMed1996

Ca(2+)-independent contraction induced by hyperosmolar K(+)-rich solutions in rat uterus.

The present experiments were designed to investigate the mechanisms involved in the contractile responses evoked by KCl, added either isoosmotically or hyperosmotically, in the rat uterus. Exposure of uterine strips to a Ca(2+)-free, 3 mM EGTA-containing solution abolished the responses induced by isoosmotic KCl solutions. Conversely, addition of hyperosmolar KCl induced concentration-dependent tonic responses in a Ca(2+)-free, 3 mM EGTA-containing solution. The maximum increase in tension was reached with 210 mM K+. The response to hyperosmotic K+ was unaffected by previous depletion of intracellular Ca2+ stores with oxytocin (1 microM), by inhibition of refilling of the intracellular Ca2+ stores using cyclopiazonic acid (10 microM) or by increasing the concentration of EGTA in the medium to 10 mM. Sucrose and mannitol (60-420 mM) induced concentration-dependent sustained contractions which were not reproducible and were significantly smaller in size than those evoked by the maximally effective concentration of hyperosmotic K+ (210 mM). The contraction induced by hyperosmotic K+ in Ca(2+)-free solution was not altered by the calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7, 100 microM), the Ca2+/calmodulin protein kinase II inhibitor 1-[N,O-bis(1,5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4-phenyl piperazine (KN-62, 10 microM) or the tyrosine kinase inhibitor genistein (10 microM). The protein kinase C inhibitor calphostin C (1-3 microM) failed to modify the K(+)-effect curve, which was however partially inhibited in the presence of the non-selective protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2 methylpiperazine dihydrochloride (H-7, 3-100 microM). The protein kinase inhibitor staurosporine (30-300 nM) depressed the contraction induced by hyperosmolar K+ in a concentration-dependent manner. The contraction induced by sucrose in Ca(2+)-free solution was unaffected by W-7 (100 microM) and KN-62 (10 microM) but was partially reduced by calphostin C (1 microM), H-7 (30 microM), staurosporine (100 nM) and genistein (10 microM). These results suggest that different mechanisms are involved in the responses evoked by isoosmotic and hyperosmotic KCl in the rat uterus. A component of the contraction induced by hypertonic KCl seems mainly independent of both external and internal Ca2+ and of hyperosmolar stress. This contraction is not mediated by protein kinase C, Ca2+/calmodulin-dependent kinases or protein tyrosine kinases but involves activation of other, at the present unknown, staurosporine-sensitive protein kinase(s).

Animals↗
PubMed1996

Changes in satellite cell population associated with regenerating muscle fibers in rats.

Qualitative and quantitative analysis of satellite cells in regenerating muscles was performed at 4, 7 and 30 days after necrosis induced by mepivacaine injection. At 4 days, the small regenerating fibers were accompanied by a high number of satellite cells showing signs of activation; at 7 days, the number of satellite cells decreased and two morphological types of these cells were observed; at 30 days, satellite cells were similar in both number and characteristics to those of the control group. These results would indicate that satellite cells may vary both in number and morphological and morphometric features, according to the degree of maturity of the regenerating muscle fiber.

Animals↗
PubMed1995

Influenza A virus-specific H-2d restricted cross-reactive cytotoxic T lymphocyte epitope(s) detected in the hemagglutinin HA2 subunit of A/Udorn/72.

BALB/c mice immunized with a vaccinia virus recombinant expressing the influenza A virus (A/Udorn/72; subtype H3) hemagglutinin HA2 (H3HA2) induced a strong CD8+ cytotoxic T lymphocyte (CTL) response which was H-2d-restricted. Two peptides, derived from the primary sequence of the H3HA2 and consistent with the predictive motif for Kd-restricted epitopes, were tested for their ability to be presented to the CTLs by P815 cells. Peptides corresponding to the amino acids 93SYNAELLVAL102 and 181GYKDWILWI189 of the HA2 primary sequence sensitized target cells for lysis by the HA2-specific CTLs. Secondary in vitro stimulation with dendritic cells as a source of antigen presenting cells treated with peptide 93-102, or infected with recombinant vaccinia virus (HA2-VACC), induced type A cross-reactive CTLs from A/Udorn/72 immune spleen cells. This CD8+ CTL epitope overlaps with an H3HA2 I-Ad-restricted T helper epitope 96-104 recently reported by others. The H3HA2 epitope described here is the first CTL epitope in the influenza hemagglutinin which is found in all three subtypes of influenza A virus.

Alleles↗
PubMed1995

Prolines and amyloidogenicity in fragments of the Alzheimer's peptide beta/A4.

Although it is well accepted that the structure of amyloid fibrils is dominated by some form of antiparallel beta-sheet, there are few details on the secondary structural arrangements of the constituent peptides and how these peptides pack together in the fibril. We describe here the use of scanning proline mutagenesis to map the secondary structural roles of each residue in amyloidogenic peptide fragments of the Alzheimer's amyloid peptide beta/A4. In two series of fragments related to residues 15-23 and 12-26 of beta/A4, we show that Pro replacement of any residue in the amyloidogenic sequence LVFFAED, corresponding to residues 17-23, leads to essentially complete loss of fibril formation and to excellent peptide solubility. Since peptidyl-prolyl bonds are incapable of forming standard extended chain conformations, the results suggest that residues 17-23 make up the beta-sheet core of the fibrils formed by these fragments. In contrast to the proline replacements, alanine substitutions at residues 17, 18, and 20 have no effect on fibril formation, while replacement of Phe19 reduces fibril formation to 15% of the level found for the wild type sequence. Scanning proline mutagenesis should play a useful role in mapping the secondary structural features of larger amyloidogenic peptide sequences, including longer, physiologically relevant forms of beta/A4. In addition, these results suggest explanations for some amyloidogenic effects observed in disease-related peptides and also suggest a possible role for aggregation-inhibiting insertion of prolines in protein evolution and protein design.

Alzheimer Disease↗
PubMed1995

Calcium dependence of the mechanical response evoked by okadaic acid in smooth muscle.

The effects of okadaic acid (OA), obtained from a culture of the marine dinoflagellate Prorocentrum lima were studied on isolated strips of rat myometrium. The contractile response evoked by OA at 5, 10, and 20 microM in normal physiological solution was unaffected in the presence of tetrodotoxin (10 microM), indomethacin (3 microM), or a cocktail of antagonists which blocked muscarinic, adrenergic, histaminergic, serotonergic, and opioid receptors. Similarly, the response to OA was unaffected in the presence of nifedipine at a concentration (1 microM) which completely or highly blocked the response to KCl (60 mM), oxytocin (1 microM), or acetylcholine (100 microM). In a Ca(2+)-free 1 mM EGTA-containing solution, the response to 10 and 20 microM OA was slightly but significantly reduced whereas the response to 5 microM OA was abolished. However, a response similar to that evoked in Ca(2+)-containing solution was observed when 5 microM OA was added to the bath in the presence of 1 microM oxytocin or 160 microM vanadate in a Ca(2+)-depleted solution with 1 mM EGTA. These data suggest that the response of rat myometrium to OA (> or = 5 microM) is not mediated through activation of membrane receptors or neurotransmitter release nor by cyclo-oxygenase products. The response to OA (10 and 20 microM) is highly resistant to the absence of calcium in the medium and does not seem to involve calcium entry through dihydropyridine-sensitive Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of okadaic acid on the human isolated bronchus.

The effects of okadaic acid, a polyether derivative of a 38-carbon monocarboxylic fatty acid obtained from a culture of the marine dinoflagellate, Prorocentrum lima, were studied on the human isolated bronchus. In low concentrations (0.01 and 0.03 microM), okadaic acid had no significant effect of its own on the human isolated bronchus, but in higher concentrations (0.1-10 microM) it induced a series of contractions and relaxations. The first contraction was of low intensity (5% of maximum response to acetylcholine 3 mM) and occurred early. The second contraction had a higher amplitude (30% of maximum response to acetylcholine 3 mM) and reached its peak with okadaic acid 0.3 microM. At higher concentrations (1-10 microM), following a relaxation phase, a later rebound contraction occurred between 70 and 120 min and corresponded to 40% of the maximum response to acetylcholine 3 mM. In addition, okadaic acid inhibited or abolished the contractile response evoked by either KCl 60 mM or acetylcholine 3 mM with IC50 of 0.04 and 0.12 microM, respectively. The second contraction evoked by 0.3 microM okadaic acid was partially inhibited in the presence of the Ca2+ channel blocker, nicardipine 1 microM, or after incubation of the human bronchus in a Ca(2+)-free solution and it was completely abolished in the presence of CdSO4 0.1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

The coronary risk of unsuspected renal artery stenosis.

PURPOSE: This study was designed to determine the prevalence of unsuspected renal artery stenoses (RAS) in patients undergoing arteriography for evaluation of aneurysmal or occlusive vascular disease and whether symptomatic coronary artery disease (CAD) is more prevalent among patients with unsuspected RAS. METHODS: We reviewed the arteriograms and medical records of 346 consecutive patients with aortic aneurysms or occlusive disease in whom RAS was unsuspected on clinical grounds. RESULTS: Aortography revealed unsuspected RAS (50% or greater diameter loss) in 98 patients (28%). Patients with RAS had a higher prevalence of mild, controlled hypertension (p < 0.001) and mild renal insufficiency (p < 0.001), but in no case was arteriography obtained to diagnose renovascular hypertension or ischemic nephropathy. Fifty-seven patients (58%) with unsuspected RAS had clinically overt CAD (documented myocardial infarction, positive coronary catheterization, previous coronary revascularization, ischemic electrocardiography changes, or angina pectoris), compared with 96 patients (39%) without RAS (p = 0.002). The correlation between the prevalence of CAD and RAS severity was highly significant (p < 0.001), and the relative odds ratio of CAD was highest for RAS measuring 75% or greater. Stepwise logistic regression analysis demonstrated three variables to be significantly and independently associated with CAD: 75% or greater RAS (p = 0.001), aortic aneurysm disease (p = 0.01), and hypertension (p = 0.001). RAS measuring 75% or greater diameter loss was associated with the highest estimated odds ratio: patients with this degree of RAS had a fourfold increase in the prevalence of clinically overt CAD. We also evaluated the relationship between RAS, mesenteric artery stenosis, and CAD; although RAS was more frequent among patients with mesenteric artery stenoses, mesenteric artery stenoses were not associated with CAD. CONCLUSIONS: Unsuspected RAS is common among patients with peripheral vascular disease and should be considered an independent marker for CAD.

Adult↗
PubMed1992

Extrathoracic carotid reconstruction: the subclavian-carotid artery bypass.

Although the predominant location of symptomatic carotid artery occlusive disease is the carotid bifurcation, proximal common carotid artery lesions cause similar symptoms. Common carotid artery lesions occur as isolated disease or in tandem with carotid bulb disease. Restoration of carotid artery inflow from subclavian based extraanatomic bypasses should provide adequate reconstruction of these lesions. To evaluate subclavian-carotid artery bypass, a retrospective review of all patients undergoing this procedure from Jan. 1, 1977, to Feb. 20, 1989, was performed. Twenty patients (14 men, 6 women) with a mean age of 60 years were treated. Fifteen patients (75%) were admitted with transient ischemic attacks. Five (25%) had nonfocal symptoms (e.g., dizziness, syncope). Arteriographic evaluation demonstrated severe proximal occlusive disease of the common carotid artery in all cases. Reconstruction bypasses were performed to the carotid bulb (45%), internal carotid artery (30%), and external carotid artery (25%). Four patients underwent endarterectomy of the internal carotid artery in conjunction with subclavian-carotid artery bypass. Bypass conduits included saphenous vein (75%) and prosthetic grafts (25%). Asymptomatic phrenic nerve neuropraxia was identified by postoperative chest radiography in four cases, with no resultant respiratory disease. No perioperative strokes occurred. One postoperative death (5%) resulted from a myocardial infarction. Long-term results were available for 18 patients (90%), with a mean follow-up of 50 months (range, 1 to 122 months). Four patients have died of causes unrelated to carotid vascular disease. Serial duplex scans have documented graft patency in all 18 patients. A single patient returned with focal neurologic symptoms as a result of a posterior circulation infarct.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗