Search PubMed⌕ Search

Biomedical subjects

L Rosenthal

Publications and source records attributed to L Rosenthal.

At least 91 records · Page 5Linked to original sources

Mode of action of alpha-latrotoxin: role of divalent cations in Ca2(+)-dependent and Ca2(+)-independent effects mediated by the toxin.

The potent neurotoxin alpha-latrotoxin (alpha LTx), from black widow spider venom, induces neurotransmitter release in both Ca2(+)-containing and Ca2(+)-free medium, following interaction with a specific cell surface receptor. Binding studies revealed two populations of alpha LTx binding sites in bovine synaptosomal membranes, showing the same high affinity (Kd, 0.3 x 10(-10) M) for alpha LTx, with approximately 50% of the sites being Ca2+ sensitive and the rest being Ca2+ insensitive. In contrast, in PC12 cells alpha LTx binding was completely unaffected by the removal of extracellular Ca2+ (Kd, 5 x 10(-10) M). The use of La3+ as an inhibitor of alpha LTx action, previously shown in synaptosomes, was extended to PC12 cells. In this system, La3+ (100 microM) was shown to inhibit Ca2+ influx, both Ca2(+)-dependent and -independent dopamine release, and polyphosphoinositide (PPI) hydrolysis induced by alpha LTx. At the same time, La3+ did not block alpha LTx binding or dopamine release evoked by either the ionophore ionomycin (0.5 microM) or the phorbol ester tetradecanoylphorbol acetate (100 nM). La3+ also blocked the influx of Mn2+ ions through the alpha LTx-induced cation channel, as measured by quenching of fura-2 fluorescence. In this PC12 cell line, PPI hydrolysis could also be induced by ionomycin, but only when it was present at concentrations that caused an elevation of free intracellular Ca2+ ([Ca2+]i) that was not transient but was as persistent as that evoked by alpha LTx. Our conclusions with regard to the mode of action of alpha LTx are as follows. (i) All the effects of alpha LTx in PC12 cells (dopamine release, PPI hydrolysis, and Ca2+ influx) can be mediated via a single, Ca2(+)-insensitive alpha LTx receptor. (ii) alpha LTx-induced PPI hydrolysis is most likely due to the activation of a Ca2(+)-sensitive phospholipase C following the persistent rise in [Ca2+]i elicited by the toxin in Ca2(+)-containing medium, and not via direct coupling of the alpha LTx receptor to the enzyme. (iii) Toxin-evoked Ca2(+)-independent dopamine release can be blocked by La3+ at the extracellular level, most likely by prevention of the entry of divalent cations.

Animals↗

Clinical, HLA, and roentgenological follow up study of patients with juvenile arthritis: comparison between the long term outcome of transient and persistent arthritis in children.

Fifty two patients with juvenile chronic arthritis (JCA) and 22 patients with arthritis of short duration (transient arthritis, TA) were studied in a follow up investigation. Nineteen (37%) of the patients with JCA had peripheral arthritis or sequelae in the form of contractures at follow up, and in addition one patient was treated with corticosteroids. In contrast, only one (5%) of the 22 patients with TA had peripheral arthritis at follow up. Back pain or limitation, or both, was registered in many of the men. Sacroiliitis, verified by x ray, was often found both in JCA (39/46, 85%) and in TA (16/21, 76%). For JCA an association was confirmed with HLA-A2 and HLA-DRw8 and a negative association with HLA-DR4, and in pauciarticular JCA, in addition, a decrease of DR7. A new finding was a low prevalence of HLA-B27 in women with JCA and grade 3 or 4 sacroiliitis (2/14, 14%).

Adolescent↗

DERM/INFONET: a concept becomes a reality.

The DERMatology INFOrmation NETwork (DERM/INFONET) of the American Academy of Dermatology has become a reality. DERM/INFONET consists of a number of data bases providing information and educational programs for the dermatologist. Currently the components are: DERM/MLS (Medical Literature Search), DERM/RX (dermatologic therapy), DERM/USP (United States Pharmacopeia data base), DERM/ALLERGENS (Food and Drug Administration and Environmental Protection Agency Listings of allergens); Melanoma Prognosis Model; Electronic Mail; Bulletin Board; Meetings Calendar; ICD/CPT (International Classification of Diseases/Current Procedural Terminology) codes; AAD Membership/Committee Directories; and Dermatology Quiz. Additional data bases are planned. As audiovisual and alphanumeric communication systems evolve, newer opportunities for enhancing the DERM/INFONET Biomedical Communication Network will undoubtedly provide even greater opportunities for aiding the dermatologist in delivering state-of-the art management for their patients.

Computer Communication Networks↗

Peripheral mucociliary clearance with high-frequency chest wall compression.

We investigated the effects of high-frequency chest wall compression (HFCWC) on peripheral and tracheal mucus clearance in anesthetized spontaneously breathing dogs. HFCWC was achieved by oscillating the pressure in a thoracic cuff with a piston pump. Regional lung retention of a technetium-99m sulfur colloid aerosol was monitored with a gamma camera. A peripheral mucus clearance index (PMCI) was defined for each region of interest. The tracheal mucus clearance rate (TMCR) was determined by bronchoscopic visualization of marker particle transport. Phase I: In seven dogs, 30 min of HFCWC at 13 Hz with peak cuff pressure (Pcuff) 100-120 cmH2O was found to significantly enhance PMCI in regions immediately under the cuff. (delta PMCI = 24.4 +/- 4.6 in the basal peripheral region.) Phase II: Because of subpleural hemorrhage in phase I, the effect of HFCWC on TMCR at various Pcuff levels was studied in five dogs. The enhancement of TMCR by HFCWC reached a plateau level at Pcuff = 50 cmH2O. Phase III: HFCWC at 13 Hz with Pcuff = 50-60 cmH2O was found to significantly enhance PMCI in five dogs without the consequence of hemorrhage. Correlations were found between the enhancement of PMCI and TMCR by HFCWC. These results demonstrate that HFCWC is effective in enhancing both peripheral and central mucus clearance in dogs and safe when moderate pressures are applied.

Animals↗

Periodic movements during sleep, sleep fragmentation, and sleep-wake complaints.

To better understand the relation of sleep complaint to sleep continuity and periodic movements during sleep (PMS), two groups of patients were studied retrospectively. One group of 51 patients, 26 men and 25 women, with a mean age of 56.4 years, complained of insomnia. The other group of 29 patients, 20 men and nine women, with a mean age of 55.8 years, complained of excessive daytime sleepiness. Sleepy patients differed significantly from insomnia patients in that they fell asleep faster and slept longer. They showed more frequent arousals (shifts to stage 1 sleep and number of awakenings) than insomnia patients who had longer arousals (mean duration of awakenings). Insomnia patients had more series of PMS, but sleepy patients had more PMS bursts per series.

Arousal↗

[Sacroiliitis].

Explore the source record for details and available documents.

Arthritis↗

Dynamic and biochemical responses to single and repeated doses of clonidine during dynamic physical activity.

Beta-adrenoceptor blockade increases serum K, which may be related to renin inhibition, hypoaldosteronism, and exercise-induced skeletal muscle release of serum K. We report on the dynamic and biochemical response to clonidine (C) after single (S) 0.2-mg and repeated (R) 0.1-mg bid doses of C to six normal subjects at rest, 2 hr after dosing and immediately before dynamic physical activity (DPA) on a treadmill, and at peak activity and 2 hr after DPA. Blood pressure (BP), heart rate (HR), plasma renin concentration (PRC), aldosterone (ALD), serum K, epinephrine (E), and norepinephrine (NE) were measured in standing subjects before and 2 hr after placebo or C (S or R), at peak DPA, and 2 hr after exercise. K, BP, and HR were also determined during all stages of DPA. Results show a parallel rise in K at peak over rest after C (S or R) and after placebo. NE, E, and PRC decreased after 1 wk of C (P less than 0.01), but the fall of ALD was only slight. The fall in NE at rest suggested a relationship to the decrease in systolic BP and rate pressure product after 1 wk on C. With DPA there is a normal yet smaller increase in systolic BP and also a smaller rise in HR with S- and R-dose C. There is no adverse rise in K in C-treated subjects during DPA.

Aldosterone↗

Biochemical and dynamic responses to single and repeated doses of methyldopa and propranolol during dynamic physical activity.

Our purpose was to describe changes in potassium disposition with antirenin antihypertensives during dynamic physical activity in normal subjects receiving methyldopa and propranolol. Before the study, 2 hr after dosing and coincident with immediate preexercise on treadmill (at graded increases of exercise), and 2 hr after exercise, blood was sampled for determination of potassium, renin, aldosterone, and catecholamine levels. Blood pressure and heart rate were measured. The results demonstrate no greater increase in potassium after single or multiple doses of methyldopa than after placebo. After the first dose of propranolol there was a greater rise in potassium over that with placebo, but it was not observed after multiple doses, which may be related to the low doses. There were minor, but significant, changes in norepinephrine, renin, and systolic pressure with multiple-dose methyldopa and in renin, heart rate, and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses to exercise win methyldopa and propranolol were biochemically altered rather than functionally impaired. The latter is related to dose and the underlying age and state of health of our subjects. Methyldopa (or clonidine) may be useful in patients with hypertension who exercise and are predisposed to pertubations in potassium disposition.

Adult↗

Potassium disposition and neuroendocrine effects of propranolol, methyldopa and clonidine during dynamic exercise.

In order to determine the changes in potassium disposition with antirenin, antihypertensives during dynamic physical activity, a double-blind placebo controlled study was undertaken using normal volunteers receiving placebo or single and multiple dose clonidine, methyldopa and propranolol 0.2 mg. followed by 0.1 mg. bid x 7 days, 500 mg. followed by 250 mg. bid x 7 days or 80 mg. followed by 40 mg. bid x 7 days, respectively. Prior to study, 2 hours post dosing and coincident with immediate pre-exercise on treadmill, at graded increases of exercise and 2 hours post exercise (approximately 4 hours post dosing), blood was sampled for potassium, renin concentration, aldosterone and catecholamines. Blood pressure (BP) and heart rate (HR) were measured. The results demonstrate no greater increase in potassium over placebo with single or multiple dose clonidine or methyldopa. Following the initial dose of propranolol, 80 mg., there was a statistically greater rise in potassium over that seen with placebo but not observed with multiple dose. This may be related to the low multiple dose regimen. There were minor but significant changes in norepinephrine, renin and systolic pressure with multiple dose clonidine and methyldopa and in renin, heart rate and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses, to exercise with methyldopa and propranolol are more biochemically altered than functionally impaired, yet the latter is related to dose and the underlying age and state of health of the group being studied.

Aldosterone↗

Clonidine and lidamidine (WHR-1142) stimulate sodium and chloride absorption in the rabbit intestine.

The effects of clonidine and lidamidine on ion transport in the intestine of the rabbit were determined. In the ileum both clonidine (10(-6) M) and lidamidine (10(-3) M) (a) decreased the short circuit current (-1.9 +/- 0.3 and -2.0 +/- 0.4 muEq/h . cm2, respectively) and potential difference; (b) increased net sodium absorption (2.0 +/- 0.6 and 1.8 +/- 0.4 muEq/h . cm2) and chloride absorption (3.4 +/- 0.5 and 3.4 +/- 0.6 muEq/h . cm2); and (c) increased tissue conductance (8.7 +/- 1.7 and 10.0 +/- 1.6 mmho/cm2). The increase in net sodium and chloride absorption was primarily due to an increase in mucosal-to-serosal movement of the ions and a decrease in serosal-to-mucosal movement of chloride. The action of clonidine on the short circuit current was quantitatively similar to the action of epinephrine. Both were readily reversed by yohimbine, a specific alpha 2-adrenergic antagonist. Further, methoxamine, an alpha 1-adrenergic agonist has no effect on the short circuit current up to the concentration of 10(-5) M; and prazosin, an alpha 1-adrenergic antagonist, did not affect the change of the short circuit current induced by epinephrine. The results indicate the presence of alpha 2-adrenergic receptors on the intestine and suggest that alpha 2-adrenergic stimulation may account for the effect of epinephrine on ion transport. Lidamidine was studied because it is structurally related to clonidine and has many similar actions. Yohimbine transiently reversed the effect of lidamidine. alpha 1-Adrenergic or dopaminergic antagonists did not reverse the effect of lidamidine, suggesting that it may affect alpha 2-adrenergic receptors. The results indicate that both clonidine and lidamidine stimulate electrolyte absorption and may be clinically useful.

Action Potentials↗

Activated T cells in the synovial fluid of arthritic patients. II. In vitro activation of the autologous blood lymphocytes.

Lymphocytes isolated from the synovial fluid of arthritic patients were shown to express characteristics of immunoactivated T cells, such as the formation of stable E rosettes and natural attachment to normal and malignant cells. During 5 days incubation in autologous serum, the synovial T cells reverted to resting state. If, however, the synovial serum was present in the culture, the activated state was maintained. The blood lymphocytes of these patients did not have the markers of activation. When blood lymphocytes were mixed in vitro with the autologous synovial T cells, a proportion of them acquired the capacity to form stable E rosettes and to express natural attachment. Synovial polymorphonuclear cells or synovial serum were without effect on the blood lymphocytes. This phenomenon may represent an in vivo mechanism for the perpetuation of the cellular immune reactivity in the joint cavity.

Arthritis, Rheumatoid↗

Aseptic arthritis after gonorrhoea.

Sixteen patients with aseptic arthritis developing after gonorrhoea and 14 patients with arthritis after nongonococcal urogenital infection have been analysed with respect to clinical course, roentgenological signs, and humoral as well as cellular immune responses to Neisseria gonorrhoeae antigen. Fifty-eight healthy blood donors were used as controls. The clinical pattern did not differ significantly between the 2 groups. Eye or skin lesions indicative of Reiter's syndrome were found in 5 patients of both groups. Signs of sacroiliac arthritis were found in 8 and 6 patients respectively. Gonococcal complement fixation was positive in 9 of 16 patients in the postgonorrhoeal arthritis group and in 0 of 14 patients in the arthritis group with nongonococcal urogenital infection. The lymphocyte stimulation induced by gonococcal antigen was significantly greater in patients with postgonorrhoeal arthritis than in healthy controls. When reference was made to the results of stimulation of the lymphocytes with PPD, there was also a significant difference in the lymphocyte reactivity to gonococcal antigen between the group of patients with postgonorrhoeal arthritis and that of patients with arthritis after non-gonococcal urogenital infection. No such difference was noted between the latter group and the healthy controls. The clinical and immunologic data argue in favour of the hypothesis that Neisseria gonorrhoeae may induce an aseptic arthritis which sometimes presents as a complete Reiter's syndrome.

Adult↗

Psychopathology among children of manic-depressive patients.

Twenty-seven individuals with bipolar illness were interviewed concerning their children who were between the ages of 6 and 18 years. The structured interview included items concerning the behavior of the child during the previous year, as well as items concerning events which may have affected the child. Of 49 children, 4 were considered to have an affective disorder and 18 were considered to have an undiagnosed disorder. A child was more likely to have a disorder if the natural parents were divorced. This difference was significant. When the child was living with both natural parents, the presence of a mental illness in the nonproband parent did not increase the likelihood of illness in the child. This difference was significant. The presence of illness in the child did not seem to be related to the severity of bipolar illness in the proband parent.

Adolescent↗