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Biomedical subjects

G Langer

Publications and source records attributed to G Langer.

At least 19 recordsLinked to original sources
PubMed1992

Plasminogen activators from the saliva of Desmodus rotundus (common vampire bat): unique fibrin specificity.

The saliva of D. rotundus contains at least four plasminogen activators (PAs) which all require fibrin as a cofactor. D. rotundus salivary PAs (DSPAs) exhibit a sequential array of structural motifs such as "Finger" (F), "EGF" (E), "Kringle" (K) and "Protease" (P) which was elucidated by cDNA cloning and sequencing. The respective domain organizations are: FEKP (DSPA alpha 1 and DSPA alpha 2), EKP (DSPA beta) and KP (DSPA gamma). In all four forms the plasmin-sensitive site of tPA is obliterated, indicating that they function as single-chain enzymes. DSPA alpha 1 differs from alpha 2 by amino acid substitutions found mainly in the F, E and K domain, 11% of the total sequence. DSPA beta and gamma, while being closely related to alpha 2, still exhibit 2 and 13 amino acid exchanges, respectively. These sequence heterogeneities, together with results of Southern blot hybridization experiments, strongly suggest that the four DSPA mRNA species originate from different genes. All four forms of DSPA have been expressed in animal cell culture and DSPA alpha 1 was chosen for a detailed pharmacological characterization. In vitro DSPA alpha 1 activity is enhanced 50,000-fold in the presence of fibrin, whereas the activity of single chain tPA is only enhanced 100-fold. At equally effective thrombolytic doses DSPA causes lower bleeding incidence in a rat mesenteric vein model and exhibits high potency, clot selectivity, and speed in the dissolution of fibrin embolized into the lung of anesthetized rats. In the copper coil-induced dog coronary heart infarction model, at doses that achieve patency at equal rates, reocclusion is significantly less frequent than with tPA. These results indicate that DSPA alpha 1 may be a safer and more efficacious thrombolytic agent than the PAs currently in clinical use.

Amino Acid Sequence↗
PubMed1992

Mechanisms of spontaneous shift of surface electrocardiographic configuration during ventricular tachycardia.

OBJECTIVES: The aim of this study was to examine, with multichannel direct cardiac mapping techniques, the mechanisms of spontaneous shift of the QRS configuration in the surface electrocardiogram during episodes of ventricular tachycardia. BACKGROUND: Ventricular tachycardias demonstrating a spontaneous shift in their surface electrocardiographic (ECG) features are occasionally encountered. It is not known whether such changes in configuration are primarily due to a significant change in the tachycardia site of origin or represent alterations in patterns of endocardial and epicardial activation. Knowledge of these features would be helpful, particularly when ablative therapy is considered for the arrhythmias. METHODS: During map-directed cardiac surgery, episodes of ventricular tachycardia were mapped from 224 epicardial and endocardial sites. Episodes of pleomorphic tachycardia were identified and isochronal maps of endocardial and epicardial activation were constructed from representative beats before and after the change in configuration. RESULTS: From 52 consecutive patients who underwent detailed intraoperative mapping, 9 patients with pleomorphic ventricular tachycardia were identified in whom 14 episodes of spontaneous shift occurred. An analysis of the epicardial activation patterns revealed that the sites of earliest epicardial breakthrough showed significant alteration at the time of QRS shift in all occurrences. In 10 of these shift episodes, however, the sites of tachycardia origin, located on the endocardial surface, remained closely adjacent (< 2 cm apart). Although these sites of origin remained relatively constant, significant alterations in the patterns of endocardial activation were seen in most episodes. These included changes in the direction of propagation of the wave front of activation and shifts between monoregional and figure eight patterns of activation. CONCLUSIONS: In most episodes of pleomorphic ventricular tachycardia, the arrhythmia site of origin remains relatively constant. However, patterns of epicardial activation do undergo significant change and appear to be the major determinant of the QRS configuration on the surface ECG.

Cardiac Pacing, Artificial↗
PubMed1979

Normal prolactin responses in tardive dyskinesia.

Tardive dyskinesia has been hypothesized to be caused by a neuroleptic-induced dopamine hypersensitivity in the nigrostriatal system. This study evaluated with dopamine antagonists the possibility that such dopamine hypersensitivity extends to the tuberoinfundibular dopamine (TIDA) system, which regulates, by inhibition, pituitary prolactin secretion. Plasma prolactin concentrations in six patients with tardive dyskinesia were assessed in four conditions: During chronic haloperidol therapy; serially after abrupt haloperidol withdrawal; while unmediated; and in response to an acute dose of 0.5 mg IM haloperidol. In all four conditions, prolactin responses did not differ from those observed in normal subjects and schizophrenic patients without tardive dyskinesia. It is concluded that there is no evidence for post-synaptic dopamine hypersensitivity in the TIDA-pituitary pathway in patients with tardive dyskinesia, consistent with other reports assessing hormonal responses to dopamine agonists in such cases. It is further suggested that neuroleptic-induced dopamine hypersensitivity does not occur in the TIDA-pituitary system in humans, since it was not manifest in these tardive dyskinesia patients who would be thought particularly prone to develop it.

Adult↗
PubMed1979

Dopaminergic factors in human prolactin regulation: a pituitary model for the study of a neuroendocrine system in man.

This study in normal male subjects further investigates the effects of dopaminergic-antidopaminergic interactions as manifested by the prolactin response to dopamine and neuroleptic drugs. Incremental doses of dopamine hydrochloride (4 microgram/min, 15 microgram/min, 60 microgram/min, 300 microgram/min) were infused at a constant rate over 90-120 min after a fixed dose of a neuroleptic drug (sufficient for about half of the maximal prolactin response) had been given IV. A dose of dopamine in the order of 15-60 microgram/min appeared to match the "loss" of endogenous dopaminergic inhibition due to the antidopaminergic effect of the neuroleptic drug. The lactotrophic cells of the pituitary gland are suggested to serve as a model in man for the study of some basic neurohormonal mechanisms.

Adult↗
PubMed1979

Diurnal variation in the response of plasma prolactin, cortisol, and growth hormone to insulin-induced hypoglycemia in normal men.

Plasma PRL, cortisol, and GH responses to a standard iv dose of regular insulin were studied during the morning and evening in seven normal young men. Hypoglycemia achieved during morning and evening in the same aubjects was equal. There was a substantially greater maximal increment in PRL in the evening compared to the morning (P less than 0.01). The peak levels of cortisol achieved in the morning and evening were equal, but the evening maximal increase was greater (P less than 0.05) because of the significantly lower evening basal cortisol level. Evening increases in GH were greater than in the morning in five subjects and were essentially the same in two subjects; for the group, the evening maximal increment in GH was significantly greater (p less than 0.05 after log transformation). Since serotonergic mechanisms appear to be involved in the PRL, GH, and cortisol responses to hypoglycemia, we suggest the possibility of a diurnal variation in hypothalamic serotonin activity which may partly mediate these differential diurnal hormonal responses to hypoglycemia (although other neurotransmitters may also be involved). The data on cortisol are discussed with regard to the reset hypothesis of feedback inhibition.

Circadian Rhythm↗
PubMed1978

Prolactin responses to neuroleptics in normal and schizophrenic subjects.

The prolactin response to neuroleptics can serve as an index of dopamine blockade in humans. Plasma prolactin increments to single doses of chlorpromazine, and prolactin decrements to single doses of levodopa, were similar in normal and schizophrenic subjects. Antischizophrenic drugs of all chemical classes stimulated prolactin release,while chemically related drugs and other psychotropic agents ineffective in schizophrenia did not. The prolactin response to neuroleptic therapy occurred in all patients, and tolerance did not develop. Within subjects, prolactin responses were graded according to neuroleptic dose, but the upper limit of sensitivity of the response curve was achieved at doses below the therapeutic range. Relative prolactin-stimulating potency in humans of chlorpromazine, thioridazine, trifluoperazine, butaperazine, and haloperidol correlated well with their relative clinical potencies.

Chlorpromazine↗
PubMed1978

Relation of plasma prolactin to clinical response in schizophrenic patients.

It has been suggested that, if dopamine antagonism is a necessary condition for the antischizophrenic action of neuroleptics, the prolactin response, as an index of dopamine blockade, would correlate with clinical response. Morning prolactin and clinical symptomatology were measured in 15 schizophrenic patients before neuroleptic therapy, and after three and six weeks of high-dose butaperazine or loxapine treatment. Prolactin levels were transiently elevated during the unmedicated admission period, probably reflecting a normal stress response. Prolactin increased in all patients during neuroleptic therapy. There was, however, no correlation between magnitude of prolactin changes and clinical response, probably because the prolactin response achieved a maximum at relatively low doses of neuroleptics.

Adult↗
PubMed1978

[Neuroendocrinology in depression and schizophrenia (author's transl)].

In the introduction the heuristic basis of neuroendocrinology and the relationship to current concepts in biological psychiatry is analyzed. Various neuroendocrinological approaches to the study of depressive and schizophrenic disorders are then exemplified by the discussion of selected papers. In contrast to studies in schizophrenic patients abnormal findings have been found, by several research approaches, in endogenous-depressive patients. These findings are consistent with the hypothesis of a disfunction of biogenic amines in endogenous depression; however, considering the neuroendocrinological methodology at hand these findings are not conclusive.

Depression↗