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Biomedical subjects

J E Kolb

Publications and source records attributed to J E Kolb.

9 recordsLinked to original sources

Brain-derived neurotrophic factor increases activity of NR2B-containing N-methyl-D-aspartate receptors in excised patches from hippocampal neurons.

Growth factors, including members of the neurotrophin gene family, play a central role in the regulation of neuronal survival and differentiation during development. In addition to these relatively long-term actions of neurotrophins, recent studies have shown that these factors also rapidly modulate synaptic transmission. Brain-derived neurotrophic factor (BDNF), in particular, regulates both pre- and postsynaptic aspects of hippocampal synaptic transmission. The postsynaptic effects include an increase in glutamate responsiveness, mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. It is not clear, however, where BDNF-trkB signal transduction is initiated, because trkB receptors are located in both pre- and postsynaptic membranes. In the present study, we used excised membrane patches from cultured hippocampal neurons to determine whether BDNF directly modulates postsynaptic NMDA receptor activity. The results indicate that acute exposure to BDNF increases NMDA single channel open probability via postsynaptic trkB receptors and that this effect is dependent on the presence of the NR2B subunit of the NMDA receptor.

2-Amino-5-phosphonovalerate↗

Ethanol modulation of GABA-activated current responses in acutely dissociated retinal bipolar cells and ganglion cells.

This study examined the effect of acute ethanol exposure on GABA-activated whole-cell current responses elicited in bipolar cells and ganglion cells of the rat retina. Acute exposure to ethanol potentiated GABA responses in 86% of the bipolar cells and in 52% of the ganglion cells tested. As determined in bipolar cells, ethanol was maximally effective at a concentration of 50 mM. In bipolar cells, a GABAC receptor-mediated component of the whole-cell response to GABA could be uncovered which was also potentiated by ethanol. However, ethanol was ineffective in enhancing bipolar cell responses to glycine. GABA-activated current responses monitored in ganglion cells that were insensitive to modulation by ethanol were sensitive to potentiation by diazepam. At higher concentrations (100-175 mM), ethanol by itself occasionally induced a chloride-mediated current but this occurred independent of an ethanol-induced potentiation of GABA responses. These data establish that ethanol can modulate the sensitivity of retinal neurons to GABA. Overall, the results presented in this study set the stage for future studies to examine the cellular and molecular bases for a differential neuronal sensitivity to an ethanol-induced modulation of GABA responses.

Animals↗

Pneumothorax and wound dehiscence related to collagenase deregulation: treatment with diphenylhydantoin.

BACKGROUND: Wound dehiscence is an uncommon complication of operation, usually related to a recognized risk factor. A clinical dilemma arises when dehiscence has no identifiable cause or treatment. METHODS: We describe the case of a previously healthy 45-year-old man in whom recurrent spontaneous pneumothoraces developed followed by multiple dehiscences of thoracotomy, diaphragmatic, and abdominal wounds. Analysis over several years of laboratory investigation of cultured tissue from test incisions was initially unsuccessful. The patient was supported symptomatically until a remarkable laboratory finding enabled us to develop an effective treatment plan. RESULTS: Cultured patient fibroblasts were ultimately found to express abnormally elevated levels of collagenase, which could be inhibited by diphenylhydantoin (phenytoin) in vitro. Treatment of the patient with a course of diphenylhydantoin allowed adequate healing of test incisions and subsequent definitive surgical treatment with successful wound healing. CONCLUSIONS: This report of the rigorous application of the scientific method to the investigation and treatment of an enigmatic case of wound dehiscence might serve as a guide to surgeons faced with similar healing problems.

Abdomen↗

The diagnostic interview for borderline patients.

The authors describe the content, administration, reliability, construct validity, and training requirements for a semistructured diagnostic interview for borderline patients. The interview is composed of operationally defined and scored variables that assess five areas of functioning considered most characteristic of borderline patients--social adaptation, impulse/action patterns, affects, psychosis, and interpersonal relations. Their results show that the interview provides a reasonably constructed and reliable method for researchers and clinicians interested in identifying the syndrome of borderline personality disorders. Although existing research supports the clinical utility of defining borderline patients with the diagnostic interview for borderline patients, both the diagnosis and the content of the interview may require revisions.

Borderline Personality Disorder↗

Diagnosing borderline patients with a semistructured interview.

As a part of an ongoing effort to provide operational criteria for a diagnosis of borderline personality disorder, the Diagnostic Interview for Borderlines (DIB) has been developed. The DIB is an hour-long, semistructured interview that evaluates five areas of borderline pathologic features--social adaptation, impulse/action patterns. affects, psychotic symptoms, and interpersonal relations. The DIBs were administered to 70 hospitalized patients and compared with clinical diagnoses made at the time of discharge. The DIB discriminates borderline patients from others, especially from schizophrenic and neurotic depressives. It reflects clinical diagnosis, yielding higher scores for patients on whom there is more agreement on the diagnosis of borderline. The instrument can be used flexibly to identify populations of borderline patients for research purposes.

Adjustment Disorders↗

Discriminating features of borderline patients.

Borderline patients were compared with schizophrenic patients, neurotic depressed patients, and a group of patients with differing diagnoses. The purpose of this comparison was to find out whether borderline patients could be discriminated from other psychopathological groups and whether a discrete list of recognizable characteristics discriminating borderline patients could be isolated. According to the results of the comparison, borderline patients can be discriminated with high accuracy from matched comparison groups with whom diagnostic confusion is common. Seven criteria provided a clinically sensible and practical means of approaching the diagnosis of borderline disorder.

Adjustment Disorders↗

Lateralized neurologic deficits and psychopathology in a Turner syndrome patient.

A Turner syndrome patient has been studied by more extensive neuropsychological testing than has previously been reported with such patients. Testing indicates impairment of a variety of functions normally subserved by the right cerebral hemisphere. If replicated with other Turner patients, a lateralized neurologic deficit is implicated as part of the syndrome. Also, this case illustrates the importance of family support and sensitive professional treatment in determining the psychological outcome of this disorder. As an important therapeutic consideration, we describe psychologically detrimental effects of delayed estrogen treatment with an older Turner syndrome patient.

Adult↗

A late defect in wound healing associated with recurrent spontaneous pneumothoraces: a presumptive role for abnormal collagenase activity.

This case report concerns an individual with a defect in wound healing which resulted in recurring, bilateral pneumothoraces during the late postoperative period. This patient had no history of systemic disease or wound healing abnormalities before his recurrent wound disruption. Physical examination and routine biochemical studies failed to identify any causative agent for the multiple wound dehiscences in the patient. Histologic examination of scar tissue showed collagen fiber bundles with a diameter 50% less than that of normal fibrils. Elastic fibers were barely visible, and the scar tissue included a large number of inflammatory cells. A significant finding was an elevated and aberrant expression of collagenase by a fibroblast cell line established from a skin biopsy specimen. This enhanced level of collagenase expression could be inhibited by treatment of the cells with diphenylhydantoin, an inhibitor of collagenase biosynthesis. After initiation of diphenylhydantoin therapy, the patient's scar formation normalized with the recurrent pneumothoraces. These findings support the conclusion that an abnormal expression of collagenase resulted in enhanced degradation of collagen in the patient's wounds, thereby leading to wound dehiscence.

Journal Article↗