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Biomedical subjects

D Gutmann

Publications and source records attributed to D Gutmann.

14 recordsLinked to original sources

Differential cellular expression of neurotrophins in cortical tubers of the tuberous sclerosis complex.

Neurotrophins and their receptors modulate cerebral cortical development. Tubers in the tuberous sclerosis complex (TSC) are characterized histologically by disorganized cortical cytoarchitecture and thus, we hypothesized that expression of neurotrophin mRNAs and proteins might be altered in tubers. Using in situ transcription and mRNA amplification to probe cDNA arrays, we found that neurotrophin-3 (NT3) and trkB mRNA expression were reduced whereas neurotrophin-4 (NT4) and trkC mRNA expression were increased in whole tuber sections. Alterations in mRNA abundance were defined in single microdissected dysplastic neurons (DNs) and giant cells (GCs). NT3 mRNA expression was reduced in GCs and trkB mRNA expression was reduced in DNs. NT4 mRNA expression was increased in DNs and trkC mRNA expression was increased in both DNs and GCs. In three patients, TSC2 locus mutations were confirmed and the mean tuberin mRNA expression levels was reduced across all nine cases. Consistent with these observations, NT3 mRNA expression was reduced but trkC mRNA expression was increased in vitro in human NTera2 neurons (NT2N) transfected with a tuberin antisense construct that reduced tuberin expression. Western analysis of tuber homogenates and computer-assisted densitometry of immunolabeled sections confirmed the neurotrophin mRNA expression data in whole sections and single neurotrophin immunoreactive cells. We conclude that alterations in NT4/trkB and NT3/trkC expression may contribute to tuber formation during brain development as downstream effects of the hamartin and tuberin pathway in TSC.

Adolescent↗

Ras-GTP levels are elevated in human NF1 peripheral nerve tumors.

Neurofibromin, the gene product of NF1, is a Ras GTPase Activating Protein. The absence of neurofibromin leads to increased levels of Ras-GTP, which contributes to the proliferation of NF1 neurogenic sarcoma cell lines. Whether this pathogenic mechanism is applicable to benign and malignant peripheral nerve tumours from NF1 and non NF1 patients is not known, due to lack of a tissue based assay. We have adapted a colorimetric enzymatic assay for determining levels of Ras bound guanine nucleotides in tissues. Ras-GTP levels were increased in NF1 neurogenic sarcomas (15 times) and benign NF1 neurofibromas (four times), compared to non NF1 schwannomas. Neurofibromin was not expressed in NF1 sarcomas, in support of its important negative Ras regulatory role in the pathogenesis of NF1 peripheral nerve tumors.

Base Sequence↗

Mourning the loss of "self as father": a longitudinal study of fatherhood among the Druze.

It is within the context of the parent-child relationship--through the processes of attachment, loss, separation and individuation--that we grow and develop interpersonally and intrapsychically (Bowlby 1969, 1980; Mahler et al. 1975; Pollock, 1989). Most developmentalists agree that changes in the parent-child relationship continue to influence both parents and children throughout the life cycle (Cohen et al. 1984; Colarusso and Nemiroff 1982). While there is a vast body of literature devoted to discussing changes that occur in the parent-child relationship during the "formative years," little has been written about what happens to that relationship after the children leave home to start families of their own. Moreover, most researchers investigate the processes of attachment, loss, separation and individuation in terms of the child's development. Little is known about how the child's quest for independence affects the psychological development of his/her parents. Those writers who have addressed the issue of individuation in later life tend to focus on the adult child's continuing struggle to separate and individuate from his/her real or imagined parents (Levinson, 1978).

Adaptation, Psychological↗

Two kinds of radicals: a discriminant analysis of a projective test.

Rorschach tests were administered to 36 subjects grouped according to ethnicity and political ideology. Pairwise discriminant analyses of scores significantly differentiated both Jewish and non-Jewish radicals from nonradicals in a manner consistent with previous survey findings.

Journal Article↗