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Biomedical subjects

J A Clausen

Publications and source records attributed to J A Clausen.

At least 19 recordsLinked to original sources

GAP-43 immunoreactivity of subepithelial and detrusor muscle nerve fibres in patients with refractory idiopathic detrusor overactivity.

AIMS: To determine the relative density of nerve fibres immunoreactive to growth associated protein-43 (GAP-43, an indicator of neuronal sprouting) in the subepithelium and detrusor of patients with idiopathic detrusor overactivity (IDO). To investigate the effect, if any, of age and previous recurrent bacterial cystitis on neuronal sprouting in such patients. MATERIALS AND METHODS: A series of 18 women with urodynamically proven IDO (median age 62 years, range 39-85), who were refractory to treatment, underwent cystoscopy and cold cup biopsy. Controls (n=26, median age 65, range 32-79) were females without urgency/urge incontinence, undergoing cystoscopy for other indications. Recurrent proven bacterial cystitis (rUTI) was documented. Frozen sections were stained with specific antibodies to GAP-43 and protein gene product 9.5 (PGP, a general neuronal marker). The area represented by immunoreactive (ir) subepithelial or muscle nerve fibres was measured. RESULTS: The density of GAP-43ir and PGPir nerves did not differ significantly between IDO patients and controls, in either subepithelium or detrusor. The GAP-43ir nerve density (as percent of PGPir) increased significantly with advancing age amongst patients with IDO in the detrusor muscle but not in the subepithelium; density in controls was unaltered. In IDO patients with rUTI, a significant increase in GAP-43 (as percent of PGPir) was observed in the subepithelium. CONCLUSIONS: Although we found no evidence of increased neuronal proliferation in patients with IDO generally, the increase in GAP-43 with age and with previous cystitis history suggests that neuronal sprouting is important in some subsets of patients with IDO.

Adult↗

The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex.

The cerebral cortex develops from the dorsal telencephalon, at the anterior end of the neural tube. Neurons are generated by cell division at the inner surface of the telencephalic wall (in the ventricular zone) and migrate towards its outer surface, where they complete their differentiation. Recent studies have suggested that the transcription factor Pax6 is important for regulation of cell proliferation, migration and differentiation at various sites in the CNS. This gene is widely expressed from neural plate stage in the developing CNS, including the embryonic cerebral cortex, where it is required for radial glial cell development and neuronal migration. We report new findings indicating that, in the absence of Pax6, proliferative rates in the early embryonic cortex are increased and the differentiation of many cortical cells is defective. A major question concerns the degree to which cortical defects in the absence of Pax6 are a direct consequence of losing the gene function from defective cells themselves, rather than being secondary to abnormalities in other cells. Cortical defects in the absence of Pax6 become much more pronounced later in cortical development, and we propose that many result from a compounding of abnormalities in proliferation and differentiation that first appear at the onset of corticogenesis.

Animals↗

[Determination of the expected day of delivery--ultrasound has not been shown to be more accurate than the calendar method].

It has been claimed that the expected day of delivery (EDD) determined on the basis of an ultrasound scan is more accurate than using a calendar method. The aim of this paper is to assess the evidence in support of this claim. A critical review of the methodologically best research revealed that among women with regular cycles and know first day of the last menstrual period, Naegele's rule predicted the EDD to be 3.3 days too early, on average, whereas prediction based on ultrasound scans was 2.0 days too late. The standard deviations of the two distributions were the same. After correction for the systematic biases, the two methods of prediction were thus equally precise. It is concluded that the EDD should be calculated by adding 283 days to the date of the last period rather than by adding 280 days. For women with regular cycles and known first day of the last menstrual period, ultrasound dating does not lead to a more precise prediction.

Delivery, Obstetric↗

A role for neurotrophins in the survival of murine embryonic thalamic neurons.

The mechanisms that determine whether developing CNS neurons live or die are poorly understood. We studied the role of the neurotrophins and fibroblast growth factors in the survival of embryonic thalamic neurons in culture. Dissociated embryonic dorsal thalamic neurons cultured at high density in defined serum-free medium survived and grew neurites. As in vivo, they expressed all the neurotrophins, fibroblast growth factor-1 and their high-affinity tyrosine kinase receptors. The survival of these cells was reduced by the addition of the protein kinase inhibitor K252a at concentrations that block neurotrophin receptor activity but not the activity of other tyrosine kinase receptors. In low-density cultures, most dorsal thalamic neurons died, but their survival was increased by co-culture with thalamic explants or with most of the neurotrophins and fibroblast growth factor-1 added singly. These results indicate that thalamic neurons have remarkably promiscuous trophic responses to a battery of neurotrophins and fibroblast growth factors. They suggest that neurotrophins endogenous to the early embryonic thalamus may be required to promote the survival of its neurons.

Animals↗

The distribution of actin immunoreactivity in rhabdomeres of tipulid flies in relation to extracellular membrane shedding.

Rhabdomeres of tipulid flies lose membrane during turnover from a 'shedding zone' composed of microvillar tips. These distal domains lack intramicrovillar cytoskeletons and appear to be empty sacs of membrane. Recent concerns about the role of ninaC mechano-enzymes in the architecture of dipteran rhabdomeral microvilli and the dynamic role that they may play in the creation of shedding zones demand an examination of the distribution of actin in tipulid rhabdomeres. We compared rhabdomeres from tipulid retinae incubated before fixation for immunocytochemistry in a buffer without additives and a stabilising buffer that contained a cocktail of cysteine protease inhibitors; both were challenged by an anti-actin antibody for immunogold labelling after embedding in LR White Resin. Shedding zones thus processed collapse to structureless detritus. Stabilised and unstabilized shedding zones were immunonegative to anti-actin. To ensure that the negative results were not consequent upon conformational changes generated by the processing protocol, we examined microvilli of degenerating rhabdomeres of the Drosophila light-dependent retinal degeneration mutant rdgBKS222 (which separate and collapse without creating a shedding zone) and found the detritus they generate to be immunopositive to anti-actin. Stabilised and unstabilized regions of basal regions of tipulid rhabdomeres were equally immunopositive. We infer that (a) actin is absent from shedding zones; (b) actin is not degraded by microvillar cysteine proteases. The implications of these conclusions are discussed in relation to some functional models of arthropod photoreceptor microvilli.

Actins↗

A competitive inhibition ELISA as a probe for studying the refolding of human serum albumin.

The refolding of iodoacetic acid-blocked human serum albumin (HSA) was studied using a modified competitive inhibition ELISA. A maximum of 89% native activity was detected 24 hours after initiating refolding using an albumin concentration of 600 micrograms/mL. The presence of both monomer and polymer HSA was studied using native polyacrylamide gel electrophoresis of thiol-blocked HSA samples. Monomer HSA was not detected until 2.5 hours after initiating refolding. Fractionated polymer and monomer HSA from a sample trapped at 72 hours after initiating refolding was determined to have 40% and 87% native activity respectively. Both polymer and monomer HSA fractions contribute to the overall immunological activity detected by the ELISA, at various times. The ELISA assay was able to detect the changing HSA conformation associated with refolding of totally reduced HSA.

Chromatography, Gel↗

Stigma and mental disorder: phenomena and terminology.

My aim in this paper is to examine the application of the concept stigma to mental disorder and to the mentally ill. I believe that the loose use of this term serves to obscure the real issues that must be confronted in attempting to change public response to mental disorder. I shall examine recent, and in my opinion ill-advised, use of the concept stigma and then present some data that bear upon social responses to mentally ill patients and former patients in contemporary America. My data are derived from a long-term study of mental patients and their families, and I shall document that their feelings of stigmatization are not so much a consequence of the response of others to their having been hospitalized for mental illness or labeled mentally ill as of self-doubts or chronic manifestations of mental illness.

Adult↗

Madness and work: short- and long-term effects of mental illness on occupational careers.

This study assesses the impact of mental illness on occupational careers. Thirty-six married men who first entered mental hospitals in the 1950s were followed up in 1972 and eighteen men who were first hospitalized in 1973-74 were interviewed. Their histories reveal the importance of the development of competence in the work role prior to the onset of mental illness. Those who were able to develop competence were likely to retain their jobs through the initial episode of illness and to remain occupationally stable in the ensuing years even in the face of persistent symptomatology. The data are interpreted as evidence that the label, "mental patient," does not constitute a master status and in and of itself does not significantly affect occupational careers.

Adult↗