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Biomedical subjects

B Nicholson

Publications and source records attributed to B Nicholson.

At least 37 records · Page 2Linked to original sources

Induction of high affinity glutamate transport activity by amino acid deprivation in renal epithelial cells does not involve an increase in the amount of transporter protein.

In renal epithelial cells amino acid deprivation induces an increase in L-Asp transport with a doubling of the Vmax and no change in Km (4.5 micronM) in a cycloheximide-sensitive process. The induction of sodium-depending L-aspartate transport was inhibited by single amino acids that are metabolized to produce glutamate but not by those that do not produce glutamate. The transaminase inhibitor aminooxyacetate in glutamine-free medium caused a decrease in cell glutamate content and an induction of glutamate transport. In complete medium aminooxyacetate neither decreased cell glutamate nor increased transport activity. These results are consistent with a triggering of induction of transport by low intracellular glutamate concentrations. High affinity glutamate transport in these cells is mediated by the excitatory amino acid carrier 1 (EAAC1) gene product. Western blotting using antibodies to the C-terminal region of EAAC1 showed that there is no increase in the amount of EAAC1 protein on prolonged incubation in amino acid-free medium. Conversely, the induction of high affinity glutamate transport by hyperosmotic shock was accompanied by an increase in EAAC1 protein. It is proposed that low glutamate levels lead to the induction of a putative protein that activates the EAAC1 transporter. A model illustrating such a mechanism is described.

Amino Acid Transport System X-AG↗

Induction of the high-affinity Na(+)-dependent glutamate transport system XAG- by hypertonic stress in the renal epithelial cell line NBL-1.

The high-affinity Na(+)-dependent glutamate transport system XAG- is induced (threefold increase in Vmax. with no change in Km) by hypertonicity in the renal epithelial cell line NBL-1. This effect is dependent on protein synthesis and glycosylation and is accompanied by an increase in EAAC1 mRNA levels. Other Na(+)-dependent transport systems in this cell line do not respond to hypertonic stress. In contrast to recent findings [Ruiz-Montasell, Gomez-Angelats, Casado, Felipe, McGivan and Pastor-Anglada (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9569-9573] showing that increased system A activity after hyperosmotic shock results from induction of a regulatory protein, this is the first demonstration that hypertonicity may increase the expression of the gene for an amino acid transport protein itself.

Amino Acid Transport System X-AG↗

Differential expression of gap junction connexins in endocrine and exocrine glands.

We have investigated the expression of three gap junction proteins and their corresponding mRNAs by secretory cells of a variety of endocrine and exocrine rat glands. By immunostaining cryostat sections (indirect immunofluorescence) with antibodies against connexins (Cx) 26, 32, and 43 and by hybridizing total glandular RNA (Northern blot) with cRNAs for these proteins, we have found that several endocrine glands (pituitary, parathyroid, pancreatic islets, and adrenal) express Cx43, variable levels of Cx26, and no Cx32, whereas several exocrine glands (lacrimal gland, salivary glands, pancreas, prostate, and seminal vesicle) express high levels of Cx32 and variable levels of Cx26, but no Cx43. Thus, different sets of proteins comprise the gap junctions of endocrine and exocrine glands. Together with the findings that an endocrine gland (thyroid) that discharges secretory products extracellularly before releasing them in the vascular compartment expresses both Cx43 and Cx32 and that an exocrine gland (preputial gland) that has a pheromonal role expresses Cx43, these observations suggest that the differential expression of gap junction connexins may be required to specify the endocrine or exocrine differentiation of a secretory cell.

Adrenal Glands↗

Molecular cloning of mouse connexins26 and -32: similar genomic organization but distinct promoter sequences of two gap junction genes.

Connexins26 and -32 are subunit proteins of gap junctions that are coexpressed in hepatocytes and several tissues but individually expressed in other cells. Molecular cloning of both corresponding mouse genes revealed similar genomic organization, i.e., each gene consists of two exons with the complete coding region located in the second exon. The first exon of each gene is preceded by a TATA-less promoter region. The promoter of the mouse Cx26 gene has at least two transcription start sites and is located in a very GC-rich region which is reminiscent of promoters of house-keeping genes. Putative consensus sequences for a metal response element, the transcription factor NFkappaB, and several GC-boxes were found within 600 bp upstream of the Cx26 transcription start sites. The promoter region of the mouse Cx32 gene contains two putative binding sites for the transcription factor HNF-1 and consensus motifs for NF-1 as well as NFkappaB within 680 bp upstream of the main transcription start site. Thus the sequence comparison of mouse Cx26 and Cx32 promoter regions provides hints for possible consensus elements that could control individual expression as well as common regulation of these gap junction genes in various tissues. Cx26 mRNA is much more abundant in adult mouse skin than in adult kidney and liver where Cx32 transcripts are relatively strongly expressed.

Amino Acid Sequence↗

The hidden component in census-derived migration data: assessing its size and distribution.

Comparison of Norwegian "linked" decennial census data with statistics compiled from 10 years' migration registrations showed that the amount of movement omitted by census data was considerable. This hidden movement was of a similar order at every administrative level, but only when total movement was considered. There was wide variation between regions, migration directions, and streams. In some cases census data misrepresented the direction of net movement. Available evidence suggests that these patterns are not confined to Norway, raising the possibility that research findings based on census-derived migration data may merely be artifacts of the data.

Demography↗

Sequence diversity of gap junction proteins.

This paper summarizes our understanding of the molecular organization of gap junction proteins. There appear to be overall similarities in the organization of heart and liver junctions in terms of general domains, even though the molecular sizes of the two proteins are quite different. Sequence data on the amino-terminal regions of these two proteins show 43% of the residues to be identical and 25% more to be homologous. The major intrinsic protein of lens (MIP), believed by many to be the lens-fibre junction protein, does not show such sequence homology with the known portions of junction proteins from either heart or liver. Yet the sequence of MIP, which is completely known, suggests a conformation for this molecule quite compatible with a junctional role. It thus appears that molecules potentially involved in junction formation will prove to form a rather diverse family, with special characteristics of organ-specific molecules that may well be related to their function.

Amino Acid Sequence↗

Object relations and differential treatment response to methadone maintenance.

The authors report results from a psychiatric study of narcotic addicts in which the relationship between specified aspects of object relations development and treatment response to methadone maintenance was examined. Two groups were defined as high and low drug users (in addition to the prescribed methadone dose) depending upon the frequency and intensity of additional drug use; a middle group was excluded. Thirty subjects participated. The dimensions of separation/individuation, narcissistic development, and self and object representations were measured by 12 scaled variables; scores of the high and low drug users were compared by t-test. In all cases, the high use group was found to be more impaired than the low use group. However, the dimensions differed greatly in their ability to differentiate the groups. The strongest group differences were found in the area of narcissistic development, with the high user group significantly more impaired than the low user group. The strength of these findings lends empirical support to the notion that an addict population can be differentiated on diagnostic and ego psychological measures. This has important implications for methadone maintenance treatment programs, and, possibly, for drug programs in general.

Adult↗

Revision of the first web space: technics and results.

Between 1975 and 1980, 91 patients in our series with involvement of 103 webs had revision of a contracted first web space. The five main causes of impairment were burns, trauma, congenital defects, cerebral palsy, and cerebrovascular accident. Technics used were simple Z-plasty; four-flap Z-plasty; modified double-opposing Z-plasty; and rotational flaps from the dorsum of the thumb, index finger, or hand. No pedicled, tubed, or distant flaps were needed. Simple Z-plasty was sufficient for increases to 1 cm; for greater increases a modified double-opposing Z-plasty or local rotational flap was necessary. The modified double-opposing Z gave excellent depth. Release of all contracting elements and addition of sufficient supple skin to the web are required for success.

Burns↗

Cell junctions and intercellular communication.

We have compared intercellular communication in normal and regenerating rat liver. Gap junctions are greatly reduced in size and numbers 29 to 35 hr after hepatectomy, but we still find some 90% of hepatocytes coupled by electrophysiological criteria. The spread of dyes such as carboxyfluorescein however is very limited in the regenerating organs as compared to the situation in the controls. We show how the apparent discrepancies between morphological and physiological data can be reconciled. We also present a summary of preliminary findings on the biosynthesis of gap junction protein and some of the conclusions one can draw from the sequence of 58 amino acids at the amino terminal of the protein.

Animals↗

DSM-III personality type and dose levels in methadone maintenance patients.

The authors report results from a psychiatric study of narcotic addicts using diagnostic criteria from DSM-III and other clinical data. Evidence is presented for a strong relationship between personality disorder and methadone dose, in which patients with schizoid-like disorders had significantly higher stabilization doses than patients with other types of diagnoses. The treatment implications of individual differences in drug and personality interaction are noted, and the findings are discussed in terms of a psychodynamic understanding of addiction.

Adult↗