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Biomedical subjects

A Norris

Publications and source records attributed to A Norris.

At least 37 records · Page 2Linked to original sources

Ascorbic acid recycling in Nb2 lymphoma cells: implications for tumor progression.

Analysis of cultured rat "Nb2 lymphoma" cell lines, showing different degrees of malignant progression, can lead to identification of phenotypic changes associated with this phenomenon in T-cell cancers. In the present study we have compared the metastatic sublines, Nb2-11 and Nb2-SFJCD1, with regard to ascorbate and glutathione recycling, important processes in cellular protection from oxidative stresses. Whereas the Nb2-11 subline is prolactin (PRL)-dependent, the genetically related Nb2-SFJCD1 subline is growth factor-independent and shows more chromosomal alterations, indicative of more advanced progression. The Nb2-SFJCD1 cells, compared to the Nb2-11 cells, were less sensitive to toxic effects of dehydroascorbate, a potentially toxic oxidation product of ascorbate. Results were consistent with a significantly higher production of reducing equivalents (e.g., NADPH, GSH) and an accelerated reduction of dehydroascorbate by homogenates of Nb2-SFJCD1 cells. However, the increased resistance was apparently not directly related to the cellular uptake and reduction of dehydroascorbate by whole cells, which was similar in both cell lines. Observations indicate that Nb2 lymphoma cells, in their progression to malignancy, can acquire an enhanced capability to protect themselves from oxidative damage assisting them in withstanding the oxidative stress that anti-neoplastic drugs can cause. The adaptation may also be a mechanism that is utilized by tumor cells in suppressing apoptosis and other protective cellular functions facilitating, or potentiating, a tumor cell's ability to become more metastatic. However, the mechanism leading to this augmented capacity of Nb2 lymphoma cells to resist oxidative stress in not known and is the subject for further study.

Animals↗

Should adult patients drink fluids before discharge from ambulatory surgery?

UNLABELLED: We studied 726 consenting patients to determine whether withholding oral fluids from adult ambulatory surgical patients before discharge would decrease the incidence of postoperative nausea and vomiting (PONV) and shorten the duration of stay in the ambulatory surgery unit (ASU). Patients were randomly assigned to the drinking or nondrinking group. Both groups received a standard regimen of general anesthesia, fluid replacement, and analgesia. In the ASU, patients in the drinking group were given mandatory oral fluids to drink before discharge. Nausea and pain were assessed by using a visual analog scale 15, 30, 60, 90, 105, 120, 150, and 180 min postoperatively. The time to drink, sit up, void, and ambulate, and the time until discharge were recorded. Patients were interviewed by telephone 24 h postoperatively. There was no significant difference in the frequency of PONV between the drinking and the nondrinking groups either in the hospital or after discharge. Patients in the drinking group required more time to begin ambulating (105 +/- 38 vs 98 +/- 34 min; P < 0.02) and to void (112 +/- 40 vs 105 +/- 37 min; P < 0.01). Patients in the drinking group also stayed in the ASU longer (85 +/- 49 vs 81 +/- 47 min; P < 0.03). Time to postanesthetic discharge was also significantly longer in the drinking group than the nondrinking group (106 +/- 40 vs 98 +/- 36 min; P < 0.015). A similar percentage of patients in both groups were "very satisfied" with their ambulatory surgical care. There was no difference in postoperative complications and need for medical help. Withholding early postoperative oral fluids facilitated earlier ambulation and decreased the stay in the ASU but did not decrease the incidence of PONV. Thus, in this ambulatory surgical population, there does not seem to be justification to require drinking before discharge. IMPLICATIONS: To answer the question of whether adult outpatients should drink before discharge after minor surgical procedures, 726 patients were randomized to either drink approximately 150 mL of liquid or not to drink. Neither drinking nor nondrinking worsened postoperative nausea or vomiting or prolonged hospital stay. Therefore, patients should be allowed to choose whether they drink before discharge.

Adolescent↗

Promoting equity in health.

There is evidence that widening income gaps are a global phenomenon; that in many advanced industrialised countries unemployment rates are rising; that globalisation of the world economy has led to several countries becoming marginalised with a concomitant increase in poverty; and that the absolute number of poor has steadily increased over the last decade. All of these phenomena emphasise the need to focus on equity as a global concern.

Adolescent↗

Characterization of human SHC p66 cDNA and its processed pseudogene mapping to Xq12-q13.1.

SHC is an adapter protein in the Ras-MAPkinase pathway that is involved in the regulation of cell growth and differentiation. The p46 and p52 isoforms are thought to be produced by the use of two alternative translation initiation sites in a 3.4-kb transcript from the SHCA gene, which maps to chromosome 1q21. The p66 isoform could be encoded by a different 3.8- or 2.8-kb transcript of the same gene or alternatively by a SHC-related gene. To characterize other putative genes coding for SHC-like proteins, primers from the 3' UTR of the SHCA gene were used to screen a yeast artificial chromosome (YAC) library by polymerase chain reaction (PCR). Two YAC clones, 20D11B and 36D1D, were isolated and used as probes for fluorescence in situ hybridization analysis. Both these probes hybridized to chromosome Xq12-q13.1. This novel SHC-related sequence was characterized by direct sequencing of vectorette library PCR products produced from clone 20D11B. A transcript of 3.2 kb that was 85% identical to the mouse Shc cDNA encoding the p66 isoform was identified. Sequence analysis demonstrated the presence of multiple stop codons identifying this isoform of SHC as a processed pseudogene. Using primers designed on the basis of the nucleotide sequence of the pseudogene, we have now amplified and sequenced a human cDNA that encodes the SHC p66 protein. Thus, we have characterized the human SHC p66 isoform cDNA and identified a processed SHC pseudogene that maps to chromosome Xq12-q13.1.

Adaptor Proteins, Signal Transducing↗

Sexual networks of African-American and Hispanic youth.

BACKGROUND AND OBJECTIVES: To describe the characteristics of several types of sexual partners of African-American and Hispanic urban youth and to determine the association of these characteristics with condom use, contraceptive use, experience with sexually transmitted diseases, and sexual practices. STUDY DESIGN: Data were drawn from personal interviews with a probability sample of low-income urban youth, age 15 to 24 years, conducted in Detroit in 1991 (N = 1,435). RESULTS: Although both ethnic groups tended to form partnerships most often within their own group. Hispanics had sexual partners who varied by ethnicity much more than did African Americans. Furthermore, the longer-term relationships, those that resulted in marriage or cohabitation, were more likely to be with Hispanic partners than were other relationships. Hispanic men were also more likely to report white partners than were Hispanic women. In contrast, for African-American men and women, most reported relationships were with other African Americans. Regardless of ethnicity or relationship type, women had older partners than did men. Partner differences in age or ethnicity showed few or no differences in condom use, reports of sexually transmitted disease, oral intercourse, or use of contraceptive methods. CONCLUSIONS: Although relationships with people of similar age and ethnicity are common, bridges exist for transmission of sexually transmitted infection between different age and ethnic groups.

Adolescent↗

Vectorette PCR isolation of microsatellite repeat sequences using anchored dinucleotide repeat primers.

We have developed a vectorette PCR approach to provide an improved method for isolation of microsatellite repeats. The modified procedure relies on PCR amplification using a vectorette-specific primer in combination with one of a panel of anchored dinucleotide repeat primers. The target DNA to be screened for microsatellite sequences can be from YAC, P1, cosmid, bacteriophage or plasmid clones. We have used this technique to isolate novel, polymorphic microsatellite repeats from clones containing the amelogenin gene (AMGX) located on human chromosome Xp22.3.

Amelogenin↗

Asthma prophylaxis agents alter the function of an airway epithelial chloride channel.

A number of recent observations suggest a link between airway Cl-transport and asthma. We have previously described the properties of a voltage- and Ca2+ -dependent chloride channel present in airway epithelium. We now show that agents able to prevent indirectly induced bronchoconstriction (sodium cromoglycate, nedocromil sodium, and furosemide) reduce either the single-channel conductance or the open probability of this channel. The effects of these agents and the Ca2+ dependence of the channel are localized to the same surface, and we show that the channel possesses a specific divalent cation binding site, which responds to concentrations of Ca2+ found on the airway mucosal surface. No alteration of the single-channel properties of this channel were seen in cystic fibrosis epithelium. These data suggest a mechanism by which structurally diverse agents may influence asthma.

Animals↗

The expression of the c-kit receptor by epidermal melanocytes may be reduced in vitiligo.

The proto-oncogene c-kit encodes the transmembrane tyrosine kinase receptor that has a role in the growth regulation of various cell types including melanocytes. In the present study we have examined the expression of the c-kit protein in the skin of seven patients with vitiligo. Melanocytes positive for c-kit protein were observed in the basal layer in non-lesional skin and the mean number of 25.8 +/- 5.2 (per 200 basal cells) compared with that of 21.8 +/- 3.5 from six control subjects. In perilesional skin there was a reduction in the numbers of c-kit positive melanocytes (6.7 +/- 2.6) and this was especially noticeable in six of the seven patients. Such a reduction was less obvious following staining with MEL-5 and in only two subjects were the numbers of melanocytes below the normal range. This suggests that the reduction in c-kit staining was the result of decreased expression of the protein rather than a loss of melanocytes. No melanocytes, positive for c-kit protein, or after staining with MEL-5, were identified in lesional skin although isolated tyrosinase-positive melanocytes were seen in one subject. There was no apparent change in the numbers of mast cells expressing c-kit protein and the intensity of staining in the dermis even in lesional skin was similar to that in the controls. These results demonstrate that c-kit protein is present on melanocytes in adult human skin and that in perilesional skin of some vitiligo patients there is a reduction in the numbers of melanocytes expressing this receptor. Whether this may contribute to the defective melanocyte growth and/or survival that occurs in vitiligo or whether it is a consequence of melanocyte damage remains to be seen.

Adult↗

Modulations of histamine release from mast cells by interleukin-2 is affected by nedocromil sodium.

We have previously demonstrated that histamine release from immunologically activated mast cells (MC) is enhanced by their preincubation (1 h) with interleukin-2(IL-2), and that IL-2 induces slow-chronic histamine release by MC in long-term cultures (6 days). In the present study we assessed whether nedocromil sodium can interfere with IL-2 modulation of MC histamine release. IL-2 enhancing effects nedocromil sodium activity were studied in cocultures of rat peritoneal MC with 3T3 fibroblasts (MC/3T3). MC/3T3 were preincubated for 1 h with IL-2 (50 micrograms/ml) and activated with either rabbit anti-rat IgE or compound 48/80. In chronic experiments MC/3T3 were long-term (5-6 days) incubated with IL-2 (50 micrograms/ml). Nedocromil sodium was used at 10(-5) M. MC activation both when added during the preincubation period (no tachyphylaxis was present) and when added together with the MC activators (30-50% inhibition). Washing out IL-2 before addition of the anti-IgE antibodies did not affect its histamine-release enhancing activity. Removal of nedocromil sodium before addition of the stimulus completely abrogated its effect. Continuous presence of IL-2 in the culture medium enhanced spontaneous histamine release by 37% and this effect was completely abolished in the presence of nedocromil sodium. Furthermore, nedocromil sodium decreased MC basal histamine release by 23% in long-term cocultures. Since IL-2 is known to be elevated in some pathological conditions, our results show that nedocromil sodium inhibits MC activation in an in vitro system which may represent a close resemblance to the in vivo allergic response.

Animals↗

Pathology of canine bladder and urethral cancer and correlation with tumour progression and survival.

Biopsy and necropsy specimens, comprising 107 primary carcinomas and three mesenchymal tumours, were reviewed from 110 dogs with cancer of the bladder, urethra, or both. Histological classifications developed for the assessment of human bladder cancer were found to be readily applicable to the dog. These classifications are based on histological features, including the pattern of growth, the cell type, the grade of transitional tumour and the depth of invasion of the bladder wall. Features associated with localized disease in canine transitional cell carcinoma included papillary architecture, "in-situ" tumour, low tumour grade and a strong peritumoral lymphoid cell reaction. Features of tumours with metastasis included infiltrating and non-papillary architecture, increasing tumour grade, depth of invasion, vascular invasion and presence of peritumoral fibrosing reaction. Wide variability was found within single tissue samples, indicating that multiple sample sites are necessary for the adequate characterization of a given lesion. Statistically significant correlations were found between: tumour grade and depth of invasion (P < 0.0001); tumour grade and presence of metastases (P < 0.029); and peritumoral desmoplasia and metastases (P < 0.029). It was concluded that canine bladder cancer could be classified for the purpose of clinical management with a modified World Health Organization system as developed for human tumours.

Animals↗

Inhibition of volume-activated chloride currents in endothelial cells by chromones.

1. We have studied the effects of the reported chloride channel blocker, sodium cromoglycate, on volume-activated Cl- currents in endothelial cells from bovine pulmonary artery by means of the whole-cell patch clamp technique. Cl- currents were activated by challenging the cells with a hypotonic extracellular solution of 60% of the normal osmolarity. 2. Half maximal activation of the current at +95 mV occurred after exposure of the cells for 148 +/- 10 s (n = 6) to hypotonic solution (HTS). At the same membrane potential but in the presence of 100 microM sodium cromoglycate (disodium-1,3-bis (2'-carboxylate-chromone-5'-yloxy)-2-hydroxy-propane) activation was delayed (253 +/- 25 s, n = 6) and the maximal current amplitude was reduced to 63 +/- 7% of the control (n = 13). 3. In comparison, an equimolar concentration of NPPB (5-nitro-2(3-phenyl) propylamino-benzoic acid), another Cl- channel blocker, completely blocked the volume-activated current in less than 20 s. 4. Sodium cromoglycate, applied at the time when the HTS-induced current was completely activated, dose-dependently inhibited this current with a concentration for half maximal inhibition of 310 +/- 70 microM. Data for nedocromil sodium were not significantly different from those for sodium cromoglycate. 5. Sodium cromoglycate, loaded into the endothelial cells via the patch pipette in ruptured patches, resulted in a decline of the HTS activated current with a time course that was compatible with diffusion of the compound from the pipette into the cell. Intracellulary applied sodium cromoglycate was also more effective and at 50 microM caused a decrease in the amplitude of the current to 25 +/- 6% (n = 10) of the control current.6 It is concluded that blockade of volume-activated Cl- currents by extracellular sodium cromoglycatemay be due to an intracellular action following its permeation across the cell membrane.

Animals↗

Elevated porphyrins following propofol anaesthesia in acute intermittent porphyria.

A patient with acute intermittent porphyria was anaesthetised with propofol for a minor orthopaedic procedure. Postoperative urinary porphyrins were markedly raised compared to pre-operative values, although the patient remained clinically well. Caution should continue to be exercised when propofol is used in patients with acute porphyrias.

Adult↗

Sexual behavior and condom use among urban, low-income, African-American and Hispanic youth.

Low income, urban, African-American, and Hispanic youth have been identified as a group for which there is concern about the spread of HIV. Using data from a household probability sample of 1,435 minority youth aged 15 to 24 in Detroit, this paper evaluates levels of sexual activity, condom use, and reasons for condom use and non-use. Comparisons with national samples of minority youth indicated that Detroit low-income youth have similar patterns of sexual behavior to national samples, although males and African-American females began their sexual experiences earlier and were less likely to have used condoms or other protection from pregnancy or sexually transmitted diseases (STDs) at first intercourse. Recent levels of condom use also left many Detroit youth unprotected from STDs. Less than half used a condom at least intercourse in the last year with nonmarital partners that they "knew well." In addition, condom use with partners that they "did not know well" was very low for Hispanic youth: Among those who had at least one casual partner in the last year, only 30% to 33% had ever used a condom with that partner. Analysis of reasons for use indicate that both pregnancy prevention and disease prevention were important motivations for condom use. However, many youth did not use condoms for reasons such as unavailability of condoms or unplanned sex.

Acquired Immunodeficiency Syndrome↗

Urban minority youth: alcohol and marijuana use and exposure to unprotected intercourse.

This article focuses on the use of alcohol and marijuana in the context of sexual relationships and the impact of these substances on the consistency of condom use by urban, minority youth. Regression models are presented to test for the effects of alcohol and marijuana use with sexual partners while controlling for the effects of respondents' sexual history. The results indicated that when alcohol or marijuana was used with a partner, the consistency of condom use decreased even when other variables related to sexual history were controlled for. Alcohol use had a greater negative effect on condom use for Hispanic men and marijuana for African-American women than it did for Hispanic women and African-American men. These findings argue for the need for targeted safer-sex intervention programs for urban, low-income, minority youth, and suggest that such programs may need to emphasize the increased risk of human immunodeficiency virus exposure that may result from substance use, casual sex, and sex with multiple partners.

Adolescent↗

Arrhythmogenic right ventricular dysplasia: an uncommon cause of ventricular tachycardia in young and old?

Right ventricular dysplasia is a little understood condition and is almost certainly underdiagnosed as an important cause of recurrent ventricular tachycardia and sudden death. This report describes two patients with right ventricular dysplasia. Their clinical presentation reflects the remarkable diversity of the disease while the potentially life-threatening nature of their arrhythmias and their lack of response to medical treatment justified the antiarrhythmic surgical procedure of right ventricular disarticulation.

Adolescent↗