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Biomedical subjects

A Noble

Publications and source records attributed to A Noble.

63 records · Page 4Linked to original sources

New data on the pharmacokinetics of adriamycin and its major metabolite, adriamycinol.

Twenty-two days after administration by intravenous bolus, of 50 mg of adriamycin to several patients we found concentrations of adriamycin and adriamycinol of the order of 100 pcg/ml. In theory, however, with a terminal half-life of 30 h, the plasma levels of adriamycin and adriamycinol should be close to 0.1 pcg/ml. Further pharmacokinetic investigation was therefore necessary. We have retained for this study nine male patients, aged between 53 and 69 years who received 25 to 50 mg of adriamycin by slow intravenous injection. The HPLC method permitted the detection of 50 pcg/ml of adriamycin and adriamycinol, with the possibility of monitoring their elimination during 120 h (and in one case during 160 h). The terminal half-lives of elimination estimated in 8 patients were respectively 110 +/- 52 h for adriamycin and 92 h 50 min +/- 43 h for adriamycinol. Surface ratios under adriamycinol curves against calculated adriamycin was 1.10 +/- 0.26. Plasma levels found during the To in certain patients correspond to the end of the drug elimination of the previous treatment. It is difficult with a half-life to 110 h to predict the effects of residual concentrations of adriamycin and adriamycinol.

Aged↗

Prenatal substance abuse in California: findings from the Perinatal Substance Exposure Study.

This article reports the overall statewide findings of an epidemiological study that included 29,494 pregnant women who had been admitted for delivery in more than 200 hospitals in California and who were tested for alcohol and other drugs via blind urine toxicology screens. Results were matched to demographic data. The article includes analysis and discussion of four major variables: race/ethnic group differences, acculturation, source of payment for birth, and prenatal care status. Regional results are also discussed. The authors emphasize the high rate of alcohol use and self-reported tobacco use in comparison to relatively low rates of illicit drug use. Alcohol use rates were fairly stable, while use of illicit drugs and tobacco tended to vary according to social and demographic variables. The findings establish the need for both broad-based and targeted prevention and intervention programs to better disseminate the risks involved in drinking alcohol, smoking tobacco, and using drugs during pregnancy.

Acculturation↗

IL-4 inhibits human CD8 T cell expression of the common IL-2 receptor gamma chain.

Previous studies in both rats and humans have shown that interleukin (IL) 4 can suppress the generation of IL-2-producing CD8 T cells. In an attempt to elucidate the mechanism by which this suppression is brought about, we set out to investigate whether the IL-4 signal interferes with the IL-2 receptor system. It has already been reported that IL-2 can affect the expression of its own receptor and thus provide a means of controlling its own activities. In this study, we demonstrate that the IL-2 Ralpha- and the IL-2 Rgamma-chains are dramatically upregulated following stimulation of CD8 T cells, whereas lower levels of beta-chain are observed. IL-4 did not affect the expression of the alpha- or beta-chains, but was found to inhibit the generation of common gamma-chain-expressing cells. Moreover, CD4 T cells were found to express much lower levels of this subunit and appeared less sensitive to the effects of IL-4. We postulate that the differential expression of the gamma-chain subunit, in the presence and absence of IL-4, may provide a tool for identifying functionally distinct subpopulations of CD8 T cells.

Animals↗

T cytotoxic 1 and T cytotoxic 2 CD8 T cells both inhibit IgE responses.

BACKGROUND: It is well recognized that CD8 T cells inhibit IgE responses. In this study, we investigated the mechanism of CD8 T cell-mediated IgE suppression by comparing the capacity of T cytotoxic 1 (Tc1) and T cytotoxic 2 (Tc2) CD8 T cells to inhibit IgE responses to ovalbumin (OVA). METHODS: Tc1 and Tc2 CD8 T cells were generated from OVA(257-264)-specific Vbeta5.2 T cell receptor (TcR) transgenic mice by stimulation with anti-CD3 and anti-CD28 under Tc1 and Tc2 polarizing conditions. Tc1 and Tc2 Vbeta5.2 TcR CD8 T cells (10(6)) were adoptively transferred to syngeneic mice, and following immunization with 100 micro of OVA/alum, serum IgE antibodies were measured by passive cutaneous anaphylaxis and expressed as the highest dilution that gave a detectable skin response. RESULTS: Both Tc1 and Tc2 CD8 T cells from OT-I mice inhibited IgE. CONCLUSION: Both Tc1 and Tc2 CD8 T cells promote Th1 immunity and inhibit IgE responses. This process appears to be independent of CD8 T cell-derived IFN-gamma, as both Tc2 (IFN-gamma-) and Tc1 (IFN-gamma+) CD8 T cells inhibited IgE.

Adoptive Transfer↗

Interleukin-4 and interferon-gamma regulate differentiation of CD8+ T cells into populations with divergent cytokine profiles.

The ability of CD8+ T cells to synthesise and secrete cytokines before and after culture with interleukin (IL)-4 and anti-interferon (IFN)-gamma was investigated. Purified rat splenic CD8+ and CD4+ T cells and CD4-CD8- cells were stimulated with phorbol myristate acetate (PMA) and ionomycin for 6 h and expression of mRNA for IL-2, IL-4, IL-5, IL-6, IL-10 and IFN-gamma determined using a quantitative PCR technique. Secreted IFN-gamma and IL-2 were measured by ELISA and bioassay, respectively, 24 h after restimulation. The highest levels of IL-4, IL-5 and IFN-gamma mRNA were expressed by CD8+ T cells, the highest levels of message for IL-2 were expressed by CD4+ T cells and the highest levels of message for IL-6 and IL-10 by CD4-CD8- splenocytes. Purified rat splenic CD8+ T cells were cultured for 6 days with PMA, ionomycin and IL-2 with or without IL-4 or anti-IFN-gamma and restimulated with PMA and ionomycin. Those CD8+ T cells cultured with IL-4 expressed increased levels of IL-4, IL-5 and reduced levels of IL-2 and IL-6 mRNA, while CD8+ T cells cultured with IL-4 and anti-IFN-gamma expressed increased levels of mRNA for IL-10 and IFN-gamma. Comparable effects were seen for secreted IFN-gamma and IL-2. These results indicate that CD8+ T cells have the potential to produce large amounts of Th2 cytokines and are able to differentiate into different subpopulations with distinct cytokine profiles under the control of IL-4 and IFN-gamma.

Animals↗

Cytokine production by highly purified human CD8+ T cells.

We have systematically investigated the capacity of highly purified human peripheral CD8+ T cells to produce interleukin (IL)-4 and interferon (IFN)-gamma when triggered by different stimuli. CD8+ T cells were isolated from peripheral blood by positive selection to > 99% purity and stimulated with one of three different stimuli: phytohaemagglutinin (PHA) and IL-2, phorbol myristate acetate (PMA) and ionomycin, and plate-bound anti CD3 and PMA. On their own, ionomycin and IL-2 failed to stimulate significant CD8+ T cell proliferation while PHA, plate-bound anti-CD3 and PMA induced weak proliferation. A combination of PHA and IL-2, PMA and ionomycin, or plate-bound anti-CD3 and PMA all induced vigorous CD8+ T cell proliferation. IFN-gamma was produced following all three stimuli, but was greatest from cells cultured with PMA and ionomycin. However, IL-4 secretion was only detected in cell cultures stimulated with PMA and ionomycin. These results indicate that, with sufficient stimulation, human CD8+ T cells have the potential to produce Th2 as well as Th1 cytokines.

CD3 Complex↗

[Frequency of gastric lymphoma at 6 hospitals in Mexico City].

BACKGROUND: Gastric lymphoma has been traditionally considered a rare neoplasm that constitutes 1-5% of malignant gastric tumors. Two studies performed in Mexico in 1960 and 1966 found that only 1.9% and 1% of gastric neoplasms were lymphomas. Nevertheless, some studies made in the U.S. and in some European countries in recept decades have revealed an increase in the frequency of this neoplasm. A recent study made at two National Health Institutes in Mexico City (Instituto Nacional de Cancerología and Instituto Nacional de la Nutrición) revealed a remarkable increase in the frequency of gastric lymphoma (9.3% and 10.3%, respectively) in recent years. AIM: To define whether there is an actual increase of lymphoma in our population and whether it includes other hospitals in Mexico City that provides attention to populations different from those who attend referral centers. MATERIALS AND METHODS: Six hospitals in Mexico City were selected, including two National Health Institutes (Instituto Nacional de la Nutrición and Instituto Nacional de Cancerología), two private general hospitals used by patient with a high socioeconomic level (Hospital Español and Hospital Inglés), and two public general hospitals frequented by low-income patients (hospital Juárez and Hospital General de México). In each case, the gastric lymphomas diagnosed in each participant hospitals in the last 5 years were registered. For comparative purpose, diagnosed cases of gastric adenocarcinoma during the same period were also registered. Other types of gastric neoplasms were excluded from the study because they formed a very heterogeneous group and represented a minimal proportion of malignant gastric tumors. Age and sex of each patient were included for all lymphomas. RESULTS: A total of 879 malignant gastric neoplasms were included in our study. The relative percentage for gastric lymphoma by institution in descendent order was Hospital Español 25.4%; Instituto Nacional de la Nutrición 13.7%, Hospital Inglés 11.5%, Hospital General de México 8.5%, Instituto Nacional de Cancerología 6%, and Hospital Juárez 6%. Mean general frequency taking into account the six hospitals was 9.1%. CONCLUSIONS: Frequency of gastric lymphomas in all analyzed institutions was higher than that reported in most series in the medical literature (1-5%) and that reported for the Mexican population in 1960 and 1966. The increase was most remarkable in hospitals attended by patients with high incomes (Hospital Español, Hospital Inglés), although the total number of neoplasms reported by these institutions was smaller than that reported by hospitals were by patients with lower incomes (Hospital Juárez, Instituto Nacional de Cancerología). The reason for this increase is unknown, but one might speculate that some strains of Helicobacter pylori, nutritional factors, and ethnic differences could be involved. Both gastroenterologists and pathologists must recognize the increase of this neoplasm because unlike gastric adenocarcinoma, gastric lymphoma is a curable disease in a high percentage of cases.

Adult↗

[Transrectal endoscopic ileal decompression as treatment of small intestine pseudoobstruction. Report of a case].

BACKGROUND: Intestinal pseudo-obstruction is a syndrome characterized by recurrent signs and symptoms of intestinal pseudo-obstruction or dilation without any evidence of mechanical pseudo-obstruction. Its cause is unknown, and it is associated with severe alterations of gastrointestinal motility. AIMS: To report the transendoscopic treatment in a case of intestinal pseudo-obstruction as an alternative to a poor response to medical treatment. METHODS: The diagnosis of intestinal pseudo-obstruction was made in a 34-year old male patient who had not responded to conservative treatment; therefore, a colonoscopy was performed and an ileal drainage was introduced with its distal end 50 cm beyond the ileocecal valve. RESULTS: Twenty-four hours after the procedure was performed clinical and radiological improvement was evident. Such improvement was completed at 72 hours when the patient tolerated oral ingestion. CONCLUSIONS: Transrectal ileal drainage could be an alternative to consider in those patients that do not respond to conservative treatment.

Adult↗