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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 199 records · Page 11Linked to original sources
PubMed1995

The relational determinants of condom use with commercial sex partners in Thailand.

OBJECTIVE: To analyze the extent and determinants of condom use with commercial sex partners among lower socioeconomic status groups in the Thai population. DESIGN: Respondents were sampled in Udon Thani, Saraburi and Bangkok in 1992. Completed sample size was 678 women in brothels, 330 male truck drivers and 1,075 men aged 17-45 years. Behavioral data and local sexual network information were collected using structured questionnaires (face-to-face interviews), focus groups and in-depth unstructured interviews. METHODS: Data were analyzed using univariate and multivariate logistic regression. RESULTS: Condom use with commercial partners remains inconsistent. Consistent use was reported by 61% of women in brothels, 25% of truck drivers, and 29% of men in the low-income population. The single strongest predictor of consistent condom use for all groups is type of partnership. Consistent use drops significantly with regular (multivisit) commercial sex partners compared with casual (single visit) commercial partners; adjusted odds of consistent use are 0.22 for women and 0.25 for men. Brothel women report that one in five of their commercial partners is a 'regular', and 20% of the young men who report a commercial partner report a 'regular'. DISCUSSION: The strongest determinant of consistent condom use is the nature of the relational bond between the partners, rather than their individual characteristics, knowledge or attitudes. To raise condom use further, programs will have to move beyond the standard knowledge-attitudes-practices paradigm focus on individual attributes to address the contextual determinants of behavior.

Adolescent↗
PubMed1995

Social and sexual networks: their role in the spread of HIV/AIDS among young gay men.

This article examines how networks of social and sexual relations affect risky sexual behavior and HIV seroprevalence among young gay men. Social networks can transmit information and cultural norms regarding safer sex, while networks of sexual partners channel the risk of exposure to HIV infection. These two network effects may help to explain some of the behavior and seroconversion differentials in the gay community. A number of recent studies have shown higher rates of unsafe sex among younger gay men. In the Longitudinal AIDS Impact Project, for example, younger gay men (18-24) report unsafe receptive anal sex at rates double that for any other age group (30% vs. 14-16%). One possible explanation is that younger men have watched fewer friends and colleagues contract HIV or AIDS, and are correspondingly less cautious. We test this hypothesis by comparing the personal networks of younger and older gay men to see whether those who practice safer sex have more exposure to persons with HIV or AIDS. The results give only weak support for the hypothesis that personal exposure to the effects of HIV and AIDS increases adherence to safer sex practices. Seroprevalence patterns among young men may be the result of their sexual networks, with those choosing older partners more likely to be exposed to HIV infection. We examine this hypothesis by comparing the age composition of the unsafe sexual partner network for seropositive and seronegative young men. The results strongly support the hypothesis that younger gay men with older partners are the leading edge of the epidemic in their cohort.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Intact protein electrospray ionization tandem mass spectrometry can be the sole technique used for confirming the structure of a variant hemoglobin.

A mutation within the human alpha-globin resulting in an 18 u mass increment was characterized by sequencing the intact M(r) 15000 protein in the gas phase by electrospray ionization tandem mass spectrometry. No separation of the variant protein from its normal counterpart and other components of the hemolysate was performed prior to mass spectrometric analysis. Collision-induced dissociation of the globin molecules carrying 18 protons was affected by their exposure to methane in the collision cell of a triple quadrupole mass spectrometer equipped with an electrospray ion source. Consideration of the major fragmentation ions (b758+, y"284+ and y"617+) narrowed down the mutation site to the last 28 amino acid residues within the protein sequence. Examination of low-abundance product ions allowed the unequivocal identification of the mutation as alpha 136 Leu --> Met, a hemoglobin previously named Hb Chicago.

Amino Acid Sequence↗
PubMed1994

Calcium and cAMP mediated stimulation of Fos in cultured hypothalamic tyrosine hydroxylase-immunoreactive neurons.

Immediate-early genes, such as c-fos, couple extracellular signals to genetic changes in the cell. We have previously demonstrated that depolarization with 50 mM KCl increases Fos immunoreactivity in hypothalamic tyrosine hydroxylase (TH) and oxytocin immunoreactive (-ir) neurons in primary culture. This Fos activation occurs within 1.5-2 h in TH-ir cells. In the present study, we examined the effects of depolarization, glutamate receptor activation and adenylyl cyclase stimulation on Fos-ir to determine the possible mechanism(s) of Fos activation in TH-ir neurons. Hypothalamic cultures were treated with KCl, glutamate or forskolin, and Fos and TH were visualized immunocytochemically. Forskolin increased the percentage of Fos/TH-ir neurons in a dose-dependent manner, with a maximal stimulation of 53.4 +/- 4.5% Fos/TH-ir neurons at 30 microM forskolin. The dose-response curve for glutamate was steep, with a maximal stimulation of 24.8 +/- 2.1% Fos-ir neurons at 100 microM. 50 mM KCl resulted in 50.0 +/- 0.8% Fos/TH-ir neurons. Pretreatment with verapamil decreased KCl induced Fos-ir by 57%, glutamate by 65% and forskolin by 39%. Combined drug administration demonstrated significant additivity between forskolin and glutamate, and forskolin and KCl, however, no significant additivity was found with KCl and glutamate. The results are discussed in terms of cAMP and calcium mediation of the Fos response to these stimuli.

Animals↗
PubMed1994

Effect of sexual behavior change on long-term human immunodeficiency virus prevalence among homosexual men.

Substantial changes in human immunodeficiency virus (HIV)-related sexual behavior have been reported by virtually every survey of homosexual/bisexual men in the last decade. This paper uses a behavior-based simulation to examine how such changes are likely to affect the long-term future of the acquired immunodeficiency syndrome (AIDS) epidemic among homosexual men. Data from the Longitudinal AIDS Impact Project in New York City are used to estimate age-specific patterns of unprotected anogenital contact and behavioral change from 1980 to 1991. Model projections are validated using New York City surveillance data on AIDS incidence from 1981 to 1991. The current levels of unsafe sex reported in the Longitudinal AIDS Impact Project are shown to be almost exactly on the epidemic threshold. If this behavior were maintained, HIV prevalence would slowly decline in the population, but with just one additional unsafe sexual partner per year HIV would instead become endemic, with seroprevalence of about 65% in the oldest group and about 25% in the youngest. Transmission dynamics in the youngest group are analyzed in detail. For this group, the assortative age-matching bias in partner selection patterns raises the unsafe behavior threshold slightly in the long run.

Acquired Immunodeficiency Syndrome↗
PubMed1994

D2 inhibition of stimulated Fos immunoreactivity in cultured tyrosine hydroxylase-ir hypothalamic neurons.

We have previously demonstrated that Fos immunoreactivity can be stimulated by KCl, forskolin or glutamate in cultured tyrosine hydroxylase-immunoreactive (TH-ir) hypothalamic neurons. The present study was performed to determine whether agents that regulate dopaminergic activity, particularly D1 and D2 receptor agonists, modulate the intracellular cascade leading to Fos expression. Dissociated hypothalamic cultures were prepared from neonatal rats. The cultures were treated with D1- or D2-specific agonists, followed by KCl, forskolin or glutamate. Cultures were fixed after 2 h and immunocytochemically stained for tyrosine hydroxylase and Fos. Pretreatment of the cultures with the D2 agonist LY163502 inhibited KCl- and forskolin-stimulated Fos-ir in TH-ir neurons in a saturable dose-dependent manner. The maximal effective dose was 30 microM LY163502, which decreased Fos-ir by 23% in cultures treated with 50 mM KCl and by 33% in those treated with 30 microM forskolin. The D2 agonist had no effect on glutamate-stimulated Fos-ir. LY163502 inhibition of Fos-ir was blocked by D2 antagonist or Bordetella pertussis toxin pretreatment which demonstrates that the effect is mediated by D2 receptor activation of an inhibitory G protein. Treatment of the cultures with the D1 agonist SKF82526 had no effect on basal or stimulated levels of Fos-ir. These results demonstrate that in neonatal TH-ir hypothalamic neurons the D2 receptor system may regulate levels of the immediate-early gene product Fos and, therefore, subsequent genetic expression in these neurons.

Animals↗
PubMed1994

The influence of tumor size and morphology on the outcome of patients with FIGO stage IB squamous cell carcinoma of the uterine cervix.

PURPOSE: To define the influence of tumor size and morphology on rates of central tumor control (CTC), pelvic tumor control (PTC), and disease-specific survival (DSS) in patients treated with radiotherapy for squamous cell carcinoma of the intact uterine cervix. METHODS AND MATERIALS: Records of 1526 patients treated with radiotherapy for FIGO Stage IB squamous cell carcinoma of the intact uterine cervix between 1960 and 1989 were retrospectively reviewed. The maximum tumor or cervical diameter was determined from clinical descriptions for 1494 patients. Tumors were divided into nine size categories. Tumors > or = 4 cm were further classified according to the dominant morphology (i.e., exophytic or endocervical). Median follow-up was 12.2 years. Five-year CTC, PTC, and DSS rates were calculated actuarially. RESULTS: CTC, PTC, and DSS rates correlated strongly with tumor diameter (p < 0.0001). Overall, CTC, PTC, and DSS rates for patients with tumors < 5 cm were 99%, 97%, and 88%, respectively. For patients with tumors 5-7.9 cm these rates were 93%, 84%, and 69%, respectively. There were no significant differences in the rates of PTC, CTC, or DSS between subgroups of patients with lesions 5-7.9 cm in diameter. The rates of CTC (97%) and DSS (76%) for patients with 5-7.9 cm exophytic tumors were significantly better than those for patients with endocervical tumors of the same size (91% and 66%, respectively); there was no difference in the PTC rate. CONCLUSION: Although the CTC rates were excellent for all patients with tumors < 8 cm in diameter, these rates for tumors < 5 cm (99%) and for exophytic tumors 5-7.9 cm (97%) make it difficult to justify the use of adjuvant hysterectomy. Although patients with tumors of 5-7.9 cm had consistently poorer PTC and DSS rates than did patients with smaller tumors, the control rates achieved with aggressive radiotherapy were still excellent. The strong correlation between tumor size and outcome suggests that tumor diameter should be assessed when tumors are clinically evaluated and staged and when treatment results are reported for patients with FIGO Stage IB carcinoma of the uterine cervix.

Adult↗
PubMed1994

Characterization of an acetylcholine receptor alpha 3 gene promoter and its activation by the POU domain factor SCIP/Tst-1.

Genes encoding neuronal nicotinic acetylcholine receptors exhibit restricted patterns of expression in the nervous system. We are interested in elucidating the molecular mechanisms responsible for establishing these patterns of expression. This paper presents the characterization of regulatory elements upstream of the neuronal nicotinic acetylcholine receptor alpha 3 gene. We have identified a GC-rich multistart site promoter adjacent to the alpha 3 coding region. Similar alpha 3 start sites were identified in PC12 cells and sympathetic ganglion neurons, suggesting similar control mechanisms in the clonal line and peripheral neurons. The start site region lacks TATA-like sequences but does contain initiator-like sequences. We show, in transient transfection assays, that the POU domain transcription factor, SCIP/Tst-1, specifically activates alpha 3 in a neural context. Other POU domain factors tested only weakly activated or repressed alpha 3. Unexpectedly, we found that alpha 3 basal activity and SCIP/Tst-1 activation of alpha 3 is not dependent on the SCIP/Tst-1 binding sites found upstream of the gene. In addition, mutations in the SCIP/Tst-1 coding region that prevent the factor from binding to DNA with high affinity do not obliterate alpha 3 activation. These results lead us to propose that alpha 3 activation by SCIP/Tst-1 is achieved via protein-protein interactions between SCIP/Tst-1 and a specific complement of transcription factors that act directly on the promoter.

Animals↗
PubMed1994

Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure.

OBJECTIVES: The aim of this study was to characterize cardiac sympathetic nervous function in patients with severe heart failure and to investigate the influence of the cause of heart failure, hemodynamic variables and central nervous system catecholamine release on cardiac sympathetic tone. BACKGROUND: Although heart failure is generally accompanied by sympathoexcitation, the integrity of cardiac sympathetic nerve function in heart failure remains controversial, particularly in relation to nerve firing activity and to the capacity of sympathetic nerves to recapture norepinephrine. Additionally, the location of the afferent and central neural pathways implicated in heart failure-induced sympathoexcitation remains unclear. METHODS: Radiotracer techniques were applied in 41 patients with severe heart failure and 15 healthy control subjects to study the biochemical aspects of whole body and cardiac sympathetic activity. Hemodynamic indexes of cardiac performance were measured in the heart failure group, and their association with sympathetic activity was studied. Jugular venous catechol spillover was measured to study the central noradrenergic control of sympathetic outflow. RESULTS: Sympathoexcitation was evident in the heart failure group, reflected by a 62% increase (p < 0.001) in total body and a 277% increase (p < 0.001) in cardiac norepinephrine spillover rates. These changes were accompanied by significant increases in the cardiac spillover of the norepinephrine precursor dihydroxyphenylalanine, the sympathetic cotransmitter neuropeptide Y and the extraneuronal metabolite 3-methoxy-4-hydroxyphenylglycol. The level of cardiac sympathetic activity was significantly correlated (r = 0.59, p < 0.001) with the mean pulmonary artery pressure. An increase in the spillover of dihydroxyphenylalanine and 3-methoxy-4-hydroxyphenylglycol from the brain was present, suggesting activation of central noradrenergic neurons. CONCLUSIONS: Cardiac sympathetic activation is present in severe heart failure, bearing a close relation with pulmonary artery pressures, independent of heart failure etiology. Activation of noradrenergic neurons in the brain is also present and may be the underlying central nervous mechanism of the sympathoexcitation observed in heart failure.

Brain↗
PubMed1994

Alteration of lymphocyte microtubule assembly, cytotoxicity, and activation by the anticancer drug taxol.

We studied the effect of the anticancer drug taxol on the cytotoxic mechanism of major histocompatibility complex nonrestricted lymphocytes and their activation with interleukin 2. Unseparated lymphocytes or highly enriched natural killer or T-cells were treated with 0.2-10 micrograms/ml of taxol for various times and tested for cytotoxicity against the K562 cell line and the ovarian cell line, OV-2774. Taxol caused a dose- and time-dependent suppression of lymphocyte cytotoxicity. The most pronounced suppression was noted after treatment with 10 micrograms/ml of taxol for 6 h; a lower but significant decrease in cytotoxicity was observed after treatment with 2 and 5 micrograms/ml of taxol. In addition, taxol inhibited activation of lymphocytes with interleukin 2; however, the cytotoxicity of interleukin 2-preactivated lymphocytes was less sensitive to taxol treatment. Mechanism studies showed that taxol was not directly toxic to lymphocytes and did not alter their ability to form conjugates with target cells. Taxol treatment decreased a rate of kinetics of lysis and lymphocyte recycling ability. The immunofluorescence and electron microscopic analysis showed polymerization of microtubules in taxol-treated lymphocytes. These data demonstrate that taxol impairs lymphocyte cytotoxic function and activation and indicate the role of microtubules in these functions. Clinically, these findings suggest that activation of lymphocytes prior to taxol treatment may increase the therapeutic benefit of this drug.

Adult↗
PubMed1994

The relationship between brachytherapy dose and outcome in patients with bulky endocervical tumors treated with radiation alone.

PURPOSE: To evaluate the relationship between brachytherapy dose and outcome in patients treated with external radiotherapy (40 Gy to the whole pelvis) and intracavitary radium therapy for bulky endocervical tumors. METHODS AND MATERIALS: Between 1962 and 1985, 98 patients with Stage IB-IIB bulky endocervical carcinomas (> or = 6 cm in diameter) treated with radiotherapy alone received 40 Gy to the whole pelvis followed by 2 or more intracavitary treatments. Twenty-five patients received < 6000 mg-hr of intracavitary treatment and 73 received > or = 6000 mg-hr (an average dose to point A of approximately 49 Gy). Brachytherapy exposures ranged from 4800-7885 mg-hrs. RESULTS: Patients who received < 6000 mg-hr tended to have unfavorable (narrow) vaginal anatomy (p < 0.01) and to be treated in the later years of the study (p < 0.01). The high-dose group included a somewhat greater proportion of patients with positive lymphangiograms or poor responses to initial external beam treatment. Despite having somewhat more favorable tumors, patients who received less than 6000 mg-hr had a higher rate of pelvic disease recurrence at 5 years (33%) than those who received higher doses (16%) (p = 0.03). Actuarial survival rates at 5 years were 44% and 60% for the low- and high-dose groups, respectively (p = 0.14). Among those who received more than 6000 mg-hr, there was no significant relationship between brachytherapy dose and pelvic disease control. Calculated actuarially, the rate of major (> or = grade 3) complications at 5 years was 23% in the low-dose group and 10% in the high-dose group (p = 0.1). CONCLUSIONS: The relatively high incidence of pelvic disease recurrence and complications in patients who receive less than 6000 mg-hr reflects the narrow therapeutic window for complication-free pelvic disease control in patients with bulky central disease and unfavorable normal tissue anatomy. The results also demonstrate a high pelvic control rate and acceptable morbidity in patients with favorable anatomy treated with high-dose radiotherapy alone.

Brachytherapy↗
PubMed1994

Primary structural confirmation of components of the bacitracin complex.

The bacitracin antibiotic peptide complex has been analyzed using liquid chromatography in conjunction with ion spray tandem mass spectrometry and multiple reaction monitoring techniques. Fragmentation patterns were determined from the product ion spectrum of bacitracin A (mol. wt 1421.8 Da), a compound of well-established structure. Primary structural information has been determined for seven minor components of the bacitracin complex with regard to the extent of amino acid substitution taking place.

Amino Acid Sequence↗
PubMed1994

Enterovesical fistula following radiotherapy for gynecologic cancer.

Enterovesical fistula is a rare complication of pelvic radiotherapy. Recurrent disease is the cause of fistulization in most patients. We identified 14 patients who developed enterovesical fistula in the absence of tumor recurrence. These women were at high risk for radiation morbidity due to prior surgery, pelvic inflammatory disease, adjuvant hyperbaric oxygen, or locally high doses of radiotherapy caused by suboptimal geometry and technique. All patients underwent radiographic imaging including barium enema, intravenous pyelogram, and upper gastrointestinal study with small bowel follow-through. The range of radiation morbidity was great: some patients had small fistulae, others had extensive fistulization and radionecrosis. Six patients had colovesical fistulae, five had enterovesical fistulae, and three had fistulae involving both the small and large bowel. Twelve patients underwent 13 surgical procedures. Healing or successful repair of the fistula was achieved in 1 of 3 patients treated with diversion (loop colostomy), 2 of 4 patients treated with isolation of the fistulized bowel loop and urinary conduit, and 5 or 6 treated with bowel resection with or without urinary conduit. Two of three perioperative deaths occurred in the isolation group managed without urinary conduit and were related to ongoing sepsis. Surgical procedures which resect necrotic fistulized bowel and result in complete separation of the gastrointestinal and genitourinary tracts provided the best results in patients with radiation-induced enterovesical fistulae. CT scan of the abdomen and pelvis is recommended in the evaluation of the majority of patients with suspected enterovesical fistula.

Adult↗
PubMed1994

Oncolytic activity of NK cells against SW-756 squamous cervical carcinoma cell line: role of interferons alpha and gamma and CD54 adhesion molecule in oncolysis.

We investigated the sensitivity of a cervical tumor cell line SW-756 to lysis by peripheral blood mononuclear cells (MNC), natural killer (NK) cells, and major histocompatibility complex (MHC)-nonrestricted (MHC-NR) T cells from cervical cancer patients and normal donors. We found that SW-756 was resistant to lysis mediated by naive (unstimulated) MNC and MHC-NR T cells, but sensitive to lysis by naive NK cells. However, the cytotoxic function of MNC could be activated with interleukin-2 (IL-2) and interferon (IFN) alpha or gamma. Although IFNs were effective in enhancement of effector cell cytotoxicity and inhibited proliferation of cervical tumor cells, they also exerted an adverse effect on cytotoxicity; specifically, pretreatment of SW-756 cells with IFNs significantly decreased their susceptibility to lysis by effector cells. Analysis of surface phenotype of SW-756 cells after treatment with IFNs showed up-regulation of expression of HLA class I determinants, the phenomenon that may be responsible for decreased sensitivity of this tumor to MHC-NR NK cells. The studies on the involvement of CD54 adhesion molecule in cytotoxic functions indicated that expression of this molecule on effector cells (but not on target cells) was important for cytotoxicity against SW-756 tumor cells. The therapeutic implication of these studies for patients with cervical cancer is discussed.

Carcinoma, Squamous Cell↗
PubMed1994

A phase II study of carboplatin and cisplatin in advanced or recurrent squamous carcinoma of the uterine cervix.

Between March 1990 and July 1992, 42 women with squamous carcinoma of the uterine cervix were prospectively treated with carboplatin (260 mg/m2) on Day 1 and cisplatin (50 mg/m2) on Day 2 every 28 days. Patients had either stage IVb (FIGO) cancer (5 patients) or recurrent cancer (37 patients) and a Zubrod score < or = 2. Forty-one patients had received either radiation or surgery as primary therapy; 179 cycles of chemotherapy were delivered. The mean number of cycles administered to each patient was 4 (range, 2-8 cycles). Dose escalation was possible in 32 cycles (23.4%) and dose reduction was required in 10 cycles (7.3%). The dose-limiting toxic effect was myelosuppression, with grade 3-4 thrombocytopenia in 39 cycles (22%) and neutropenia in 19 cycles (11%). Neurotoxic effects were observed in 3 patients. Forty-two patients were evaluable for response: 1 had a complete response and 11 had a partial response (response rate 28.6%, 95% confidence interval, 14.9-42.3%). For all patients and for responders, median progression-free interval was 4.4 and 9.5 months, respectively, and median length of survival was 8.9 and 9.5 months, respectively. This regimen was well tolerated and had significant activity in the treatment of cervical cancer. Comparison to other platinum-based regimens in a Phase III trial should be considered.

Adult↗
PubMed1994

Nucleolar organizer regions: a potential prognostic factor in adenocarcinoma of the endometrium.

Nucleolar organizer regions, which are evaluated using a silver stain for paraffin-embedded sections (AgNOR), can be used as a measurement of cellular proliferative activity. In the endometrium significant differences have been seen between benign and malignant lesions. To determine if AgNOR counts are of prognostic value in endometrial cancer, we examined 28 patients who developed recurrent disease after surgical stage Ib and Ic endometrial cancer and compared this group with a matched control group of patients who did not develop recurrence. The mean AgNOR number per cell was significantly higher in patients with recurrent disease (P = 0.001). Only five of these patients had values less than 4, whereas only three of the control group had values higher than 4. There was also a significant difference in the percentage of cells with more than 5 and more than 8 AgNORs (P = 0.001). After radiation therapy, the number of AgNORs per cell decreased. Recurrent tumors had higher AgNOR counts than the respective primary tumors. In conclusion, patients at increased risk for recurrent endometrial cancer can be identified by high AgNOR counts. Further evaluation of this parameter and comparison to other prognostic factors seems warranted.

Adenocarcinoma↗