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Biomedical subjects

M Perry

Publications and source records attributed to M Perry.

At least 19 recordsLinked to original sources
PubMed2025

The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures.

Leishmania spp. regulate gene expression largely post-transcriptionally, yet untranslated regions (UTRs) remain poorly delineated. We generated high-quality genome and transcriptome datasets for Leishmania donovani strain 1S2D (Ld1S) by combining PacBio HiFi de novo assembly with Oxford Nanopore direct RNA sequencing of promastigotes and axenic amastigotes. The genome assembly consists of 65 scaffolds totaling ~33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including some reshuffling genes among polycistronic transcription units and validated by polycistronic reads from RNA sequencing. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in UTRs. We also noted that 31.9% and 11.5% were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a comprehensive annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms, and, overall, points to an important role of 3' UTR in post-transcriptional regulation in L. donovani.

Journal Article↗
PubMed1992

Life events and breast cancer prognosis.

OBJECTIVE: To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN: Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING: Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS: 204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES: Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS: After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION: These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.

Breast Neoplasms↗
PubMed1992

Cisplatin, doxorubicin, cyclophosphamide, and etoposide combination chemotherapy for small-cell lung cancer.

Because of potential synergistic interactions, we added 25 mg/m2 i.v. cisplatin (P) 25 given on days 1-5 to the combination of 45 mg/m2 i.v. doxorubicin (A) given on day 1, 800 mg/m2 i.v. cyclophosphamide (C) given on day 1, and 50 mg/m2 i.v. etoposide (E) given on days 1-5. The resulting PACE regimen was given every 21 days for the first three courses and then every 28 days for the next five courses. PACE was used in two trials: the first, for both limited and extensive disease, was conducted at the University of Maryland Cancer Center and North Shore University Hospital; and the second, for extensive disease, was carried out as a Cancer and Leukemia Group B pilot study. Chest irradiation was not used. Prophylactic cranial irradiation at a dose of 3,000 cGy was given to all patients achieving a complete response (CR). A total of 33 subjects were entered in the first study; 8 of the 15 (53%) presenting with limited disease and 7 of the 18 (39%) exhibiting extensive disease achieved a CR. A partial response (PR) was obtained in 27% and 33% of cases, respectively. Of the 34 patients entered in the second study, 25 were eligible; 8 (32%) achieved a CR and 6 (24%) showed a PR. Toxicity was severe in both studies, including greater than 90% severe or life-threatening leukopenia and thrombocytopenia. Serial creatinine-clearance evaluations in the first study indicated progressive deterioration, which required discontinuation of the cisplatin before the planned completion of treatment in most cases. Since the response rate was no higher than the historic data reported for the three-drug ACE combination and because the toxicity was severe, the studies were stopped and patients were followed for survival. After a follow-up period of greater than 6 years, the median survival was 24 months for limited disease, with 33% and 27% of the patients being alive at 3 and 6.5 years, respectively. The median survival for extensive disease was 15 and 11 months in the first and second studies, respectively. These pilot studies suggest that the addition of cisplatin may augment the activity of the ACE regimen, but at the cost of severe toxicity. Further studies seem warranted if the myelotoxicity can be better controlled.

Adult↗
PubMed1992

The Canadian four-centre study of anaesthetic outcomes: I. Description of methods and populations.

The objectives of this study were first to develop and institute a methodology for the study of anaesthetic outcome for parallel use in four teaching hospitals in Canada and second, to compare rates of morbidity and mortality associated with anaesthesia between the four centres. The basic design of the study was occurrence screening with anaesthetists entering data on patient demographics, anaesthetic and surgical factors. Research nurses reviewed anaesthetic records and hospital charts and interviewed patients postoperatively. Data on 37,665 anaesthetics were collected during 1988-89 in the four teaching centres. There were major differences found across the hospitals, particularly with regard to volume, patient case-mix, anaesthetic drugs and monitoring used. The use of parallel training, repeated consultations and use of rounds and inservices contributed to the reliability and validity of the data collection. We conclude that outcome surveillance can be instituted in different hospital Departments of Anaesthesia with sufficient confidence to form the basis of comparison of anaesthetic outcome.

Anesthesia↗
PubMed1992

Prenatal education--how effective is it?

Are provision of knowledge and skills the major factors to influence behaviour changes that will in turn affect psychological and physiological outcomes in pregnancy and childbirth? This paper argues that courses for expectant parents must not be considered or promoted in isolation. Rather, they should be viewed as part of a complex, interrelated structure of variables that serve to create, influence, modify, support and reinforce factors considered to be indicators of favourable birth outcomes. The potential for health promotion activities is highlighted and problems of marketing, access, and restrictive obstetric management practises emphasised. Relevant research is discussed and areas for urgent action and further research are identified.

Female↗
PubMed1992

The aggression questionnaire.

A new questionnaire on aggression was constructed. Replicated factor analyses yielded 4 scales: Physical Aggression, Verbal Aggression, Anger, and Hostility. Correlational analysis revealed that anger is the bridge between both physical and verbal aggression and hostility. The scales showed internal consistency and stability over time. Men scored slightly higher on Verbal Aggression and Hostility and much higher on Physical Aggression. There was no sex difference for Anger. The various scales correlated differently with various personality traits. Scale scores correlated with peer nominations of the various kinds of aggression. These findings suggest the need to assess not only overall aggression but also its individual components.

Adolescent↗
PubMed1992

Histone H2B gene transcription during Xenopus early development requires functional cooperation between proteins bound to the CCAAT and octamer motifs.

The ubiquitously expressed transcription factor Oct-1 and several other members of the POU domain protein family bind to a site, termed the octamer motif, that functions in the promoter and enhancer regions of a variety of genes expressed under diverse conditions. An octamer motif present in a conserved histone H2B-specific promoter element is required for S-phase-specific transcription of mammalian histone H2B genes in cultured cells. We have previously shown that the octamer motif in a Xenopus histone H2B gene promoter was inactive in nondividing frog oocytes. Here we show that the octamer motif, in addition to regulatory elements (TATAA, CCAAT, and ATF motifs) that are active in oocytes, is required for maximal H2B gene transcription in developing frog embryos. Factors binding to each of the H2B upstream promoter elements are present in oocytes and increase slightly in abundance during early development. The activity of the H2B octamer motif in embryos is not specifically associated with increased binding by Oct-1 or the appearance of novel octamer-binding proteins but requires the presence of an intact CCAAT motif. Our results indicate that synergistic interactions among promoter-bound factors are important for octamer-dependent H2B transcription. We suggest that the activity of the H2B promoter is regulated primarily by changes in the interactions between proteins already bound to the promoter rather than by alterations in their intrinsic abilities to bind DNA.

Activating Transcription Factors↗
PubMed1992

Sequential expression of multiple POU proteins during amphibian early development.

The octamer motif is a common cis-acting regulatory element that functions in the transcriptional control regions of diverse genes and in viral origins of replication. The ability of a consensus octamer motif to stimulate transcription of a histone H2B promoter in frog oocytes suggests that oocytes contain a transcriptionally active octamer-binding protein(s). We show here that frog oocytes and developing embryos contain multiple octamer-binding proteins that are expressed in a sequential manner during early development. Sequences encoding three novel octamer binding-proteins were isolated from Xenopus cDNA libraries by virtue of their homology with the DNA binding (POU) domain of Oct-1. The predicted POU domains of these proteins were most highly related to mammalian Oct-3 (also termed Oct-4), a germ line-specific gene required for mouse early development. Transcripts from these amphibian POU-domain genes were most abundant during early embryogenesis and absent from most adult somatic tissues. One of the genes, termed Oct-60, was primarily expressed as a maternal transcript localized in the animal hemisphere in mature oocytes. The protein encoded by this gene was present in oocytes and early embryos until the gastrula stage of development. Transcripts from a second POU-domain gene, Oct-25, were present at low levels in oocytes and early embryos and were dramatically upregulated during early gastrulation. In contrast to the Oct-60 mRNA, translation of Oct-25 mRNA appeared to be developmentally regulated, since the corresponding protein was detected in embryos during gastrulation but not in oocytes or rapidly cleaving embryos. Transcripts from the third POU protein gene, Oct-91, were induced after the midblastula transition and reached their highest levels of accumulation during late gastrulation. The expression of all three genes decreased during late gastrulation and early neurulation. By analogy with other members of the POU-domain gene family, the products of these genes may play critical roles in the determination of cell fate and the regulation of cell proliferation.

Amino Acid Sequence↗
PubMed1992

AIDS education of college students: the effect of an HIV-positive lecturer.

Seventy-five introductory psychology students participated in an experiment to assess the effectiveness of 2 types of AIDS education. In the "disclosed" and "undisclosed" conditions, students were given a lecture about AIDS/human immunodeficiency virus (HIV) by a person who has been diagnosed with HIV disease. The lecturer revealed his HIV status in the disclosed but not in the undisclosed condition. A control group received no education. Significant differences were found in a 3 x 3 (Time x AIDS Education) analysis of variance. Knowledge and Attitude posttest scores were significantly higher than pretest scores. Students in the disclosed condition scored higher than students in the control condition on both Knowledge and Attitude posttests. For Behavioral Intent, students in the disclosed condition scored higher than students in the control condition. Subjective comments made by the students indicated that a lecturer with HIV disease had a dramatic impact on their perceptions about AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cytosine arabinoside and cisplatin for advanced breast cancer. A phase II study of the Cancer and Leukemia Group B.

Forty-four women with advanced breast cancer participated in a prospective clinical trial to evaluate the efficacy and toxicity of a regimen consisting of cytosine arabinoside and cisplatin. All patients had previously received chemotherapy. Three patients (7%) responded to therapy with response durations of 153, 160, and 441 days. The median time to disease progression and median survival time in all 44 patients were 2.3 and 5 months, respectively. This regimen had significant toxicity, with most patients experiencing severe or life-threatening hematologic, renal, or infectious complications. This regimen cannot be recommended for previously treated patients with advanced breast cancer.

Adult↗
PubMed1991

Carboplatin and vinblastine in advanced non-small-cell lung cancer: a phase II study.

Between July 2, 1987, and August 21, 1987, Cancer and Leukemia Group B (CALGB) conducted a phase II evaluation of carboplatin (CBDCA) and vinblastine (VBL) in advanced non-small-cell lung cancer. Of the 58 patients who entered the study, 55 were eligible and produced follow-up data. Chemotherapy, which was carried out in 28-day cycles, consisted of 4 mg/m2 VBL given on days 1 and 3 and 125 mg/m2 CBDCA given on days 1-3. Partial responses were observed in 10 cases (18%), and 1 patient (2%) exhibited regression of evaluable disease. No complete responses were achieved. The overall objective response rate was 20%. The median survival was 6.1 months, and the median time to treatment failure was 3.3 months. Life-threatening (grade 4) toxicity was mainly leukopenia (20%), followed by anemia (7%), infection (4%), thrombocytopenia (2%), fever (2%), nausea and vomiting (2%), and weight loss (2%). There were two deaths due to infection. The results of this study demonstrate that the combination CBDCA/VBL is active in advanced NSCLC; however, whether this combination is more active than either CBDCA or VBL alone is unknown.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Transport kinetics for superoxide dismutase and catalase between plasma and interstitial fluid in the rat small intestine.

The purpose of these studies was to determine the initial rates (first 5 h) of plasma-to-interstitial fluid transport for superoxide dismutase, catalase, and albumin in the rat small intestine. In all experiments, the renal vascular pedicles were ligated to prevent the renal excretion of these macromolecules. Plasma and intestinal interstitial fluid (lymph) samples were collected at timed intervals after bolus intravenous administration of SOD, catalase, or 125I-labeled albumin. Before injection of the proteins, the plasma concentrations (43.8 +/- 16.9 and 7.6 +/- 1.2 U/mL, respectively), interstitial fluid (lymph) concentrations (28.8 +/- 7.6 and 1.6 +/- 0.8 U/mL, respectively), and the lymph-to-plasma (L/P) protein concentration ratios (0.59 +/- 0.13 and 0.22 +/- 0.09, respectively) for endogenous SOD and catalase were determined. The plasma disappearance rate for exogenously administered catalase far exceeded the rates for SOD or albumin. However, the rate of catalase disappearance from the plasma was markedly reduced in animals in which the circulation through the liver was eliminated, suggesting that the hepatic route may be important for elimination of exogenously administered catalase. Maximal interstitial fluid catalase concentrations were achieved within 30 min while SOD and albumin required 45-90 min. The L/P ratios for exogenously administered SOD and albumin increased to 0.22 +/- 0.06 and 0.19 +/- 0.03 within 60 and 120 min of injection, respectively, and remained at these levels for the remainder of the experimental protocol. The catalase L/P ratio increased to 0.24 +/- 0.07 within 90 min of injection and subsequently declined to levels measured for endogenous catalase over the remaining 3.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A variant octamer motif in a Xenopus H2B histone gene promoter is not required for transcription in frog oocytes.

Xenopus oocytes, arrested in G2 before the first meiotic division, accumulate histone mRNA and protein in the absence of chromosomal DNA replication and therefore represent an attractive biological system in which to examine histone gene expression uncoupled from the cell cycle. Previous studies have shown that sequences necessary for maximal levels of transcription in oocytes are present within 200 bp at the 5' end of the transcription initiation site for genes encoding each of the five major Xenopus histone classes. We have defined by site-directed mutagenesis individual regulatory sequences and characterized DNA-binding proteins required for histone H2B gene transcription in injected oocytes. The Xenopus H2B gene has a relatively simple promoter containing several transcriptional regulatory elements, including TFIID, CBP, and ATF/CREB binding sites, required for maximal transcription. A sequence (CTTTACAT) in the H2B promoter resembling the conserved octamer motif (ATTTGCAT), the target for cell-cycle regulation of a human H2B gene, is not required for transcription in oocytes. Nonetheless, substitution of a consensus octamer motif for the variant octamer element activates H2B transcription. Oocyte factors, presumably including the ubiquitous Oct-1 factor, specifically bind to the consensus octamer motif but not to the variant sequence. Our results demonstrate that a transcriptional regulatory element involved in lymphoid-specific expression of immunoglobulin genes and in S-phase-specific activation of mammalian H2B histone genes can activate transcription in nondividing amphibian oocytes.

Animals↗
PubMed1991

Socioeconomic status and cancer survival.

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.

Adolescent↗
PubMed1991

Differential expression of two distinct MyoD genes in Xenopus.

We previously reported the isolation of several complementary DNAs from Xenopus laevis that encode distinct MyoD proteins. Two of these genes, Xlmf1 and Xlmf25, appear to represent a gene duplication as a consequence of the polyploid Xenopus genome. Although both MyoD genes are expressed exclusively in skeletal muscle in adult animals, they have very different temporal patterns of expression in early development. In the present work, we show that Xlmf1 transcripts rapidly accumulated to high levels shortly after activation of the zygotic genome at the midblastula transition. In contrast, Xlmf25 was expressed as a maternal transcript that was maintained at a relatively constant level throughout early development. Xlmf25, like Xlmf1, was capable of converting 10T1/2 fibroblasts to a myogenic phenotype. In addition, both proteins directly transactivated reporter genes linked to muscle-specific regulatory elements. Xlmf1 was twice as active in this regard as Xlmf25 and required a carboxy-terminal domain for its function. The absence of apparent effect of the maternally expressed myogenic gene in early embryos, but not in transfected fibroblasts, suggests the existence of regulatory mechanisms that repress the function of this gene in cells with nonmuscle fates during early amphibian development.

Animals↗
PubMed1991

An investigation into the effect of different intakes of vitamin C on drug metabolism in Gambian men.

Hepatic mixed-function oxidase activity was measured in Gambian men during a period of low seasonal vitamin C intake and after vitamin C supplementation. Demethylation of methoxyphenylacetamide (methacetin) was followed using a breath test, in which the exhalation of 13C-enriched CO2 was measured following an oral dose of 13C-methacetin. Vitamin C supplementation, sufficient to increase plasma levels significantly, did not influence methacetin metabolism. However, methacetin metabolism in unsupplemented men appeared normal in the majority of cases. Hepatic tissue may not have been sufficiently depleted of vitamin C to impair the activity of the mixed function oxidase system.

Acetamides↗