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Biomedical subjects

A Roman

Publications and source records attributed to A Roman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Human papillomavirus type 6 E7 protein is a substrate in vitro of protein kinase C.

The E7 proteins of 'low-risk' and 'high-risk' human papillomaviruses (HPV) are phosphorylated by casein kinase II. In this study, we report that the 'low-risk' HPV 6 E7 protein, but not the 'high-risk' HPV 16 E7 protein, can be phosphorylated in vitro on threonine at amino acid position 7 by protein kinase C. This is the first example of a qualitative biochemical difference between the HPV 6 E7 and HPV 16 E7 proteins.

Amino Acid Sequence↗
PubMed1995

Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey.

OBJECTIVES: To assess patient responses to radical prostatectomy and its effects. METHODS: A national sample was taken of 1072 Medicare patients who underwent radical prostatectomy for prostate cancer (1988 through 1990) by mail, telephone, and personal interviews. The effects of the surgery and its complications on these patients' lives were studied through: (1) patient ratings of the extent to which sexual and urinary dysfunctions were "problems" in their lives; (2) two general measures of quality of life, the Mental Health Index and the General Health Index; (3) patient reports of how they felt about the results of treatment and whether they would choose surgery again. RESULTS: On average, dripping urine, particularly to the point where subjects were wearing pads, had a more significant effect on patients than loss of sexual function; incontinence had significant adverse effects on the measures of quality of life and self-reported results of surgery. Overall, postsurgical patients scored comparatively high on the quality of life measures (similar to a cohort of patients with benigh prostatic hyperplasia who had undergone transurethral resection of the prostate), reported feeling positive about the results (81%), and would choose surgical treatment again (89%). Nonetheless, there was variability in patient response to the effects of surgery. CONCLUSIONS: The results demonstrate the ability of many Medicare patients to adapt to adverse outcomes, such as loss of sexual function and incontinence. They also provide evidence of the variability of individual patients' responses to surgical results and reinforce the importance of individualized decision making for patients facing a decision about radical prostatectomy for prostate cancer.

Aged↗
PubMed1995

Sequence variation in the extreme 5' end of the human papillomavirus type 6a long control region.

A sequence analysis of human papillomavirus (HPV) type 6a isolates from 15 exophytic condylomata acuminata lesions was done to determine the prototype sequence for this region of HPV 6a, which sequences are conserved and which vary, and whether the variability might be useful in epidemiologic studies. The long control region (LCR) was amplified by the polymerase chain reaction and approximately 242 bp were directly sequenced. The data indicate that all isolates contain a 94-bp insertion relative to prototype HPV 6b and confirm that this insertion should be considered a part of the HPV 6 LCR. Seven of the 15 isolates were in 1 group, and the rest were distributed among 4 groups. There was no strong correlation between DNA group and location of lesion, sex of patient, or pregnancy status. In addition, although there was variation among isolates, a region implicated by deletional analysis to have transcriptional silencing activity was conserved.

Base Sequence↗
PubMed1995

Methylene blue administration in septic shock: a clinical trial.

OBJECTIVE: A release of nitric oxide has been incriminated in the cardiovascular alterations of septic shock. Since guanylate cyclase is the target enzyme in the endothelium-dependent relaxation mediated by nitric oxide, we studied the acute effects of methylene blue, a potent inhibitor of guanylate cyclase in patients with septic shock. DESIGN: Prospective clinical trial. SETTING: Medical-surgical intensive care unit in a university hospital. PATIENTS: Fourteen patients with severe septic shock requiring adrenergic therapy. INTERVENTIONS: Short-term intravenous infusion of methylene blue. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were obtained at baseline, and 30, 60, and 90 mins after the infusion of 2 mg/kg of methylene blue. Methylene blue administration was followed by a progressive increase in mean arterial pressure (from 61.1 +/- 7.6 to 71.7 +/- 12.0 mm Hg at 60 mins, p < .01). Pulmonary arterial pressure, cardiac filling pressures, cardiac output oxygen delivery, and oxygen consumption were not significantly affected. Left ventricular stroke work increased from 42.5 +/- 17.9 to 48.9 +/- 14.5 g.m after 60 mins (p < .05). Arterial lactate concentration decreased from 3.4 +/- 1.4 to 2.7 +/- 1.3 mmol/L (p < .05). Since these effects were transient, a second dose of methylene blue was administered 90 mins later to six patients and was followed by a similar response. No adverse effect was observed. CONCLUSIONS: In septic shock patients, the administration of methylene blue results in a transient and reproducible increase in arterial pressure, associated with an improvement in cardiac function, but does not increase cellular oxygen availability. The significant reduction in blood lactate concentration is probably related to the reductor effect of methylene blue, rather than to an improvement in tissue oxygenation.

Adult↗
PubMed1995

Detection of silencer activity in the long control regions of human papillomavirus type 6 isolated from both benign and malignant lesions.

Human papillomavirus type 6 (HPV-6) DNA is the predominant HPV type found in condyloma acuminata: it is rarely found in carcinomas. We have previously reported cloning and characterizing an HPV-6 from a vulvar condyloma (HPV6-W50) and an HPV-6 from a vulvar carcinoma (HPV6-T70). The E5, E6 and E7 proteins encoded by the two genomes were identical, however, the two genomes differed in the long control region (LCR). Cloning of the entire LCR into the enhancerless plasmid pSVEcat showed that the two LCRs had comparable enhancer activity. Since the major differences between the two LCRs resided in the 5' end of the LCR, upstream of the L1 polyadenylation signal, we subcloned the two LCRs to analyse more closely their effect on cat gene expression. The data indicated that LCR subclones of the two genomes had comparable chloramphenicol acetyltransferase (CAT) activity. A negative regulatory region was detectable when the test plasmids were transfected into HeLa and C33A cells and in primary keratinocytes. A decrease in CAT activity was also detected when the SV40 early promoter was replaced with the putative HPV-6 E6 promoter. The negative regulatory region functioned in a position- and orientation-independent manner, thus fulfilling the definition of a silencer.

Base Sequence↗
PubMed1994

Measuring public priorities for insurable health care.

The goal of this research was to develop and evaluate a way to measure the value people place on various medical services in their decisions about what health insurance should cover. A vignette approach to measuring consumer values was developed. People were asked to assign priority and desire to have insurance cover 64 different services. A national probability sample of 206 adults was interviewed by telephone. Their ratings were compared with those of a sample of 47 corporate benefits officers of Fortune 500 companies. Priorities were not significantly associated with respondent characteristics. They were positively correlated with independent assessments of the seriousness of the patient's condition and the likely efficacy of the services. Priorities and desire to cover were virtually the same when respondents were asked about insurance for a low-income population as for a general population. Two-thirds of the ratings of the public were the same as those of benefit officers. The public gave higher ratings than benefits officers to long-term care and services to relieve worries, and the public gave lower ratings to the value of treatment of substance abuse and services when the patient could be viewed as at fault. This pilot test indicates this is an efficient, feasible, useful strategy for measuring the extent to which people value various medical services that could contribute to the process of making decisions about health insurance coverage.

Adult↗
PubMed1994

Immunoreactivity of ageing C57BL female mice rendered tolerant to the H-Y antigen.

Transplantation tolerance to the H-Y antigen, induced in neonatal or young adult C57BL female mice, beneficially affected their immunoreactivity during the process of ageing. The tolerance acquired in 2-month-old females significantly increased their splenocyte graft-versus-host (GVH) reactivity and the production of interleukin-2 (IL-2) at the age of 18 months. The neonatally induced tolerance also resulted in a higher weight of the thymus and a significantly enhanced GVH reactivity of thymocytes in 18-month-old females compared to control mice of the same age.

Aging↗
PubMed1994

Effect of immobilization stress on tumor growth in mice.

The effect of immobilization stress applied daily for 2 h on the development of MF-RSV tumor graft in mice and on survival of the hosts was studied. While a single acute stress applied to mice simultaneously with a transfer of MF-RSV cells stimulated antitumor defense, chronic stress applied both before and/or after tumor cell implantation accelerated the death of recipients. The shortest survival time was found in mice which were stressed for 3 weeks before implantation and on, until their death. Heat shock applied to MF-RSV tumor cells before implantation significantly reduced their growth ability in the hosts.

Animals↗
PubMed1993

The anomalous electrophoretic behavior of the human papillomavirus type 16 E7 protein is due to the high content of acidic amino acid residues.

In the presence of sodium dodecyl sulfate and 2-mercaptoethanol, the human papillomavirus 16 E7 protein migrates as a 17 kD protein during polyacrylamide gel electrophoresis. However, the theoretical molecular mass of this protein is approximately 11 kD. Substitution of 2 basic amino acids for 2 acidic residues in the amino terminus of the protein restored normal electrophoretic mobility. Furthermore, neutralization of negative charge through chemical modification of the wild type protein normalized migration. These results indicate that the substantial net negative charge of the wild type E7 protein is responsible for its anomalous electrophoretic behavior.

Amino Acid Sequence↗
PubMed1993

Patient-reported complications and follow-up treatment after radical prostatectomy. The National Medicare Experience: 1988-1990 (updated June 1993).

To estimate the probabilities of complications and follow-up treatment, a sample of Medicare patients who underwent radical prostatectomy (1988 through 1990) was surveyed by mail, telephone, and personal interview. Respondents reported their current status with respect to continence and sexual function as well as post-surgical treatments they had had to treat residual or recurrent cancer or surgical complications. Over 30 percent reported currently wearing pads or clamps to deal with wetness; over 40 percent said they drip urine when they cough or when their bladders are full; 23 percent reported daily wetting of more than a few drops. About 60 percent of patients reported having no full or partial erections since their surgery, and only 11 percent had any erections sufficient for intercourse during the month prior to the survey. Six percent had surgery after the radical prostatectomy to treat incontinence; 15 percent had treatments or used devices to help with sexual function; 20 percent report having had post-surgical treatment for urethral strictures. In addition 16 percent, 22 percent, and 28 percent reported follow-up treatment for cancer (radiation or androgen deprivation therapy) at two, three, and four years after radical prostatectomy. These estimates of complication and follow-up treatment rates are generally higher, and almost certainly more representative for older men, than estimates previously published. Patients and physicians may want to weight heavily the complications and need for follow-up treatments when considering radical prostatectomy for prostate cancer.

Aged↗
PubMed1992

Mutagenesis of human papillomavirus types 6 and 16 E7 open reading frames alters the electrophoretic mobility of the expressed proteins.

The E7 open reading frames of human papillomavirus type 6 (HPV-6) and HPV-16 encode proteins consisting of 98 amino acids that are quite similar in sequence yet different in electrophoretic mobility. Moreover, these proteins vary strikingly in oncogenicity. To investigate the molecular basis of the differences in structure and function, site-directed mutagenesis was used to exchange non-conserved amino acid residues between the two proteins. The mutated coding regions were expressed as fusion proteins in Escherichia coli and identified by Western blotting. Comparative analysis of the affinity-purified mutated E7 fusion proteins in polyacrylamide slab mini-gels in the presence of SDS and 2-mercaptoethanol revealed altered electrophoretic mobilities. This analysis suggests that the aspartic acid at residue 4 (Asp 4) contributes to the characteristic aberrant migration of the HPV-16 E7 protein in SDS-polyacrylamide gels.

Amino Acid Sequence↗
PubMed1991

Relative enhancer activity and transforming potential of authentic human papillomavirus type 6 genomes from benign and malignant lesions.

Human papillomavirus type 6 (HPV-6) is predominantly associated with benign genital warts whereas HPV-16 and HPV-18 are detected predominantly in carcinomas of the lower genital tract; HPV-6 is found rarely in such carcinomas. Experiments were designed to discriminate between two hypotheses concerning the role of HPV-6 in the genesis of a genital tract carcinoma: (i) the HPV-6 in the carcinoma (HPV6-T70) differs genetically from HPV-6 in a benign lesion (HPV6-W50), giving HPV6-T70 properties similar to those of HPV-16/18: (ii) HPV6-T70 and HPV6-W50 have similar biological activity, suggesting that the role of HPV-6 in oncogenesis is different from that of HPV-16/18. Restriction enzyme digestion and DNA sequence determination established that HPV6-T70 differs from HPV6-W50 in the upstream regulatory region (URR) but not in the proteins encoded by open reading frames (ORFs) E5, E6 or E7, ORFs implicated in oncogenesis. To determine whether the difference in the URR sequence could alter the level of expression of viral genes, the URRs were cloned into the enhancerless plasmid pSVEcat. Analysis of chloramphenicol acetyltransferase activity after transfection into HeLa and Vero cells showed that the URRs had comparable enhancer activity. Cotransfection of baby rat kidney (BRK) cells with HPV6-T70 and an activated ras gene indicated that, in contrast to HPV-16 and HPV-18, this HPV-6 genome could not cooperate with ras to transform BRK cells. The data suggest that HPV6-T70 and HPV6-W50 have similar enhancer activity and transforming potential.

Animals↗
PubMed1991

Analysis of invasive squamous cell carcinoma of the vulva and vulvar intraepithelial neoplasia for the presence of human papillomavirus DNA.

We have analyzed a number of invasive squamous cell carcinomas for the presence of human papillomavirus (HPV) DNA using dot blot and Southern blot analysis. Seven of 31 samples (23%) were positive by dot blot and/or Southern blot analysis. In contrast, six of 11 (55%) of vulvar intraepithelial neoplasias contained HPV DNA by dot blot and/or Southern blot hybridization. Less than 50% of the invasive vulvar carcinomas contained detectable HPV DNA. The average age at onset of vulvar carcinoma is higher than that for cervical carcinoma (in which HPV DNA is detected in over 80% of cases). Therefore, the role of HPV in the genesis of vulvar carcinoma may be different from the role of HPV in the genesis of cervical carcinoma.

Adult↗
PubMed1990

Dobutamine administration in septic shock: addition to a standard protocol.

Dobutamine administration has been shown to increase oxygen delivery in various conditions, but there are little data to document its effects in septic shock. We investigated the effects of dobutamine infusion at a rate of 5 micrograms/kg.min in 18 patients (mean 60 +/- 16 yr) with septic shock initially characterized by hypotension, oliguria, and hyperlactatemia in the presence of a documented source of sepsis. Early resuscitation had consisted of fluid administration and vasopressors when required. When added to this standard regimen, dobutamine had no significant effect on mean arterial pressure (MAP) (from 71 +/- 12 to 73 +/- 13 mm Hg), but markedly increased cardiac index (from 3.0 +/- 0.7 to 3.9 +/- 1.0 L/min.m2, p less than .001), stroke index (from 32 +/- 8 to 37 +/- 9 ml/m2, p less than .001) and oxygen transport (from 410 +/- 105 to 530 +/- 146 ml/min.m2, p less than .001). Oxygen consumption (VO2) increased concurrently (from 137 +/- 42 to 162 +/- 66 ml/min.m2, p less than .002). MAP increased (from 68 +/- 9 to 76 +/- 11 mm Hg) in 12 patients and decreased moderately (from 76 +/- 18 to 69 +/- 17 mm Hg) in six patients. The two subgroups of patients had similar hemodynamic profiles before the dobutamine infusion, but vasopressor therapy was already used in one of the 12 patients in the first subgroup and in three of the six patients in the second subgroup (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Oxygen uptake/supply dependency. Effects of short-term dobutamine infusion.

The present study explored the possibility of using a short-term dobutamine infusion to disclose oxygen uptake/supply dependency. The effects of a standard dose of 5 micrograms/kg/min of dobutamine on oxygen-derived variables were studied in 73 acutely ill patients with heart failure (n = 24) or sepsis (n = 49). In each group, patients were separated according to their blood lactate concentrations (either above or below 2 mEq/L). In all patient groups, dobutamine resulted in significant increases in cardiac output and oxygen transport. However, oxygen consumption increased significantly only in patients with elevated blood lactate levels (cardiac failure: from 108 +/- 26 to 131 +/- 25 ml/min/M2, n = 8, p less than 0.01; sepsis: from 139 +/- 44 to 167 +/- 68 ml/min/M2, n = 16, p less than 0.01) and not in the other patients (heart failure: from 121 +/- 29 to 115 +/- 31 ml/min/M2, n = 28, NS; sepsis: from 158 +/- 39 to 166 +/- 45 ml/min/M2, n = 21, NS). These data, therefore, indicate that dobutamine at the dose used does not increase oxygen consumption in critically ill patients unless there is coexistent tissue hypoxia reflected by increased blood lactate levels. A short-term dobutamine infusion can be used to disclose an oxygen uptake/supply dependency phenomenon.

Acidosis, Lactic↗