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Biomedical subjects

M Rose

Publications and source records attributed to M Rose.

At least 163 records · Page 9Linked to original sources
PubMed1991

Purification and crystallization of yeast hexokinase isoenzymes. Characterization of different forms by chromatofocusing.

The yeast hexokinase isoenzymes PI and PII have been purified in large amounts (20 mg) from overproducing yeast strains. The purification procedures of hexokinase PI and PII include anion-exchange chromatography on DEAE-Sephacel and chromatofocusing on PBE 94, hydrophobic interaction chromatography on phenyl-Sepharose (necessary for the isolation of the isoenzyme PI); in the final step either a Mono Q HR 5/5 or a Fractogel EMD TMAE 650(S) column was used. Hexokinase preparations were characterized before crystallization by chromatofocusing on a Mono P HR 5/20 FPLC column, where different forms of hexokinase can be rapidly distinguished by their elution behaviour. From both purified hexokinase PI and PII, large crystals were grown that diffract X-rays to high resolution.

Chromatography, Ion Exchange↗
PubMed1991

Glucose repression in Saccharomyces cerevisiae is directly associated with hexose phosphorylation by hexokinases PI and PII.

Genetic and biochemical analyses showed that hexokinase PII is mainly responsible for glucose repression in Saccharomyces cerevisiae, indicating a regulatory domain mediating glucose repression. Hexokinase PI/PII hybrids were constructed to identify the supposed regulatory domain and the repression behavior was observed in the respective transformants. The hybrid constructs allowed the identification of a domain (amino acid residues 102-246) associated with the fructose/glucose phosphorylation ratio. This ratio is characteristic of each isoenzyme, therefore this domain probably corresponds to the catalytic domain of hexokinases PI and PII. Glucose repression was associated with the C-terminal part of hexokinase PII, but only these constructs had high catalytic activity whereas opposite constructs were less active. Reduction of hexokinase PII activity by promoter deletion was inversely followed by a decrease in the glucose repression of invertase and maltase. These results did not support the hypothesis that a specific regulatory domain of hexokinase PII exists which is independent of the hexokinase PII catalytic domain. Gene disruptions of hexokinases further decreased repression when hexokinase PI was removed in addition to hexokinase PII. This proved that hexokinase PI also has some function in glucose repression. Stable hexokinase PI overproducers were nearly as effective for glucose repression as hexokinase PII. This showed that hexokinase PI is also capable of mediating glucose repression. All these results demonstrated that catalytically active hexokinases are indispensable for glucose repression. To rule out any further glycolytic reactions necessary for glucose repression, phosphoglucoisomerase activity was gradually reduced. Cells with residual phosphoglucoisomerase activities of less than 10% showed reduced growth on glucose. Even 1% residual activity was sufficient for normal glucose repression, which proved that additional glycolytic reactions are not necessary for glucose repression. To verify the role of hexokinases in glucose repression, the third glucose-phosphorylating enzyme, glucokinase, was stably overexpressed in a hexokinase PI/PII double-null mutant. No strong effect on glucose repression was observed, even in strains with 2.6 U/mg glucose-phosphorylating activity, which is threefold increased compared to wild-type cells. This result indicated that glucose repression is only associated with the activity of hexokinases PI and PII and not with that of glucokinase.

Enzyme Repression↗
PubMed1991

[Recovery after ambulatory vasectomy].

The recovery after outpatient vasectomy, with particular attention to general postoperative complaints, was investigated by means of a questionnaire. A material of 115 patients who were submitted to operation during the period 1.1.1988-31.12.1988 was covered by the investigation. Replies were obtained from 81%. The frequency of complaints/complications apart from the first 24 hours postoperatively was found to be unexpectedly high as 77% had from one to seven complaints/complications (average 2.8), pain and swelling being the commonest. 32% had complaints for three weeks or more while 90% were free from complaints after nine weeks. The secondary consequences of the complaints were apparent inconsiderable preoperative illness and a great number of postoperative contacts with the general practitioner. 23% had sick-leave for more than the first 24 hours postoperatively, 6% for more than one week and a total of 47 contacts with the practitioner occurred in 82 men. It is recommended that thorough information about the postoperative course should be provided by the departments in order to reduce the number of days of postoperative sick-leave and the number of contacts with the health services.

Adult↗
PubMed1991

Prison medicine.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1991

Low-dose simvastatin for the treatment of hypercholesterolaemia in recipients of cardiac transplantation.

There is increasing evidence that hypercholesterolaemia is an important contributor to the development of accelerated coronary arterial disease in the cardiac allograft. The optimal drug therapy of hypercholesterolaemia in recipients after cardiac transplantation, however, has not been defined. Simvastatin (an inhibitor of hydroxy-methyl glutaryl-coenzyme A reductase), at a dose of 10 mg/day, was administered to 12 recipients with serum total cholesterol greater than or equal to 7.8 mmol/l and serum triglyceride less than or equal to 4.5 mmol/l refractory to dietary measures during a follow-up period of 1-5 years after cardiac transplantation. All patients received maintenance doses of cyclosporin A and, in some instances, azathioprine and prednisolone. After 2 months treatment with simvastatin, serum total cholesterol was significantly reduced from 8.8 +/- 0.3 mmol/l (mean +/- SEM) to 5.5 +/- 0.5 mmol/l, P less than 0.001, low density cholesterol from 6.6 +/- 0.4 to 3.8 +/- 0.3 mmol/l, P less than 0.001 and triglycerides from 2.4 +/- 0.2 mmol/l to 1.8 +/- 0.2 mmol/l, P less than 0.005. These changes were maintained after a period of treatment of 8 months. Serum high density cholesterol, hepatic transaminase levels, serum creatinine, creatine kinase and cyclosporin A blood levels were not altered by treatment with simvastatin. It is concluded that, in this study group, low-dose simvastatin appears to be well tolerated and has favourable lipid modifying properties.

Adult↗
PubMed1991

Immunocytochemical markers of activation in cardiac transplant rejection.

Immunocytochemical analysis of endomyocardial biopsies from cardiac transplant patients has defined changes in expression of antigens, expressed on both the myocardium and endothelium which are characteristic of rejection. Biopsies taken from normal donor heart (prior to transplantation) have been compared with biopsies showing histological signs of rejection. There is induction of MHC class I antigen on the normally negative myocardial plasma membrane and induction of the adhesion molecule ICAM-1 on the intercalating discs. Capillary endothelial cells, which constitutively express Class II DR antigen and ICAM-1 in normal heart show increased of endothelial antigens Pal-E and FVIII-RA during rejection. These results demonstrate perturbation of the endothelial system during rejection and possibly indicate damage to the capillary endothelial cells.

Antigens, CD↗
PubMed1991

Cyclosporin treatment does not impair the release of nitric oxide in human coronary arteries.

OBJECTIVE: It has been hypothesised that compromised endothelial function can contribute to the toxic manifestations associated with cyclosporin therapy. In vitro animal studies have implicated inhibition of release of the endothelium derived relaxing factor, nitric oxide; however, this has not been investigated in human tissue. The present study investigated the effect of cyclosporin A on nitric oxide release in human coronary arteries. DESIGN: Study of in vitro organ bath preparations and in vivo angiographic measurements in the coronary circulation. PATIENTS: For the in vitro experiments coronary arteries were harvested from the excised hearts of 10 patients requiring transplantation for reasons other than ischaemic heart disease. Three of these patients were being re-transplanted for obliterative bronchiolitis and had been receiving cyclosporin for a mean of 22 months. The in vivo study was performed on a group of 12 cardiac transplant recipients who were clinically well 1-5 years postoperatively and were not undergoing allograft rejection at the time of assessment. RESULTS: Isolated vessel segments in vitro relaxed in a dose dependent manner in response to substance P (10(-11)-10(-7) mol/l). The maximum response was 76.6 (7.4)% of the response to 1 microgram/ml glyceryl trinitrate. Incubation with 1000 and 2000 ng/ml cyclosporin reduced the response to 63.0 (11.5)% and 62.2 (11.1)% respectively; this was not statistically significant. In segments taken from the explanted hearts of three patients requiring re-transplantation, the mean maximum response was 78.0 (11.0)% and there was no correlation between maximum response in segments from each patient and the duration of cyclosporin therapy. The effect of intracoronary substance P in 12 cardiac transplant recipients was also examined (mean cyclosporin blood concentration 228.9 (42.8) ng/ml). The mean maximum dilatations measured as the percentage diameter change induced by substance P and isosorbide dinitrate were 22.1 (3.2)% and 26.0 (2.5)% respectively. There was no correlation between the degree of endothelium mediated vasodilatation in response to substance P and cyclosporin concentration. CONCLUSIONS: The nitric oxide response was preserved in the coronary arteries of patients exposed to cyclosporin. The mechanisms that initiate cyclosporin associated toxicity remain to be elucidated.

Coronary Vessels↗
PubMed1991

Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data.

Between 1962 and 1984, a total of 433 patients were treated at Yale-New Haven Hospital with conservative surgery and radiation therapy (CS + RT) to the intact breast. As of January 1990, with a minimum assessable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Of all clinical factors tested, young age was the most significant prognostic factor for local recurrence (P less than .03). In addition, patients with pathologically involved lymph nodes were noted to have a lower local recurrence rate than patients with pathologically negative axillae (P less than .05). These findings were especially notable given the fact that the node-positive group had a higher percentage of T2 tumors and a higher percentage of patients in the young age group. These paradoxical findings, however, may be explained by the fact that 88% of the node-positive patients underwent adjuvant systemic therapy in the form of either systemic chemotherapy or hormonal therapy, while only 8% of node-negative patients underwent any adjuvant systemic therapy. When analyzed as a function of adjuvant therapy, those patients receiving adjuvant therapy had a lower local recurrence rate than those patients not receiving adjuvant therapy (P less than .08). We conclude that adjuvant systemic therapy impacts on the ipsilateral breast recurrence rate in patients treated with CS + RT. The implications of this study in light of the widespread use of adjuvant systemic therapy are discussed.

Actuarial Analysis↗
PubMed1991

Duplex sonography in splenomegaly.

The aetiology of splenomegaly is seldom clear from either clinical or imaging assessment of the spleen. In the majority of cases sonographic assessment of the spleen produces a homogeneous enlargement of variable echodensity, but with very poor correlation with pathology. A study has been undertaken to assess the Doppler characteristics of the splenic artery in splenomegaly, excluding cases of portal hypertension in an attempt to provide further diagnostic information. Duplex assessment of 18 normal subjects and 10 patients with splenomegaly due to five different causes was undertaken. Analysis of waveform, peak frequency and pulsatility index were compared and failed to demonstrate any significant change. In the normal subject there is a broad systolic spectrum related to the tortuosity of the splenic artery, with persistence of forward flow throughout diastole, a reflection of the low peripheral resistance of the spleen. In splenomegaly the broad systolic spectrum is unchanged, since vessel tortuosity persists. Pathological and physiological assessment of the spleen in splenomegaly shows that a low resistance circulation persists, explaining maintenance of the diastolic flow pattern in splenomegaly. Increased blood flow to the spleen in splenomegaly occurs either as a result of an increase in vessel diameter or an increase in flow velocity, or a variable combination of the two which does not seem to be governed by specific pathology. An increase in peak frequency in some cases reflected some increase in flow velocity but provided no useful correlation. Analysis of the pulsatility index supported the above findings without adding further information.

Adolescent↗
PubMed1991

Human monocyte antigens in a random sample from Japan.

We studied a random sample of Japanese and compared both Japanese and German monocyte antigen frequencies and performed a segregation analysis in Japanese families. In Japanese, the following gene frequencies were established: 0.1033 for HMA-A1; 0.0299 for HMA-A3; 0.0033 for HMA-A6; 0.1521 for HMA-B2. Data on the gene frequency in Germans were presented by Rose. In this comparison, the frequency for HMA-B2 in Japanese is more than two times higher; for antigen HMA-A6, the Japanese is a fifth of the German quantity. The antigen HMA-B4 was not found in Japanese. The results we obtained from family analysis confirmed an unambiguous autosomal, codominant inheritance of the examined HMA antigens.

Gene Frequency↗
PubMed1991

Legal proof of child sexual abuse in the absence of physical evidence.

Child sexual abuse criminal court cases from a 12-month period were reviewed to determine the frequency and significance of physical evidence in legally "proven" felony cases with penetration. One hundred fifteen consecutive cases were reviewed, and 87 (76%) had resulted in conviction of the perpetrator on felony charges. Charges of vaginal rape were made in 88 cases, and oral and/or anal sodomy in 67 cases. Physical evidence was present in only 23% of all cases that resulted in felony convictions. Felony convictions were obtained in 67 (79%) of 85 cases without physical evidence and in only 20 (67%) of 30 cases with physical evidence. Eight of the 10 cases without physical evidence that did not result in conviction involved victims younger than 7 years of age. Cases involving the youngest victims had a significantly lower conviction rate (12 of 23), despite a very high frequency (13 of 23) of physical evidence (P less than .0005). Physical evidence was neither predictive nor essential for conviction. Successful prosecution, particularly in cases involving the youngest victims, depended on the quality of the verbal evidence and the effectiveness of the child victim's testimony.

Adolescent↗
PubMed1990

Vomiting after Roux-en-Y biliary diversion: relationship to surgical technique.

Vomiting is a frequent complaint after revisional gastric surgery using a Roux-en-Y biliary diversion. This is believed to be due to gastric stasis or stasis in the jejunal component of the Roux-en-Y. Thirty-three patients, ten with a satisfactory outcome following Roux-en-Y diversion and 23 with an unsatisfactory outcome, were studied using a semisolid, radiolabelled meal and compared with 12 normal subjects. Outcome was assessed by modified Visick grading. Seven patients with an unsatisfactory outcome because of frequent vomiting had gastric stasis and two had delay in emptying of the jejunal component of the Roux-en-Y. Vomiting was more likely in patients with a dependent sump (P less than 0.006) and emptying was significantly prolonged where a sump was present (P = 0.0009). Surgical technique contributed to the dependent sump.

Adult↗
PubMed1990

Stain analysis using oligonucleotide probes specific for simple repetitive DNA sequences.

The use of oligonucleotide fingerprinting is evaluated in practical forensic work, using both artificially and systematically produced stains as well as actual case work material. The probes (CAC5/(GTG)5 are superior because of their individualizing potential in comparatively fresh specimens with little DNA degradation, whereas (GACA)4, still produces substantial information when high molecular weight DNA is lacking. The overall limitations and the advantages of this technology are discussed in detail and compared to the classical minisatellite probes.

Blood Stains↗
PubMed1990

High-dose cytosine arabinoside plus etoposide as initial treatment for acute myeloid leukaemia: a single centre study.

In a single centre, 52 newly diagnosed patients with acute myeloid leukemia (AML) under the age of 56 years received induction chemotherapy commencing with high-dose cytosine arabinoside (Ara-C) and etoposide (Protocol BF11), followed by Ara-C, 6 thioguanine (6TG). A total of 67% of patients entered remission using these drugs. An anthracycline was added for those patients not in remission. The overall remission rate (CR) was 86.5% (45/52), with a minimum follow-up of 90 days. Patients are hospitalised for relatively short periods, and consequently require less blood product and antibiotic support. Patients in continuing first remission following induction with Ara-C and etoposide are similar in number to those in continuing first remission who initially received an anthracycline. This would imply that the efficiency of Ara-C and etoposide in inducing long-term disease-term survival is comparable with anthracycline-containing regimens. We conclude that high-dose Ara-C and etoposide used in the first induction cycle for treating AML have good antileukaemic effect with acceptable toxicity.

Adolescent↗
PubMed1990

Some problems with antihypertensive drug studies in the context of the new guidelines.

A dose-response analysis establishes the efficacy of most drugs. The medical literature is replete with so-called "Dose-Responses" to antihypertensive agents. The majority of these have failed. The use of a placebo helps minimize bias, though most studies here simply compared a test drug with the old drug. Short-acting drugs can have their duration of effect prolonged by giving larger doses than necessary. In order to produce more meaningful data, the Food and Drug Administration gathered together a group of experts who collectively proposed a set of Guidelines for studying these drugs. Though the final version has not yet been issued, investigators and clinicians working with this class of drugs are vitally interested in these guidelines, and have already encountered several problems. We identify some of these problems and propose some solutions.

Antihypertensive Agents↗
PubMed1990

Immunohistology of Epstein-Barr virus-associated antigens in B cell disorders from immunocompromised individuals.

Proliferating B cell lesions developing in a series of immunosuppressed organ transplant recipients and patients with X-linked lymphoproliferative syndrome were examined for Epstein-Barr virus and cellular gene expression using immunocytochemistry and immunoblotting techniques. Results indicate that all the lesions examined from the patients in this series expressed Epstein-Barr virus gene products that were consistent with a latent, nonproductive type of infection. No lytic cycle antigens associated with productive viral infection were detected. This pattern is similar to the viral gene expression in normal B cells immortalized by Epstein-Barr virus in vitro. The demonstration in this study of Epstein-Barr virus viral gene expression in posttransplant and X-linked proliferative syndrome B cell disorders provides important new evidence for the primary role of Epstein-Barr virus in the development of these lesions. This is in contrast to the subsidiary role that the Epstein-Barr virus has in the etiology of Burkitt's lymphoma.

Antibodies, Monoclonal↗
PubMed1990

Immunohistochemical demonstration of human cardiac innervation before and after transplantation.

Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide.

Adolescent↗