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Biomedical subjects

P Browne

Publications and source records attributed to P Browne.

At least 37 records · Page 2Linked to original sources

Intravascular large B-cell lymphoma: the CD5 antigen is expressed by a subset of cases.

The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. We observed CD5 antigen expression in a subset of cases of intravascular large B-cell lymphoma (IVLBL), and we report here five cases. The patients, two men and three women, ranged in age from 59 to 81 years. Biopsy specimens were obtained from kidney, lung, bone marrow, abdominal wall, and neck, the latter involving a lymphangioma. All of the cases had histologic features typical of IVLBL, with large and atypical lymphoid cells located predominantly within blood vessels. Immunohistochemical studies performed using routinely fixed, paraffin-embedded tissue sections showed that the neoplastic cells were B cells, positive for the CD20 antigen and negative for the CD3 or CD43 antigens. All cases were also positive for the CD5 antigen. One case had an immunoglobulin heavy chain gene rearrangement shown by using a polymerase chain reaction method. The finding of CD5 antigen expression in a subset of IVLBL cases adds to other evidence in the literature suggesting that IVLBL is a heterogeneous entity. We considered the possibility that these cases were related to or represented unusual histologic forms of transformation from either chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. All of the cases, however, were negative for the CD23 antigen and cyclin D1 (bcl-1) protein, which is evidence against this interpretation. The biologic significance of CD5 antigen expression in cases of IVLBL is uncertain. These neoplasms might arise from a separate lineage of CD5-positive B cells or from a specific, early stage of B-cell differentiation. Alternatively, some investigators have suggested that CD5 antigen expression by B cells is a marker of activation.

Aged↗

Circulating activated endothelial cells in sickle cell anemia.

BACKGROUND: The vascular wall participates in the pathogenesis of sickle cell disease. To determine whether the endothelium is activated in this disease, we studied the number, origin, and surface phenotype of circulating endothelial cells in patients with sickle cell anemia. METHODS: We used immunohistochemical examination of buffy-coat smears to enumerate circulating endothelial cells, and we evaluated the surface phenotype by applying preparations of circulating endothelial cells. An immunofluorescence microscopy panel of antibodies was used, including a specific anti-endothelial-cell antibody, P1H12. RESULTS: Mean (+/-SD) numbers of circulating endothelial cells in normal blood donors, patients with sickle cell trait, and patients with hemolytic anemias not due to hemoglobin S were 2.6+/-1.6, 3.0+/-2.6, and 2.0+/-0.8 per milliliter of whole blood, respectively. Patients with sickle cell anemia who presented with acute painful episodes had 22.8+/-18.2 circulating endothelial cells per milliliter of blood (P<0.001 for the comparison with normal donors), and patients with no such events within one month before or after blood sampling had 13.2+/-11.8 circulating endothelial cells per milliliter of blood (P=0.002 for the comparison with normal donors and P=0.019 for the comparison with patients with acute events). Serial observations of three patients showed a tendency toward higher levels of circulating endothelial cells at the onset of acute painful crises. The average viability of circulating endothelial cells was 66+/-30 percent. In patients with sickle cell anemia, regardless of clinical status, the circulating endothelial cells were predominantly microvascular in origin (CD36-positive), and most of the cells expressed four markers of endothelial-cell activation: intercellular adhesion molecule 1, vascular-cell adhesion molecule 1, E-selectin, and P-selectin. CONCLUSIONS: Our studies suggest that the vascular endothelium is activated in patients with sickle cell anemia, regardless of the patients' clinical status. Adhesion proteins on activated endothelial cells may have a role in the vascular pathology of sickle cell disease.

Adolescent↗

Diploid hydatidiform moles with fetal red blood cells in molar villi. 1--Pathology, incidence, and prognosis.

It is believed that fetal development does not occur in complete mole (CM); when present, it is usually interpreted as proof of partial mole (PM), in most cases a triploid conception with a low incidence of persistent trophoblastic disease (PTD). However, histological examination of 3180 moles in 8 years showed 60 moles (1.8 per cent) with features of CM and either embryonic tissues or amnion in the sample. Flow cytometry (FC) in 40 showed diploid complement in all. In ten of the 40, there was evidence of a twin; in 17, there was only amnion, which could belong to a twin; in the remaining 13, there was no evidence of a twin and nucleated fetal red blood cells (FRCs) were seen within molar vessels in ten (0.3 per cent). Seven of the 40 patients (17.5 per cent) and one of the ten with FRCs in villi (10 per cent) developed PTD, an incidence comparable to that of CM. Genetic studies in seven of these tea are reported separately. Finding fetal tissues with a mole or FRCs in molar vessels is not enough to classify it as PM, since it can be a CM with a twin, fetal development CM, or possibly a third type of mole. These rare diploid moles with fetal tissues have histological appearances and prognosis similar to those of CM.

Adult↗

Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival.

BACKGROUND & AIMS: The E-cadherin-catenin complex plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components is believed to result in loss of cell-cell adhesion and contribute to neoplasia. The aim of this study was to examine the expression of E-cadherin and alpha-, beta-, and gamma-catenin in gastric carcinoma and dysplasia and determine any relationship with tumor characteristics and survival. METHODS: Immunoperoxidase staining of E-cadherin and alpha-, beta-, and gamma-catenin was performed using 89 gastric carcinomas, lymph node metastases, and gastric biopsy specimens from 14 patients with dysplasia and 10 healthy controls. RESULTS: Membranous staining was observed in control biopsy specimens for all components of the complex. Up to 57% of gastric dysplasia and 90% of tumors stained abnormally for one or more components of the cadherin-catenin complex. Abnormal E-cadherin and gamma-catenin staining occurred more frequently in diffuse than intestinal tumors (P < 0.0005 and < 0.05, respectively). No association with tumor grade or stage was found. A survival advantage was noted in intestinal and diffuse tumors retaining membranous expression of beta-catenin, independent of tumor type, grade, or stage (P < 0.005). CONCLUSIONS: Abnormal expression of the E-cadherin-catenin complex occurs frequently in gastric carcinoma. The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker.

Adult↗

A clinical, histopathological and flow cytometric study of 149 complete moles, 146 partial moles and 107 non-molar hydropic abortions.

We have compared the clinical and histological features of 149 complete moles with 146 triploid partial moles and 107 diploid non-molar hydropic abortions initially registered as moles for human chorionic gonadotrophin (hCG) follow-up. Forty-one patients with complete moles, five with partial moles and one with hydropic abortion received chemotherapy for hCG elevations interpreted as persistent trophoblastic disease. Complete moles were aborted or were evacuated significantly earlier than partial moles (means of 12.1 and 15.4 weeks; P < 0.001) and hydropic abortions significantly earlier than complete moles (mean 10.7 weeks; P < 0.005). The means of the highest recorded hCG were higher in complete moles (184,056 i.v.) than in partial moles (66,259 i.v.) and hydropic abortion (7942 i.v.). When hCG became normal without chemotherapy, this occurred earlier in patients with hydropic abortion than in those with partial moles (means of 46.7 days and 62.8 days; P < 0.001) and earlier in partial moles than in complete moles (mean 78.3 days; P < 0.005). The incidence of partial moles was comparable throughout fertile years but rose to 1.9 times the average after 40 years. Complete moles were commoner between 14 and 25 years and after 35 years, reaching 4.8 times the average after 40 years. Hydropic abortions were rare before 25 years and increased with age to 12 times the average after 40 years. Stromal karyorrhexis and shape of villi, before they become hydropic, discriminate well between complete and partial mole. Hydrops increased and vascularity decreased with molar age and the presence of non-hydropic villi or vessels did not discriminate between partial mole and the younger complete moles evacuated nowadays.

Abortion, Spontaneous↗

A comparison of the effects of human and ovine corticotropin-releasing hormone on the pituitary-adrenal axis.

To compare the clinical efficacy of ovine and human sequence corticotropin-releasing hormone (CRH), we examined the effects of both peptides on ACTH and cortisol secretion in normal human volunteers, obese subjects, and patients with pituitary-dependent (Cushing's disease) and adrenal-dependent Cushing's syndrome. All subjects in each group were studied twice in random order. One hundred micrograms of CRH were administered as an iv bolus through an in-dwelling forearm cannula at 0930 h, and thereafter, blood was drawn every 15 min for 2 h for the measurement of ACTH and cortisol. In the normal subjects, the peak ACTH, peak incremental ACTH, and mean area under the curve after CRH treatment were greater with ovine CRH than human CRH, although there was no difference in the cortisol response, however it was analyzed. There was no difference in the ACTH or cortisol response to the two preparations in the obese subjects, and no significant difference was found, for either cortisol or ACTH, between obese subjects and normal volunteers. With both varieties of CRH, Cushing's disease resulted in greater responses for ACTH and cortisol than those seen in the other 2 groups (P < 0.001 for all comparisons), but there was no difference between the sequences. However, a significant cortisol response, defined as an increase of greater than 4 times the coefficient of variation of the assay (24%), was seen in all 10 Cushing's patients with human CRH, but in only 8 with ovine CRH. In 3 patients with adrenal tumors, serum cortisol did not change after the administration of either preparation, whereas plasma ACTH remained undetectable throughout the study. We suggest that although ovine sequence CRH causes more prolonged and greater ACTH, and possibly cortisol, secretion compared to human CRH, the discriminatory value of the CRH test, in terms of either the diagnosis or differential diagnosis of Cushing's syndrome, is comparable for the two peptide sequences.

Adrenocorticotropic Hormone↗

Analysis of the regulation of penicillin biosynthesis in Aspergillus nidulans by targeted disruption of the acvA gene.

To analyse the regulation of the biosynthesis of the secondary metabolite penicillin in Aspergillus nidulans, a strain with an inactivated acvA gene produced by targeted disruption was used. acvA encodes delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), which catalyses the first step in the penicillin biosynthetic pathway. To study the effect of the inactivated acvA gene on the expression of acvA and the second gene, ipnA, which encodes isopenicillin N synthase (IPNS), A. nidulans strain XEPD, with the acvA disruption, was crossed with strain AXB4A carrying acvA-uidA and ipnA-lacZ fusion genes. Ascospores with the predicted non-penicillin producing phenotype and a hybridization pattern indicating the presence of the disrupted acvA gene, and the fusion genes integrated in single copy at the chromosomal argB locus were identified. Both fusion genes were expressed at the same level as in the non-disrupted strain. Western blot analysis (immunoblotting) revealed that similar amounts of IPNS enzyme were present in both strains from 24 to 68 h of a fermentation run. In the acvA disrupted strain, IPNS and acyl-CoA: 6-aminopenicillanic acid acyltransferase (ACT) specific activities were detected, excluding a sequential induction mechanism of regulation of the penicillin biosynthesis gene ipnA and the third gene aat.

Acyltransferases↗

A circadian distribution to febrile episodes in neutropenic patients.

Four-hourly temperature charts relating to 63 febrile neutropenic episodes in 32 patients were assessed for a circadian distribution to the onset of fever (> 37.5 degrees C) using the Edward's test. A highly significant distribution was found with the maximum incidence of febrile events between the hours of 5 p.m. and midnight (acrophase 9.30 p.m.). Patients were 5.53 times more likely to develop fever at 9.30 p.m. that 9.30 a.m.

Adolescent↗

A new method for the determination of the characteristic shape of an isokinetic quadriceps femoris muscle torque curve.

It has been suggested that visual analysis of isokinetic quadriceps femoris muscle torque curve (TC) shapes may have potential use in the diagnosis and prognosis of knee pathologies. The primary purpose of this pilot study was to develop a method for analyzing the shape of an isokinetic TC. Our method normalizes and averages the TC, and then uses curvilinear analysis of the TC shape to aid in diagnosis and prognosis. For demonstration, the method was applied to isokinetic quadriceps femoris muscle TC data collected using a LIDO digital dynamometer from 25 healthy volunteer subjects and retrospectively acquired from the uninvolved limbs of 37 patients with unilateral knee pathologies. The preliminary results revealed (1) that a common quadriceps femoris muscle TC shape existed for the volunteer group at 60 degrees and 180 degrees/s; (2) that the uninvolved limbs of the patient group exhibited the same shape at 60 degrees/s, but not at 180 degrees/s; and (3) that the quadriceps femoris muscle TC shape demonstrated no significant differences with respect to limb dominance or gender for either group. Further testing of this quantitative method on a larger sample is needed to determine its usefulness in the analysis and implications of TC shape concerning pathology and diagnosis.

Adult↗

Regulation of Aspergillus nidulans penicillin biosynthesis and penicillin biosynthesis genes acvA and ipnA by glucose.

Expression of the Aspergillus nidulans penicillin biosynthesis genes acvA and ipnA, encoding delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase and isopenicillin N synthetase, respectively, was analyzed. The intergenic region carrying the divergently oriented promoters was fused in frame in both orientations to Escherichia coli lacZ and E. coli uidA reporter genes. Each construct permits simultaneous expression studies of both genes. Transformants of A. nidulans carrying a single copy of either plasmid integrated at the chromosomal argB locus were selected for further investigations. Expression of both genes was directed by the 872-bp intergenic region. ipnA- and acvA-derived gene fusions were expressed from this region at different levels. ipnA had significantly higher expression than did acvA. Glucose specifically reduced the production of penicillin and significantly repressed the expression of ipnA but not of acvA gene fusions. The specific activities of isopenicillin N synthetase, the gene product of ipnA, and acyl coenzyme A:6-aminopenicillanic acid acyltransferase were also reduced in glucose-grown cultures.

Acyltransferases↗

Use of services in old age: data from three surveys of elderly people.

It has been suggested that home sharers, particularly spouses, act as substitutes for formal health and social care provision. This hypothesis was investigated in relation to three independent samples of elderly people, using comparable methodology in London (urban area) and Essex (semi-rural area). The uniqueness of the study lies in the ability to make comparisons between younger and older elderly people, in particular with those aged 85 and over. Utilisation of health and social services was found to be higher in the urban area, and it increased with age. Marital status was not associated with service use nor with contact with general practitioners in any age group or area. The social network variables analysed had little or no predictive ability in relation to recency of contact with general practitioners (GPs). Household size was associated with total use of health and social services, and social services in particular. The multivariate analysis confirmed that household size was a strong predictor of use of home help and meals on wheels services; functional status was the best predictor of use of district nursing services.

Activities of Daily Living↗

Beta-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes.

A cosmid clone containing closely linked beta-lactam antibiotic biosynthetic genes was isolated from a gene library of Flavobacterium sp. SC 12,154. The location within the cluster of the DNA thought to contain the gene for delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), the first step in the beta-lactam antibiotic biosynthetic pathway, was identified by a novel method. This DNA facilitated the isolation, by cross-hybridization, of the corresponding DNA from Streptomyces clavuligerus ATCC 27064, Penicillium chrysogenum Oli13 and Aspergillus nidulans R153. Evidence was obtained which confirmed that the cross-hybridizing sequences contained the ACVS gene. In each case the ACVS gene was found to be closely linked to other beta-lactam biosynthetic genes and constituted part of a gene cluster.

Anti-Bacterial Agents↗

Program helps nurses develop spiritual care skills.

Recognizing the registered nurse's (RN's) important role in providing spiritual care, the Catholic Health Association of Wisconsin has created a program to prepare nurses to identify and respond to patients' spiritual needs. The program features instruction in theological and ethical issues and a three-month practicum, during which nurses evaluate their abilities to incorporate an awareness of spirituality into professional practice. A patient questionnnaire enables an objective measurement of the program's effect on nurses' care-giving skills. The program's ultimate goal is to formalize the RN's role as a member of the spiritual care team in the Catholic health care facility. The program represents not only an opportunity to contribute to the RN's professional growth but also to advance the Catholic health care mission.

Catholicism↗

An evaluation of the role of a pyroglutamyl peptidase, a post-proline cleaving enzyme and a post-proline dipeptidyl amino peptidase, each purified from the soluble fraction of guinea-pig brain, in the degradation of thyroliberin in vitro.

The degradation of thyroliberin (less than Glu-His-Pro-NH2) to its component amino acids by the soluble fraction of guinea pig brain is catalysed by four enzymes namely a pyroglutamate aminopeptidase, a post-proline cleaving enzyme, a post-proline dipeptidyl aminopeptidase and a proline dipeptidase. 1. The pyroglutamate aminopeptidase was purified to over 90% homogeneity with a purification factor of 2868-fold and a yield of 5.7%. In addition to catalysing the hydrolysis of thyroliberin, acid thyroliberin and pyroglutamate-7-amido-4-methylcoumarin the pyroglutamate aminopeptidase catalysed the hydrolysis of the peptide bond adjacent to the pyroglutamic acid residue in luliberin, neurotensin bombesin, bradykinin-potentiating peptide B, the anorexogenic peptide and the dipeptides pyroglutamyl alanine and pyroglutamyl valine. Pyroglutamyl proline and eledoisin were not hydrolysed. 2. The post-proline cleaving enzyme was purified to apparent electrophoretic homogeneity with a purification factor of 2298-fold and a yield of 10.6%. The post-proline cleaving enzyme catalysed the hydrolysis of thyroliberin and N-benzyloxycarbonyl-glycylproline-7-amido-4-methylcoumarin. It did not catalyse the hydrolysis of glycylproline-7-amido-4-methylcoumarin or His-Pro-NH2. 3. The post-proline dipeptidyl aminopeptidase was partially purified with a purification factor of 301-fold and a yield of 8.9%. The post-proline dipeptidyl aminopeptidase catalysed the hydrolysis of His-Pro-NH2 and glycylproline-7-amido-4-methylcoumarin but did not exhibit any post-proline cleaving endopeptidase activity against thyroliberin or N-benzyloxycarbonyl-glycylproline-7-amido-4-methylcoumarin. 4. Studies with various functional reagents indicated that the pyroglutamate aminopeptidase could be specifically inhibited by 2-iodoacetamide (100% inhibition at an inhibitor concentration of 5 microM), the post-proline cleaving enzyme by bacitracin (IC50 = 42 microM) and the post-proline dipeptidyl aminopeptidase by puromycin (IC50 = 46 microM). Because of their specific inhibitory effects these three reagents were key elements in the elucidation of the overall pathway for the metabolism of thyroliberin by guinea pig brain tissue enzymes.

Aminopeptidases↗

The purification and characterization of a proline dipeptidase from guinea pig brain.

A proline dipeptidase (EC 3.4.13.9) from guinea pig brain was purified to over 90% homogeneity by a combination of ammonium sulfate fractionation, DEAE-cellulose chromatography, calcium phosphate-cellulose chromatography, chromatofocusing, and gel filtration on Sephadex G-200. A purification factor of 2718-fold was obtained with a yield of 7%. The purified enzyme was found to have an apparent molecular weight of 132,000 and to consist of two dissimilar subunits of molecular weights 64,000 and 68,000. The substrate specificity of the enzyme is not that of a strict proline dipeptidase. Although it preferentially hydrolyzes proline dipeptides (Leu-Pro) it also hydrolyzes prolyl dipeptides (Pro-Leu) and dipeptides not containing proline (Leu-Leu). The purified enzyme preparation exhibited weak aminoacylproline aminopeptidase activity against Arg-Pro-Pro but it did not exhibit any post-proline dipeptidyl aminopeptidase, post-proline cleaving endopeptidase, proline iminopeptidase, prolyl carboxypeptidase or carboxypeptidase P activities when tested with a large variety of peptides and arylamides. With all of the proline and prolyl dipeptides examined the enzyme exhibited biphasic kinetics (two distinct slopes on Lineweaver-Burk plots). However, with Leu-Leu as substrate normal Michaelis-Menten kinetics were obeyed.

Animals↗

Effect of vibration on tactile sensitivity.

Tactile hypersensitivity is a common sequela of traumatic hand injury. Vibration is used clinically to reduce this hypersensitivity. The purpose of this study was to determine if vibration has an effect on tactile threshold and if so to determine the duration of that effect. Mean tactile thresholds were determined for 24 healthy adults by means of a pressure aesthesiometer. The experimental group (6 men, 6 women) received 10 minutes of vibration. Mean tactile thresholds were redetermined at the end of the 10-minute treatment period in the experimental group and after a 10-minute rest period in the control group (6 men, 6 women). Thresholds were also redetermined at 5-minute intervals for the next 20 minutes in all subjects. The experimental group showed a significant change in mean tactile threshold after 10 minutes of vibration (p less than .001). This difference remained at 5 (p less than .001) and 10 (p less than .05) minutes postvibration but not at 15 and 20 minutes. No significant change in mean tactile threshold was found in the control group. The results indicate that vibration does increase tactile threshold in "normal" hands and the effect lasts for at least 10 minutes. The application of this information to the clinical setting is discussed.

Adult↗