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Biomedical subjects

R Nolan

Publications and source records attributed to R Nolan.

At least 19 recordsLinked to original sources
PubMed2001

Platelet dysfunction in type 2 diabetes.

Insulin resistance is a uniform finding in type 2 diabetes, as are abnormalities in the microvascular and macrovascular circulations. These complications are associated with dysfunction of platelets and the neurovascular unit. Platelets are essential for hemostasis, and knowledge of their function is basic to understanding the pathophysiology of vascular disease in diabetes. Intact healthy vascular endothelium is central to the normal functioning of smooth muscle contractility as well as its normal interaction with platelets. What is not clear is the role of hyperglycemia in the functional and organic microvascular deficiencies and platelet hyperactivity in individuals with diabetes. The entire coagulation cascade is dysfunctional in diabetes. Increased levels of fibrinogen and plasminogen activator inhibitor 1 favor both thrombosis and defective dissolution of clots once formed. Platelets in type 2 diabetic individuals adhere to vascular endothelium and aggregate more readily than those in healthy people. Loss of sensitivity to the normal restraints exercised by prostacyclin (PGI(2)) and nitric oxide (NO) generated by the vascular endothelium presents as the major defect in platelet function. Insulin is a natural antagonist of platelet hyperactivity. It sensitizes the platelet to PGI(2) and enhances endothelial generation of PGI(2) and NO. Thus, the defects in insulin action in diabetes create a milieu of disordered platelet activity conducive to macrovascular and microvascular events.

Animals↗
PubMed1999

A model phosphatase 2C --> phosphatase 1 activation cascade via dual control of inhibitor-1 (INH-1) and DARPP-32 dephosphorylation by two inositol glycan putative insulin mediators from beef liver.

Two inositol phosphoglycans (IPG) isolated from beef liver and designated as putative insulin mediators were demonstrated to reciprocally enhance the dephosphorylation of inhibitor-1 (INH-1) and DARPP-32, thus directly activating phosphatase 2C and disinhibiting phosphatase 1 in a potential protein phosphatase 2C --> phosphatase 1 cascade mechanism. One IPG termed pH 2.0, containing Dchiro-inositol and galactosamine, stimulated the dephosphorylation of INH-1 and DARPP-32 in a dose-dependent manner in the low micromolar range. A second, termed pH 1.3, containing myo-inositol glucosamine and mannose acted reciprocally to inhibit the cAMP-dependent protein kinase phosphorylation of INH-1 and DARPP-32 in a dose-dependent manner in the low micromolar range. These model experiments are discussed in terms of the observed dephosphorylation of INH-1 with insulin action documented in the literature and the activation of both phosphatase 1 and 2C described in intact cells and in vivo with insulin action.

Animals↗
PubMed1999

An epidemic of burkholderia cepacia transmitted between patients with and without cystic fibrosis.

Burkholderia cepacia is an important pathogen in cystic fibrosis (CF) and an infrequent cause of nosocomial infection in non-CF patients. This report describes a large hospital outbreak that appeared to involve both patient groups, a previously unrecognized phenomenon. Ribotype restriction fragment length polymorphism (RFLP) profiles and pulsed-field gel electrophoresis-resolved macrochromosomal RFLPs were analyzed, a ribotype-based phylogenic tree was constructed, and case-control and cohort studies were performed. A single dominant clone was found in both CF and non-CF groups. Phylogenic analysis suggests that it has evolved independently and that such highly transmissible strains can emerge rapidly and randomly. Acquisition risk in the CF patients was linked to hospitalization (odds ratio=5.47, P=.0158, confidence interval=1. 28-26.86) and was associated with significantly increased mortality rates. Infection control policies must now consider this threat of transmission between non-CF and CF patients.

Adolescent↗
PubMed1998

A nondenaturing purification scheme for the DNA-binding domain of poly(ADP-ribose) polymerase, a structure-specific DNA-binding protein.

Poly(ADP-ribose) polymerase (PARP) is thought to be involved in DNA repair given its ability to recognize and bind to DNA strand breaks. During apoptosis, PARP is proteolytically cleaved into two stable fragments, the N-terminal 25-kDa DNA-binding domain (DBD) and the 85-kDa fragment containing the automodification and catalytic domains. To understand the DNA-binding properties of PARP, we expressed a recombinant hexahistidine tagged protein (His-DBD) in Escherichia coli. We modified expression to facilitate protein folding by including zinc and reducing the induction temperature. Properly folded, the DNA-binding domain of PARP binds to single- and double-stranded DNA in a structure-specific manner. To eliminate contamination with bacterial DNA that occurred during the purification process, a purification procedure was developed to produce DNA-free protein. In addition, to remove the hexahistidine tag from the recombinant protein, thrombin cleavage was carried out while the recombinant protein was bound to a DNA column. This procedure stabilized the recombinant protein and resulted in nearly 100% cleavage with no appreciable loss to unwanted proteolytic degradation. This nondenaturing purification scheme results in high-quality, native PARP-DBD for use in structural and biochemical studies.

Amino Acid Sequence↗
PubMed1998

The influence of short-term nutrient changes on follicle growth and embryo production following superovulation in beef heifers.

Acute decreases in nutrient intake can improve embryo quality in sheep, although reductions in ovulation rate can also occur. In cattle, short-term nutrient restriction prior to ovulation has been shown to increase subsequent pregnancy rates. Thus, the objective was to determine the effect of a severe reduction in food intake on follicle growth and embryo quantity and quality in heifers superovulated with FSH. Beef heifers (n = 61) were offered a diet of grass silage and concentrates (ratio of 5:1, on a fresh weight basis), which was adjusted to provide a predicted intake of 28.6 Mcal/kg ME/d (H) or 9.6 Mcal/kg ME/d (L). Heifers were synchronized with a progesterone-releasing device for 7 d. They were allocated to oocyte recovery (n = 16/treatment) after 3 (225 IU) or 8 (600 IU) injections of FSH given at 12-h intervals. Oocytes were matured, fertilized and cultured individually in vitro. The remaining heifers (n = 14/treatment) were superovulated using FSH (600 IU), and embryos were recovered 7 d after breeding. The embryos were morphologically graded and subsequently cultured for 24 h before differential staining to determine inner cell mass and trophectoderm cell numbers. Follicle numbers increased following 8 (16.6 +/- 2.0) compared with 3 (6.7 +/- 0.6) injections of FSH (P < 0.0001). Heifers on the L diet had more follicles than those on the H diet (13.5 +/- 2.4 vs 9.6 +/- 1.2; P < 0.06), which was predominantly due to an increase in the number of 7- to 10-mm follicles. However, this effect was only evident after 8 injections of FSH. There was no nutritional effect on cleavage rates in vitro (55.6 +/- 8.1 vs 53.8 +/- 9.0 for H vs L diets, respectively). However, cleavage rates were lower in oocytes collected after 8 than after 3 injections of FSH (31.3 vs 69.2%; P < 0.0001). There was no significant effect of nutrition on ovulation rate after FSH (14.4 +/- 1.9 vs 16.3 +/- 3.0 for H vs L diet, respectively). The number of embryos recovered was not different between heifers on H (10.4 +/- 1.3) and L (11.3 +/- 2.4) diets. Following culture for 24 h, a significantly higher proportion of embryos from heifers on the L diet developed to the blastocyst stage (72.9 vs 41.5%; P < 0.01). Total cell numbers on Day 8 were greater in embryos from heifers on the L diet (98.3 vs 75.4; P < 0.0001); yet the inner cell mass as a percentage of total cells was not different (21 vs 20%). These data indicate that low energy intake prior to and during superovulation resulted in more follicles and in improved embryo quality, as evident from the increased number of blastocysts formed and higher cell numbers.

Animal Nutritional Physiological Phenomena↗
PubMed1997

Adaptation to coronary artery disease: first pilot study in the military.

To determine how a group of 29 male military patients with coronary artery disease (CAD-MIL group) have adapted physically and psychosocially, we compared results from standard questionnaires with those from 39 healthy military men (WELL-MIL group) and 27 male civilian patients with coronary artery disease (CAD-CIV group). There was no difference in the degree of severity of coronary artery disease between the two groups with the disease. The WELL-MIL group reported a higher activity level than the CAD-MIL group, which reported a higher activity level than the CAD-CIV group. Both the CAD-MIL group and WELL-MIL groups had lower levels of state anxiety compared with the CAD-CIV group, and the CAD-MIL group had a better overall psychosocial adjustment score compared with that of the CAD-CIV group. Thus, male military patients with coronary artery disease reported better physical and psychosocial adjustment to their illness than a group of male civilian patients with a similar degree of disease severity. but they were less physically active than healthy military men.

Adaptation, Psychological↗
PubMed1994

Gender and depression in an undergraduate population.

The Beck Depression Inventory was administered to 417 undergraduate students (308 women and 109 men). Within the total group the item concerning "tiredness", gave the best discrimination between men and women. A cut-off score of 10 was used to divide depressed from nondepressed individuals. When only depressed individuals (n = 105) were considered, seven items were identified as discriminating between genders.

Adult↗
PubMed1991

HLA disease association and protection in HIV infection among African Americans and Caucasians.

In a previous investigation, we demonstrated an increased progression of overt AIDS in the African American population compared to the Caucasian population as reflected by the significantly lower absolute number of CD4+ lymphocytes detected in the African American population in an earlier study. The present study elucidates some of the possible genetic factors which may contribute to disease association or protection against HIV infection. The HLA phenotypes expressed as A, B, C, DR and DQw antigens were revealed by the Amos-modified typing procedure. NIH scoring was utilized to designate positive cells taking up trypan blue. A test of proportion equivalent to the chi 2 approximation was used to compare the disease population (n = 62; 38 African Americans, 24 Caucasians) to race-matched normal heterosexual local controls (323 African Americans, 412 Caucasians). Significant p values were corrected for the number of HLA antigens tested. HLA markers associated with possible protection from infection for African Americans were Cw4 and DRw6, whereas Caucasians expressed none. Disease association markers present in the African American population were A31, B35, Cw6, Cw7, DR5, DR6, DRw11, DRw12, DQw6 and DQw7, whereas in the Caucasian population A28, Aw66, Aw48, Bw65, Bw70, Cw7, DRw10, DRw12, DQw6 and DQw7 were demonstrated. The highest phenotypic frequency for a disease association marker in the study was for HLA-DR5 (62.9%) in the HIV-infected African American population without Kaposi's sarcoma compared to a frequency of 28.9% for the regional control group (p = 0.0012). We conclude that genetic factors do have a role in HIV infection since only 50-60% of those exposed to the AIDS virus will become infected.

Black People↗
PubMed1988

Computerized tomography in the investigation of groin masses following femoral catheterization.

Pseudoaneurysm of the femoral artery is an uncommon complication of retrograde arteriography. It is sometimes difficult to clinically differentiate a pseudoaneurysm from a large hematoma. We present 13 cases of suspected femoral pseudoaneurysm following angiography which were investigated by computed tomography (CT). It is suggested that this is a useful procedure in the investigation of groin masses after catheterization.

Aneurysm↗
PubMed1988

CT visualization of medullary sponge kidney.

Recognizing the changes of medullary sponge kidney (MSK) on computed tomographic (CT) scans may be of value in both diagnosis and in differentiating this from other disease states. The appearance on CT of MSK has not previously been well described. A case is reported that demonstrates ectatic renal collecting tubules visualized by CT, and techniques are suggested to optimize visualization of these changes.

Aged↗
PubMed1987

Percutaneous renal surgery.

Percutaneous renal surgery was developed initially to remove renal calculi safely without the attendant morbidity of standard open pyelolithotomy. As familiarity with techniques has been obtained, other intrarenal diseases have been treated using this approach. This report reviews the current applications of percutaneous renal surgery and discusses its relation to extracorporeal shock-wave lithotripsy in the management of renal calculi.

Humans↗
PubMed1984

Left ventricular changes after chronic therapy with enalapril maleate in moderate to severe hypertensive patients.

A randomized double-blind trial was carried out to determine the relationship of the changes in blood pressure and heart rate with changes in echocardiographic left ventricular indices in moderate to severe hypertensive patients with established left ventricular hypertrophy who were being treated chronically with enalapril or hydrochlorothiazide plus propranolol for 26 weeks. After a 2-week period on placebo, drug dosages in the two groups were adjusted to individual needs until blood pressure was normalized (diastolic less than 90 mmHg). Patients in Group I received 10 to 40 mg enalapril/day; those in Group II received 50 mg hydrochlorothiazide plus 80 to 240 mg propranolol/day. Echocardiographic measurements were made at the end of the placebo and 26-week active treatment periods. Significant correlations were observed between the changes in four pairs of variables in each group. In the 8 patients receiving enalapril, there were negative correlations between interventricular septal thickness and supine systolic blood pressure, erect and supine heart rates, and a positive correlation between relative wall thickness and erect diastolic blood pressure. In the 7 patients on hydrochlorothiazide plus propranolol, there were negative correlations between relative wall thickness and erect and supine heart rate, and positive correlations between left ventricular mass and erect diastolic blood pressure, and the percentage change in internal diameter of the left ventricle and supine systolic blood pressure. Possible explanations for and implications of these regional changes are discussed.

Adult↗
PubMed1984

The correlation of changes in systolic blood pressure with regional anatomical regression of hypertensive left ventricular hypertrophy in patients on chronic antihypertensive therapy (greater than 1 year): alpha-methyldopa compared to propranolol.

Twenty patients with mild to moderate hypertension and evidence of left ventricular hypertrophy (relative wall thickness greater than or equal to 0.45), who previously had not received either alpha-methyldopa or propranolol, were allocated at random to treatment with one or other of these drugs as monotherapy after a 2-week baseline period on no medication. Dosage was titrated until normotension was attained and patients were then maintained on this treatment for a year. Analysis of blood pressure measurements and echocardiograms taken before and during maintenance therapy showed that there were significantly correlated changes in systolic blood pressure and heart rate with left ventricular cavity and regional wall changes during chronic drug administration. In the alpha-methyldopa group there were significant correlations between changes in erect and supine systolic blood pressure and the posterior wall index, and in erect systolic blood pressure and left ventricular mass. In the propranolol group, there were significant correlations between changes in supine systolic blood pressure and interventricular septal thickness, and in erect heart rate and supine systolic blood pressure with the percentage change in internal diameter of the left ventricle. It is suggested that these observations may have important therapeutic implications for hypertensive patients with documented left ventricular hypertrophy.

Adult↗