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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 325 records · Page 18Linked to original sources
PubMed1994

Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men.

To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, we studied seven lean (66 +/- 1 kg) sensitive and seven age-matched obese (96 +/- 3 kg) insulin-resistant men after an overnight fast. Both groups were normotensive; however, the obese exhibited higher basal blood pressure, 90.8 +/- 2.2 vs. 83.4 +/- 1.6 mmHg, P < 0.04. Each subject was studied on two separate days during either saline (S) infusion or a euglycemic hyperinsulinemic clamp (I) achieving insulin concentrations of approximately 70 microU/ml. After 180 min of either S or I, NE was infused systemically at rates of approximately 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body ([3-3H]glucose) and in leg by the balance technique. The results indicate: (a) the NE/pressor dose-response curve was decreased (shifted to the right) during I in lean but not in obese subjects, (b) I enhanced NE metabolic clearance by 20% in lean but not in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a approximately 20% increase in insulin-mediated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and decreased NE metabolic clearance. Both of these mechanisms can potentially contribute to the higher incidence of hypertension in obese man. Insulin resistance is likely to be a predisposing but not sufficient factor in the pathogenesis of hypertension. Because the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further studies will be required to clarify this issue.

Blood Glucose↗
PubMed1994

Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.

The purpose of this study was to examine whether insulin's effect to vasodilate skeletal muscle vasculature is mediated by endothelium-derived nitric oxide (EDNO). N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, was administered directly into the femoral artery of normal subjects at a dose of 16 mg/min and leg blood flow (LBF) was measured during an infusion of saline (NS) or during a euglycemic hyperinsulinemic clamp (HIC) designed to approximately double LBF. In response to the intrafemoral artery infusion of L-NMMA, LBF decreased from 0.296 +/- 0.032 to 0.235 +/- 0.022 liters/min during NS and from 0.479 +/- 0.118 to 0.266 +/- 0.052 liters/min during HIC, P < 0.03. The proportion of NO-dependent LBF during NS and HIC was approximately 20% and approximately 40%, respectively, P < 0.003 (NS vs. HIC). To elucidate whether insulin increases EDNO synthesis/release or EDNO action, vasodilative responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) were studied in normal subjects during either NS or HIC. LBF increments in response to intrafemoral artery infusions of MCh but not SNP were augmented during HIC versus NS, P < 0.03. In summary, insulin-mediated vasodilation is EDNO dependent. Insulin vasodilation of skeletal muscle vasculature most likely occurs via increasing EDNO synthesis/release. Thus, insulin appears to be a novel modulator of the EDNO system.

Adult↗
PubMed1994

MAINTENANCE OF DYNAMIC STRAIN SIMILARITY AND ENVIRONMENTAL STRESS FACTOR IN DIFFERENT FLOW HABITATS: THALLUS ALLOMETRY AND MATERIAL PROPERTIES OF A GIANT KELP

We have focused on the giant kelp Nereocystis luetkeana to examine the mechanical scaling of benthic marine organisms loaded in tension by hydrodynamic forces. If we consider simply the allometry of the kelp's morphological characters, we conclude that their stipes are underscaled relative to the blade area they support (i.e. that the kelp do not maintain stress or elastic similarity as they grow). However, a closer look at the characteristics of these kelp in the field reveals (1) that they have different blade shapes (and hence drag coefficients) and stipe material properties in different hydrodynamic environments, and (2) that they show a decrease in drag coefficient as they become larger. One consequence of these adjustments of blade and stipe morphology is that the maximum stresses in N. luetkeana stipes, when the kelp are pulled by peak tidal currents in their respective habitats, are similar for kelp of different sizes and for kelp from different sites. Hence, sessile organisms such as these kelp can, via their growth responses in different mechanical environments, show a phenomenon analogous to dynamic strain similarity. In addition, N. luetkeana also maintain a constant environmental stress factor, the ratio of the stress required to break a component of an organism (in this case the stipe) at some stage in its life to the maximum stress normally encountered in the habitat by that component during that stage (in this case, stress due to the drag on a kelp exposed to the peak tidal currents typical of the site at which it lives), both between habitats and as they grow.

Journal Article↗
PubMed1994

Autosomal dominant polycystic kidney disease in blacks: clinical course and effects of sickle-cell hemoglobin.

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent cause of ESRD, but its frequency in blacks has not been well delineated and its course and the effects of sickle hemoglobin in this disease in blacks have not been previously reported. The occurrence of ADPKD in blacks and whites was determined in two ESRD populations: all ESRD patients seen over a 16-yr period in one area of Southeast Tennessee and all ESRD patients in 15 hemodialysis units in Tennessee and Atlanta, GA. The frequency of sickle hemoglobin was determined and compared in a group of nonrelated blacks with ESRD with and without ADPKD. The age at onset of ESRD and factors that might affect ADPKD such as gender, hypertension, and hemoglobin type were examined. ADPKD was a less frequent cause of ESRD in blacks than whites (1.4 versus 6.8%). However, after adjusting for the population rate, the incidence rates in blacks and whites were similar (0.48 and 0.47 of 100,000). There was a higher incidence of sickle hemoglobin in nonrelated blacks with ADPKD versus other black ESRD patients (50 versus 7.5%; P < 0.005). Blacks had an earlier onset of ESRD than whites (43.2 versus 55.4 yr; P < 0.0001), as did blacks with sickle-cell trait versus blacks without (38.2 versus 48.1 yr; P < 0.003). In this population, hypertension and gender had no effect on the onset of ESRD. ADPKD accounted for a smaller percentage of blacks than whites with ESRD because of the high percentage of blacks with renal disease from other causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Bone marrow transplantation for Glanzmann's thrombasthenia.

Allogeneic matched bone marrow transplantation (BMT) was performed in a patient with type I Glanzmann's thrombasthenia, a rare, inherited bleeding disorder caused by a deficiency in the platelet membrane glycoprotein IIb-IIIa complex. The patient was a 2-year-old girl with a history of frequent hospitalisation. She was successfully transplanted with BM from her HLA-identical sibling. Engraftment was monitored by analysis of the platelet GPIIb-IIIa complex and by RFLP analysis using a minisatellite probe. Complete engraftment was seen at day +25. The patient has been clinically stable for 19 months. It is proposed that BMT is a suitable treatment for this condition where a matched, related donor is available and at an early stage, before the development of anti-platelet antibodies as a result of repeated transfusions.

Blood Platelets↗
PubMed1994

Vasoactive intestinal peptide stimulates neuropeptide Y gene expression and causes neurite extension in PC12 cells through independent mechanisms.

Vasoactive intestinal peptide (VIP) is widely recognized as a regulator of tyrosine hydroxylase via a mechanism of trans-synaptic activation. Subsets of adrenal medullary cells and postganglionic sympathetic nerves coexpress the peptide neurotransmitter neuropeptide Y (NPY) with catecholamines. Using PC12 cells transiently expressing a fusion gene in which the bacterial enzyme chloramphenicol acetyltransferase (CAT) is under the control of 700 base pairs of the 5' flanking region of the NPY gene, we have studied the role of VIP and the related peptide pituitary adenylate cyclase activating peptide (PACAP) in regulating NPY gene transcription. Both VIP and PACAP stimulated expression of the NPY gene through activation of cAMP-dependent protein kinase. PACAP was 1000-fold more potent in eliciting this response compared to VIP and activity resided in its N-terminal 27 amino acids. Both VIP and PACAP caused a subpopulation (approximately 50%) of PC12 cells to undergo profound morphological changes in that the cells extended long, slender neurites with prominent growth cones. This change in morphology was unaffected by preincubating cells with inhibitors of either cAMP-dependent protein kinase or calcium/phospholipid-dependent protein kinase. A trophic role for either VIP or PACAP in regulating sympathetic nerve function is proposed.

Animals↗
PubMed1993

Functional abilities at age 4 years of children born before 29 weeks of gestation.

OBJECTIVES: To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN: Cohort study of a geographically defined population of babies. SETTING: Oxford Regional Health Authority. SUBJECTS: All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES: Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS: Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS: With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.

Child, Preschool↗
PubMed1993

Flow cytometric clonal excess analysis of peripheral blood, routine handling, and pitfalls in interpretation.

Clonal excess (CE) analysis by flow cytometry is a convenient method to detect minimal involvement of peripheral blood and bone marrow by B-cell lymphoma. The method is based on evaluation of the congruity between kappa and lambda light chain distributions within a normal B-cell population. By using the Kolmogorov-Smirnov method for evaluation of histogram identity, the maximum difference (D value) between distributions is calculated. However, variable adsorption of cytophilic plasma immunoglobulin (Ig) to CD16 positive cells, T-cell subsets, and the B cells themselves may cause incongruity between the light chain distributions that might simulate or disguise a true clonal excess and thus create major pitfalls in the interpretation of the CE analysis. These phenomena are observed both in normal blood donors and in patients with non-Hodgkin's lymphoma. In the present report we describe: (1) how freezing of the isolated mononuclear cells before immunostaining effectively removes most of the adsorbed cytophilic Ig, (2) how by exclusion of the CD16 positive population further resolution of the relevant histogram shape is obtained to avoid false interpretations of incongruity, and (3) how adsorption of Ig to B-cells creates a typical pattern of "reciprocal labeling" that can be mistaken for a clonal excess. Based on our observations we argue against an uncritical use of normal D values for definition of clonal excess and advocate an analytic evaluation of the kappa and lambda overlay distribution by dual immunofluorescence, either by excluding CD16 positive cells or by including only B cells, to reveal the nature of the different deviations.

Cell Separation↗
PubMed1993

Organoapatites: materials for artificial bone. III. Biological testing.

This article reports on the in vivo testing of new artificial bone materials we have termed "organoapatites." These materials consist of mineral networks in which organic polymers are intimately dispersed by nucleation and growth of apatite crystals from a mother liquor containing the organic substances. Organoapatites were tested as implants in adult canine cortical bone for periods in the range from 12-35 weeks and fluorochromes were used in the model to investigate the kinetics of bone growth or repair. The analysis of histological samples was carried out using histomorphometric methods as well as fluorescence microscopy. Results showed excellent apposition of poly(amino acid) organoapatites with mineralized bone and fibrous encapsulation when a synthetic polyelectrolyte was the only organic component. This observation suggests that the molecularly dispersed organic dopant amounting to only 2-3% by weight of the microstructure can play a critical role in the tissue response to the implant. Relative to apatite controls, organoapatites were also found to have greater resistance to fragmentation in vivo and those containing amino acid units revealed interfacial bioerosion accompanied by regeneration of mineralized tissue. Design of organoapatite compositions and microstructures may therefore be useful in achieving the specific rate of biological response which is clinically desired.

Animals↗
PubMed1993

Impact of anomalous vertebral segmentation on measurements of bone mineral density.

In anteroposterior (AP) bone mineral density (BMD) measurements of the lumbar spine (LS), the presence of ribs is used to identify vertebra T12. Similarly, in lateral LS-BMD measurements, the position of the iliac crest is used to identify the lumbar vertebrae. The aim of this study was to determine the impact of variations in spinal segmentation and iliac crest position on BMD measurements. In 375 women (ages 50-85 years) radiographs were taken of the thoracic and lumbar spine, as well as AP measurement of LS-BMD, by dual-energy x-ray absorptiometry (DXA). In 121 subjects lateral decubitus LS-BMD was also measured. Anomalous spinal segmentation was found in 16.5%, and L1 would have been incorrectly identified on the AP-DXA image in 13%. The change in BMC and BMD between adjacent vertebrae was greater in the upper than the lower lumbar spine. Misidentification of L1 for T12 resulted in underestimation of the bone mineral content in grams (BMC) of L1 by a mean of 11.5 +/- 14.4% (SD; range -33.5 to 33.5%). For the usual region of interest, L2-4, the BMC (g) was underestimated by 8.4 +/- 8.7% (range -1.5 to 29.2%), with the BMD (g/cm2) underestimated by 3.6 +/- 4.8% (range -5.4 to 11.6%). The position of the iliac crest on the lateral decubitus DXA scans would have led to misidentification of either L2 or L4 for L3 in 15 cases (12%). This resulted in the BMD of L3 being underestimated by 2.7 +/- 19.4% (range -242.4 to 34.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1993

Malignant melanoma of the perineum.

We conducted a retrospective review of the medical records of 18 patients diagnosed at the University of Colorado with perineal melanoma. Clinical characteristics including Clark's level, recurrence, and survival were studied. Ten patients (55.6%) had vulvar melanoma, 2 patients (11.1%) had vaginal disease, and the remaining 6 patients (33.3%) had primary rectal melanoma. All patients were treated surgically at the time of diagnosis. At a median follow-up of 32.7 months, 15 patients had evidence of recurrence. Nine of these patients are dead and six are alive with disease. The average time to recurrence was 14 months and the most common site was the regional lymph nodes in 10 of the 14 patients (71.4%). This study confirms the poor prognosis in perineal melanoma and the only effective treatment to date is early diagnosis and complete resection.

Adult↗
PubMed1993

The effect of low density lipoprotein composition on the regulation of cellular cholesterol synthesis: a comparison in diabetic and non-diabetic subjects.

This study investigates compositional differences in low density lipoprotein (LDL) subfractions and their relationship to cellular cholesterol synthesis. We examined ten normocholesterolaemic (serum cholesterol < 6.5 mM) non-diabetic subjects (group 1) and compared them with ten normocholesterolaemic (group 2) and ten hypercholesterolaemic (group 3) (serum cholesterol > 6.5 mM) type 2 (non-insulin-dependent) diabetic patients. Serum cholesterol levels for groups 1, 2 and 3 were 5.19 +/- 0.27, 5.20 +/- 0.27 and 7.51 +/- 0.31 mM. LDL (density 1.006-1.028 g/l) and LDL2 (1.028-1.063 g/l) were isolated by density gradient ultracentrifugation. A significantly greater proportion of cholesterol was carried in LDL2 than LDL1 in all groups. There was a significantly lower cholesterol/protein ratio in LDL1 from the hypercholesterolaemic diabetic patients compared with controls. The LDL esterified/free cholesterol ratio was significantly greater in both LDL1 and LDL2 in the hypercholesterolaemic diabetic patients compared with the other two groups. There was a negative correlation between inhibition of cholesterol synthesis and the esterified/free cholesterol ratio of both LDL1 (r = 0.56, P < 0.002) and LDL2 (r = 0.63, P < 0.001). Cellular cholesterol of 41.0 +/- 0.3 microgram/mg cell protein in the hypercholesterolaemic diabetic patients was also significantly higher compared with values of 30.32 +/- 2.0 and 34.1 +/- 4.2 micrograms/mg cell protein for the normocholesterolaemic non-diabetic and diabetic groups. In vitro LDL esterification led to a decrease in LDL receptor-mediated binding and resulted in a 40% reduction in the ability of the LDL to suppress cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1993

Glycosylated low density lipoprotein is more sensitive to oxidation: implications for the diabetic patient?

Oxidised low density lipoprotein (LDL) is considered to be atherogenic. This study examined the relationship between glycosylation and oxidation of LDL from 10 normocholesterolaemic Type 2 diabetic patients, 10 hypercholesterolaemic Type 2 diabetic patients, and 10 normocholesterolaemic non-diabetic subjects. LDL was isolated by sequential ultracentrifugation and susceptibility to oxidation assessed by measuring thiobarbituric reactive substances (TBARS) during a 4-h oxidation period. LDL glycosylation was measured by aminophenylborate gel chromatography. Results demonstrated an increased susceptibility to oxidation in LDL from both diabetic groups, the mean 3-h TBARS values being 35.2 +/- 2.1 and 36.4 +/- 2.6 nmol MDA/mg LDL protein for normocholesterolaemic and hypercholesterolaemic diabetic patients compared with 24.5 +/- 2.5 nmol MDA/mg LDL protein for control subjects. LDL glycosylation of 2.20% +/- 0.11% and 2.89% +/- 0.46% for normocholesterolaemic and hypercholesterolaemic diabetic LDL was significantly higher than that for the non-diabetic control subjects of 1.60% +/- 0.12% (P < 0.02). There was a significant positive correlation (P < 0.005) between LDL glycosylation and LDL oxidation. The esterified/free cholesterol ratio which correlated positively with oxidation (P < 0.01) was significantly higher in LDL from both diabetic groups compared with LDL from control subjects (P < 0.01). Thus the increased incidence of atherosclerosis in diabetes may be related to glycosylation of LDL through its increased susceptibility to oxidation.

Cholesterol↗
PubMed1993

Trapeziectomy and ligament reconstruction for osteoarthrosis of the base of the thumb. A prospective study of 100 operations.

100 thumbs with primary osteoarthrosis of the joints of the trapezium were treated by trapeziectomy and a FCR sling arthroplasty to reconstruct a first intermetacarpal ligament by the method described by Burton and Pellegrini (1986). Pain at rest remained in five. Some pain at or after exertion persisted in 46, and 49 became completely pain-free. 88 were satisfied with the procedure and there was a significant increase in pinch strength and in the ability to perform activities of daily life. It has become our preferred procedure for treating osteoarthrosis of the basal joint of the thumb.

Activities of Daily Living↗
PubMed1993

The impact of counselling with a practical statistical model on patients' decision-making about treatment for epilepsy: findings from a pilot study.

To ascertain the impact of a computer-based predictive model on patients' decisions about continuing treatment of their epilepsy, 72 subjects were asked to complete questionnaires prior to and following counselling with the model. The subjects were attending the neurology out-patient clinic in a large UK hospital, and were identified from medical records as eligible for withdrawal of AEDs. The effect of counselling with the model was to make the majority of patients opt to continue AED therapy. Positive or negative framing of risk information appeared to influence the decisions of patients who were initially uncertain about continuing treatment, as did patients' perceptions of the clinician's views. The prognostic model appeared to allow relatively complex statistical information to be conveyed to patients in an accessible form. We suggest its use will aid clinicians in counselling patients and will help patients reach better-informed decisions about treatment.

Counseling↗