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Biomedical subjects

S Anderson

Publications and source records attributed to S Anderson.

At least 325 records · Page 18Linked to original sources
PubMed1993

Enrichment of glutamate-like immunoreactivity in primary afferent terminals throughout the spinal cord dorsal horn.

Although several lines of evidence indicate that glutamate is a neurotransmitter in primary afferent terminals, controversies exist on the proportion and types of such terminals that release glutamate. In the present study quantitative analysis of immunogold labelling was used to assess the presence of glutamate-like immunoreactivity in primary afferent terminals in laminae I-V of the rat spinal cord dorsal horn. Anterograde transport of choleragenoid-horseradish peroxidase from a spinal ganglion and tetramethyl benzidine histochemistry were used to identify primary afferent terminals in laminae I and III-V. Presumed C-fibre terminals in lamina II were identified on morphological criteria (dense sinusoid axon terminals). Primary afferent terminals in all dorsal horn laminae displayed significantly higher levels of glutamate-like immunoreactivity than pleomorphic vesicle-containing profiles in laminae III-IV and large neuronal cell bodies in laminae III-V. The density of gold particles over primary afferent terminals also significantly exceeded the average density of gold particles over laminae II and III-IV. The highest densities of gold particles were present over dense sinusoid axon terminals in lamina II. These findings suggest that glutamate, alone or in combination with other neuroactive compounds, is involved in the transfer of all sensory modalities from primary afferent fibres to dorsal horn neurons.

Afferent Pathways↗
PubMed1993

Evidence of hepatitis in patients receiving transfusions of blood components containing antibody to hepatitis C.

When hepatitis C virus antibody (anti-HCV) enzyme immunoassay (EIA1) testing became available in 1990, we tested samples from previously transfused blood units, traced the recipients of reactive units, and evaluated the recipients for HCV infection during the 12 months after transfusion. Ten of 42 recipients of EIA1-reactive blood were anti-HCV reactive on follow-up by EIA1 and 12 were reactive by a second-generation assay (EIA2). Reverse transcriptase-polymerase chain reaction (RT-PCR) detected HCV RNA in 5 seronegative recipients. In all, 17 of 42 recipients (40%) of EIA1-reactive blood had evidence of HCV infection. In comparison, 54 surgery patients, who received either no transfusion or autologous EIA1-nonreactive blood, remained EIA1 nonreactive and RT-PCR negative for 1 year; 1 patient (1.8%) became EIA2 reactive (P < or = .01). Of the recipients of anti-HVC reactive blood transfusions (reactive by both EIA1 and a supplemental 4-antigen strip immunoblot assay [RIBA2]), 14 (93%) of the recipients had evidence of HCV infection compared with only 3 of 27 recipients (11%) of EIA1-reactive, RIBA2-nonreactive blood (P < or = .01). Thus, blood components reactive for anti-HCV EIA1 may have transmitted HCV up to 40% of the time, but blood components found reactive by both EIA1 and RIBA2 may transmit HCV with a frequency of greater than 90%.

Adult↗
PubMed1993

Arg15-Lys17-Arg18 turkey ovomucoid third domain inhibits human furin.

Turkey ovomucoid third domain with Leu18 in its reactive site is a potent inhibitor of many serine proteinases: subtilisins, chymotrypsins, and elastases. Previous studies showed that an L18K mutation made it a moderately strong inhibitor of trypsin, while an L18E mutation made it a strong inhibitor of Glu-specific Streptomyces griseus proteinase (GluSGP). For human furin substrates the consensus optimal sequence is RXKR decreases. Therefore the A15R, T17K, and L18R mutations were made in turkey ovomucoid third domain. The mutant inhibits human furin with a Ka of 1.1 x 10(7) M-1. As human furin catalyzes an obligatory step in human immunodeficiency virus proliferation, this inhibitor, along with the others already available, deserves further study.

Amino Acid Sequence↗
PubMed1993

Pathologic findings from the National Surgical Adjuvant Breast Project protocol B-06. 10-year pathologic and clinical prognostic discriminants.

BACKGROUND: Prognostic pathologic and clinical features for 10-year survival were determined from 22 pathologic and 5 clinical variables encountered in 1090 node-negative and 651 node-positive patients enrolled in NSABP protocol B-06. METHODS: All factors were first screened univariately. Those exhibiting P values < 0.01 were entered into multivariate Cox regression models. The model with the best fit consisted of 951 negative-node and 496 node-positive patients. RESULTS: Better survival in node-negative patients was noted for whites rather than blacks, for patients with favorable tumor types (tubular, mucinous, papillary) rather than intermediate (lobular invasive, classical medullary, and not otherwise specified [NOS] combinations) or unfavorable forms (NOS pure and atypical medullary), and for tumors with good rather than poor nuclear grade. Number of nodal metastases, degree of tumor elastosis, and patient age younger than 40 years of age and 65 years of age and older in addition to nuclear grade and race were found significant for node-positive patients. Relative risks for combinations of these prognostic factors were multiplicative. CONCLUSIONS: The prognostic factors for node-negative patients were similar to those observed for this cohort at 8 years. Some differences noted between patients of both nodal groups in NSABP B-04 and B-06 may be related to selection requirements in the latter and hence different patient characteristics or more speculatively a change in tumor biology.

Adult↗
PubMed1993

Pharmacy follies.

Stuart Anderson describes a national study which failed to find any significant differences between the economic performance of pharmacy services in public and private hospitals.

Efficiency↗
PubMed1993

Indium detoxification in Pseudomonas fluorescens.

The interaction between indium, a non-essential toxic element, and a soil bacterium was studied. Although the presence of 0.5 mm indium complexed to citrate, the sole source of carbon, had an inhibitory influence on growth rate and cellular yield, Pseudomonas fluorescens circumvented the toxicity of the trivalent metal via its insolubilization as a phosphorus residue. The inclusion of 20 microm iron (III) arrested the negative impact of indium and no diminution of cellular yield was recorded. In this instance indium homeostasis was also attained by elaboration of an extracellular phosphorus-containing deposit. Electrophoretic analyses of the cytoplasmic extracts revealed several dissimilar patterns. Notably, two polypeptides with apparent molecular masses of 57 kDa and 18 kDa were induced in the metal-stressed bacteria. An increment in extracellular carbohydrates in metal-supplemented media was observed. No citrate was detected in the spent fluid at the cessation of cellular bilization may have potential application in metal pollution management.

Journal Article↗
PubMed1993

Pharmacokinetics of a novel antiarrhythmic drug, actisomide.

The pharmacokinetics of a novel antiarrhythmic drug, actisomide, were examined in the rat, dog, monkey, and human. The terminal half-life of actisomide was similar (1.15-1.89 hr) across species, regardless of dose. The total plasma clearance was higher in the monkey (13.5-16.4 mL/min/kg) than in the dog (9.01-9.32 mL/min/kg), rat (8.6-9.8 mL/min/kg), or human (6.79 +/- 1.07 mL/min/kg). Excretion of the parent drug was higher in urine than in feces in the dog and rat, whereas in the monkey and human, urinary and fecal excretions of actisomide were similar. In humans, atypical plasma concentration-time curves with double peak concentrations were observed following oral doses. Systemic availability of actisomide was higher in the dog than in the rat, monkey, and human. Further, the systemic availability appeared to increase with dose in the rat and monkey. The species-dependent systemic availability appeared to be due primarily to species-dependent absorption of actisomide, and not to species-dependent first-pass metabolism, biliary excretion, and/or renal elimination. The absorption of actisomide in the rat and its in vitro uptake in CaCo-2 cells were pH dependent. The higher systemic availability of actisomide observed in the dog may be due partly to the higher pH in the gastrointestinal (GI) tract of the dog. However, the pH differences in the GI tract of the different species alone did not appear to be enough to explain the difference in systemic availability of actisomide.

Administration, Oral↗
PubMed1993

Hypoglycaemia: a common problem among uncomplicated newborn infants in Nepal.

Among a cross-sectional sample (stratified by weight and age after birth) of 226 uncomplicated term newborns from the delivery and postnatal wards of a busy government maternity hospital in Kathmandu, the period prevalence of hypoglycaemia (corrected blood glucose of < 2.6 mmol/l) during the first 50 hours after birth was 38 per cent. (This compares with a reported prevalence rate of 12 per cent from studies of uncomplicated term newborns in the UK.) Hypothermia, young maternal age, low birth weight and early sampling after birth were independent risk factors for hypoglycaemia. Of 31 infants studied longitudinally during the same period, 27 (87 per cent) had at least one blood glucose measurement of < 2.6 mmol/l and 25 (81 per cent) a rectal temperature of < 35.5 degrees C. Fourteen infants (44 per cent) had three or more episodes of hypoglycaemia and seven infants (22 per cent) had three or more episodes of hypothermia. Hypoglycaemia is a common, preventable and neglected problem in many maternity hospitals in developing countries. Simple low-cost measures to reduce the incidence of hypoglycaemia may have a major impact on early infant mortality and neurodevelopmental sequelae of perinatal origin.

Adolescent↗
PubMed1993

Biotinylated platelets: a new approach to the measurement of platelet life span.

The in vivo life span of dog platelets was determined by derivatizing whole blood with N-hydroxysuccinimido biotin, reinfusing the biotinylated blood and subsequently monitoring the survival of the biotinylated platelets with flow cytometry. We found that the biotinylated platelets had a mean life span of 6.0 +/- 1.1 d as determined by curve-fitting the platelet disappearance data to gamma functions. These data are in good agreement with literature values of platelet life span for canine platelets labelled with either 111Indium-oxine or 51Chromium. Biotinylated platelets were analysed after reinfusion and found to aggregate normally in response to the agonists adenosine diphosphate and phorbol myristate acetate. These experiments demonstrate that biotinylated platelets survive normally in vivo and that this labelling method can be used for determining platelet life spans.

Animals↗
PubMed1993

Neutralizing linear epitopes of B19 parvovirus cluster in the VP1 unique and VP1-VP2 junction regions.

Presentation of linear epitopes of the B19 parvovirus capsid proteins as peptides might be a useful vaccine strategy. We produced overlapping fusion proteins to span the viral capsid sequence, inoculated rabbits, and determined whether the resulting antisera contained antibodies that neutralized the ability of the virus to infect human erythroid progenitor cells. Antibodies that bound to virus in an enzyme-linked immunosorbent assay were present in antisera raised against 10 of 11 peptides; strongest activity was found for antisera against the carboxyl-terminal half of the major capsid protein. However, strong neutralizing activity was elicited in animals immunized with peptides from the amino-terminal portion of the unique region of the minor capsid protein and peptides containing the sequence of the junction region between the minor and major capsid proteins. The development of neutralizing activity in animals was elicited most rapidly with the fusion peptide from the first quarter of the unique region. A 20-amino-acid region of the unique region of the minor capsid protein was shown to contain a neutralizing epitope. Multiple antigenic peptides, based on the sequence of the unique region and produced by covalent linkage through a polylysine backbone, elicited strong neutralizing antibody responses. Synthetic peptides and fusion proteins containing small regions of the unique portion of the minor capsid protein might be useful as immunogens in a human vaccine against B19 parvovirus.

Antibodies, Viral↗
PubMed1993

Nef from primary isolates of human immunodeficiency virus type 1 suppresses surface CD4 expression in human and mouse T cells.

The human immunodeficiency virus type 1 (HIV-1) nef gene was originally described as a negative regulator of transcription from the viral long terminal repeat promoter. This observation has been disputed, and the function of Nef remains unclear. In vivo experiments have indicated that an intact nef gene is required for disease progression in macaques infected with simian immunodeficiency virus, suggesting a role for Nef in the pathogenesis of AIDS. We and others have previously shown that expression of Nef in cells bearing surface CD4 results in a sustained decrease in surface CD4 expression. This was demonstrated for Nef from two laboratory strains of HIV-1, Bru and SF2. Because both of these isolates were passaged in vitro prior to molecular cloning and in vitro passage can result in mutations which might alter nef gene function, we have analyzed two primary isolates of Nef for their ability to suppress cell surface CD4 expression. The nef genes of HIV-1 isolates from two patients with fewer than 200 CD4+ T cells per mm3 of blood were introduced into human and mouse T-cell lines by retrovirus-mediated gene transfer. Expression of Nef from both isolates correlated with a decrease in surface expression of both human and mouse CD4. To determine whether the ability to suppress surface CD4 expression is a general function of Nef, we also tested an artificially generated consensus nef gene derived from analysis of 54 patient isolates of HIV-1. Expression of the consensus Nef protein also correlated with decreased cell surface CD4 expression in both mouse and human T-cell lines. These results suggest that the ability to suppress cell surface CD4 expression is an intrinsic feature of HIV-1 Nef.

Acquired Immunodeficiency Syndrome↗
PubMed1993

p21ras and protein kinase C function in distinct and interdependent signaling pathways in C3H 10T1/2 fibroblasts.

Both p21ras and protein kinase C (PKC) are believed to function downstream of plasma membrane-associated tyrosine kinases in cellular signal transduction pathways. However, it has remained controversial whether they function in the same pathway and, if so, what their relative position and functional relationship in such a pathway are. We investigated the possibilities that p21ras and PKC function either upstream or downstream of each other in a common linear pathway or that they function independently in colinear signal pathways. Either decreased expression of endogenous normal ras in fibroblasts transfected with an inducible antisense ras construct or overexpression of a mutant ras gene reduced the capacity of the phorbol ester tetradecanoyl phorbol acetate to trigger expression of the tetradecanoyl phorbol acetate-responsive and ras-dependent reporter gene osteopontin (OPN). PKC depletion decreased basal OPN mRNA levels, and the overexpression of ras restored OPN expression to the level of non-PKC-depleted cells. We propose a model in which ras and PKC function in distinct and interdependent signaling pathways.

Animals↗
PubMed1993

Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biological correlations.

Recent evidence indicates a role for the renin-angiotensin system (RAS) in the pathogenesis of glomerular injury in diabetes. To further explore the RAS in diabetes, studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic (DM) rats. In DM rats, both acute and chronic therapy with the specific angiotensin II (ANG II) receptor antagonist losartan did not affect glomerular hyperfiltration or hyperperfusion but selectively normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. To determine the basis of intrarenal hemodynamic responsiveness to RAS inhibition, we conducted biochemical, molecular biological, and immunohistochemical studies to assess endogenous RAS activity. Values for plasma renin concentration and serum angiotensin-converting enzyme (ACE) activity in DM rats were normal. In contrast, intrarenal renin protein content, and renin and angiotensinogen mRNAs, were increased in DM rats, suggesting disproportionate activation of the intrarenal RAS. Total renal ACE activity was significantly reduced in DM rats, but immunohistochemical studies indicated redistribution of ACE in the diabetic kidney. Proximal tubule ACE activity was reduced, but ACE immunostaining intensity was enhanced in glomeruli and renal vasculature. Together, these observations indicate increased RAS activity in those sites (glomeruli and vasculature) most likely to regulate hemodynamic function, potentially explaining the prominent responses to pharmacological blockade of ANG II formation and/or action.

Angiotensin Receptor Antagonists↗
PubMed1993

Pathogenesis of glomerular injury in the fawn-hooded rat: early glomerular capillary hypertension predicts glomerular sclerosis.

Fawn-hooded rats spontaneously develop focal and segmental glomerular sclerosis, systemic hypertension, and proteinuria at a young age. Micropuncture and morphological studies were performed in two inbred strains of fawn-hooded rats, FHH and FHL, with different susceptibilities to develop chronic renal failure. FHH rats have higher values for systolic blood pressure and proteinuria and more rapid development of focal and segmental glomerular sclerosis and subsequent chronic renal failure as compared with genetically closely related FHL rats. FHH and FHL strains and a Wistar control strain, WAG, were matched for age and were studied at 16 wk. FHH, FHL, and WAG-old (WAG-O) strains were matched for weight, and the last group was studied at 22 wk. WAG were also matched for weight to a young group of FHH rats (FHH-Y), and these were studied at 8 wk. In comparison with WAG and WAG-O rats, FHH and FHH-Y rats exhibited an increased in mean glomerular capillary hydraulic pressure (WAG, 52 +/- 1 mm Hg; WAG-O, 47 +/- 2 mm Hg; FHH, 60 +/- 2 mm Hg; FHH-Y, 65 +/- 1 mm Hg), whereas values in FHL animals were intermediate (56 +/- 2 mm Hg). No significant differences in glomerular volume were found among groups. Moderate focal and segmental glomerular sclerosis developed in FHH and FHH-Y rats, with values for older FHH rats being significantly greater than those for WAG, WAG-O, and FHL animals. Thus, the genetically determined sensitivity to develop proteinuria, focal and segmental glomerular sclerosis, and chronic renal failure in fawn-hooded rats correlated with early evidence of glomerular capillary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Glomerular preload and afterload reduction as a tool to lower urinary protein leakage: will such treatments also help to improve renal function outcome?

It has been well documented that different therapeutic strategies, including angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, and dietary protein restriction, lower urinary protein excretion in patients with diabetic and non-diabetic nephropathy. Experimental evidence suggests that this antiproteinuric effect is, at least in part, related to a reduction in the glomerular capillary hydraulic pressure. ACE inhibitors appear to achieve this reduction in glomerular capillary pressure, mainly through a fall in postglomerular arteriolar resistance, whereas dietary protein restriction and non-steroidal antiinflammatory drugs appear to invoke the response predominantly through an increase in preglomerular resistance. This leads to the suggestion that both "glomerular preload reduction" (afferent vasoconstriction) and "glomerular afterload reduction" (efferent vasodilation) will result in an anti-proteinuric response. Interestingly, these same therapeutic regimens, particularly the ACE inhibitors and low-protein diets, have been proven to prevent progressive glomerulosclerosis in animal models. This concept of influencing glomerular hemodynamics both at the afferent and efferent arteriolar level may open new perspectives in the treatment of patients with renal protein loss and renal failure. At present, however, it is too early to conclude whether the fall in proteinuria induced by these treatments will also contribute to a better renal survival of these patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Pathogenesis of glomerular injury in the fawn-hooded rat: effect of unilateral nephrectomy.

Fawn-hooded (FH) rats with congenital proteinuria and systemic and glomerular hypertension are very susceptible to renal damage at a young age. In this study, the effects of unilateral nephrectomy (UNX) on the function and structure of the remaining kidney in the FHH substrain were assessed. A long-term study was performed to determine the changes in systemic blood pressure, renal function, and proteinuria during the development of chronic renal failure in UNX-FHH and two-kidney (2K) FHH rats. Renal micropuncture and morphologic studies were performed at 4 wk after surgery. The long-term study showed that, after UNX, systolic blood pressure did not differ significantly (from that of 2K-FHH rats. After UNX, there was compensatory hyperfiltration, at about 70% of the 2K level, that could be maintained for 12 wk only. The subsequent fall in GFR was preceded by severe proteinuria. The mean survival time of UNX-FHH rats was only 35 wk. Micropuncture studies showed that the high mean glomerular capillary pressure of 2K-FHH rats was further elevated after UNX. The glomerular capillary ultrafiltration coefficient did not differ significantly between UNX-FHH and 2K-FHH rats. The weight of the remaining kidney and the mean glomerular tuft volume in UNX-FHH were, on average, 36 and 31% greater than in 2K rats. The results indicate that the FHH rat is extremely vulnerable to the adverse renal effects of UNX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗