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Biomedical subjects

A J Watson

Publications and source records attributed to A J Watson.

At least 181 records · Page 10Linked to original sources
PubMed1990

Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin.

PURPOSE: The purpose of this study was to determine the efficacy of recombinant human erythropoietin (rHuEPO) given subcutaneously three times/week in patients with chronic renal failure and anemia (predialysis). PATIENTS AND METHODS: Eleven patients with predialysis chronic renal failure participated in a double-blind, placebo-controlled study of subcutaneously administered erythropoietin. For 12 weeks, patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo. After 12 weeks of placebo, patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved. Throughout the study, blood pressure was monitored closely and blood work was obtained regularly for hemoglobin, hematocrit, reticulocyte count, and iron profile determinations. RESULTS: At 12 weeks, the hematocrit of the treated group had risen from 29% +/- 2% to 35% +/- 2% (p less than 0.001). The placebo group baseline hematocrit was 28% +/- 2% and at 12 weeks 26% +/- 2% After 12 weeks of rHuEPO therapy, the hematocrit of the prior placebo group was 32% +/- 2% (p less than 0.001 versus baseline). No significant change in biochemical parameters was noted. Mean blood pressure values were comparable before and after treatment. All protein ultimately required iron supplementation. In two patients, the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued. CONCLUSIONS: It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis.

Adult↗
PubMed1990

Differentiation of an epithelium: factors affecting the polarized distribution of Na+,K(+)-ATPase in mouse trophectoderm.

Na+,K(+)-ATPase is a marker of the basolateral plasma membrane domain of polarized epithelial cells, including the mural trophectoderm of the mammalian blastocyst (Watson and Kidder (1988). Dev. Biol. 126, 80-90). We have used this marker to explore the factors governing the establishment and maintenance of apical/basolateral polarity during differentiation of trophectoderm. A polyclonal antiserum (anti-GP80) against human cell-CAM 120/80, a homolog of the mouse cell-cell adhesion protein, uvomorulin, was used to prevent cell flattening (compaction) and formation of the epithelial junctional complex. The majority of treated embryos failed to develop a blastocoel; instead their blastomeres developed fluid-filled cavities that expanded while untreated control embryos were cavitating. Immunocytochemistry revealed that the catalytic subunit of Na+,K(+)-ATPase was contained within the membranes lining these cavities, as well as within numerous punctate foci in the cytoplasm. The down-regulation of expression of the enzyme that normally occurs in the ICM and polar trophectoderm did not take place, since the immunoreactivity remained equally strong in all blastomeres. The enzyme could not be detected in plasma membranes. We conclude that uvomorulin-mediated cell adhesion is involved in spatially restricting the expression of the catalytic subunit and is a prerequisite for the insertion of enzyme-laden vesicles into plasma membranes, but not for expression of the catalytic subunit gene. When fully developed blastocysts were treated with cytochalasins to disrupt the epithelial junctional complex, the catalytic subunit shifted from the basolateral to the apical plasma membrane. This finding suggests a primary role for the apical plasma membrane in the process of polarization, and implies that tight junctions are a manifestation of polarity that serve to maintain the separation between apical and basolateral markers.

Animals↗
PubMed1990

Rabbit ileal villus cell brush border Na+/H+ exchange is regulated by Ca2+/calmodulin-dependent protein kinase II, a brush border membrane protein.

Ileal brush border membranes contain an endogenous Ca2+/calmodulin (CaM)-dependent protein kinase activity that modulates the activity of the apical membrane Na+/H+ exchanger. To further characterize this kinase, synapsin I, a substrate for Ca2+/CaM-dependent protein kinases, was added to preparations of ileal brush border membranes. In the presence of Ca2+/CaM, synapsin I was phosphorylated. Phosphopeptide mapping demonstrated that the addition of Ca2+/CaM to brush border membranes stimulated the phosphorylation of sites in synapsin I specific for Ca2+/CaM-dependent protein kinase II. Immunoblots containing brush border and microvillus membrane proteins were probed with an antibody that recognizes the 50-kDa subunit of rat brain Ca2+/CaM-dependent protein kinase II. This antibody labeled major and minor species of 50 and 53 kDa, respectively, with more labeling of the brush border than the microvillus membranes. Right-side-out ileal villus cell brush border vesicles were prepared containing CaM, ATP, and 350 nM free Ca2+. Na+/H+ exchange was inhibited by the presence of Ca2+/CaM/ATP within the vesicles. A 21-amino acid peptide inhibitor of CaM kinase II was enclosed within some vesicle preparations by freeze-thaw. The effect on Na+/H+ exchange of Ca2+/CaM/ATP was partially reversed by the inhibitor peptide. These studies demonstrate the presence of Ca2+/CaM-dependent protein kinase II in rabbit ileal villus cell brush border membranes. Based on the effect of a specific inhibitor peptide of Ca2+/CaM kinase II, it is concluded that this kinase inhibits brush border Na+/H+ exchange, which participates in the regulation of ileal Na+ absorption.

Animals↗
PubMed1990

Psoralen/UV inactivation of HIV-1-infected cells for use in cytologic and immunologic procedures.

A rapid procedure for the inactivation of HIV-1-infected cells using psoralen and ultraviolet (UV) light is described. Exposure of HIV-1-infected cells to 5 micrograms/ml psoralen followed by UV irradiation (320-380 nm) for 5 minutes yields cells that are noninfectious as assessed by extended infectivity assays. The psoralen/UV inactivation procedure described is effective with cells chronically or acutely infected with HIV-1 and is unaffected by cell densities up to 12 x 10(6)/ml. At 5 micrograms/ml psoralen does little damage to cellular permeability as shown by the ability of treated cells to exclude trypan blue and propidium iodide. Psoralen/UV treatment of HIV-1-infected cells does not cause a significant decrease in the reactivity of HIV-1 core and envelope antigens or cellular antigens to monoclonal antibodies. Experiments are presented demonstrating the use of these cells for flow cytometry studies and for cell surface labeling using the lactoperoxidase 125I iodination procedure.

Cell Count↗
PubMed1990

Effect of octreotide on mouth-to-caecum transit time in healthy subjects and in the irritable bowel syndrome.

The effect of a single subcutaneous injection of octreotide (50 micrograms) on mouth-to-caecum transit time was determined in patients with the irritable bowel syndrome who complained of bowel frequency, and in healthy volunteers. The assessment of mouth-to-caecum transit time was performed by monitoring breath hydrogen concentration and noting a sustained 10 p.p.m. rise after ingestion of lactulose 40 ml. Measurements were performed fasting, and on a separate day, after a standard breakfast which included 40 ml lactulose. The studies were performed double-blind in a pre-determined random order. Octreotide prolonged mouth-to-caecum transit time in irritable bowel syndrome patients and healthy subjects by factors of 2.4 and 2.6 after lactulose when fasting, respectively, and by factors of 2.8 and 2.6 after the breakfast which contained lactulose. The upper gastrointestinal transit rate was similar in irritable bowel syndrome patients and healthy controls.

Adult↗
PubMed1990

The results of tubal surgery in the treatment of infertility in two non-specialist hospitals.

The results of surgery for tubal damage, other than reversal of sterilization, were studied in two large hospitals. This is the first recent study from centres claiming no special expertise in this surgery. An unusually high follow-up rate was obtained. The term pregnancy rate for patients operated on for bilateral distal tubal occlusion was 4%. The success rate is lower than the lowest reported, overall success rates for each cycle of in vitro fertilization (IVF) and very much lower than cumulative term pregnancy rates for tubal surgery reported by most other authors. Patients with distal tubal occlusion but minimal adhesions had the best prognosis. Our results suggest that, provided in vitro fertilization is available, only those patients with good prognostic factors should undergo tubal surgery. These represent the minority of all patients with non-iatrogenic tubal blockage.

Adult↗
PubMed1990

Acetate absorption in the normal and secreting rat jejunum.

Acetate absorption was studied in rat jejunum using steady state perfusion in vivo. Absorption conformed to apparent saturation kinetics and was similar in magnitude to glucose absorption. When compared with normal saline, acetate perfusion was associated with luminal alkalinisation. There was no difference in total CO2 secretion when similar rates of acetate and glucose absorption were compared, suggesting that total CO2 secretion was the result of mucosal metabolism. Absorption of acetate and propionate were mutually inhibitory. Acetate absorption was also inhibited by Tris-Hepes pH 7.0. When the gut was pretreated with cholera toxin to induce a secretory state, acetate absorption was reduced by 41.9%. This effect could be reproduced if similar water secretion was osmotically induced by the addition of mannitol. These data suggest that acetate is absorbed, at least, partially by non-ionic diffusion in the rat jejunum and that its absorption is reduced in the secreting intestine by solvent drag.

Acetates↗
PubMed1990

The effect of sulindac on colonic tumour formation in dimethylhydrazine-treated mice.

Dimethylhydrazine has been used to produce colonic tumours in mice. If sulindac, a non-steroidal anti-inflammatory drug, is administered simultaneously fewer microadenomata and fewer macroscopic tumours are produced. Those which do appear are comparable in size to the ones in the mice which do not receive sulindac. Sulindac therefore appears to exert an anti-tumour influence at the stage between dysplasia and the formation of microadenomata.

Adenoma↗
PubMed1990

Case management of the anemic patient. Focus on blood pressure and rHuEPO therapy.

As the use of Epoetin alfa to treat the anemia of chronic renal failure (CRF) expands, nurses play an ever-increasing role in patient monitoring and control. One area that relies heavily on nurses is blood pressure monitoring. Clinical trials with Epoetin alfa in hemodialysis patients indicate that its use may be associated with the onset or aggravation of elevated blood pressure as the hematocrit level increases. Because high blood pressure is a risk factor for left ventricular hypertrophy and cardiovascular mortality in this patient population, use of an agent that may cause high blood pressure requires careful monitoring. As the following two cases reports illustrate, sufficient data to provide better insight into the clinical aspects of this potential problem have now been accumulated.

Adult↗
PubMed1989

A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss.

A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin. Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died for liver failure after 3 months. Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients. No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p less than 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p less than 0.05), as did trabecular bone volume (-6% vs. -2.8%, p less than 0.005) and resorption surface (-11% vs. +2%, p less than 0.02) on serial bone biopsy. Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the "cost/benefit" ratio.

Adult↗
PubMed1989

Proliferative status of colonic mucosa in organ culture: 3H-thymidine-labelling studies and computer modelling.

3H-thymidine labelling studies and a computer simulation have been employed to assess proliferative status and cellular organisation in colonic explants maintained in culture for 5 to 7 days. The one-hour flash labelling index (Is) for crypts within the middle region of explants (5.2%) was considerably lower than that observed in vivo (8.8%). Crypt length and the distribution of labelled cells appeared similar for both situations. A computer simulation program for crypt-cell proliferation was devised, facilitating the modulation of a number of parameters including the cell-cycle time (Tc) and its component phases, the cut-off position, and cell loss at mitosis. This simulation was employed to model continuous labelling (72 h) data obtained in vitro and provided an estimate of various kinetic parameters. Data for the middle region of explants was fitted with a Tc of 62 h, an S phase of 8 h and a cell loss factor (20%) which was consistent with histological findings. A fit to the experimental data obtained in vitro could be achieved by a model based upon a mode of cellular organisation known to occur within crypts in vivo. Therefore in vitro, the dynamic processes of crypt-cell proliferation and migration appear to be organised in the same manner as seen in vivo.

Animals↗
PubMed1989

Adverse effects of therapy for the correction of anemia in hemodialysis patients.

The traditional options available for the correction of hemodialysis-related anemia are blood transfusions and androgen therapy to stimulate erythropoiesis. A new therapeutic option, recombinant human erythropoietin (r-HuEPO; EPOGEN, AMGEN Inc, Thousand Oaks, CA), is currently undergoing clinical trials. Each treatment alternative has certain attendant adverse effects. The adverse effects of transfusion include transmission of infections such as hepatitis or acquired immunodeficiency syndrome, iron overload, and sensitization to histocompatibility antigens. Androgen therapy can cause masculinization of women and children and, in some forms, is associated with a high incidence of abnormal liver function. Treatment with r-HuEPO has some potential adverse effects, including hypertension, thrombosis of arteriovenous fistulae, prolonged duration of dialysis, hyperkalemia, and iron deficiency. Gradual and careful introduction of r-HuEPO should prevent hypertension from becoming problematic.

Androgens↗