Biomedical subjects

C R Baker

Publications and source records attributed to C R Baker.

At least 19 recordsLinked to original sources

PubMed1992

Case-mix groups for VA hospital-based home care.

The purpose of this study is to group hospital-based home care (HBHC) patients homogeneously by their characteristics with respect to cost of care to develop alternative case mix methods for management and reimbursement (allocation) purposes. Six Veterans Affairs (VA) HBHC programs in Fiscal Year (FY) 1986 that maximized patient, program, and regional variation were selected, all of which agreed to participate. All HBHC patients active in each program on October 1, 1987, in addition to all new admissions through September 30, 1988 (FY88), comprised the sample of 874 unique patients. Statistical methods include the use of classification and regression trees (CART software: Statistical Software; Lafayette, CA), analysis of variance, and multiple linear regression techniques. The resulting algorithm is a three-factor model that explains 20% of the cost variance (R2 = 20%, with a cross validation R2 of 12%). Similar classifications such as the RUG-II, which is utilized for VA nursing home and intermediate care, the VA outpatient resource allocation model, and the RUG-HHC, utilized in some states for reimbursing home health care in the private sector, explained less of the cost variance and, therefore, are less adequate for VA home care resource allocation.

Aftercare↗

PubMed1992

Kinin metabolism in the perfused ventilated rat lung. II: Influence of ventilation, perfusion, and perfusate composition variation on bradykinin metabolism in uninjured lung.

Bradykinin metabolism by peptidases of the pulmonary endothelium has been investigated in the previously uninjured, ventilated, and asanguinously perfused rat lung. The influence of short-duration (up to 20 min) abnormal ventilation and perfusion conditions on bradykinin metabolism was assessed. Neither variation of the oxygen concentration (0 to 45%) nor omission of carbon dioxide in the ventilatory gas altered bradykinin metabolism significantly. Tidal volume variation did not alter bradykinin metabolism, and exclusion of one lung from the perfusion circuit reduced the capacity to degrade bradykinin proportionately. Acidification of the perfusion medium to pH 5 did not alter bradykinin metabolism. Acetylsalicylic acid in the perfusate protected the lung from an otherwise irreversible pressure increase associated with high-dose bradykinin perfusion. Endotoxin and hydrogen peroxide in the perfusate did not alter bradykinin metabolism. However, ammonia in the ventilatory gas caused immediate pulmonary edema, diminished lung capacity to metabolize bradykinin and altered the pattern of bradykinin metabolic products. The pulmonary endothelium itself, in the absence of blood, maintains its capacity to metabolize bradykinin under an extraordinary range of conditions.

Amino Acid Sequence↗

PubMed1991

Kinin metabolism in the perfused ventilated rat lung. I: Bradykinin metabolism in a system modeling the normal, uninjured lung.

Bradykinin (BK) in an asanguinous salt solution was perfused through intact rat lung. BK concentration varied from 0.0015 to 89 microM. Below 17 microM, the amount degraded was greater than or equal to 90% of the dose. The BK fragment distributions expressed as a percentage of the BK dose degraded were constant. The BK fragments formed and percentage yields were Pro-Pro (2-3) 49%, Arg-Pro-Pro-Gly-Phe (1-5) 32%, Pro-Pro-Gly-Phe-Ser-Pro (2-7) 6%, Arg-Pro-Pro-Gly-Phe-Ser-Pro (1-7) 6%, Arg-Pro-Pro (1-3) 3% and residual BK 4%. Above 17 microM, the amount of BK degraded was not proportional to the dose. Captopril and enalaprilat inhibited BK degradation, and their maximum inhibitions were about 50% and 30%, respectively. The percentage yield of the 1-5 fragment was greatly reduced by both inhibitors, but the percentage yields of the 2-3 and 1-8 fragments were moderately increased. It was concluded that (1) the intact rat lung itself has a very large capacity to degrade BK in the range of 2 mumoles/min/kg body weight; (2) two major and several minor enzyme pathways exist to degrade BK; (3) the relative contributions of these pathways to overall BK degradation remain essentially constant over a bradykinin concentration range from 0.0015 to 17 microM; (4) ACE/kininase-II catalyzed hydrolysis is one of the major pathways but is not the single major route for BK degradation; and (5) the other major BK degradation pathway involves enzymes cleaving the Arg1-Pro2 and Pro3-Gly4 bonds of BK.

Amino Acid Sequence↗

PubMed1989

Human lung membrane-bound neutral metallo-endopeptidase-catalyzed hydrolysis of bradykinin.

Human lung membrane-bound neutral metallo-endopeptidase (NME; EC 3.4.24.11) has been purified; this enzyme occurred in two forms, NME-I and NME-II. The total NME activity was purified 2,143-fold with the final specific activities for NME-I and NME-II being 750 and 1,124, respectively. The two NME forms were resolved in the final purification step involving ion exchange; in all earlier steps including gel filtration and affinity chromatography (phenyl sepharose) both forms behaved similarly and eluted simultaneously. NME-I and NME-II both had a Mr value of 97,000, and neither form dissociated into subunits. Catalytic actions of NME-I and NME-II upon bradykinin were identical; the Gly4-Phe5 and Pro7-Phe8 bonds of bradykinin were cleaved with the final hydrolytic products for each enzyme being the tetrapeptide, Arg-Pro-Pro-Gly, the tripeptide, Phe-Ser-Pro, and the dipeptide, Phe-Arg. The intermediate products were the heptapeptide, Arg-Pro-Pro-Gly-Phe-Ser-Pro, and the pentapeptide, Phe-Ser-Pro-Phe-Arg. Neither NME-I nor NME-II were inhibited by the angiotensin-converting enzyme inhibitor, captopril. Both enzymes were inhibited by phosphoramidon, dithiothreitol and EDTA. Other peptidase inhibitors and heavy metals were not effective NME inhibitors. Both NME-I and NME-II cleaved angiotensin-I at the Pro7-Phe8 bond, and substance-P at the Glu6-Phe7 bond, with the latter being much slower than the former.

Amino Acid Sequence↗

PubMed1987

A high-molecular-mass neutral endopeptidase-24.5 from human lung.

A high-Mr neutral endopeptidase-24.5 (NE) that cleaved bradykinin at the Phe5-Ser6 bond was purified to apparent homogeneity from human lung by (NH4)2SO4 fractionation, ion-exchange chromatography and gel filtration. The final enzyme preparation produced a single enzymically active protein band after electrophoresis on a 5% polyacrylamide gel. Human lung NE had an Mr of 650,000 under non-denaturing conditions, but after denaturation and electrophoresis on an SDS/polyacrylamide gel NE dissociated into several lower-Mr components (Mr 21,000-32,000) and into two minor components (Mr approx. 66,000). The enzyme activity was routinely assayed with the artificial substrate Z-Gly-Gly-Leu-Nan (where Z- and -Nan represent benzyloxycarbonyl- and p-nitroanilide respectively). NE activity was enhanced slightly by reducing agents, greatly diminished by thiol-group inhibitors and unchanged by serine-proteinase inhibitors. Human lung NE was inhibited by the univalent cations Na+ and K+. No metal ions were essential for activity, but the heavy-metal ions Cu2+, Hg2+ and Zn2+ were potent inhibitors. With the substrate Z-Gly-Gly-Leu-Nan a broad pH optimum from pH 7.0 to pH 7.6 was observed, and a Michaelis constant value of 1.0 mM was obtained. When Z-Gly-Gly-Leu-Nap (where -Nap represents 2-naphthylamide) was substituted for the above substrate, no NE-catalysed hydrolysis occurred, but Z-Leu-Leu-Glu-Nap was readily hydrolysed by NE. In addition, NE hydrolysed Z-Gly-Gly-Arg-Nap rapidly, but at pH 9.8 rather than in the neutral range. Although human lung NE was stimulated by SDS, the extent of stimulation was not appreciable as compared with the extent of SDS stimulation of NE from other sources.

Cations↗

PubMed1987

A multicatalytic high-molecular-weight neutral endopeptidase from human kidney.

A multicatalytic endopeptidase (ME) with three distinct activities, chymotrypsin-like, cucumisin-like, and trypsin-like, occurred in all rat tissues examined with highest activities in kidney, testes, liver, and spleen; they were assayed with benzyloxycarbonyl-Gly-Gly-Leu-p-nitroanilide (Z-Gly-Gly-Leu-pNA), benzyloxycarbonyl-Leu-Leu-Glu-2-naphthylamide (Z-Leu-Leu-Glu-2NA), and benzyloxycarbonyl-Gly-Gly-Arg-2-naphthylamide (Z-Gly-Gly-Arg-2NA), respectively. All three activities were recovered from a single protein band on a polyacrylamide gel after electrophoresis of purified human kidney ME. The native enzyme had a Mr of 650,000, and it consisted of about 5,135 amino acid residues. After denaturation and electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gels kidney ME dissociated into several low Mr components ranging from 23,000 to 33,000. Kidney ME had a pH optimum of 7.6-8.1 with Z-Gly-Gly-Leu-pNA, 7.3 with Z-Leu-Leu-Glu-2NA, and 9.8 with Z-Gly-Gly-Arg-2NA. SDS enhanced chymotrypsin- and cucumisin-like activities by two to three times whereas trypsin-like activity was not enhanced. The specificity constant (kappa cat/Km) of human kidney ME for Z-Gly-Gly-Leu-pNA was 6.7 X 10(3) M-1 S-1; Z-Gly-Gly-Leu-2NA was not hydrolyzed. The specificity constant for Z-Leu-Leu-Glu-2NA was similar to, and for Z-Gly-Gly-Arg-2NA was one half of that for Z-Gly-Gly-Leu-pNA. ME cleaves only the Phe5-Ser6 bond of bradykinin (BK); however, all three ME activities were inhibited by BK. Strong inhibition of ME by albumin suggests that ME is involved in cleavage of larger polypeptides. Antipain and leupeptin almost completely inactivated the trypsin-like activity whereas they had no significant effect on the other two activities. ME is not a metal-loenzyme nor is the serine residue essential for its activities; however, thiol groups are involved. Na+ and K+ inhibited all ME activities. Trypsin-like activity was more sensitive to divalent cations than the other two.

Amino Acids↗

PubMed1986

Human lung post-proline endopeptidase: purification and action on vasoactive peptides.

Post-proline endopeptidase (PPE, EC 3.4.21.26) was purified 3,450 times from human lung. PPE was routinely assayed with the artificial substrate, carbobenzoxy-glycyl-L-prolyl-p-nitroanilide (Z-Gly-Pro-pNA). The pH optimum was 7.4, and the Mr was 77,000. Thiol blocking agents were strongly inhibitory but serine blocking agents were not inhibitory. No metal ions were required for activity, but heavy metal ions such as Hg2+, Cu2+, Cd2+, and Zn2+ completely inactivated the enzyme. Both dithiothreitol (DTT) and ethylenediaminetetraacetic acid (EDTA) were required to stabilize PPE activity. Michaelis constant values for Z-Gly-Pro-pNA and carbobenzoxy-glycyl-L-prolyl-2-naphthylamide were 0.36 and 0.10 mmol/l, respectively. PPE cleaved vasoactive peptides including bradykinin (BK) and des-(Arg9)-BK (Pro3-Gly4 and Pro7-Phe8 bonds), angiotensins I and II (Pro7-Phe8 bond), substance P (Pro4-Gln5 bond), and oxytocin (Pro7-Leu8 bond). Each of these peptides inhibited PPE-catalyzed hydrolysis of Z-Gly-Pro-pNA competitively. BK had the lowest Ki value (2.35 mumol/l) and oxytocin had the highest Ki value (84.0 mumol/l). PPE was not inhibited by captopril, a potent inhibitor of angiotensin converting enzyme, which also cleaves the Pro7-Phe8 bond of BK.

Cations, Divalent↗

PubMed1986

Comparison of metoclopramide and metoclopramide plus dexamethasone for complete protection from cisplatinum-induced emesis.

Metoclopramide was compared to a metoclopramide plus dexamethasone combination in patients receiving high-dose cisplatinum. Metoclopramide 2 mg/kg intravenously was given every 2 hours for 4 doses during two consecutive chemotherapy cycles. A randomized double-blind crossover was used with placebo or dexamethasone 20 mg given intravenously before the first metoclopramide dose. Thirty-six patients completed both study arms. There was no difference in mean vomiting episodes (1.92 for metoclopramide versus 1.33 for the combination, p = 0.20). However complete protection (no vomiting episodes) was achieved in 56% receiving the combination but only 36% receiving metoclopramide alone (p less than 0.08). No significant difference in toxicity or patient preference was noted. Late nausea or vomiting lasting 2 to 7 days appeared in 26% of cycles and was associated with but not completely explained by a greater number of acute vomiting episodes. Combination antiemetic therapy can achieve a higher incidence of complete protection from cisplatinum-induced vomiting. However, late nausea and vomiting may require modification of present regimens.

Adult↗

PubMed1986

The colon in the pseudoobstructive syndrome.

Colonic pseudoobstruction can occur as part of a generalized chronic intestinal pseudoobstruction syndrome or as an isolated entity. Isolated colonic pseudoobstruction can occur in two unrelated forms: the acute and chronic forms. Acute colonic pseudoobstruction is frequently a hospital-acquired disease that arises as a complication of other illnesses. The syndrome must be recognized and treated with early colonoscopic decompression to prevent cecal or colonic perforation. Chronic colonic pseudoobstruction is a syndrome of many causes. The prognosis of patients with chronic colonic pseudoobstruction is much better than that of generalized chronic intestinal pseudoobstruction, because the patients become asymptomatic with appropriate operations. The pathogenesis of acute colonic pseudoobstruction and several types of chronic colonic pseudoobstruction is not known. Further investigations should include bacteriologic study, histopathologic studies (examinations of smooth muscle and myenteric plexus), and examination of extrinsic nerves of the colon. With these approaches, a better understanding of the pathogenesis of these syndromes will be achieved.

Colonic Diseases↗

PubMed1977

The rate of membrane turnover by the hairy cells of leukemic reticuloendotheliosis: a kinetic study of a receptor for IgM.

The kinetics of turnover of a surface receptor for IgM were studied in six cases of hairy cell leukemia and four cases of chronic lymphocytic leukemia and the results were used as an indicator of membrane turnover in the pathologic cells of these two chronic leukemias. Rosette formation, shedding, and reexpression with EA (IgM) by hairy cells, a process which was shown to require protein synthesis, followed a cyclical pattern with a modal peak-to-peak reexpression time of 6 hr. Membrane turnover time in the cases of chronic lymphocytic leukemia was 12 hr or more. This work indicates that a reduced membrane turnover rate is not an essential feature of chronic leukemias. The more general application of this type of approach to the study of membrane turnover in normal cells and their pathologic counterparts are discussed.

Binding Sites, Antibody↗

PubMed1976

Complications and management of methods of dialysis access for renal failure.

The management of dialysis access requires the awareness that any single access site is finite. A commitment to maintain access is reasonable with a planned approach. Dialysis for the end-stage renal disease patient must continue acutely during the management of access complications, and chronically. The goal of treatment is to return the patient to a routine dialysis regimen as soon as possible. Suspected infections should be treated immediately with systemic antibiotics specific for resistant Staphylococcus aureus. Systemic infection should be controlled before a new foreign body is implanted. My personal philosophy of access includes the following principles. (1) distal is good, (2) preserve all possible sites, (3) arm is better than leg, and (4) everything is relative.

Anti-Bacterial Agents↗

PubMed1975