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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 307 records · Page 17Linked to original sources
PubMed1988

Toxicological effects of dietary Maillard reaction products in the rat.

The effects of dietary glutamate/glucose Maillard reaction products (MRP) on the rat were studied. Rats fed 5 and 10% MRP developed severe diarrhoea that persisted throughout the 5-wk feeding study. An increase in water consumption by these animals was attributed to excessive faecal water losses due to diarrhoea. Body weights were significantly depressed in animals fed 10% MRP compared with rats fed a control isocaloric diet or a diet containing 10% of an unreacted mixture of glutamate/glucose. MRP ingestion also resulted in a dose-related caecal enlargement, which was accompanied by a decrease in the osmolality of caecal contents, compared with control values. Relative kidney and liver weights were significantly increased in rats fed 10% MRP. Despite a high background incidence of cortico-medullary nephrocalcinosis in all groups in the study reported here, the condition was significantly more pronounced in rats fed MRP, as assessed by mineral analysis and histological examination. In addition, bladder urothelial thickness was significantly greater in rats fed either level of MRP compared with values for control animals. Finally, caecal goblet cell density was significantly reduced in rats fed MRP compared with counts for control animals.

Animals↗
PubMed1988

The feasibility of a potentially 'ideal' system of integrated diabetes care and education based on a day centre.

A new system of clinical and educational care designed to replace traditional diabetic clinics is described. The overall aims were to provide adequate consultation time, patient access according to diabetic and social needs, minimal waiting time, continuity with experienced staff and objective based learning programmes in an environment suited to learning. This was achieved by changing the role of the diabetes nurse specialist from undertaking delegated tasks to providing primary consultative care, reorganization of existing staff and provision of a purpose designed unit. This gave sufficient flexibility to arrange daily early morning and weekly evening clinic sessions for routine diabetes counselling and medical audit with primary education scheduled at other times. A year's experience showed that our major targets had been met, with the provision of adequate consultation time, halving of waiting time, ease of patient access and continuity with either the doctor or nurse in consulting role. Default rates have fallen and patient and staff morale has improved substantially. Apart from an underestimate of receptionist and a small increase in technician hours, these changes have been achieved within the predicted small revenue cost.

Appointments and Schedules↗
PubMed1988

Comparison of BACTEC 13A medium and Du Pont isolator for detection of mycobacteremia.

BACTEC 13A medium (Johnston Laboratories, Towson, Md.) was compared with Isolator (Du Pont Co., Wilmington, Del.) concentrate for sensitivity, speed, and technical ease of isolation of mycobacteria from paired patient blood samples. Of 72 positive cultures, 63 were positive by both systems. Five positive cultures were detected by BACTEC 13A medium alone, and four were detected by Isolator alone. The median numbers of days to positivity were 12 for BACTEC 13A medium and 14 for Isolator concentrate. BACTEC 13A medium has an advantage over the Isolator in requiring less laboratory manipulation of the specimen but has the disadvantages of not providing isolated colonies or quantitation of organisms. Some technical problems with contamination in both systems are also discussed.

Colony Count, Microbial↗
PubMed1988

Preradiation high-dose intravenous methotrexate with leucovorin rescue for untreated primary childhood brain tumors.

Although high-dose intravenous (IV) methotrexate (MTX) with leucovorin rescue (HDMTX) is effective for certain recurrent primary brain tumors, concern for inducing leukoencephalopathy has restrained its use as adjuvant therapy following therapeutic brain irradiation (RT). We have conducted a phase I to II clinical trial using four biweekly courses of HDMTX (8 g/m2) in a neoadjuvant setting in ten patients with newly diagnosed high-risk pediatric primary brain tumors. Four patients experienced an objective response after two to four courses of HDMTX alone (medulloblastoma, one; pineoblastoma, one; malignant cerebral astrocytoma, two). All ten patients subsequently received a course of therapeutic RT, and in seven cases, adjuvant chemotherapy with other agents. One patient acquired an acute transient encephalopathy before RT that completely resolved, and another developed a seizure disorder following RT associated with white matter abnormalities on a magnetic resonance imaging (MRI) scan. Five patients have survived a minimum of 33+ months, and four remain in continuous remission. The acute and delayed neurotoxicity of neoadjuvant HDMTX is acceptable, and we favor further use of this neoadjuvant approach in the context of a phase III trial.

Adolescent↗
PubMed1988

MR of cranial and spinal meningeal carcinomatosis: comparison with CT and myelography.

Thirty-nine patients with histologically proved primary neoplasms, focal neurologic deficits, and positive CSF cytology were evaluated by enhanced cranial CT and MR, or complete myelography and MR of the spine. Intracranial abnormalities were noted on CT in 56% of cases and included abnormal enhancement of subarachnoid space and ventricular walls, ventricular dilatation, obliteration of cortical sulci, and enhancing nodules within the subarachnoid cisterns and lumen of the lateral ventricles. Although the degree of ventricular enlargement and intraventricular tumor deposits were equally well seen on CT and MR, involvement of ventricular walls, tentorium, subarachnoid cisterns, or subarachnoid space interpreted as abnormal enhancement on CT was not readily appreciated on routine T1- and T2-weighted spin-echo sequences. Forty-four percent of CT and 65% of MR studies were interpreted as normal. There was high correlation of myelographic findings with clinical diagnosis, and no false-negative myelograms. Nodular filling defects within the subarachnoid space, thickening and crowding of roots of the cauda equina, irregularity of individual roots, and scalloping of the subarachnoid membranes were demonstrated. MR was rather insensitive in detecting these changes, revealing a definite abnormality of the subarachnoid space in 27% of patients with positive myelograms. False-negative interpretation of MR of the spine was made in 44% of cases.

Brain Neoplasms↗
PubMed1988

Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats. Possible role for macrophages in pathogenesis of IDDM.

Use of monoclonal antibodies directed against rat macrophages and serial pancreatic biopsy in the prediabetic period have enabled us to document the involvement of macrophages in the pancreatic events leading to onset of diabetes in the spontaneously diabetic BB/E rat. A few weeks before onset of disease, there is marked recruitment and accumulation of ED1+ macrophages at periductal and perivascular locations adjacent to noninfiltrated islets. These recruited cells, distinct from the resident ED2+ tissue macrophages, then infiltrate the islets. Infiltration of the pancreas by ED1+ macrophages is therefore a very early event in the prediabetic period and suggests a possible role for macrophages in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) in this animal model.

Animals↗
PubMed1988

Transplantation in Manitoba.

1. Renal transplantation can be performed at small regional centers as successfully as at large centers. 2. Immunosuppression should be individualized for the patient thereby avoiding the use of costly and often clinically complicated immunosuppressive regimens. 3. Small centers need to participate in large regional pools in order to give highly presensitized patients a reasonable chance of successful transplantation. 4. Long-term patient compliance is a major problem and requires careful surveillance of patients' adherence to their prescribed therapy. Frequent follow-up also allows for the detection of late rejection episodes which can often be reversed.

Graft Survival↗
PubMed1987

Anthraflavic acid is a potent and specific inhibitor of cytochrome P-448 activity.

Consideration of the computer-optimised dimensions of anthraflavic acid indicates that it is essentially a planar molecule with a large area/depth ratio, that would preferentially interact with the polycyclic aromatic hydrocarbon-induced family of cytochrome P-450 proteins (cytochromes P-448). Anthraflavic acid was a potent inhibitor of the O-deethylations of ethoxycoumarin and ethoxyresorufin, both catalysed primarily by cytochromes P-448, in Arochlor-1254-induced hepatic microsomes. Similarly anthraflavic acid markedly inhibited the mutagenicity of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-I) in the Ames test. In contrast, it has no effect on the dealkylation of pentoxyresorufin, a reaction catalysed primarily by the phenobarbital-induced cytochromes P-450, and NADPH-dependent reduction of cytochrome c. It is concluded that anthraflavic acid is a potent and specific inhibitor of cytochrome P-448 activity.

Animals↗
PubMed1987

Pertussis toxin triggers rapid second messenger production in human T lymphocytes.

Pertussis toxin (PT) is a known mitogen for T lymphocytes. The mechanism by which the toxin stimulates proliferation has remained obscure and paradoxical because, in some types of cells, the toxin also inhibits growth factor-mediated signal transduction. It has previously been shown that the adenosine-diphosphate ribosyltransferase activity of the toxin is not required to produce the mitogenic effect. A biochemical explanation for the mitogenic activity has therefore remained obscure. We investigated the biochemical basis for the mitogenic activity of PT by using the transformed human T cell line, Jurkat. PT stimulated a rapid rise in cytosolic-free [Ca2+] from both intra- and extracellular sources. This was associated with an increase in the cellular diacylglycerol and inositol triphosphate levels with a concomitant decrease in the levels of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate. The half-maximal effective dose of PT was 1.7 nM. PT also stimulated the production of interleukin 2. Only the holotoxin or B-oligomer (the presumptive membrane-binding subunit) was capable of stimulating an increase in [Ca2+] in these cells. This activity of PT mimicked that of some anti-T3-T cell antigen receptor complex monoclonal antibodies that also stimulate increases in the second messengers, diacylglycerol and Ca2+. The effects of PT and anti-T3 complex antibody were identical and not additive in Jurkat cells, suggesting that both agents were activating the same signal transduction pathway. These data provide a mechanistic explanation for the mitogenic effects of PT and suggest that the toxin may be interacting with a specific receptor in the T lymphocyte plasma membrane.

Antigens, Surface↗
PubMed1987

Confirmation of clorsulon residues in cattle kidney by capillary gas chromatography-negative-ion chemical-ionization mass spectrometry.

A confirmatory assay for residues of the anthelmintic agent clorsulon [4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide] in cattle kidney tissue has been developed. The assay involves isolation of a drug-containing fraction by solvent extraction, methylation of the analyte, and fused-silica capillary column gas chromatography-negative-ion chemical-ionization mass spectrometry of the pentamethyl derivative of clorsulon. The intensities of four negative ions [m/z 406 and 408 (trichloro species) and m/z 413 and 415 (dichloro species)] are monitored. Confirmation of the presence of drug in an analyte requires that all four ions appear at the appropriate retention time with their intensity ratios within 10-15% of those arising from analysis of the reference standard, methylated clorsulon; the lower limit of detection is 3 ppb. Quantification of the drug is based on the intensity of the m/z 406 ion. Identification and quantification of residues by the gas chromatographic-mass spectrometric assay gave results in good agreement with those obtained with an electron-capture gas chromatographic assay.

Animals↗
PubMed1987

Tissue identification and histologic study of six lung specimens from Egyptian mummies.

Twenty-eight specimens obtained either from organ bundles in the body cavities of intact mummies, from damaged mummies, or from isolated canopic jars were examined for tissue identification and histopathologic study. The methods of rehydration and fixation were optimized by application to 40 dehydrated modern samples before studies of mummified tissue were undertaken. The tissue of origin could be definitely identified in 24 of the 28 specimens. Even small fragments obtained from isolated canopic jars proved suitable for histologic study. Six lung specimens were selected for more detailed study. All six showed focal deposition of anthracotic pigment. Electron diffraction and electron microprobe analysis of one of the small, polarizable crystals associated with the anthracosis indicated a mineral content of silica, aluminum, and iron. Two specimens showed focal areas of calcification consistent with old mycobacterial disease. Other histopathologic findings included evidence of pulmonary edema, emphysema, and pneumonia.

Egypt↗
PubMed1987

PCNU and recurrent childhood brain tumors.

PCNU, the latest nitrosourea analogue to be subjected to clinical trials, held promise as a superior chemotherapy agent for brain tumors because of more favorable biochemical and cytotoxic characteristics in laboratory studies. Thirty-nine children with a variety of recurrent primary CNS tumors, all of whom had evaluable disease, participated in a phase II PCNU trial. Their mean age was 9.7 (3-20) years. PCNU was administered as a 2 hour intravenous infusion in one of 2 dose schedules at 6-7 week intervals; 100-125 mg/m2 for minimally treated patients and 70-90 mg/m2 for heavily treated patients. Response was assessed after 2 courses of chemotherapy after attempting to taper the steroid dose. The overall objective response rate was 18% (7/39) for a mean of 5.9 months (2+ -12). Only partial responses were observed. Disease-specific responses rates were: brainstem glioma--18% (3/17); cerebral glioma--27% (3/12); ependymoma--1/1; and primitive neuroectodermal tumors--(0/9) including 5 medulloblastomas, 2 pineoblastomas and 3 cerebral primitive neuroectodermal tumors. Toxicity was primarily hematologic and clinically significant thrombocytopenia (less than 50,000 mm3) was encountered in 30/38 (79%) patient trials. Modest activity of PCNU in recurrent childhood gliomas is confirmed. Our response rates, using objective CT criteria, are somewhat lower than those reported for BCNU and CCNU. Because of comparable hematologic toxicity and efficacy, intravenous PCNU does not appear to offer a clinical advantage to existing nitrosoureas for children with recurrent brain tumors using a 2 hour intravenous infusion schedule.

Adolescent↗
PubMed1987

Comparison of the short-term hepatic effects of orally administered citral in Long Evans hooded and Wistar albino rats.

The short-term effects of citral on the liver have been studied in two strains of rat. Hepatomegaly was accompanied in citral-treated rats by an altered distribution of lipid and glycogen in the liver and peroxisome proliferation occurred in a manner reminiscent of that associated with some hypolipidaemic compounds. Specific biochemical markers supported the morphological changes in the peroxisomes. Cyanide-insensitive palmitoyl CoA oxidation showed, at the maximum, fourfold and threefold inductions in Wistar albino and Long Evans hooded rats, respectively. In addition, induction of cytochrome P-450 levels was greater in the Long Evans than in the Wistar rats, the maximal increases recorded being 81 and 27% respectively. A peroxisome-associated polypeptide of molecular weight 80,000 daltons (PPA-80) was induced, especially in Long Evans rats. No alterations in plasma triglycerides or total cholesterol were detected. The differential induction of the mixed-function oxidase system and the differential proliferation of peroxisomes in these two strains of rat suggest that citral may be metabolized differently in the two strains. The study indicates that peroxisomal and possibly also mitochondrial changes are involved in the action of citral on lipid metabolism.

Acyclic Monoterpenes↗
PubMed1987

Comparison of the metabolism of sulfated and unsulfated heptadecapeptide gastrin in humans.

The metabolism of synthetic human sulfated heptadecapeptide gastrin (G-17) was studied in normal human volunteers. Plasma concentrations were measured by radioimmunoassay using antibodies specific for intact G-17, and for the C- and N- terminus of G-17, during and after infusion of both sulfated and unsulfated G-17. With all three antibodies, plasma concentrations at a steady state were higher during infusion of sulfated compared with unsulfated G-17. In addition, the half-life in plasma measured by the three antibodies was two to five times higher for sulfated G-17 compared with unsulfated G-17. The half-life measured by N-terminal-specific antibodies was greater than that with antibodies specific for C-terminal or intact G-17. The difference was accounted for by the production during infusion of N-terminal fragments of relatively long half-life. The pattern of fragments generated during infusion of sulfated G-17 resembled that during unsulfated G-17 infusion, but there was no evidence of desulfation in the systemic circulation. The results indicate that in humans, sulfation protects G-17 from metabolism.

Adult↗
PubMed1987

Effect of tryptamine on the mutagenic activity of 2-amino-3-methylimidazo(4,5-f) quinoline (IQ) and related azaarenes in the Ames test.

The bioactivation of the azaarenes 2-amino-3-methylimidazo(4,5-f) quinoline (IQ), 2-amino-3,4-dimethylimidazo(4,5-f) quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo(4,5-f) quinoxaline (MeIQx) to mutagens by hepatic S9 preparations derived from Aroclor-pretreated Wistar rats was inhibited by tryptamine (2-50 microM). However, with similar preparations derived from Sprague-Dawley rats, bioactivation of IQ and MeIQx was less markedly inhibited by tryptamine while metabolic activation of MeIQ was enhanced. In the absence of cytosol, activation of IQ by microsomal preparations of both rat strains was inhibited by tryptamine. Cytosolic fractions from both rat strains were incapable of activation of IQ per se but increased the mutagenicity of the microsomal metabolite(s). This potentiation of the mutagenic activity by cytosol derived from Wistar rats was also inhibited by tryptamine whereas no significant inhibition was observed with cytosolic preparations from Sprague-Dawley rats. There appear to be two alternative pathways of microsomal metabolism of IQ: a tryptamine-sensitive pathway, probably involving the formation of the N-hydroxymetabolite; and a tryptamine-insensitive pathway producing weakly mutagenic or non-mutagenic metabolites which are activated to a potent mutagen by the cytosol. The tryptamine-insensitive pathway appears to be the major route of activation of the azaarenes in microsomal preparations from Sprague-Dawley rats and the principal activation route for MeIQ in both rat strains.

Animals↗