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Biomedical subjects

J Rogers

Publications and source records attributed to J Rogers.

At least 271 records · Page 15Linked to original sources
PubMed1993

Nuclear DNA polymorphisms in a wild population of yellow baboons (Papio hamadryas cynocephalus) from Mikumi National Park, Tanzania.

Yellow baboons (Papio hamadryas cynocephalus) from Mikumi National Park, Tanzania were studied for polymorphisms in nuclear DNA. The study population consists of four social groups that inhabit overlapping home ranges and exchange males. As a result, these groups are considered to be members of a single interbreeding population. Human DNA clones were used as probes to screen five loci (AT3, REN, HEXB, VIM, and APOB) for restriction fragment length polymorphisms (RFLP). A total of 14 polymorphisms, at least one at each locus, was detected in a panel of 27 baboons tested using six restriction enzymes for each locus. Eleven of these RFLP systems have average heterozygosity values greater than 0.40. This initial screening demonstrates that human DNA clones can be used to detect significant numbers of informative DNA polymorphisms in single-copy nuclear genes of this species and suggests that the average proportion of nucleotides polymorphic across nuclear loci in this population may be between 1.0% and 1.3%.

Animals↗
PubMed1993

New technique to measure mucosal metabolism and its use to map substrate utilization in the healthy human large bowel.

A new method of assessing substrate utilization in gastrointestinal mucosal specimens is described. Small human endoscopic biopsy specimens with wet weights ranging between 1.4 and 12.2 mg were used to quantify the oxidation of three metabolic substrates, glucose, glutamine and butyrate, through to carbon dioxide over a 2-h period. The technique proved to be reproducible and capable of distinguishing variations in mucosal metabolism between individuals (P < 0.0001 for each substrate). Results were similar to those obtained previously using human and rat colonocytes. To characterize the metabolism of the healthy large bowel, specimens were obtained from five regions in 15 patients who had a normal colonoscopic examination. The results show that butyrate is the preferred fuel source of large bowel mucosa, followed by glutamine, then glucose (P < 0.01). There was no significant regional variation in utilization of the three substrates between the five regions; with respect to glutamine, this is contrary to previous findings.

Adult↗
PubMed1993

Association cortex, cerebellum, and serum concentrations of C1q and factor B in Alzheimer's disease.

Concentrations of C1q, the first subcomponent of the classical complement pathway, were assayed by Western blot analysis of sera and brain homogenates from Alzheimer's disease (AD) and nondemented (ND) control patients. Immunoreactive serum C1q concentrations did not differ in the two groups, whereas AD superior frontal gyrus exhibited nearly 4-fold more immunoreactive C1q than ND superior frontal gyrus. Cerebellar C1q concentrations were significantly lower than those in superior frontal gyrus, and ND cerebellar C1q was lowest of all. Parallel immunohistochemical experiments showed a linkage between the extent of beta-amyloid immunoreactivity or AD pathology in a structure and the extent of C1q immunoreactivity. These data support and extend the hypothesis that complement mediated processes are related to beta-amyloid deposition and may be involved in the pathogenesis of AD.

Adult↗
PubMed1993

The role of pet dogs in casual conversations of elderly adults.

Casual conversations were recorded as elderly persons routinely walked their dogs through a familiar mobile home park in the United States. Control observations included walks without dogs by owners and non-owners of dogs. All owners talked to and about their dogs. Transcribed conversations indicated that dogs were a primary focus of conversation. A majority of sentences to dogs were imperatives; the owners were instructing the dogs. Dog owners frequently included dogs' names or nicknames in their sentences when they spoke to the dogs and made reference to the dogs' wishes or needs. Speaking to dogs was also associated with frequent repetition of sentences. Passersby talked to the owners about their dogs whether or not the dogs were present. When dog owners spoke with other people, their conversations often concerned activities that were occurring in the present, whereas conversations of non-owners focused on stories about past events. Dog owners reported taking twice as many daily walks as non-owners. Dog owners also reported significantly less dissatisfaction with their social, physical and emotional states.

Aged↗
PubMed1993

The impact of histological review on clinical management of testicular cancer.

Accurate histological diagnosis and staging are critically important in determining the optimal management of patients with testicular cancer. We have assessed the importance of histological review of "outside" pathology reports from 87 patients referred to the Urological Cancer Research Unit. In 28 patients (32%), the reviewed pathology report differed from the outside report. In 10 of these patients (11%), the pathology review resulted in a change of treatment or prognosis from that which would have obtained in the absence of such histological review. Pathology review at a major cancer centre with a subspecialist interest in tumour pathology and a large experience in the management of germ cell malignancy is an essential first step in the treatment of testicular cancer.

Adult↗
PubMed1993

Oral cyclophosphamide for the management of hormone-refractory prostate cancer.

Thirty patients with hormone-refractory prostate cancer were treated with cycles of oral cyclophosphamide (100 mg/m2/day for 14 days, with a 14-day gap). Eighteen patients had a significant improvement in symptoms of advanced disease, 6 had objective partial remissions and 13 had stabilisation of disease (criteria of National Prostatic Cancer Project). The median survival from the time of diagnosis was 33.3 months, and from the commencement of cyclophosphamide 12.7 months. The treatment was well tolerated. oral cyclophosphamide is active in the treatment of advanced hormone-refractory prostate cancer and yields symptomatic and objective remissions without undue side effects. This observation requires validation, with further testing of its impact on survival in randomised clinical trials.

Administration, Oral↗
PubMed1993

Effect of catecholamines on the ventricular myocyte action potential in raised extracellular potassium.

We describe the relationship between catecholamines and raised extracellular potassium ([K+]o) on action potential parameters and calcium currents in isolated ventricular myocytes of the guinea-pig and relate these findings to the problem of understanding how the heart is protected from exercise-induced hyperkalaemia ([K+]a up to 8.5 mM). Action potential duration (APD90), amplitude and upstroke velocity were recorded in stimulated (2Hz) guinea-pig ventricular myocytes using whole-cell patch electrode recordings (37 degrees C). Cells were superfused with normal K+ Tyrode and with raised K+ Tyrode in the presence of either noradrenaline, adrenaline or raised calcium. Inward calcium current was measured using voltage clamp. Raised K+ (8, 12, 16 mM K+ Tyrode) caused a significant (P < 0.01) depolarisation, shortened the APD90 and decreased the action potential amplitude and upstroke velocity. In raised K+ Tyrode addition of noradrenaline (0.08-0.1 microM) or adrenaline (0.1-0.2 microM) increased action potential amplitude (P < 0.01), APD90 (P < 0.01) and upstroke velocity (P < 0.01) (measured only in 16 mM K+ Tyrode). In 12 mM K+ Tyrode raised Ca2+ (5-6 mM) increased action potential amplitude (P < 0.05) and shortened APD90 (P < 0.05). Addition of NA (0.08-0.1 microM) increased the inward Ca2+ current. All effects were fully reversible. In raised [K+]o increases in catecholamines and [Ca2+]o cause changes in action potential parameters that would be expected to maintain propagation of the cardiac action potential in the whole heart. Thus, in the ventricular myocyte the increase in conductance to Ca2+ caused by catecholamines may be one factor that is important in minimising the potentially adverse effects of exercise-induced hyperkalaemia.

Action Potentials↗
PubMed1993

Cephalic phase of colonic pressure response to food.

A cephalic phase of colonic pressure response to food was sought in five normal subjects (mean age (22.6) years, 22-24), studied on six separate occasions by recording intraluminal pressures in the unprepared sigmoid colon. Gastric acid secretion was measured simultaneously by continuous aspiration through a nasogastric tube. After a 60 minute basal period, one of five 30 minute food related cephalic stimuli, or a control stimulus was given in random order; records were continued for a further 120 minutes. The cephalic stimuli were: food discussion, sight and smell of food without taste, smell of food without sight or taste, sight of food without smell or taste, and modified sham feeding; the control stimulus was a discussion of neutral topics. Colonic pressures were expressed as study segment activity index (area under curve, mm Hg.min) derived by fully automated computer analysis. Gastric acid output was expressed as mmol/30 min. Food discussion significantly (p < 0.02, Wilcoxon's rank sum test) increased colonic pressure activity compared with control or basal activity. Smell of food without sight or taste also significantly (p < 0.03) increased the colonic pressure activity compared with control and basal periods. Sham feeding and sight and smell of food without taste significantly (p < 0.02 and p < 0.03) increased colonic pressures compared with control but not basal activity. The increase in colonic activity after sight of food without smell or taste was not significantly different from control or basal activity (p = 0.44 and p = 0.34). Food discussion was the strongest colonic stimulus tested. Food discussion and sham feeding significantly (p<0.02) stimulated gastric acid output above control and basal values. Sight and smell of food without taste significantly (p<0.02) increased acid output above basal. Smell of food without sight or taste and sight of food without smell or taste did not significantly (p=0.06, p=0.34) increase acid output. In contrast with the effect on colonic pressures, sham feeding was the best stimulus of acid output. Increased colonic pressure activity after food discussion correlated significantly (r=0.45, p<0.02) with gastric acid output. There was no correlation (r=-0.1, p>0.5) between colonic pressure activity and gastric acid output in the control study. These data show that there is a cephalic phase of the colonic response to food.

Adult↗
PubMed1993

Clinical trial of indomethacin in Alzheimer's disease.

In a 6-month, double-blind, placebo-controlled study, 100 to 150 mg/d indomethacin appeared to protect mild to moderately impaired Alzheimer's disease patients from the degree of cognitive decline exhibited by a well-matched, placebo-treated group. Over a battery of cognitive tests, indomethacin patients improved 1.3% (+/- 1.8%), whereas placebo patients declined 8.4% (+/- 2.3%)--a significant difference (p < 0.003). Caveats include adverse reactions to indomethacin and the limited scale of the trial.

Aged↗
PubMed1992

Complement activation by beta-amyloid in Alzheimer disease.

Alzheimer disease (AD) is characterized by excessive deposition of the beta-amyloid peptide (beta-AP) in the central nervous system. Although several lines of evidence suggest that beta-AP is neurotoxic, a mechanism for beta-AP toxicity in AD brain remains unclear. In this paper we provide both direct in vitro evidence that beta-AP can bind and activate the classical complement cytolytic pathway in the absence of antibody and indirect in situ evidence that such actions occur in the AD brain in association with areas of AD pathology.

Alzheimer Disease↗
PubMed1992

Interfacial catalysis by phospholipase A2: the rate-limiting step for enzymatic turnover.

The kinetics of the phospholipase A2-catalyzed hydrolysis of bilayer vesicles and mixed micelles of several oxyglycero and thioglycero analogues of phospholipids have been studied. The results with vesicles show that, depending on the source of the enzyme, the rates of hydrolysis of the oxy-containing long-chain phosphatidylmethanols are 2.5- to 28-fold higher compared to the rates of hydrolysis of the analogous thio substrates. The oxygen to sulfur substitution does not significantly alter the affinities of the enzymes for the reaction products or calcium. Since it is unlikely that sulfur substitution changes the rate constants for the formation and dissociation of the enzyme-product complex by the same factor, the element effects seen in the rates of hydrolysis of the oxy- and thioester phospholipids in vesicles are primarily due to a change in the rate constant for the chemical step of the catalytic turnover cycle. For bovine pancreatic phospholipase A2, various mutants with lower catalytic activity were used to show that the value of the element effect does not increase in the mutants. These results establish that, for the pancreatic phospholipase A2, the element effect is fully expressed, and the chemical step is fully rate-limiting for both oxyglycero and thioglycero phospholipids in vesicles. It was found that the element effect decreases from 7 to 1 when long-chain phosphatidylmethanols are present in micelles of a neutral diluent. This result suggests that the chemical step is not rate-limiting during the hydrolysis of these mixed micelle substrates.

Animals↗
PubMed1992

Basis for the anomalous effect of competitive inhibitors on the kinetics of hydrolysis of short-chain phosphatidylcholines by phospholipase A2.

The effect of four specific competitive inhibitors on the kinetics of hydrolysis of short-chain diacyl-sn-glycero-3-phosphocholines below their critical micelle concentrations was examined. The kinetics of hydrolysis of short-chain substrates dispersed as solitary monomers were generally consistent with the classical Michaelis-Menten formalism; i.e., hydrolysis began without any latency period, the steady-state rate was observed at higher substrate concentrations, the steady-state initial rate showed a linear dependence on the enzyme concentration, and the hyperbolic dependence of the initial rate on the substrate concentration could be described in terms of KM and Vmax parameters. The competitive nature of the inhibitors used in this study has been established by a variety of techniques, and the equilibrium dissociation constants for the inhibitors bound to the enzyme were measured by the protection method [Jain et al. (1991) Biochemistry 30, 7306-7317]. The kinetics of hydrolysis in the presence of competitive inhibitors could be described by a single dissociation constant. However, the value of the dissociation constant obtained under the kinetic conditions was comparable to that obtained by the protection method for the inhibitor-enzyme complex bound to a neutral diluent, rather than to the value of the dissociation constant obtained with solitary monomeric inhibitors and the enzyme in the aqueous phase. Spectroscopic methods showed that the effectively lower dissociation constant of an inhibitor bound to PLA2 at the interface is due to the stabilization of the enzyme-inhibitor complex by interaction with other amphiphiles present in the reaction mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1992

Augmentation of in vivo cytotoxic T lymphocyte activity and reduction of tumor growth by large multivalent immunogen.

Class I alloantigen incorporated into cell-size supported membranes provides an effective stimulus for in vitro stimulation of CTL responses. When alloantigen-bearing cell-size (5 microns) microspheres, termed large multivalent immunogen (LMI), were administered in vivo, no primary cytotoxic response to the Ag could be detected. However, coadministration of LMI and allogeneic tumor stimulator cells resulted in substantial augmentation of the resulting CTL response, compared with that obtained from mice that received just stimulator cells. Responses were augmented only when the same alloantigen was present on the LMI and on the stimulator cells, and the effector cells remained specific for the cognate alloantigen-bearing targets. The physical form of the alloantigen was critical for augmentation; alloantigen in liposomes had no effect on response levels. Tumor cell Ag in the form of purified plasma membrane vesicles can also be incorporated onto the surface of cell-size microspheres. As with allogeneic responses, tumor Ag on LMI specifically augmented the in vivo CTL activity generated in response to irradiated tumor cells in syngeneic mice. Administration of Ag-bearing LMI to mice inoculated i.p. with live P815, EL4, or RDM4 tumor cells resulted in a significant reduction in growth of the tumors in their syngeneic hosts. Similarly, LMI treatment significantly reduced growth of P815 as a solid s.c. tumor. LMI-mediated growth reduction occurred only when plasma membrane Ag from the cognate tumor was used to prepare the LMI, and Ag in the form of free plasma membrane vesicles was not effective. Although Ag has been used to manipulate in vivo humoral and Th responses, this has proven to be much more difficult for CTL responses. The ability of Ag-bearing LMI to affect significantly the in vivo levels of cytolytic response and to reduce syngeneic tumor growth has potential for application to tumor immunotherapy and, possibly, treatment of other diseases in which CTL can provide a protective effect.

Adjuvants, Immunologic↗
PubMed1992

Time out.

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Efficiency↗
PubMed1992

Riding the dinosaur.

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Medical Staff, Hospital↗
PubMed1992

Raw deal.

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Continuity of Patient Care↗