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Biomedical subjects

C L Allen

Publications and source records attributed to C L Allen.

At least 19 recordsLinked to original sources
PubMed2001

Developmental and morphological regulation of clathrin-mediated endocytosis in Trypanosoma brucei.

Essentially all macromolecular communication between Trypanosoma brucei and its host is confined to vesicular trafficking events occurring at or around the flagellar pocket. The vertebrate stage bloodstream form trypomastigote exhibits an extremely high rate of endocytosis required for nutrient uptake and probably also evasion of the host immune system. However, the rate of endocytosis is very low in the procyclic vector parasite, indicating that endocytosis is subject to a marked level of developmental regulation. Previous ultrastructural studies and crude biochemical fractionations have indicated the presence of coated pits and vesicles that are analogous to clathrin coats in the bloodstream form, but not in the procyclic. However, a definitive description of the components of this coat and its molecular function in T. brucei has remained elusive. We describe the molecular cloning and initial characterisation of components of the T. brucei endocytic coats: clathrin heavy chain (TbCLH) and a beta-adaptin (TbAPbeta1). TbCLH is markedly upregulated in the bloodstream form compared with the procyclic, whereas TbAPbeta1 is subject to more limited developmental regulation. We generated antisera against both proteins and show that the clathrin coat is tightly associated with the flagellar pocket in both major life stages. However, in bloodstream parasites TbCLH is also extensively distributed throughout the posterior end of the cell on numerous large vesicular and tubular structures. By cryo-immuno EM, clathrin is localised to collecting tubules at the flagellar pocket and is also associated with the trans-Golgi network. These EM data confirm that the electron dense coats reported on trypanosome vesicles and tubules contain clathrin. The TbAPbeta1 exhibits an atypical distribution relative to previously characterised adaptins, associating not only with the trans-Golgi but also with other tubular-vesicular elements. Localisation of TbAPbeta1 is also subject to developmental regulation. These data describe major endocytic coat proteins in T. brucei for the first time, and indicate stage-specific expression of the clathrin heavy chain. Modulation of clathrin expression is likely to be an important factor in the developmental regulation of endocytosis and recycling in the African trypanosome.

Adaptor Protein Complex beta Subunits↗
PubMed1999

Fetal behavior in diabetic and nondiabetic pregnant women: An exploratory study.

To characterize differential behavior and the relationship between maternal blood glucose levels and behavior in fetuses of diabetic (n = 10) and nondiabetic (n = 20) women at 33 and 36 weeks gestational age (GA), spontaneous changes in fetal heart rate (FHR), body and breathing movements, and vibroacoustic stimulus elicited (3 stimulus/3 no-stimulus control trials) FHR changes and body movements were compared. Measures of maternal blood glucose levels were obtained immediately following testing; measures varied within normal range. Spontaneous behaviors showed no differences between groups and no relationship to maternal blood glucose levels. Sensory stimulation elicited similar average peak FHR accelerations (M = 17. 1/20.0 BPM) and average movement scores (2.0/2.6) across groups. In the diabetic group at 33 weeks GA, the nature of the FHR change over time, showed more varied patterns of response, a shorter latency to peak acceleration, was less organized, and less mature; as average maternal blood glucose levels increased, elicited body movements decreased. These findings suggest immaturity and differential functional development of sensory-motor response systems in fetuses of diabetic mothers.

Arousal↗
PubMed1990

A prospective, double-blind study of metoclopramide hydrochloride for the control of migraine in the emergency department.

STUDY OBJECTIVE: To determine the effectiveness of IV metoclopramide as sole therapy for relieving the pain of acute migraine in the emergency department. DESIGN: Prospective study. Fifty patients were divided randomly into subjects and placebo controls with blinding of the treating physician and the patient. PARTICIPANTS: Patients presenting to the ED with migraine requiring parenteral treatment. INTERVENTIONS: Subjects received 10 mg IV metoclopramide and controls received IV normal saline; patient assessment of relief was followed by means of a numerical scale. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of subjects compared with 19% of controls had effective pain relief within one hour (P less than .001). Subjects achieved mean relief scores of 2.46 compared with 1.69 for controls (P less than .02). No significant side effects were observed. CONCLUSION: IV metoclopramide as a single agent is effective and safe therapy for migraine in the ED.

Adult↗
PubMed1988

Regulation of the procoagulant activity within the bronchoalveolar compartment of normal human lung.

The nature of the procoagulant activity of normal bronchoalveolar fluid was examined both qualitatively and quantitatively. Unconcentrated, cell-free lavage freshly obtained from normal volunteers clotted normal plasma in a mean of 84 +/- 20 s. The procoagulant activity was initiated by Factor VII-tissue factor complexes as judged by differential activity in various plasmas genetically deficient in single clotting factors, by neutralization of the procoagulant activity with antibodies to either Factor VII or tissue factor, and by a Factor X activation assay. Preincubation of the lavage with calcium was required to demonstrate Factor VII activity in unconcentrated samples. The cell-free fluid contained about 8,500 thromboplastin units/mg protein, equivalent to a third of the thromboplastin standard and indicating high amounts of cofactor. Quantitation of Factor VII was estimated by functional analysis in coagulation and amidolytic assays with reference to dilutions of normal plasma of known Factor VII concentration. When lavage and diluted plasma were adjusted to yield equivalent amidolytic activities, the average ratio of the Factor VII-clotting activity of the alveolar fluid relative to plasma Factor VII was 19 +/- 7, suggesting the presence of Factor VIIa in lavage. In contrast to previous reports with serum or activated plasma, immunoblots of concentrated lavage revealed only single-chain Factor VII, and 125I-Factor VII added to the fluid was not converted to 125I-Factor VIIa, suggesting a unique control mechanism in the lung compartment which differs from plasma. When equivalent Factor VII amidolytic activities in diluted plasma and cell-free lavage were compared, the rates of Factor Xa formation were very similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors↗
PubMed1986

Abnormalities in pathways of alveolar fibrin turnover among patients with interstitial lung disease.

Fibrin deposition is prominent in the histopathologic features of chronic interstitial lung disease. Human alveolar macrophages can potentially modulate this process because normal macrophages synthesize and express the initial enzymes of both coagulation and fibrinolytic pathways. In the present study, we examined the cell-associated procoagulant activity of macrophages lavaged from patients with sarcoidosis (n = 14) or idiopathic pulmonary fibrosis (n = 13) and compared the enzyme activities with that of a group of normal volunteers (n = 16). Cells from sarcoid patients had a mean (+/- 1 SD) tissue factor activity of 1,491 +/- 2,160 units/5 X 10(5) cells, as compared with a mean of 480 units (range, 140 to 1,000 units) for normal control subjects. The same cells had a mean plasma Factor VII equivalent of 4.7 ng/10(6) cells, as compared with 0.81 ng/10(6) cells (range, 0.2 to 2.0 ng) for the normal control subjects. The enhanced activity correlated with disease activity as judged by radiographic stage: only patients with Stage II or Stage III disease had consistently elevated procoagulant activity. There was no correlation of procoagulant activity with the percentage of lymphocytes in the alveolar fluid. Cells from patients with idiopathic pulmonary fibrosis also had increased tissue factor (mean, 2,980 +/- 2,619 units) but less consistently elevated Factor VII. There was considerable variation in both procoagulant activity and cell differentials between lavage sites in 10 patients in whom 2 separate lobes were studied concurrently. In addition, we examined the plasminogen activator (PA) activities of lavaged cells and concentrated alveolar fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Human alveolar macrophages synthesize factor VII in vitro. Possible role in interstitial lung disease.

Both fibrin and tissue macrophages are prominent in the histopathology of chronic inflammatory pulmonary disease. We therefore examined the procoagulant activity of freshly lavaged human alveolar macrophages in vitro. Intact macrophages (5 X 10(5) cells) from 13 healthy volunteers promoted clotting of whole plasma in a mean of 65 s. Macrophage procoagulant activity was at least partially independent of exogenous Factor VII as judged by a mean clotting time of 99 s in Factor VII-deficient plasma and by neutralization of procoagulant activity by an antibody to Factor VII. Immunoprecipitation of extracts of macrophages metabolically labeled with [35S]methionine by Factor VII antibody and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a labeled protein consistent in size with the known molecular weight of blood Factor VII, 48,000. The addition of 50 micrograms of unlabeled, purified Factor VII blocked recovery of the 48,000-mol wt protein. In addition, supernatants of cultured macrophages from six normal volunteers had Factor X-activating activity that was suppressed an average of 71% after culture in the presence of 50 microM coumadin or entirely by the Factor VII antibody indicating that Factor VII synthesized by the cell was biologically active. Endotoxin in vitro induced increases in cellular tissue factor but had no consistent effect on macrophage Factor VII activity. We also examined the tissue factor and Factor VII activities of freshly lavaged alveolar cells from nine subjects with clinical and/or histologic evidence of sarcoidosis. Four of the nine subjects expressed increased tissue factor and seven of nine had increased Factor VII activity over the normal range (P less than 0.01). We estimate the mean Factor VII associated with the cells of sarcoid patients to be 4.7 ng/10(6) cells (range 0.4-20) as compared to a mean of 0.74 ng/10(6) cells (range 0.2-2) for that of normal subjects. Along with previous data showing synthesis of plasminogen activator, these findings indicate that human alveolar macrophages normally synthesize and express measurable amounts of the initial enzymes of proteolytic reactions regulating both fibrin deposition and fibrin resorption. Abnormalities in Factor VII activity in a small group of patients with sarcoidosis raise the possibility that modulation of fibrin turnover by macrophages may contribute to the pathology of this and perhaps other interstitial lung diseases.

Blood Coagulation↗
PubMed1983

Effect of cold exposure on various sites of core temperature measurements.

Rectal, esophageal, auditory canal, gastrointestinal tract, and sublingual temperature were recorded on five young Caucasian males who, in an environment of -32 degrees C and 11-km/h wind, sat during one 90-min exposure and walked on a treadmill at 2.9 km/h during another. The clothing permitted cooling of their torsos while giving adequate protection to their extremities. Control exposures involved subjects sitting in still air at 24-26 degrees C dressed only in thermal underwear. In the control environment all of the internal body temperatures measured gave comparable and consistent values; however, cold exposure affected the various sites differently. Esophageal temperatures fluctuated rapidly as a result of subjects swallowing cold saliva. Sublingual temperatures were below the lower limit of a clinical thermometer, possibly because of facial cooling. Auditory canal temperatures were low, perhaps also because of facial cooling. Rectal temperatures were high as were the gastrointestinal tract temperatures, due perhaps to local heat production in response to cold stimulation. Metabolic rate increased initially in the cold and again toward the end of the cold exposure.

Body Temperature↗
PubMed1983

The relationship between aerobic fitness and certain cardiovascular risk factors.

Aerobic fitness and the incidence of risk factors related to cardiovascular disease (CVD) were compared for 2501 Canadian servicemen 18-50 years of age. Aerobic power (VO2max) was predicted from heart rate measured during submaximal bicycle exercise. The risk factors--serum cholesterol, serum triglycerides, blood pressure and body fat (sum of three skinfolds)--were measured; the incidence of cigarette smoking was obtained from a questionnaire. The total population tested was divided into three age groups which were subdivided into four fitness categories. An inverse relationship was demonstrated between fitness category and the mean values for all measured risk factors. Although this relationship was most evident in the older subjects, it is significant that it was also present in men under 30 years of age. A similar inverse relationship was demonstrated for all age groups between fitness category and the percent of subjects considered to have an elevated cholesterol, triglyceride, blood pressure, or skinfold thickness. The incidence of cigarette smoking was inversely related to fitness category only in those 30 years of age and over. Although this type of cross-sectional study does not establish cause and effect, there is evidence to suggest that participation in a program to improve physical fitness may lead the individual to modify other components of his lifestyle.

Adolescent↗
PubMed1982

Synergistic activation by collagen and 15-hydroxy-9 alpha,11 alpha-peroxidoprosta-5,13-dienoic acid (PGH2) of phosphatidylinositol metabolism and arachidonic acid release in human platelets.

Collagen stimulates the activation of phosphatidylinositol (PI)-specific phospholipase C (EC 3.1.4.10) in human platelets, as manifested by the disappearance of PI, the transient formation of diacylglycerol (DG), and release of myoinositol. Platelets exposed to collagen also form lysophosphatidylinositol (LPI). Maximum formation of DG occurs within 60 s of the addition of collagen and is in proportion to the concentration of collagen provided, up to 100 micrograms/2 x 10(9) platelets/ml. Hydrolysis of PI, formation of DG, and release of arachidonic acid are all inhibited approximately 68% by aspirin or indomethacin, both of which inhibit platelet cyclooxygenase. This inhibition is reversed by the product of cyclooxygenase activity, 15-hydroxy - 9 alpha,11 alpha - peroxidoprosta - 5,13 - dienoic acid (PGH2), or by the PGH2 analogue and agonist, U-46619. The counteracting effects of either PGH2 or the PGH2 analogue can be blocked, in turn, by a PGH2 antagonist, U-51605. Neither PGH2 nor its stable analogue is, by itself, an efficient stimulus for PI breakdown to DG and LPI in platelets. However, in conjunction with collagen, these agents synergistically promote the net breakdown of PI and the release of arachidonic acid in aspirin-treated platelets. Our findings thereby imply that PGH2 has an important role in regulating both the release of its precursor, arachidonic acid, and the metabolism of PI induced by collagen. Dibutyryl cyclic AMP or prostaglandin D2 (PGD2), a prostaglandin that elevates concentrations of cAMP in platelets by stimulating adenylate cyclase, inhibits the hydrolysis of PI induced by collagen by 70%. The activation of PI metabolism by collagen appears to be inhibited by cAMP independently of any effects of this inhibitor on the formation of PGH2.

Arachidonic Acids↗
PubMed1981

Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods into the epithelium, trapping invading G. muris and enclosing them in phagolysosomes. In normal mice, which clear G. muris in 4 to 6 weeks, macrophages containing digested G. muris were surrounded by rosettes of lymphoblasts in the epithelium. In nude mice deficient in lymphocytes, there was apparent hyperplasia of macrophages, which filled the follicle domes, resulting in more frequent entrapment of G. muris but no contact between macrophages and lymphoblasts in the epithelium. In nude mice, which require 6 months to control G. muris infection, lymphoblast contact with macrophages containing distinctive microtubular remnants of G. muris was only identified in the follicle dome. This close physical association of lymphoblasts and macrophages containing G. muris remnants suggests that this macrophage activity represents intraepithelial antigen processing as well as a defense against the effects of the uncontrolled entrance of microorganisms and other antigenic particles into Peyer's patch lymphoid follicles.

Animals↗
PubMed1981

Geriatric education in a teaching hospital: the role of geriatric services.

Geriatric education and training are most successful when taught in a setting that provides the medical and social services that elderly persons often require. At Mount Zion Hospital and Medical Center, medical students and trainees participate in several geriatric services that introduce them to the special health needs of the elderly, including the ambulant and the homebound. In the Mount Zion/University of California, San Francisco, geriatric education and training program, we have defined three principles of geriatric medicine that are unique to the field and are best applied directly within the service setting. This setting emphasizes (1) the special body of knowledge regarding aging and health care of the elderly, (2) the importance of assessing functional capacity and (3) the role of the health team. Our experience indicates that when students and trainees observe the application of these principles in a range of geriatric services they begin to understand the complex health problems with which geriatric medicine is concerned.

California↗
PubMed1979

A survey of aerobic fitness levels in a Canadian military population.

Aerobic fitness was assessed for 3171 men aged 17-55 years and for 610 women aged 17-29 years serving in almost every segment of the Canadian Forces (CF). Maximal oxygen uptake (Vo2 max) was predicted from heart rate measured during submaximal exercise. The survey showed that recruit training markedly improved Vo2 max for both men and women but that, after graduates were assigned to their trades and classifications and fitness training was no longer compulsory, fitness returned to pre-training levels. The relationship between daily activity and aerobic fitness was further demonstrated by comparing land, air, and sea elements in the CF. The active life of the young infantry soldiers is reflected in their relatively high Vo2 max. The available evidence indicates that, unless their duties involve compulsory fitness training (recruits) or hard physical work (infantry soldiers), the military in Canada have aerobic fitness levels which are not markedly higher than their civilian counterparts.

Adolescent↗
PubMed1978

A method of treating post-irradiation rectovaginal fistulas.

A sphincter-saving operative method of treating post-irradiation rectovaginal fistulas is presented. The technique involves the peranal anastomosis of healthy colon to the mid-anal canal using a 'sleeve' anastomosis. Four patients have been treated with cure of the fistula and a return to normal bowel habit. A fifth, with an irradiation ulcer causing intractable pain, also obtained complete relief of symptoms.

Aged↗