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Biomedical subjects

P McBride

Publications and source records attributed to P McBride.

18 recordsLinked to original sources
PubMed1996

Replication of scrapie in spleens of SCID mice follows reconstitution with wild-type mouse bone marrow.

SCID mice are resistant to intraperitoneal infection with 10(3) and 10(4) intracerebral ID50 units of ME7 scrapie agent whereas they develop disease after intracerebral challenge. However, higher doses introduced, by intraperitoneal or subcutaneous routes, produce disease. Immunocompetent mice of the same strain (CB20) developed scrapie following either intracerebral or intraperitoneal infection. Bioassay of spleens from SCID mice infected with 10(-1) dilutions of ME7 scrapie by intraperitoneal, intracerebral or abdominal subcutaneous injection showed traces or low levels of infectivity in spleen. However, subcutaneous injection beneath the skin of the neck failed to infect the spleen. CB20 bone marrow reconstitution of SCID mice resulted in the regeneration of a normal lymphoid architecture in the spleen. Spleens from these reconstituted mice, infected intracerebrally with a 10(-1) dilution of ME7 contained high levels of infectivity. These results suggest that the ability to replicate scrapie agent in spleen or lymphoid tissue depends on the restoration of normal lymphoid structure and in particular the presence of differentiated follicular dendritic cells. The possibility that SCID mice can select minor strains of scrapie which are normally unrecognized in cloned ME7 is discussed.

Animals↗
PubMed1995

Laparoscopic Nissen fundoplication.

Most patients with gastroesophageal reflux disease (GERD) can be treated effectively with medical therapy; however, in patients with severe GERD who are unresponsive to medical therapy, the lower esophageal sphincter (LES) is often found to be mechanically incompetent. Surgical therapy, which improves the LES antireflux barrier, may then be a good option. A very effective and popular antireflux procedure is the Nissen fundoplication, which can be safely done via the laparoscopic route. Preoperative evaluation should include contrast radiography, esophagoduodenoscopy (EGD) with biopsies, esophageal manometry, and 24-hour pH monitoring. Indications for surgery include failure or inability to continue on medical therapy, GERD-related respiratory symptoms, and severe complications of GERD, such as ulceration, stricture, and Barrett's esophagus. A short, loose Nissen fundoplication is ideal for patients with normal esophageal body motility. Operative complications are infrequent, and they include gastric perforation, bleeding, and pneumothorax. Following the laparoscopic approach, nearly all patients can leave the hospital on the first or second postoperative day. Follow-up esophageal manometry and 24-hour pH monitoring show the same good long-term results as seen after open Nissen fundoplication. Laparoscopic Nissen fundoplication can be performed safely and effectively with all of the advantages of a minimally invasive approach.

Esophagus↗
PubMed1993

Canine cardiac sarcoplasmic reticulum is not altered with endurance exercise training.

To investigate the effect of exercise training on calcium movements by isolated cardiac sarcoplasmic reticulum (SR), mongrel dogs either remained sedentary (S) or were exercise-trained (E) via running for a period of 8-10 wk. The trained state was confirmed by the increase in skeletal muscle citrate synthase activity and decreases in submaximal exercise heart rates in the E group but not in the S dogs. The properties of isolated cardiac SR were identical between the groups. The variables tested included ATP-dependent calcium transport and calcium-stimulated ATPase activity. Importantly, there was no difference in spontaneous calcium release which occurred after peak ATP-dependent calcium accumulation was reached. Calcium release from passively loaded vesicles induced by calcium and ionophore also did not differ in the SR isolated from the E dogs. The change in the affinity of the SR Ca ATPase for calcium after the addition of the polyanion, heparin, was similar in both groups, indicating that the regulation of calcium-stimulated ATPase activity by the SR protein, phospholamban, is not modified by exercise training. We conclude that exercise training of 8-10 wk duration does not alter the calcium handling properties of cardiac SR isolated from mongrel dogs.

Animals↗
PubMed1992

The prion protein gene: a role in mouse embryogenesis?

The neural membrane glycoprotein PrP (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases. During pathogenesis, PrP accumulates in and around cells of the brain from which it can be isolated in a disease-specific, protease-resistant form. Although the involvement of PrP in the pathology of these diseases has long been known, the normal function of PrP remains unknown. Previous studies have shown that the PrP gene is expressed tissue specifically in adult animals, the highest levels in the brain, with intermediate levels in heart and lung and low levels in spleen. Prenatally, PrP mRNA has been detected in the brain of rat and hamster just prior to birth. In this study we have examined the expression of the PrP gene during mouse embryonic development by in situ hybridisation and observed dramatic regional and temporal gene expression in the embryo. Transcripts were detected in developing brain and spinal cord by 13.5 days. In addition, PrP gene expression was detected in the peripheral nervous system, in ganglia and nerve trunks of the sympathetic nervous system and neural cell populations of sensory organs. Expression of the PrP gene was not limited to neuronal cells, but was also detected in specific non-neuronal cell populations of the 13.5 and 16.5 day embryos and in extra-embryonic tissues from 6.5 days. This cell-specific expression suggests a pleiotropic role for PrP during development.

Animals↗
PubMed1992

The effect of minor degrees of glucose intolerance on the incidence of neonatal macrosomia.

The incidence of neonatal macrosomia in infants of mothers who have only one abnormal value in a 3-hour glucose tolerance test (GTT) is greater than normal. Often, corrections for gestational age have not been used in the analysis, and in the few studies in which corrections were made, the results conflicted. In this study, the birth weights of infants from 157 patients who had only one abnormal GTT value were compared with the birth weights of infants from normal mothers, with and without correction for gestational age. Analysis using three different GTT criteria revealed that the incidence of birth weight greater than 4000 g was 20% or greater in the infants of mothers who had only one abnormal GTT value and only 12.4% in controls. However, when adjusted for gestational age, there were no differences in the birth weights and percentage of large for gestational age (LGA) infants in the study groups versus controls. The mean and gestational age-adjusted birth weights of the greater-than-4000-g neonates born to women with one abnormal GTT value were no different than those of controls. However, at delivery, the gestational ages of patients with one abnormal GTT value tended to be slightly greater than those of controls by 0.1-0.6 weeks, suggesting that minor degrees of abnormal glucose metabolism may prolong pregnancy in some patients. When compared with the literature, the findings of this study suggest that the National Diabetes Data Group criteria may be too high as a screen for LGA infants.

Female↗
PubMed1991

Development and operation of the Wisconsin Research Network.

In 1987, the Wisconsin Academy of Family Physicians developed the Wisconsin Research Network (WReN) to support practice-based primary care research throughout Wisconsin. WReN has three objectives: to support the research efforts of individual physicians in community practices, to facilitate collaborative research among practicing physicians, and to provide academically based investigators with access to community practice sites. Due to a policy of actively encouraging membership, WReN has grown to 460 members during its 4-year history. Five WReN-supported papers have been published, and 22 state and national level presentations of WReN-supported research results have been made. Competitive grants totaling more than $2 million have been awarded to university-based investigators for studies using the resources of WReN. This paper describes the development, organization, and success of WReN as well as the challenges which must be addressed.

Family Practice↗
PubMed1990

Ubiquitin conjugate immunoreactivity in the brains of scrapie infected mice.

Sections of brain from normal mice or clinically-ill mice infected with either the 87V or the ME7 strains of sheep scrapie were immunostained to show the localization of ubiquitin-protein conjugates or a specific marker of disease, the scrapie-associated fibril protein (PrP). In both scrapie models immunoreactive ubiquitin-protein conjugates were seen in thread-like structures found throughout the neuropil, in inclusion bodies within vacuolated neurones, and in areas surrounding anti-PrP positive amyloid plaques. The PrP protein was visualized in diffuse deposits in highly vacuolated parts of the scrapie-affected brain, and focally in amyloid plaques, microglia and neuronal processes. The ubiquitin-protein conjugate staining of scrapie amyloid plaques is very similar to that seen in the plaques of Alzheimer's disease. The ubiquitinated intraneuronal inclusion bodies seen in scrapie resemble the granulovacuolar lesions also seen in Alzheimer's disease, but appear much larger and possibly correspond to material in giant autophagic vacuoles. We suggest that these inclusions may be the result of ubiquitinated abnormal proteins being directed to the lysosomal system, and that scrapie and Alzheimer's disease share at least some common processes of neurodegeneration.

Amyloid↗
PubMed1989

Use of plasma histamine levels to monitor cutaneous mast cell degranulation.

A simple, minimally invasive procedure for monitoring cutaneous mast cell degranulation in vivo in man is described. Plasma histamine levels in venous blood draining the site of intradermal histamine, morphine, and antigen challenges were determined with a modified radioenzymatic assay. Elevations in plasma histamine above baseline levels of 0 to 0.6 ng/ml were measured after intradermal histamine; levels of 1.4 to 85.2 ng/ml were obtained after a 2 microgram intradermal challenge in 16 subjects. After antigen testing, peak plasma histamine levels ranged from 1.1 to 24.4 ng/ml (n = 9), and after morphine sulfate skin testing peak plasma histamine levels ranged from 2.3 to 12.7 ng/ml (n = 4). The time to achieve peak plasma histamine levels ranged from 2 to 10 minutes after histamine, from 5 to 15 minutes after antigen, and from 1 to 8 minutes after morphine challenges. Plasma levels returned to baseline within 30 minutes after histamine and morphine challenges but took more than 60 minutes for antigen challenges. With careful choice of the skin test site in relation to venous drainage, plasma histamine increases after either histamine or antigen were reproducible and reliable. Plasma histamine levels peaked 5 to 10 minutes before maximal development of the wheal-and-flare responses after histamine, antigen, or morphine skin tests. The wheal-and-flare skin tests continued to increase in magnitude despite rapidly declining plasma histamine levels. Thus skin tests eliciting reactions ordinarily seen in an allergist's office cause measurable increases in plasma histamine levels that can be used to directly monitor mast cell degranulation in man in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1989

Industry's contribution to the development of renal care.

In the early days of dialysis, the practitioner was required to use whatever componentry that was available in order to construct dialysis equipment. Sausage casing, industrial pumps, and other nonmedical components were used to construct the crude dialysis devices. As time passed, industry began to take an interest in this unique medical treatment and developed systems that were especially designed for dialysis. The collaboration of medicine and industry was critical in the development of dialysis as we know it today.

Equipment Design↗
PubMed1988

Evaluation of a radioimmunoassay for histamine measurement in biologic fluids.

A new radioimmunoassay for the measurement of histamine in biologic fluids was evaluated. Assay selectivity and specificity were achieved by "succinyl-glycinamide derivatization" of histamine in samples to mimic the immunogen used to generate the monoclonal antibody. The assay exhibits a linear response from 0.1 to 5.0 ng/ml of histamine and the monoclonal antibody used has partial recognition of only N-methylhistamine (other than histamine). With minimal modifications, the assay can accurately measure histamine in plasma, urine, and buffer. Normal ranges for human subjects were established: plasma levels are 0.193 +/- 0.08 ng/ml (n = 40) and urine levels are 20.9 +/- 11.2 micrograms histamine/gm creatinine (n = 10).

Body Fluids↗
PubMed1983

Chronic pain.

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Back Pain↗