PubMed Health⌕ Search

Biomedical subjects

P O'Brien

Publications and source records attributed to P O'Brien.

At least 199 records · Page 11Linked to original sources
PubMed1983

The microvasculature and gastric luminal pH of the forestomach of the rat: a comparison with the glandular stomach.

The microvasculature of the rat forestomach was compared with that of the glandular stomach using scanning electron microscopy of vascular corrosion casts and conventional transmission electron microscopy. The forestomach stratified mucosa is relatively poorly vascularized, having a simple 2 dimensional array of continuous capillaries located subepithelially. This contrasts with the extensive mucosal microvascular network of the glandular stomach, where fenestrated capillaries are closer to adjacent cells. pH measurements were taken at the mid-forestomach luminal surface and midfundic luminal surface of the glandular stomach. The H+ concentration was 200 x lower at the forestomach luminal surface. There was always food within the stomach. The pH of the food bolus, which extended throughout the stomach, reflected the pH of the adjacent mucosa. Because of their microvascular differences, the portal transport of HCO3- purported to protect the glandular mucosa from luminal acidity cannot operate at the forestomach mucosa. We speculate that the low forestomach acidity results from the buffering action of the food bolus and that the anatomically distinct dividing ridge restricts direct access of fundic secretions to the forestomach mucosa.

Animals↗
PubMed1982

Cytotoxicity of cancer patient's macrophages for tumor cells.

Monocyte derived macrophages were isolated from the peripheral blood of 66 patients with either breast, colon, gynecological or hematological cancers. The macrophages from the breast and gynecologic cancer patients generally did not acquire enhanced cytotoxicity for human tumor cells after incubation with bacterial lipopolysaccharide (LPS). However, when the macrophages isolated from colon and hematologic cancer patients were studied, more than 50% of these patients possessed cytotoxic macrophages. LPS induced macrophage mediated cytotoxicity was also found to be inhibited by factors present in many cancer patient's plasma. Twenty-three of the 50 cancer patients studied possessed a plasma inhibitor capable of suppressing macrophage mediated cytotoxicity by more than 50%. Furthermore, of these 50 patients, 47 were incapable of killing the tumor cells in vitro either because they possessed nonresponsive macrophages and/or they possessed a plasma inhibitory factor. Thus, although macrophage cytotoxic function may be normal in some patients with cancer, cytotoxicity may be inhibited in some patients by factors in autologous plasma thereby rendering the macrophages ineffective in vivo.

Adenocarcinoma↗
PubMed1982

Allele frequencies in a multidimensional Wright-Fisher model with general mutation.

A formula is obtained for the probability that two genes at a single locus, sampled at random from a population at time t, are of particular types. The model assumed is a diffusion approximation to a neutral Wright-Fisher model in which mutation is general and not necessarily symmetric. An example is given of a population in which one allele has a high mutation rate, and the others have an equal, low mutation rate. The matrix Q, with elements given by the probability of sampling two alleles of particular types, is calculated exactly and approximately for this case. A formula is given for the distribution of the number of segregating sites occurring in two randomly sampled finite sequences of completely linked sites, with general mutation at a site and identical mutation structure between sites.

Alleles↗
PubMed1982

Relationship of the suppression of macrophage mediated tumor cytotoxicity in conjunction with secretion of prostaglandin from the macrophages of breast cancer patients.

Peripheral blood monocyte derived macrophages obtained from breast cancer patients are non-cytotoxic towards human tumor cells. However, when indomethacin, a prostaglandin synthetase inhibitor, was added to the macrophage tumor cell incubation mixture, the breast cancer patient's macrophages became capable of killing the tumor cells. Furthermore, the macrophage preparations obtained from breast cancer patients demonstrated a 64% increase in the secretion of PGE2, when compared with macrophages obtained from normal donors. It is already known that prostaglandin can inhibit both natural lymphocyte cytotoxicity and antibody dependent cell-mediated cytotoxicity against human tumor cells in vitro. These results indicate that increased synthesis of prostaglandin can also inhibit macrophage mediated cytotoxicity. Therefore, it is possible that manipulation of this mechanism might enhance the effectiveness of the macrophage response and should be a consideration in assessing macrophage-tumor cell interaction in vitro and in vivo.

Breast Neoplasms↗
PubMed1982

Pathogenesis of progressive rod-cone degeneration in miniature poodles.

Visual cell pathologic changes and outer segment renewal were investigated in miniature poodles with progressive rod-cone degeneration. Early in this disease, visual cells in the posterior pole and equatorial regions show outer segment lamellar disorientation and vesicular profiles. Visual cells are normal in the periphery. Outer segment renewal determined after intravitreal injection of 3H-leucine was abnormally slower in affected animals than in controls. This renewal abnormality was similar in structurally normal and diseased photoreceptors, suggesting that the renewal defect is the earliest recognizable abnormality in the disease. The pigment epithelium was normal; the presence and density of pigment did not appear to affect the extent and severity of the disease or modify the abnormal renewal rate. As the disease progressed, photoreceptor outer segments were lost, and the remaining diminutive photoreceptors accumulated label in the inner segment and perinuclear zones. Sodium dodecyl sulfate gel electrophoresis of crude rod outer segment preparations showed no differences in opsin synthesis between normal and affected retinas early in the disease, but opsin synthesis decreased in the late stage of the disease.

Animals↗
PubMed1982

Acid-base imbalance and ulceration in the cold restrained rat.

Using the cold restrained rat model of stress ulceration, we have examined the influence of metabolic acidosis, metabolic alkalosis, and respiratory acidosis on the development of gastric erosions. The rats were restrained in tightly fitting perspex chambers at 6 degrees C for 3 hours. Acid-base imbalance was achieved by infusion of NH4Cl or NaHCO3 or by exposure to 5% CO2. The degree of ulceration was expressed by a lesion score of 0 to 4. The control group showed a score of 2.5 +/- 0.2 (mean +/- SEM). With metabolic acidosis the score was 3.6 +/- 0.2, and with metabolic alkalosis the score was 0.9 +/- 0.4. Both values were significantly different from control values (P less than 0.005). Respiratory acidosis was associated with a score similar to that of the control group. The values obtained appeared to be independent of gastric luminal acidity. The findings indicate that the systemic HCO-3 concentration is a significant determinant of the degree of ulceration in the cold restrained rat.

Acid-Base Imbalance↗
PubMed1982

The microvascular architecture of the glandular mucosa of rat stomach.

The circulatory pattern in the gastric mucosa of the rat and relationships of mucosal capillaries to gastric gland cells were investigated. Techniques used included the vascular corrosion cast/scanning electron microscope method, scanning electron microscopy of acid-digested tissues, conventional transmission electron microscopy and in vivo light microscopy. Arterial break-up into capillaries invariably occurs around the base of the gastric glands. The mucosal capillaries are fenestrated and vesiculated, and pass in close proximity to the abluminal aspects of the cells of the gastric glands, particularly the parietal cells. At the apices of the glands, the capillaries form a honeycomb network closely applied to the abluminal aspect of the surface epithelial cells, before draining into infrequent venules which are embedded in a substantial connective tissue sheath. No capillary drainage occurs into these venules deeper in the mucosa. No evidence of either mucosal or submucosal arteriovenous anastomoses was found. Because of the close proximity of the fenestrated mucosal capillaries to the parietal cells and surface epithelial cells and the direction of capillary blood flow, the alkaline tide of the actively secreting parietal cell must be transferred to the abluminal aspect of the surface epithelial cells. The capacity of these cells to secrete HCO3- or to neutralize back diffusing H+ ions would thereby be increased.

Animals↗
PubMed1981

The pharmacodynamics of bucainide (RHC G233): pharmacokinetic parameters and relationship between plasma levels and the effect on the electrocardiogram in the dog.

The pharmacodynamic profile of bucainide dimaleate (RHC G-233) in dogs has been studied. The first observed pharmacologic effect was a change in the ECG pattern (T-wave duration and amplitude) that occurred after an average intravenous dose of 2.7 mg/kg. The average plasma concentration of bucainide was approximately 350 ng/ml. Analysis of data from dogs that received a dual infusion of bucainide indicated that bucainide has an extensive volume of distribution, with an average value of approximately 26 l/kg. An average terminal half-life of 89 minutes was observed. Studies with the radiolabeled drug in rats and dogs also demonstrated the drug's large volume of distribution, and its initial rapid disappearance from the blood. Tissue distribution studies in the rat after administration of the radiolabeled drug showed that bucainide is rapidly taken up by the tissues.

Animals↗
PubMed1980

Urinary proteins as biological markers: bladder cancer diagnosis versus urinary tract infection.

Urine specimens from normal individuals, and from patients with bladder cancer, bladder papillomas and urinary tract infections were assayed for the presence of bladder tumor-related antigens. Ten-fold concentrated urine specimens were reacted in Ouchterlony gel diffusion against various anti-human monospecific antisera. With these antisera urine specimens from normal individuals were distinguished from those from patients with bladder carcinoma as well as bladder papilloma. However, the urine samples from individuals with urinary tract infections showed significant reactivity with many of the monospecific antisera as did specimens from patients with bladder cancer and bladder papilloma. Thus, investigations involved in the assay of bladder cancer biological markers should take the proteinuria associated with urinary tract infection into consideration. The potential importance of detecting tumor-specific components for early diagnosis and treatment of bladder neoplasms is stressed.

Antigens, Neoplasm↗
PubMed1980

Detection of tumor-associated antigens in urine from patients with bladder cancer.

An antiserum was prepared to a hypotonic saline extract of bladder tumor tissue which, after absorption with normal tissues, was used to localize tumor-associated antigens in a Sephadex G-150 elution profile of urine from patients with bladder cancer. A second antiserum was prepared to the urine fraction with tumor-associated antigens. After absorption with normal urine and plasma this antiserum was reacted in gel diffusion and complement fixation assays against urine samples from normal individuals, patients with bladder cancer and patients with proved urinary tract infections. In the gel diffusion assays none of the 23 urine specimens from normal individuals, 37 per cent of the 24 urine specimens from patients with urinary tract infections, 61 per cent of 13 urine samples from patients with papillomas and in situ tumors, and 95 per cent of 30 samples from patients with bladder cancer gave positive precipitin reactions. In complement fixation assays urine from 53 patients with papillomas through grade IV cancers showed a mean 50 per cent complement fixation at 30 micrograms. protein, 29 patients with urinary tract infections showed a mean 50 per cent complement fixation at 150 micrograms. protein and all but 6 urine specimens from more than 30 normal individuals showed 50 per cent complement fixation (mean value) at 140 micrograms. protein. Thus, an antiserum has been produced that may be used in assays for the diagnosis of bladder cancer.

Antigens, Neoplasm↗
PubMed1980

Role of acid-base status in the response of the isolated amphibian gastric mucosa to back diffusion of H+.

The effect of a period of induced back diffusion of H+ on the isolated amphibian gastric mucosa was studied under various conditions. Under standard conditions (HCO3--buffered nutrient solution; 95% O2-5% CO2), passage of an electrical current of 500 microA/cm2 for 15 min from a secretory fluid of pH 2.10 across the mucosal resulted in a decrease of the transmucosal potential difference (PD) of 10.9 +/- 1.9 mV, a decrease of resistance (R) of 48 +/- 26 ogema cm2 and a decrease of short circuit current (Isc) of 18 +/- 7 microA/cm2. Flux of the neutral molecule, erythritol from secretory (S) to nutrient (N) fluid increased by 66% and the active transport of Cl- N lead to S decreased from 2.9 to 1.9 microeq/cm2/hr. With removal of HCO3- from the nutrient fluid and with inhibition of carbonic anhydrase activity the period of back diffusion induced significantly greater change in the electrical measurements than occurred when under standard conditions. This increased effect of back diffusion of H+ was not changed by change of the nutrient fluid pH from 7.20 to either 6.6 or 8.2. Increase of the HCO3- concentration of the nutrient fluid to 35 mM or decrease of the CO2 content of the aerating gas to 1% were associated with significantly less change of the electrical measurements than occurred with standard conditions. These studies support the proposal that the the neutralizing reaction HCO3- + H+ leads to CO2 + H2O plays a central role in the gastric mucosal handling of backing diffusing H+ and suggests that the capacity and poise of the HCO3-/CO2 buffer system is an important determinant of the ability of the mucosa to tolerate luminal acidity.

Acid-Base Equilibrium↗