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Biomedical subjects

J Spencer

Publications and source records attributed to J Spencer.

At least 343 records · Page 19Linked to original sources

Homologous recombination catalyzed by human cell extracts.

Two plasmids containing noncomplementing and nonreverting deletions in a bacterial phosphotransferase gene conferring resistance to neomycin (Neor) were incubated with human cell extracts, and the mixtures were used to transform recombination-deficient (recA-) Escherichia coli cells. We were able to obtain Neor colonies at a frequency of 2 X 10(-3). This frequency was 100 to 1,000 times higher than that obtained with no extracts. The removal of riboadenosine 5'-triphosphate, Mg2+, or deoxynucleoside triphosphates from the reaction mixture severely reduced the yield of Neor colonies. Examination of plasmid DNA from the Neor colonies revealed that they resulted from gene conversion and reciprocal recombination. On the basis of these results, we conclude that mammalian somatic cells in culture have the enzymatic machinery to catalyze homologous recombination in vitro.

Cell Line↗

Basal, sham feed and pentagastrin stimulated gastric acid, pepsin and electrolytes after omeprazole 20 mg and 40 mg daily.

Gastric secretion was measured in nine patients with duodenal ulcer before, and after treatment for four weeks with omeprazole 20 mg or 40 mg daily. Basal acidity and acid output were affected variably by 20 mg, but inhibited totally by 40 mg daily. Sham feed stimulated acid output was reduced by 20 mg daily and completely inhibited by 40 mg daily. Maximal pentagastrin stimulated acid output was halved by 20 mg omeprazole daily and 84% inhibited by 40 mg daily. The reduction in acidity was always greater than the reduction of volume. Pepsin output after pentagastrin was little altered but with the reduced secretory volume pepsin concentrations were increased by both doses. The major cause of reduced aspirate acid output after omeprazole is decreased secretion of the primary acid component of the parietal cell by the proton pump H+K+ ATPase. Duodenogastric alkaline reflux is, however, markedly increased after omeprazole and is an additional factor in the resultant hypoacidity or even anacidity after this drug.

Adult↗

Gut associated lymphoid tissue: a morphological and immunocytochemical study of the human appendix.

Gut associated lymphoid tissue in 15 normal appendices has been characterised in tissue sections using both morphological criteria and immunocytochemical techniques. A panel of monoclonal and polyclonal antibodies was used including antibodies to B-cells, T-cells, macrophages, HLA DR and immunoglobulins. The lymphoid tissue in the appendix was shown to bear a strong resemblance to that in lymph nodes with the exception of the region where the appendix follicles associate with the dome epithelium, which has no lymph node equivalent. This zone of cells between the lymphoid follicles and the dome epithelium termed the 'mixed cell zone' has been shown to contain an abundance of HLA DR-bearing cells, some of which have irregular nuclear morphology and resemble follicle centre cells. These cells were seen to extend into the epithelium of the dome but not the crypts. Using a monoclonal anti-B-cell antibody a population of B-cells was detected in the equivalent areas of mixed cell zone and epithelium and quantitative studies showed that these intraepithelial B-cells comprised approximately 4-5% of the cells in the epithelium. The mixed cell zone was also seen to contain T-cells, S-100 protein-containing macrophages and occasional lysozyme-containing macrophages. Plasma cells were rarely seen in this area.

Antibodies, Monoclonal↗

The human gut contains a novel population of B lymphocytes which resemble marginal zone cells.

B cells in normal human Peyer's patches and in primary B cell lymphomas of the stomach have been characterized in terms of their cellular morphology and their reactivity with a panel of monoclonal antibodies. A population of B cells is present in normal and malignant gut-associated lymphoid tissue which is composed of neither mantle zone cells nor germinal centre cells. In Peyer's patches these cells surround the follicles merging with the mantle zone and extending both into the dome region, infiltrating between the epithelial cells and also towards the serosa. They are intermediate in size with irregular nuclear outlines and they resemble the centrocytes in the follicle centre. They are quiescent, expressing C3b- and C3d-receptors and surface IgM but not surface IgD. These centrocytes-like cells which are not seen in the peripheral lymph nodes are identical to the B cells in the marginal zone of the spleen according to all of the criteria employed in this study.

B-Lymphocytes↗

West Berkshire perineal management trial.

One thousand women were allocated at random to one of two perineal management policies, both intended to minimise trauma during spontaneous vaginal delivery. In one the aim was to restrict episiotomy to fetal indications; in the other the operation was to be used more liberally to prevent perineal tears. The resultant episiotomy rates were 10% and 51% respectively. An intact perineum was more common among those allocated to the restrictive policy. This group experienced more perineal and labial tears, however, and included four of the five cases of severe trauma. There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum. Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery. These findings provide little support either for liberal use of episiotomy or for claims that reduced use of the operation decreases postpartum morbidity.

Adult↗

Obscure gastrointestinal haemorrhage of small-bowel origin.

The records of 37 patients investigated for obscure gastrointestinal haemorrhage originating from the small bowel were reviewed retrospectively. Bleeding was caused by Meckel's diverticula in eight cases, smooth muscle tumours in seven cases, vascular anomalies in 14 cases, and other single lesions in eight cases. The lesions were identified by angiography in 18 patients, operation in 17, and barium follow through examination in two. Only one patient under 50 years of age had a lesion that would not have been found by careful laparotomy. Early laparotomy is advisable in patients aged under 50 with obscure gastrointestinal bleeding; expert selective angiography is recommended before operation in patients aged over 50 and those who have already undergone a laparotomy yielding negative results.

Adolescent↗

Randomized prospective trial of Roux-en-Y duodenal diversion versus fundoplication for severe reflux oesophagitis.

It is not widely recognized that duodenal contents are implicated in the causation of severe reflux oesophagitis and stricture formation in patients with hiatus hernia. In a randomized prospective trial, including only patients with severe oesophageal changes, standard Nissen fundoplication has been compared with antrectomy and Roux-en-Y reconstruction. Twenty-two patients were randomized to each group. The 42 surviving trial patients have been followed for an average period of over 5 years. Good results (Visick I or II) have been achieved in 91 per cent of 22 patients having antrectomy and Roux-en-Y anastomosis (Group B), compared with 65 per cent of 20 patients surviving after Nissen fundoplication (Group A). Poor results (Visick III or IV) seen in seven patients (35 per cent) in group A were almost all associated with failure of fundoplication to stop reflux. Two of these patients have subsequently had antrectomy and Roux-en-Y reconstruction with excellent results. Antrectomy with Roux-en-Y gastrojejunostomy appears to be superior to a standard anti-reflux procedure as primary surgical treatment in these patients. The technique is recommended: where the patient has a fixed irreducible hiatus hernia; where previous surgery at the hiatus has failed and rendered reoperation hazardous.

Adult↗

Effect of cimetidine and carbenoxolone on cysteamine-induced ulcers: a study of gastric mucosal histamine and histamine formation capacity in rat.

Cysteamine-induced ulcers in rat were used to study the effect of ulcer-healing agents with different modes of action on ulcer formation and mucosal histamine. Male Wistar rats were divided into 5 groups. Group I had cysteamine injection; group II had cimetidine followed by cysteamine injection; group III had carbenoxolone before cysteamine injection; group IV had carbenoxolone as group III and cimetidine and cysteamine injections; group V had saline injections (controls). In group I 20/29; group II 17/30; group III 15/29; and group IV 23/30 developed ulcers. No significant differences were found. No ulcers were found in group V. Comparison between all groups and controls showed an increase in gastric mucosal histamine and HFC. The increase in histamine was related to ulcer formation. Duodenal and oesophageal histamine did not change significantly. Gastric mucosal histamine and HFC were directly correlated.

Animals↗

Plasma histamine in pig: effect of food and pentagastrin.

Histamine may have a role in the physiological control of gastric acid secretion. We aimed to detect histamine release into the circulation during food and pentagastrin. Non-parametric statistical analysis was used. Seven pigs bearing iliac artery, iliac vein and portal vein cannulae were given a standard meal. Blood samples were collected at 10-minutes intervals over a period of 2 hours for histamine assay. There were no significant changes in whole blood and plasma histamine concentrations in the iliac arterial or venous blood. In portal venous blood, no significant changes were observed in whole blood histamine, but there were significant increases in plasma histamine 40 minutes after food (basal median: 149.0; range: 50.3-258.6 pmol ml-1; 40 minutes, median 214.9; range: 64.2-319.6 pmol ml-1). Four pigs were given pentagastrin, 6 micrograms kg-1 h-1 i.v. Iliac and portal venous bloods were collected for histamine assay before and 15 minutes after pentagastrin infusion. There were no significant changes in the whole blood histamine concentration in either iliac or portal venous blood. A small increase, mean 5%, of plasma histamine concentration was detected in the iliac venous blood (basal mean 242.9 +/- 21.7 pmol ml-1; stimulated mean 256.9 +/- 39.1 pmol ml-1). A 20% increase in the portal plasma histamine concentration was observed after pentagastrin (basal mean 240.1 +/- 13.2; stimulated mean 288.4 +/- 18.8 pmol ml-1). Both food and pentagastrin increase plasma histamine concentration in the portal vein. Pentagastrin has a greater effect than food.

Animals↗

Studies on the lymphocytes of sheep. IV. Migration patterns of lung-associated lymphocytes efferent from the caudal mediastinal lymph node.

Small lymphocytes from the efferent lymph of the caudal mediastinal lymph node (CMLN), the regional node of the lower respiratory tract, were labelled in vitro either with 51Cr, or with the fluorochrome rhodamine isothiocyanate. The labelled lymphocytes were washed and returned to the sheep by intravenous (i.v.) injection; their later appearance in the lymph from the CMLN was monitored, as was their appearance in lymph from either a peripheral somatic lymph node (PSLN) or the intestinal lymph duct. It was found that the labelled lymphocytes entered the lymph from the CMLN and PSLNs with equal facility but were significantly less able to enter the intestinal lymph. Similarly, the large lymphocytes (immunoblasts) which were released into the lymph after antigenic stimulation of the CMLN, and which were labelled in vitro with [125I]Udr, showed little tendency to enter the gut after i.v. injection and became distributed throughout the body in the same way as immunoblasts efferent from the PSLN, i.e. they went principally to the lungs, and spleen.

Animals↗

Is pentagastrin-stimulated secretion mediated by histamine?

Patients with duodenal ulcer disease received either a two hour pentagastrin infusion test or a similar test with the addition of a bolus of cimetidine, 200 mg, after one hour of pentagastrin. Pentagastrin induced secretion of acid and histamine, the secretion patterns of the two being similar. Total histamine output in the gastric aspirate in the first hour of pentagastrin infusion was related to total acid output (r = 0.58, p less than 0.01). A similar correlation was observed during the second hour of pentagastrin infusion (r = 0.61, p less than 0.05). Plasma histamine concentration rose to a peak coinciding with maximal acid secretion. After cimetidine blockade, gastric acid fell rapidly but gastric histamine output did not change. Plasma histamine concentration increased further. These results suggest that pentagastrin induced gastric histamine release is not affected by an acid inhibiting dose of cimetidine. Cimetidine caused histamine release into the circulation in both healthy volunteers and patients after total gastrectomy. The rise in plasma histamine concentration, however, was transient. In contrast, during pentagastrin infusion, the plasma histamine concentration remained high. These data support the hypothesis that histamine release induced by pentagastrin is a major stimulant of gastric acid secretion.

Cimetidine↗

IgA antibodies in the bile of rats. IV. Synthesis of secretory antibodies in irradiated rats reconstituted with spleen cells: influence of microenvironment on the regulation of IgA production.

Inbred rats were given sub-lethal doses of irradiation so that they were unable to make antibodies unless they were reconstituted with syngeneic lymphoid cells. The ability of the reconstituted rats to make antibodies of the IgA class was measured in terms of the titres of specific antibodies that appeared in their bile. After syngeneic spleen cells, together with antigen, were injected into the spleens of irradiated rats, the titres of specific antibodies that appeared in the bile were low. After the same dose of spleen cells and antigen had been injected into the GALT of irradiated rats, the titres of biliary antibodies were substantial. These results, together with those of appropriate control experiments, suggest that radio-resistant influences in the microenvironment of the GALT may be important in inducing lymphoid cells to produce antibodies of the IgA class in response to local antigen.

Agglutination Tests↗

Gastric histamine release during insulin and pentagastrin infusion in patients with duodenal ulcer.

Thirteen patients with proven duodenal ulcer were studied by a combined insulin/pentagastrin gastric secretion test. Acid output, gastric histamine output, and plasma histamine levels were measured. There were no significant changes in gastric or plasma histamine levels during insulin-induced acid secretion (median basal 0.62 nmol 10 min-1; median highest fraction 0.89; median basal plasma 4.87 nmol 1-1; median highest plasma 6.89). After pentagastrin infusion there was an immediate increase in gastric histamine to a peak (median 1.62 nmol 10 min-1 p less than 0.01) followed by a fall and then a second peak (median 3.18 p less than 0.002). The biphasic nature of the gastric histamine release is unexplained. The occurrence of acid secretion without histamine release during insulin infusion suggests that the changes induced by pentagastrin are not simply a passive "washout" of histamine during acid secretion. The lack of histamine release during insulin infusion is not compatible with the theory that histamine is the common final transmitter to the parietal cell.

Adult↗

Studies on the adjuvant action of beryllium. II. Systemic effects with particular reference to secretory immunity.

When 5 mg doses of beryllium hydroxide, Be(OH)2, were injected intravenously (i.v.) into rats, much of the injected material was retained in the lungs. When the injection of Be(OH)2 was accompanied by particulate antigens such as killed B. abortus organisms or SRBC, immune responses took place in the intra-thoracic lymph nodes (ITLN) so that antibodies of the IgA class were generated and endowed the bile with significant agglutinating activity. This did not happen when the antigens were injected without the beryllium adjuvant. Similarly, a soluble antigen, bovine serum albumin (BSA) only gave rise to significant amounts of biliary and serum antibodies after i.v. injection if Be(OH)2 was used too. The highest titres occurred when the antigen followed the adjuvant after an interval of a few seconds but substantial titres still resulted if the injection of antigen was delayed for 24 hr. The amounts of biliary antibodies generated by the parenteral injection of antigen and adjuvant were comparable to those that occurred after the same materials were injected directly into the GALT. The adjuvant action of Be(OH)2 was able to induce in athymic (nude) rats the production of measurable amounts of both biliary and serum antibodies to SRBC.

Adjuvants, Immunologic↗

Gastric mucosal histamine, histamine formation capacity (HFC) and plasma gastrin after cysteamine administration.

Cysteamine administration is followed by stomach and duodenal ulcers in rats. We aimed to establish a time relationship between changes in gastric mucosal histamine, histamine formation capacity (HFC) and plasma gastrin after cysteamine administration. Up to 4 h after cysteamine s.c., no ulcers were found. Plasma gastrin rose after cysteamine and was higher than in controls 2h after injection. Mucosal histamine fell after 4h; no other significant changes were found in mucosal histamine and HFC. A direct correlation was found between plasma gastrin and HFC in both controls and after cysteamine. It is suggested that the changes indicate that cysteamine releases gastrin, which increases HFC and thus histamine. The fall in histamine seems to indicate utilization of histamine in acid production.

Animals↗

The flow and composition of lymph from the caudal mediastinal lymph node of sheep.

By cannulating the efferent duct of the caudal mediastinal lymph node in sheep, lymph from the lower respiratory tract was collected under physiological conditions for several days. In 18 such preparations the flow rate varied from 4 to 12 ml/hr between individuals and the lymphocyte count between 4000 and 117,000/mm3. The protein content of the lymph plasma averaged nearly 60% of that of the blood, and this indication of the high permeability of the capillary bed of the lungs was confirmed by measuring the time taken for intravenous doses of 125I-albumin to equilibrate between the blood and mediastinal lymph plasma. The concentration of immunoglobulin A was higher in the mediastinal lymph than in blood serum, while the reverse was true of the concentrations of IgG1, IgG2, and IgM. This evidence for the local production of IgA by the intra thoracic lymphoid tissue was supported by the demonstration by immunoperoxidase techniques of IgA-containing plasma cells in sections cut from the caudal mediastinal nodes, and of IgA-containing immunoblasts in the lymph.

Animals↗