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Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 235 records · Page 13Linked to original sources
PubMed1989

Effects of coumarin (1,2-benzopyrone) on lymphocyte, natural killer cell, and monocyte functions in vitro.

We have demonstrated in a pilot study that the combination of coumarin (1,2-benzopyrone) and cimetidine is capable of producing objective antitumor responses in patients with advanced renal cell carcinoma. In a previous study, we used monoclonal antibody labeling techniques to monitor peripheral blood lymphocytes and monocytes in patients with advanced malignancies treated with coumarin and cimetidine. While there was no quantitative alteration in T-lymphocytes, B-lymphocytes, natural killer (NK) cells, or cells bearing Ia antigen, there was an increase in the percentage of CD-14 (M5E2+) monocytes and DR+ monocytes by 2 weeks on therapy that persisted over the 8 weeks of monitoring. Because patients received coumarin for 2 weeks prior to institution of cimetidine, these changes were attributed to coumarin. In this report, we present the results of in vitro studies designed to determine if coumarin alters the functional properties of normal peripheral blood lymphocytes, NK cells, or monocytes. In a standard NK cytolytic assay, coumarin failed to produce any significant alteration in NK activity against K562, ACHN, or Caki-2 cell lines. Coumarin did produce an augmentation of lymphocyte mitogenic response to phytahemagglutinin but not to concanavalin A or pokeweed mitogen. Coumarin produced a modest suppression of superoxide anion and hydrogen peroxide generation by monocytes but not by macrophages. The effect of coumarin on antigen processing of tetanus toxoid by macrophages was examined using normal donor cells. While an augmentation of antigen processing was noted in some normal donors, this was an inconsistent and inconclusive finding. Further studies are required to define the precise effects of coumarin on immune cell populations from both normal subjects and cancer patients.

Antigens↗
PubMed1988

Prevention of contraction of patched intestinal defects.

Neomucosal growth on a serosal patch might increase intestinal surface area in the short-bowel syndrome but is limited by contraction of the patched defect. Our aim was to reduce contraction by mechanical or pharmacologic means. Ileal defects (2 x 5 cm) were patched with colon serosa in 14 rabbits. Group 1 (n = 5) had a plastic splint sutured to the defect edge. Group 2 (n = 4) received hydrocortisone acetate and vitamin A. Group 3 (n = 5) was the control group. Four weeks after patching there was significantly less contraction in groups 1 and 2 compared with group 3 (72.3% +/- 5.6% and 50.0% +/- 5.8% vs 31.9% +/- 1.8% initial defect size). Epithelial coverage of the defect was greater in groups 1 and 3 than in group 2. Disaccharidase activity of neomucosa and surrounding mucosa was significantly decreased in the steroid-treated rabbits. Contraction of a serosal patch can be reduced by mechanical and pharmacologic measures that may enhance the clinical applicability of this technique.

Animals↗
PubMed1988

Plasma postheparin diamine oxidase activity. Development of a simple technique of assessing Crohn's disease.

Plasma diamine oxidase (DAO) activity may reflect intestinal involvement in Crohn's disease. The purpose of this study was to develop a simple heparin stimulation test for assessing postheparin plasma diamine oxidase activity in Crohn's disease. Ten volunteers and five patients with Crohn's disease received 1000 units and 3000 units of heparin intravenously and plasma samples were obtained at timed intervals. Plasma DAO activity increased significantly, compared with basal values, 30 minutes after 3000 units of heparin in both volunteers (26.2 +/- 5.0 vs. 4.5 +/- 0.5 units/ml) and patients with Crohn's disease (14.6 +/- 2.0 vs. 4.0 +/- 1.1 units/ml, P less than .05) and was significantly greater in the volunteers. There was no significant increase in DAO activity after 1000 units of heparin. Plasma DAO activity increased significantly within 15 minutes after 3000 units of heparin and remained at this high level at 60 minutes. Postheparin DAO activity correlated with the integrated area under the DAO activity curve. Plasma DAO activity correlated with the Crohn's Disease Activity Index in the patients with Crohn's disease. Plasma DAO activity, 30 minutes after the intravenous administration of 3000 units of heparin, should reflect intestinal involvement in Crohn's disease.

Adult↗
PubMed1988

Difluoromethylornithine inhibits urogastrone stimulation of neomucosal growth.

Urogastrone (UG) stimulates the growth of intestinal neomucosa on patched intestinal defects. This effect may be dependent on increased polyamine biosynthesis. The aim of this study was to determine if difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis, would inhibit urogastrone stimulation of neomucosal growth. Twenty-four New Zealand white rabbits (2.1-2.9 kg) had 2 x 5-cm ileal defects patched with adjacent cecal serosal surface. Group I (n = 6) served as controls. Group II (n = 6) received UG 1.5 micrograms/kg/hr subcutaneously. Group III (n = 6) took 2% DFMO orally. Group IV (n = 6) received the same doses of UG and DFMO simultaneously. Animals were sacrificed 7 days after patching to assess neomucosal growth. Urogastrone infusion resulted in significantly greater neomucosal coverage (54 +/- 4%) and neomucosal surface area (236 +/- 18 mm2) in the Group II animals. Neomucosal coverage and contraction of the intestinal defects and neomucosal surface area were similar in the other three groups. Crypt cell production rate (15.5 +/- 2.0 cells/hr) and disaccharidase activity were also significantly greater in Group II than in the other groups. DFMO alone (Group III) resulted in a significantly lower ornithine decarboxylase (ODC) activity, polyamine content, and crypt cell production rate. Group IV animals had lower ODC activity but not lower polyamine content or crypt cell production rate. UG resulted in a significant increase in neomucosal growth. DFMO prevented this stimulatory effect and inhibited ornithine decarboxylase activity. The stimulation of neomucosal growth by UG is dependent, at least in part, on increased polyamine biosynthesis.

Animals↗
PubMed1988

Intestinal glucose uptake is increased in aged mice.

Carbohydrate metabolism is impaired in the aged. Whether this is related to impaired glucose uptake or to other factors remains unclear. We measured changes in proliferative activity, glucose uptake, and disaccharidase activity in the intestinal mucosa of mice aged 2, 12, 24, and 30+ months to evaluate glucose absorption and its relationship to intestinal structure and proliferative activity. In vitro glucose uptake was increased significantly in the 30+ month-old mice compared to the younger animals. Similarly, crypt cell production rate and thymidine uptake were also increased. However, there were no significant changes in intestinal weight and length and villus height and crypt depth. These findings suggest that altered carbohydrate absorption in the aged is related to factors other than diminished mucosal glucose uptake. Whether this increased function is related to structural changes in the gut remains unclear.

Aging↗
PubMed1988

Cutaneous tumor of northern pike, Esox lucius L. II. Expression of surface and cytoplasmic immunoglobulins and alpha-naphthyl acetate esterase by mononuclear cells from lymphoid tissues and tumor.

Rabbit anti-pike IgM antibodies showed that up to 95% of mononuclear (MN) cells isolated on Ficoll-Isopaque gradients from peripheral blood, spleen, and head kidney of northern pikes carrying cutaneous tumors were surface (SIg) and cytoplasmic (CIg) immunoglobulin positive by indirect immunofluorescence. On the contrary, rabbit anti-winter flounder IgM antibodies gave totally negative results. Monoclonal anti-carp IgM antibodies stained approximately 40-56% of peripheral blood, splenic, and head kidney MN cells in assays for SIg and CIg. Monoclonal anti-rainbow trout IgM antibodies, however, did not cross-react with pike Ig. A maximum of 5% of MN cells from the tumor were SIg and CIg positive by anti-pike IgM as well as 6% by anti-carp IgM antibodies, and were negative by the other two antibodies even at low dilutions. A majority of cells in the tumor exhibited an intense diffuse staining pattern for alpha-naphthyl acetate esterase (ANAE) which was inhibited by sodium fluoride and was reminiscent of that noted in human monocytes. These findings show that the Aland pike neoplasm is not a B cell tumor or plasmacytoma, but more representative markers are needed to demonstrate whether it is of T lymphocytic or monocytic origin.

Animals↗
PubMed1988

The role of nontransplant procedures for sclerosing cholangitis.

Twenty-five of 38 patients with sclerosing cholangitis underwent operative therapy at our institution. Seven patients with primarily extrahepatic obstruction had biliary bypass procedures and maintained normal liver function for 1 to 96 months. Biliary procedures were performed in 11 patients with combined intrahepatic and extrahepatic disease. Seven patients underwent subsequent liver transplantation because of deteriorating hepatic function, and two patients died before transplantation could be performed. Although there were no significant differences in outcome of liver transplantation whether or not a biliary procedure had been performed previously, previous biliary tract procedures influenced the type of biliary reconstruction performed, and two complications occurred as direct results of prior operations. Nontransplant procedures should be restricted to those patients with primarily extrahepatic obstruction, whereas liver transplantation should be considered the initial procedure of choice for patients with diffuse sclerosing cholangitis.

Adolescent↗
PubMed1988

Effect of urogastrone on intestinal regeneration is dose-dependent.

Urogastrone (UG) increases the rate of intestinal regeneration in intestinal defects patched with adjacent serosal surfaces by increasing the rate of epithelial cell migration and proliferation. It also inhibits contraction of the patched intestinal defect. The purpose of this study was to determine the effect of the dose of UG on these processes. Twenty male New Zealand white rabbits (1.9-2.9 kg) had 2 x 5 cm ileal defects patched with adjacent caecal serosal surface. Group I (n = 6) served as the control group. Group II (n = 5), Group III (n = 5) and Group IV (n = 4) received UG 0.15, 1.5 and 4.5 micrograms/kg/h i.v. via mini-osmotic pumps. Seven days after patching, both epithelialization of the patched defect and neomucosal surface area were significantly increased by UG and the increases were dose-dependent. Contraction was not inhibited by the lowest dose of UG but was diminished by 1.5 micrograms/kg/h. Proliferative activity in both neomucosa and adjacent normal mucosa were increased in UG-treated animals with the greatest increase in rabbits receiving 1.5 and 4.5 micrograms/kg/h UG. The effect of UG on both epithelialization and contraction of patched intestinal defects is dose-dependent. Since the lowest dose of urogastrone increased epithelialization without increasing proliferative activity, stimulated cell migration appears to be the earliest effect of UG.

Animals↗
PubMed1988

Postoperative pancreatitis.

Our experience with 52 patients who had postoperative pancreatitis develop during a nine year period was reviewed to characterize this group, to determine the incidence of complications and to identify variables predictive of complications. Biliary tract procedures (n = 10), colectomy (n = 9) and intestinal resection (n = 9) were the most frequently performed operations preceding pancreatitis. Thirty of the procedures were near the pancreas. Pancreatitis was detected within seven days of the operation in 26 of the patients. Sixteen patients had complications related to the pancreas, 12 had other nonlethal complications and nine died. Fourteen patients had severe pancreatitis (greater than or equal to 3 Ranson's criteria) and were more likely to have a complicated course (p less than 0.05). Complications related to the pancreas included pancreatic pseudocyst (n = 9), abscess (n = 4), fistula (n = 2) and arterial hemorrhage (n = 1). Age, operation performed, serum amylase level and frequency of hypotension, renal failure and other complications were similar in patients with and without complications related to the pancreas. A high index of suspicion must remain throughout the postoperative period to recognize inflammation of the pancreas and its complications so that prompt diagnosis and management can be undertaken.

Acute Disease↗
PubMed1988

Laboratory control in predicting clinical efficacy of T cell-depletion procedures used for prevention of graft-versus-host disease: importance of limiting dilution analysis.

In an attempt to assess the usefulness of partial elimination of T lymphocytes from histocompatible donor bone marrow as a sole method of graft-versus-host disease prophylaxis in patients undergoing bone marrow transplantation, we compared in vitro and clinically the efficacy of two depletion protocols, each resulting in a different degree of T cell reduction. The protocols were based on complement-dependent T cell lysis induced either by one (T10B9) or two (T10B9 and T12A10) monoclonal antibodies, contributing respectively to 95% and 99% depletion of T cells defined functionally by limiting dilution analysis. Phenotypic analysis was unsuitable for detecting differences in the efficiency of the two depletion modalities due to very low numbers of residual OKT3-positive cells generally present. Of the 34 patients with advanced leukemias transplanted with marrow from HLA-matched sibling donors, 26 (ages 15-52) received two-antibody depleted grafts (group I) with subsequent incidence of severe acute graft-versus-host disease of 8% (in two of 24 engrafted). The T cell dose for two patients of this group whose grafts were directly evaluated by limiting dilution analysis was less than 2 x 10(5)/kg and presumably did not exceed 3.2 x 10(5)/kg for others, based on the depletion efficiency of the protocol estimated in additional small marrow samples. The remaining eight patients (ages 8-55) received one-antibody depleted grafts (group II) with 5-18 x 10(5) T cells/kg defined functionally in five grafts. Severe acute graft-versus-host disease (grade 3-4) developed in all seven engrafted subjects. Although with phenotypic analysis several grafts in this group revealed no residual T lymphocytes, they apparently carried doses of donor T cells not tolerable in a HLA-identical host unprotected by additional immunosuppression. Careful evaluation by functional T cell analysis should be considered in choosing a depletion protocol as a method for reducing the risk of graft-versus-host disease in allogeneic bone marrow transplantation.

Adolescent↗
PubMed1988

Intestinal mucosa diamine oxidase activity reflects intestinal involvement in Crohn's disease.

The activity of diamine oxidase (DAO), an enzyme found in the apical villous cells of the small intestine mucosa, should reflect the status of the intestinal mucosa. Our purpose was to determine whether DAO activity in the intestinal mucosa is diminished in patients with Crohn's disease and correlates with the severity of histological changes. Mucosal DAO activity was determined in 42 tissue specimens from patients with Crohn's enteritis (n = 15), Crohn's colitis (n = 9), and ulcerative colitis (n = 11), and from patients with no intestinal disease (n = 7). DAO activity was estimated by the metabolism of [14C]putrescine. Histologic changes were graded on a scale of 0-4. Normal histology was graded as zero, mild edema, and inflammation in the lamina propria as one, crypt abscess formation and inflammation as two, more severe inflammation plus or minus granulomata as three, and most severe inflammation with active ulceration as four. Tissue DAO activity was significantly less in patients with ileitis (4.8 +/- 3.6) compared with those with Crohn's colitis (15.0 +/- 11.6), ulcerative colitis (16.8 +/- 19.7), and normal intestine (17.6 +/- 14.3 U/mg protein/h, p less than 0.05). Intestinal DAO activity showed a positive correlation with the histologic scores. Recurrence of Crohn's disease developed postoperatively in two patients with low tissue DAO activity (1.4 and 2.9 U/mg protein/h). Intestinal DAO activity is diminished in patients with Crohn's ileitis and correlates with the severity of histologic changes. Tissue DAO activity might prove useful in predicting the risk of recurrence or anastomotic complications after resection for Crohn's disease.

Adult↗
PubMed1988

Morphologic and nutritional responses to intestinal patching following intestinal resection.

Growth of neomucosa has been investigated as a means to increase intestinal surface area in the short-bowel syndrome. Functional neomucosa grows over patched intestinal defects, but the effect of the patching procedure on absorption is unknown. The purpose of this study was to determine morphologic and nutritional responses to intestinal patching after resection. Fifteen dogs (13 to 19 kg) underwent either 75% resection of the small intestine (control group, n = 5), simultaneous resection and patching of the intestinal remnant with colon serosa (simultaneous group, n = 5), or resection with patching 12 weeks later (delayed group, n = 5). Caloric intake was standard in the three groups. Animals were killed 40 weeks after resection or patching. At that time, defects were 95% covered with neomucosa in both patched groups. Intestinal remnant length increased significantly in controls (139 +/- 20% initial length) compared to the simultaneous group (99 +/- 6%, p less than 0.05) but not to the delayed group (119 +/- 11%). Villous height of intestinal mucosa was greater in the control and delayed groups than in the simultaneous group (714 +/- 36 and 624 +/- 111 versus 535 +/- 54 micron, p less than 0.05). Fasting gastrin levels were significantly greater in patched animals than after resection alone (p less than 0.05). Intestinal transit by barium meal was significantly longer in patched animals (18 +/- 7 minutes versus 11 +/- 6, p less than 0.05). Body weight and serum albumin level were significantly lower in patched animals at death. Fecal weight, moisture, and fat excretion were significantly increased in the simultaneous group. Although intestinal patching results in the growth of neomucosa and prolonged transit time, it has a deleterious effect on absorption and nutritional status. In part, this may be related to inhibition of intestinal adaptation and gastric hypersecretion in patched animals.

Animals↗
PubMed1987

The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage.

Anti-CD3 (T3) Ab reacting with different proportions of thymocytes (anti-CD3a: UCHT1, anti-CD3b: T10B9, and anti-CD3c: OKT3) were tested for cytoplasmic (cCD3) and membrane (mCD3) expression in the bone marrow, thymus, and blood in man and selected primates. The expression of cCD3a and cCD3c in the perinuclear and Golgi area of large, BrdU-incorporating, strongly TdT+ thymic blasts probably represents one of the earliest signs of T cell commitment, because these blast cells are CD1-, CD4-, CD8-, and mCD3-. The cCD3+, TdT+ cells are normally restricted to the thymus and are absent among the TdT+ cells of bone marrow. The anti-CD3b Ab used, T10B9, co-caps and co-modulates with the other anti-CD3 Ab and is a T cell-specific reagent at a membrane level but does not bind to perinuclear cCD3. Instead, this reagent cross-reacts with a filamentous cytoplasmic network in non-T cells in man and in primates S. oedipus and M. rhesus despite their T cell negativity for mCD3. The characteristics of all T-ALL cases studied: cCD3+, CD7+ along with nuclear TdT+ suggest lineage fidelity to early thymic blasts. As a marked contrast, cCD3 is absent in common ALL and in AML, including cases that concomitantly express CD7 and myeloid antigens. Thus, the cCD3, TdT combination provides a very sensitive assay for residual T-ALL blasts outside the normal thymus.

Adult↗
PubMed1987

Growth of neomucosa after intestinal resection.

The growth of neomucosa over patched intestinal defects may prove useful in the short-bowel syndrome. This study was done to determine if the timing of intestinal patching with respect to intestinal resection affects neomucosal growth. Twelve dogs underwent 75% intestinal resection, with intestinal patching done either simultaneously or 12 weeks later. Energy intake, final body weight, albumin level, and length of remnant patched were similar in both groups. Forty weeks after patching, neomucosal coverage of the defect (95.2% +/- 2.0% vs 94.2% +/- 1.6%), neomucosal surface area (36.2 +/- 4.5 vs 31.8 +/- 2.9 cm2), and patch size (56.2% +/- 6.8% vs 51.9% +/- 9.7%) were similar in both the simultaneous and delayed groups, as were villus height of neomucosa and disaccharidase activity. Neomucosal growth is similar whether intestinal patching is performed simultaneously or 12 weeks after resection. Intestinal patching is not indicated at the initial intestinal resection.

Animals↗
PubMed1987

Strategies for preserving intestinal length in the short-bowel syndrome.

Total parenteral nutrition now permits long-term survival in patients after massive intestinal resection. Surgical therapy for the short-bowel syndrome is still largely experimental and cannot be recommended routinely. Thus, prevention of intestinal resection and conservation of intestinal length, when resection is necessary, should be emphasized. Strategies are presented that can be employed to preserve intestinal length when surgery is required in patients with a shortened bowel. These include strictureplasty, minimal resection, serosal patching, and intestinal tapering. In suitable candidates strictureplasty can relieve obstruction from strictures while avoiding resection. Minimal resection of involved intestine can be performed safely in selected patients with radiation injury or Crohn's disease. Serosal patching is an alternative to resection for the treatment of perforation or strictures of the intestine. Intestinal tapering can improve the function of dilated intestinal segments and eliminate the need for resection in intestinal atresia. The judicious use of these procedures can preserve intestinal length and obviate the need for long-term parenteral nutrition in patients after massive intestinal resection.

Aged↗