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Biomedical subjects

B Garcia

Publications and source records attributed to B Garcia.

At least 19 recordsLinked to original sources
PubMed1992

Nuclear DNA density of parathyroid lesions.

Nuclear DNA density analysis was carried out on six normal control human parathyroid glands and forty-six pathological lesions of human parathyroid tissue. The pathological glands had originally been classified as twenty hyperplasias, twenty-one adenomas, and five carcinomas in accordance with clinical-pathological information. Specimens had been obtained through the Surgical Pathology Department of the University Hospital, London, in the form of either imprints from the cut surface of a lesion, or as cell separation samples from a paraffin block. Nuclear DNA ploidy analysis of the normal glands showed, as expected, a diploid cell population. Sixty-one percent of nuclei of the carcinomas were above 2C, extending to 7C. There was a significant difference in nuclear DNA content between normal and benign tissue versus tissue classified as carcinoma. No significant difference in nuclear DNA ploidy could be established between the benign adenoma and hyperplasia tissue; however, marked significant DNA ploidy differences were found between tissue from the latter two and carcinoma. DNA ploidy from cell image analysis using Feulgen's reaction can be useful in establishing a differential diagnosis between carcinoma and benign lesions.

Adenocarcinoma↗
PubMed1992

Metalloproteinase activities expressed during development and maturation of the rat prostatic complex and seminal vesicles.

The objective of this study was to characterize proteinase activities expressed during development and maturation of the prostate gland and seminal vesicles of the rat by using gelatin-and casein-containing SDS polyacrylamide gel zymography. The prostatic complexes of 2- and 10-day-old animals and the individual lobes of the prostate (ventral, dorsolateral, and anterior [coagulating gland]) and the seminal vesicles of 15-day-old animals expressed prominent gelatinolytic activities of approximately 64, 71, and 76 kDa. These activities had properties of metalloproteinases; i.e., they were stimulated by Ca2+ and inhibited by EDTA and EGTA. They were greatly diminished by 52 days of age (immediately postpuberty) and were not detected in the dorsal lobe of the adult. Less active gelatinolytic proteinases with molecular masses of approximately 34 and 43 kDa were expressed in the developing prostatic complexes and individual lobes and seminal vesicles, but they were not detected in postpubertal animals. Weak gelatinolytic activities of 82, 85, and 89 kDa were found in the prostatic complexes; these activities were greatly diminished in all prostate lobes with sexual maturation but were expressed in the seminal vesicles at all ages. A large-molecular-mass Ca(2+)-independent proteinase of 130 kDa or greater was first detected in the dorsolateral prostate at 21 days of age. This activity was expressed in both the lateral and dorsal lobes of the adult but was greater in the lateral lobe. Proteinase activities of about 22 and 26 kDa that were not stimulated by Ca2+ were detected in the ventral prostate at 15 days of age by means of both gelatin and casein gels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Histological and immunopathological analysis of recovered encapsulated allogeneic islets from transplanted diabetic BB/W rats.

Allogeneic islets encapsulated in an alginate/poly-L-lysine membrane and transplanted into diabetic BB/W rats resulted in graft failure within 2 weeks of transplantation. Graft failure was associated with a dense pericapsular infiltrate (PCI) that resulted in necrosis of the encapsulated islets. The PCI could be inhibited by immunosuppressive agents, including cyclosporine and dexamethasone, and this resulted in a significant increase in graft survival. Immunopathological characterization of the PCI indicated that there was a predominance of macrophages. T helper cells also appeared to be present in this PCI. Empty capsules were also found to induce a similar PCI that was identical in composition to that found around encapsulated islets. Thus alginate/poly-L-lysine capsules do not appear to be biocompatible and may account for the variable results in islet graft survival found with these capsules.

Animals↗
PubMed1991

Mechanisms of rejection during OKT3 therapy: propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft.

Allograft rejection remains the single largest impediment to success in the field of transplantation. While OKT3 therapy has proven to be a significant advancement, many grafts are still lost. Late treatment, subtherapeutic OKT3 levels, anti-OKT3 antibodies, and OKT3-induced class II antigen expression are possible explanations. To determine the mechanism of OKT3 resistant rejection we propagated and characterized infiltrating T cells from the biopsy of a liver transplant patient who was rejecting while on prophylactic OKT3. The T lymphocytes demonstrated allospecific proliferation and interleukin 2 (IL2) production and showed a high degree of cytolysis of donor splenocytes. CD3 epsilon monoclonal antibodies (Mab) in concentrations up to 100 micrograms/ml did not inhibit lysis. In contrast, T lymphocytes derived from rejecting allografts of patients receiving cyclosporine and prednisone were readily inhibited from killing by CD3 epsilon Mab at doses of 1 microgram/ml. Furthermore, allospecific proliferation and IL2 production were not inhibited in the OKT3-treated patient by the addition of CD3 epsilon MaB. Incomplete modulation of the CD3-TCR complex was noted after a 72-hr incubation with CD3 epsilon Mab. The T cells did demonstrate other intact CD3-mediated functions such as a rise in intracellular calcium and CD3-dependent cytotoxicity. These results should alert clinicians that CD3 resistant cytotoxic T cells can emerge during OKT3 therapy and may cause rejection. Immunotherapy that targets additional cell surface structures may be of benefit.

Antibodies, Monoclonal↗
PubMed1991

Magnetic resonance imaging for detecting and treatment monitoring of orthotopic murine bladder tumor implants.

We assessed the feasibility of magnetic resonance imaging (MRI) for detection and treatment monitoring of early stage orthotopic murine bladder (MBT-2) tumor implants. Thirty mice were scheduled for imaging at six, 14, 18 and 21 days after tumor implantation. Using a volume imaging coil, MRI demonstrated very early orthotopic tumors, the detection of which would otherwise have been impossible by clinical signs only. Sequential accurate assessment of tumor size was achieved by inflation of the bladders with a fixed volume of Gadolinium-DTPA contrast. The presence of established MBT-2 intravesical tumors was confirmed by gross pathology and light microscopy of the corresponding whole mount bladder sections. Histological examination of the corresponding tumor specimens revealed the presence of transitional cell bladder carcinoma which correlated very well with the topography and depth of tumor involvement as indicated on MRI. The The mice tolerated repeated MR imaging well. Early tumors at day 14 were detectable on MRI (with serial tumor growth to day 21), with no clinical signs of disease. In a subsequent study, response to intravesical tumor necrosis factor alpha (TNF-alpha) immunotherapy was monitored with serial MRI. The serial MR images from six tumor-bearing mice (three controls and three TNF-alpha treated) have been selected to illustrate the consistent findings of this study. Sequential MRI scans of TNF-alpha treated mice revealed retardation of tumor growth that correlated well with the corresponding histologic examination. The orthotopic tumor and MRI model described is ideal for preclinical evaluation of new potential intravesical chemotherapy and immunotherapy agents.

Administration, Intravesical↗
PubMed1991

A comparison of heterotopic and orthotopic intestinal transplantation in rats.

Two surgical techniques are commonly used for small intestinal transplantation: heterotopic (accessory) intestinal grafting (HIT), where the small bowel is initially defunctioned with restoration of intestinal continuity at a later date, and orthotopic (in continuity) intestinal grafting (OIT), where the small bowel is immediately anastomosed to the native intestine. The present experiments were undertaken to compare the advantages and disadvantages of these two surgical models. Graft barrier function (intestinal permeability), intestinal histology, and graft survival were evaluated after heterotopic and orthotopic intestinal transplantation in the following groups of rats: group 1: isografts, group 2: untreated allografts, group 3: low-dose cyclosporine-treated allografts (subcutaneous CsA 2 mg/kg/day), and group 4: high-dose CsA-treated allografts (subcutaneous CsA 4 mg/kg/day). Intestinal permeability was consistently higher after HIT than OIT in all of the groups (ANOVA; P less than 0.01). Histological evidence of rejection appeared earlier after HIT than OIT (HIT 5th postoperative day (POD); OIT 7th POD; P less than 0.05). The mean survival of untreated allografts was longer after HIT than OIT (HIT 15.7 +/- 6 days, OIT 9.2 +/- 1 days, P less than 0.05). The rats treated with low-dose CsA after OIT lost weight and died of rejection after a mean survival time of 17.7 +/- 2 days, while the rats treated with low-dose CsA after HIT remained well until sacrifice on POD 28 (P less than 0.01). The rats with isografts and rats with allografts treated with high-dose CsA remained well after HIT and OIT until sacrifice on the 28th POD. These data suggest that nutrients and other factors in the succus entericus may improve gut barrier function and delay the onset of rejection after OIT. However, rejection of the orthotopic intestinal graft is usually fatal, while rejection of the heterotopic graft is often surprisingly well tolerated. These factors must be taken into consideration when choosing a surgical technique for intestinal transplantation in humans.

Animals↗
PubMed1991

Intestinal permeability and bacterial translocation following small bowel transplantation in the rat.

In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. The present study evaluated gut barrier function following orthotopic (in continuity) intestinal grafting in rats. Graft histology, intestinal permeability, and bacterial translocation to the grafted mesenteric lymph nodes, the host's liver, and the host's spleen were assessed on the 3rd, 5th, and 7th postoperative days. The study group received no immunosuppression after allotransplantation. The two control groups included rats with isografts and rats with cyclosporine-treated allografts. On the 7th POD, the study animals had moderate transmural inflammation due to rejection, with normal histology in the isografts and CsA-treated allografts; increased intestinal permeability, measured by urinary excretion of oral 51Cr-EDTA (P less than 0.01); and increased number of bacteria in the MLN and spleen (P less than 0.05). The number of bacteria in the MLN and spleen of the study group positively correlated with the changes in intestinal permeability (P less than 0.05). Rejection of the orthotopic intestinal graft leads to increased intestinal permeability and bacterial translocation from the lumen of the graft to the host's reticuloendothelial system. Measures to improve gut barrier function and antibiotic therapy during rejection episodes may help reduce the incidence of septic complications after intestinal grafting.

Animals↗
PubMed1990

Successful small-bowel/liver transplantation.

A patient with the short-gut syndrome and antithrombin III deficiency underwent small bowel and liver grafting a year ago. Transient, mild graft-versus-host disease and intestinal rejection occurred within 2 months of grafting and were easily managed. Parenteral nutrition was discontinued 8 weeks after surgery. The patient has maintained normal nutritional indices while on an unrestricted oral diet. Small-bowel/liver grafting is feasible for patients with the short-gut syndrome and associated liver disorders. Further experience is needed to determine the specific risks, benefits, and general applicability of this procedure.

Adult↗
PubMed1989

51Cr-EDTA: a marker of early intestinal rejection in the rat.

Intestinal permeability was studied after accessory intestinal transplantation in Lewis rats. Five groups were evaluated: Group 1--isografts (N = 6); Group 2--Lewis X Brown Norway F1 (LBN-F1) allografts (N = 6); Group 3--isografts treated with CsA 2 mg/kg/day X 10 days (N = 6); Group 4--LBN-F1 allografts treated with CsA 2 mg/kg/day X 10 days (N = 6); Group 5--LBN-F1 allografts treated with CsA 4 mg/kg/day X 28 days (N = 6). Chromium-labeled ethylenedimianetetraacetate (51Cr-EDTA) was given through the proximal stoma of the graft. Renal clearance of 51Cr-EDTA and mucosal biopsies were followed post-transplant. The biopsies of the intestinal graft showed no rejection in Groups 1, 3, and 5; fulminant rejection in Group 2; and mild atypical rejection in Group 4. 51Cr-EDTA clearance was elevated in all groups during the first 7 days post-transplant. Thereafter, 51Cr-EDTA excretion fell to lower levels in the animals with histologically normal grafts (Groups 1, 3, and 5). 51Cr-EDTA excretion in Group 4 was increased with the first histological evidence of rejection on Day 14 and remained elevated until sacrifice (P less than 0.02 compared to Groups 3 and 5). A transient permeability defect occurs after intestinal grafting. Once the graft has recovered from this injury, 51Cr-EDTA is a sensitive marker for intestinal rejection.

Administration, Oral↗