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Biomedical subjects

T Karatzas

Publications and source records attributed to T Karatzas.

36 records · Page 2Linked to original sources

An assessment of the effects of cadaver donor bone marrow on kidney allograft recipient blood cell chimerism by a novel technique combining PCR and flow cytometry.

A new technique, the PCR-flow assay is described that has allowed for the serial identification and quantitation of discrete mononuclear cell subsets of donor (or recipient) bone marrow derived cells in cadaver kidney transplant recipients infused postoperatively with donor vertebral body bone marrow cells. With fixed permeabilized cells in flow cytometry the amplification power of the polymerase chain reaction (PCR), using fluorescent-labeled primers to identify single copy HLA class II DRbeta1 genes of either donor or recipient origin, is combined with multi-color fluorochrome-labeled CD epitope-specific monoclonal antibodies. The details of the methodology are described; these support the utility of the assay. Initial observations were made on the chimeric makeup of the peripheral blood as well as iliac crest bone marrow between six months and one year posttransplantation in recipients serially followed weekly and then monthly, concomitantly compared with a control group of stable kidney transplant recipients using similar therapeutic protocols, who did not receive cadaver bone marrow. Several findings are of note. In 14 recipients of two bone marrow infusions totalling a mean of 6.29+/-2.18x10(10) cells, donor CD34 positive (+) (immature) cells were fourteen times as numerous in peripheral blood six months postoperatively as in six recipients given half as many bone marrow cells in one infusion (averaging 3.02+/-0.5x10(10)). These donor CD34+ cells unexpectedly averaged 36+/-7% of the total (donor plus recipient) CD34+ subset counted. Moreover, iliac crest bone marrow aspirates contained an average of thirteen times this number of CD34+ cells than in the peripheral blood, supporting the notion of engraftment. Of additional interest, between six months and one year posttransplant although no donor cells could be detected in peripheral blood of the controls there was an identifiable presence of donor CD34+ cells in their iliac crest bone marrow, albeit 10-fold less than the marrow-infused patients. In the clinical follow-up, although there were three unrelated mortalities, there were no additional kidney losses with current serum creatinine concentrations averaging 1.3+/-0.06 mg/dl. In conclusion, the PCR-flow assay presents the possibility of identifying discrete subsets of donor or recipient cells that may have an immunoregulatory function.

Adoptive Transfer↗

Transplant-associated autoimmune mechanisms in human hepatitis C virus infection.

In order to define factors which are important for the development of hepatitis C virus (HCV) infection and disease in transplant patients, we examined the role of class II MHC antigen restriction in viral antigen presentation to support a hypothesis of the association of this disease with an autoimmune pathogenesis. A greater degree of histocompatibility match between these donors and their HCV-negative recipients was associated with a greater predisposition to recipient HCV liver disease (ALT elevation) posttransplant. The HCV carrier state could be identified with significant amplification of autologous mixed lymphocyte reactivity (AMLR) in both long-term hemodialysis and long-term renal transplant patients, but the AMLR was absent in end-stage liver disease patients with HCV-associated cirrhosis and was insignificantly elevated in these patients with persistent infection in the first 2 years after a new liver was transplanted. There was also a moderate reduction in autologous reactivity as well as serum HCV titers among renal transplant patients who displayed biochemical evidence of chronic liver disease as opposed to those who did not. This appeared later in the course of the disease. HCV RNA could be detected in peripheral blood mononuclear cells (PBMC) of only a portion of HCV-infected renal transplant patients and these showed significantly higher autologous reactivity. In contrast, despite the fact that observations were earlier after de novo liver transplantation, HCV RNA (i.e., earlier in the course of a new or recurrent disease process) was found in PBMC of all liver transplant recipients tested. The AMLR of noninfected laboratory volunteers could be amplified by preincubating their stimulating cells (APCs) with enriched HCV possibly in immune complex (pHCV-IC). This amplification appeared only with specific combinations of HCV strains with HLA DR serotypes. In addition, HCV-primed T cells could be generated to the virus which displayed accelerated activation kinetics. Liver infiltrating lymphocytes extracted from HCV-positive end-stage diseased livers had significantly higher proliferative and cytotoxic reactivity to autologous (HCV-infected) hepatocytes than the extracted lymphocytes responding to autologous hepatocytes from HCV-negative livers. These findings offer evidence of dynamic autoimmune mechanisms in the spectrum of progression of HCV disease and may help to predict the effect of intervention at various intervals in this progression in organ transplant recipients.

Autoimmune Diseases↗

Successful treatment of postoperative external biliary fistula by selective nasobiliary drainage.

A 25-year old man presented with a high output external biliary fistula after an operation for a giant hydatid cyst of the liver. Endoscopic sphincterotomy was inadequate to close the fistula. A nasobiliary tube was selectively inserted into the leaking hepatic duct and bile was continuously aspirated. The fistula and the residual cavity healed completely. Details of the patients' management using this alternative technique, are discussed.

Adult↗

Neurotensin reduces microbial translocation and improves intestinal mucosa integrity after abdominal radiation.

The effect of neurotensin (NTN) on preventing microbial translocation and preserving intestinal mucosal integrity after abdominal radiation was studied in rats. Animals were divided into the following groups: I (control), II (radiation control) and III (radiation and NTN). Radiation (1,100 cGy) was administered on the 1st day to groups II and III. NTN (300 micrograms/kg) was given intraperitoneally to group III animals, once daily for 3 days. On the 4th day, mesenteric lymph nodes (MLN) were obtained and cultured. Villi per centimeter (V/cm), villus height (Vh) and mitoses per crypt (M/c) were evaluated from ileal mucosa. Radiation increased positive MLN cultures, while treatment with NTN reduced them significantly. V/cm and Vh also returned to normal levels after NTN treatment, while M/c were increased in all irradiated animals. It was shown that NTN reduces bacterial translocation after abdominal radiation. Examination of ileal mucosa indicates that this can be attributed to the improvement of the mucosal integrity, due to the trophic effect of the hormone on the gut.

Animals↗

Effect of glutamine on intestinal mucosal integrity and bacterial translocation after abdominal radiation.

This study evaluates the effect of oral glutamine on intestinal mucosal integrity and bacterial translocation in rats. 80 animals were randomised into four groups: group 1 (chow diet and water), group 2 (chow diet and glutamine 3%), group 3 (radiation, chow diet and water), group 4 (radiation, chow diet and glutamine 3%). Groups 1 and 2 were fed for 5 days, then sacrificed. Groups 3 and 4 were fed for 12 days, irradiated on the 5th day and sacrificed on 1st, 3rd and 7th post-radiation days. Cultures from the mesenteric lymph nodes (MLN), portal vein (PV) and aorta (A) were taken and two tissue samples were also taken from the terminal ileum for light and electron microscopic examination. In non-radiated rats glutamine did not alter the histologic parameters of villous height (VH), mitoses per crypt (M/C) and muscle thickness (MT). Group 3 rats had severe mucosal damage associated with a significant decrease of VH (p < 0.0001) and M/C (p < 0.01) on 1st and 3rd post-radiation days respectively. In contrast, group 4 rats maintained their mucosal structure and had a significant increase of VH and M/C (p < 0.0001) on post-radiation days 1 and 3. Bacterial translocation in MLN was 87.5% (p < 0.002) and 75% (p < 0.04) on 1st and 3rd post-radiation days respectively in group 3, and fell significantly to 12.5% (p < 0.002) in group 4. The data demonstrate that glutamine helps maintain the integrity of the intestinal mucosa and thereby reduces the incidence of bacterial translocation following abdominal irradiation.

Journal Article↗

Determination of upper arm muscle and fat areas using electrical impedance measurements.

An electrical impedance technique is described which enables the cross-sectional areas of fat and muscle in the upper arm to be recorded. By making comparisons with measurements obtained using the x-ray technique of computerised tomography (CT) scanning it is shown that fat can be determined to a mean accuracy of 2.3 cm2 and muscle to a mean accuracy of 1.5 mm2. These results are more accurate than a parallel set of measurements made using the traditional anthropometric technique.

Adipose Tissue↗

Mesenteric fibromatosis.

Mesenteric fibromatosis is commonly associated with Gardner's syndrome and familial polyposis. These lesions may have an insidious onset via compression of the small or large intestines, or may be noted for the first time during abdominal exploration for some other cause. Differential diagnosis may be difficult. We report a case of mesenteric fibromatosis with two recurrences, and two cases with no evidence of tumour recurrence.

Adult↗