Biomedical subjects

Z Cohen

Publications and source records attributed to Z Cohen.

At least 91 records · Page 5Linked to original sources

PubMed1997

Preliminary report on the Mount Sinai Hospital Inflammatory Bowel Disease Genetics Project.

BACKGROUND: Although the etiology of inflammatory bowel disease (IBD) is unknown, there is increasing evidence that genetic predisposition plays a major etiologic role. To provide the framework for gene identification using a positional cloning approach, ascertainment of families with multiple affected members and careful documentation of pedigrees are essential. OBJECTIVE: To report the initial findings of the IBD Genetics Project of the Mount Sinai Hospital IBD Research Unit. METHODS: All records of patients with ulcerative colitis and Crohn's disease followed at the Mount Sinai Hospital IBD Unit were reviewed. A questionnaire was sent to all patients to ascertain those with a family history of IBD. Patients with a presumed family history were contacted by a research assistant, and after confirmation of diagnosis, relevant clinical information, pedigrees, and consent to contact family members were obtained. Blood for DNA and cell line preparation were collected from affected and nonaffected family members. RESULTS: Of 2,504 patients registered in the IBD database, 231 (9.2 percent) were found to have an affected family member: 96 of 964 (10 percent) with Crohn's disease (CD) and 135 of 1,540 (8.8 percent) with ulcerative colitis (UC). A mean of 2.4 family members were affected. In families in which the proband had CD, 82.3 percent had only two affected family members, 78.1 percent had only family members affected with CD, and 82.3 percent had only first-degree family members affected. In families in which the proband had UC, 70.4 percent had only two affected family members, 71.1 percent had only family members affected with UC, and 65.2 percent had only first-degree family members affected. In the 231 families, there were 103 sibling pairs: 46 percent with CD, 28 percent with UC, and 26 percent with CD/UC. CONCLUSION: These data suggest that approximately 10 percent of IBD patients have affected family members, with the rate being similar in UC and CD. Future research is directed to genome scanning and linkage analysis in this cohort of patients.

Colitis, Ulcerative↗

PubMed1997

Chemotherapy for desmoid tumors in association with familial adenomatous polyposis.

PURPOSE: This study was designed to assess the effect of chemotherapy on complex desmoid tumors associated with familial adenomatous polyposis. METHODS: Five patients (3 males, 2 females; age range, 29-45 years) had symptomatic, unresectable intra-abdominal desmoid tumors in association with familial adenomatous polyposis that were unresponsive to conventional medical therapy. Each patient was treated with a cytotoxic chemotherapeutic regimen consisting of doxorubicin and dacarbazine followed by carboplatin and dacarbazine. Response to treatment was assessed by measurement of tumor size using computerized tomography. Follow-up has been for a mean of 22 (range, 10-30) months. RESULTS: One patient has had a complete response, and three patients have had a partial response, with a reduction in tumor volume of at least 50 percent. One patient had a minimum response to treatment and developed a rapid increase in tumor size on cessation of therapy. Complications of treatment included febrile neutropenia, severe epistaxis, and subclavian vein thrombosis. CONCLUSIONS: The cytotoxic chemotherapeutic regimen described is effective in the treatment of selected unresectable desmoid tumors associated with familial adenomatous polyposis and should be considered in symptomatic patients who do not respond to conventional medical therapy.

Adenomatous Polyposis Coli↗

PubMed1997

Outcome of the pelvic pouch procedure in patients with prior perianal disease.

PURPOSE: There is concern that patients with presumed ulcerative colitis and significant perianal disease may in fact have Crohn's disease. Moreover, prior perianal disease may be an independent factor for poor outcome of the pelvic pouch. The aim of this study was to evaluate the effect of prior perianal disease on pelvic pouch outcome. METHODS: Between 1982 and 1994, 52 of 753 patients (6.9 percent) who had a pelvic pouch procedure were prospectively identified as having perianal disease. Outcome of the pelvic pouch of these 52 patients (Group I) were compared with the outcome of 701 pelvic pouch patients with no prior perianal disease (Group II). The perianal diseases identified in Group I were fissure-in-ano (17), perianal abscesses (13), fistula-in-ano (7), rectovaginal fistula (3), and significant hemorrhoids/skin tags (25). Eleven patients (21 percent) had more than one type of perianal disease. Twenty-seven patients (52 percent) required a total of 33 perianal operations for the different anal pathologies. RESULTS: Both groups were comparable for the following characteristics: age at time of pelvic pouch procedure, pathology (ulcerative colitis or indeterminate colitis), design of pouch, and type of ileoanal anastomosis (handsewn or stapled). An ileoanal anastomosis leak developed in 21 percent of patients (n = 11) in Group I vs. 11.4 percent (n = 80) in Group II (P < 0.05). Perianal postoperative complications occurred in 11.5 percent of patients (n = 6) in Group I vs. 1.7 percent (n = 12) in Group II (P < 0.05). Total pouch failure rate was not significantly different between the two groups (11.5 vs. 7.6 percent; P > 0.05). Crohn's disease was subsequently diagnosed in 1.9 vs. 2.7 percent (P > 0.05). Subgroup analysis of Group I patients showed no significant difference in outcome according to type of perianal lesion or a history of perianal surgery. CONCLUSION: Prior perianal disease significantly increases the risk of developing an ileoanal anastomotic leak and postoperative perianal complications. However, a pelvic pouch procedure may be an acceptable surgical alternative for selected ulcerative colitis patients with prior perianal disease because the overall pouch failure rate is not significantly increased.

Adult↗

PubMed1997

Sulindac for periampullary polyps in FAP patients.

BACKGROUND: Gastro-duodenal polyps develop in up to 90% of familial adenomatous polyposis (FAP) patients and periampullary carcinoma is one of the most common extra-colonic malignancies in this syndrome. Periampullary adenomas have been shown to be precursor lesions to periampullary carcinoma. Sulindac, a non-steroidal anti-inflammatory drug, has been reported to cause regression of rectal polyps in FAP patients, however its role in periampullary polyp regression is unclear. METHODS: In May 1993, a prospective study was begun to evaluate the role of sulindac in prevention of polyp recurrence after resection of large (> 1 cm) duodenal polyps in FAP patients. Eight patients, mean age 50 years (range 35 to 65), with documented large periampullary polyps were placed on sulindac 150 mg twice daily. Prior to enrollment, all patients had their large polyps removed from the periampullary region by interventional endoscopy or by surgery. All patients had multiple small residual duodenal polyps. Follow-up was performed by one experienced endoscopist with a side-viewing video endoscope. Endoscopy was performed 6 monthly. Median follow-up time was 17.5 months (range 10 to 24 months). RESULTS: In 3 patients, sulindac was discontinued due to side effects: abdominal cramps (n = 2) and upper G-I bleeding (n = 1). None of the patients had regression of small periampullary polyps. In addition, one patient developed an invasive periampullary carcinoma while on sulindac and 3 patients developed large recurrent periampullary polyps requiring further treatment. SUMMARY: In our experience, sulindac is of no significant benefit for the control of periampullary polyps in FAP. Effective medical treatment of these polyps is still lacking.

Adenoma↗

PubMed1997

Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease.

BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic.

Actuarial Analysis↗

PubMed1997

Tissue plasminogen activator (tPA) inhibits human neutrophil superoxide anion production in vitro.

Because neutrophils contribute to reperfusion injury associated with acute myocardial infarction (MI), and because tissue plasminogen activator (tPA) is often used in the management of MI, we evaluated the effect of tPA on superoxide (O2.-) production by human neutrophils in vitro. We found that adding increasing amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced O2.- generation by neutrophils treated with phorbol myristate acetate (PMA) in vitro. Furthermore, adding tPA that had been previously treated with the protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone HCl (PPACK), also decreased neutrophil O2.- generation in vitro (P < 0.05). In contrast, adding L-arginine, a component of the tPA preparation and a precursor of nitric oxide (NO), did not inhibit PMA-induced neutrophil O2.- production. Also, adding increasing concentrations of tPA did not reduce (P > 0.05) the concentrations of O2.- produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces neutrophil O2.- generation by a mechanism that is not related to L-arginine, is not dependent on tPA proteolytic activity, and is not a function of direct scavenging. This property may account for some of the effectiveness of tPA in the treatment of MI and/or make tPA valuable for treating acute respiratory distress syndrome (ARDS) or other inflammatory disorders involving neutrophil O2.- production.

Amino Acid Chloromethyl Ketones↗

PubMed1997

Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex.

Noradrenaline (NA) has been shown to influence astrocytic and vascular functions related to brain homeostasis, metabolism, local blood flow, and blood-brain barrier permeability. In the current study, we investigate the possible associations that exist between NA-immunoreactive nerve terminals and astrocytes and intraparenchymal blood vessels in the rat frontoparietal cortex, both at the light and electron microscopic levels. As a second step, we sought to determine whether the NA innervation around intracortical microvessels arises from peripheral or central structures by means of injections of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine) (DSP-4), a neurotoxin that specifically destroys NA neurons from the locus ceruleus. At the light microscopic level, 6.8% of all NA-immunoreactive nerve terminals in the frontoparietal cortex were associated with vascular walls, and this perivascular noradrenergic input, together with that of the cerebral cortex, almost completely disappeared after DSP-4 administration. When analyzed at the ultrastructural level in control rats, NA terminals in the neuropil had a mean surface area of 0.53 +/- 0.03 micron2 and were rarely junctional (synaptic incidence close to 7%). Perivascular terminals (located within a 3-micron perimeter from the vessel basal lamina) counted at the electron microscopic level represented 8.8% of the total NA terminals in the cortical tissue. They were smaller (0.29 +/- 0.01 micron2, P < 0.05) than their neuronal counterparts and were located, on average, 1.34 +/- 0.08 microns away from intracortical blood vessels, which consisted mostly of capillaries (65%). None of the perivascular NA terminals engaged in junctional contacts with surrounding neuronal or vascular elements. The primary targets of both neuronal and perivascular NA nerve terminals consisted of dendrites, nerve terminals, astrocytes, and axons, whereas in the immediate vicinity (0.25 micron or less) of the microvessels, astrocytic processes represented the major target. The results of the current study show that penetrating arteries and intracortical microvessels receive a central NA input, albeit parasynaptic in its interaction, originating from the locus ceruleus. Particularly, they point to frequent appositions between both neuronal and perivascular NA terminals and astroglial cells and their processes. Such NA neuronal-glial and neuronal-glial-vascular associations could be of significance in the regulation of local metabolic and vascular functions under normal and pathologic situations.

Animals↗

PubMed1996

Interleukin-13, in combination with anti-interleukin-12, increases graft prolongation after portal venous immunization with cultured allogeneic bone marrow-derived dendritic cells.

Portal venous (pv) transfusion before transplant with large numbers (100 x 10(6)) of irradiated multiple minor histoincompatible spleen cells (B10.Br) augments allogeneic skin graft survival in C3H mice. We have shown in earlier studies that this is correlated with preferential activation for production of type 2 cytokines (interleukin [IL]-4 and IL-10) and decreased production of type 1 cytokines (IL-2 and interferon [IFN] gamma). We have also shown that recombinant (r)IL-12, in association with anti-IL-10 monoclonal antibody, can reverse in vivo the graft prolongation afforded by pv immunization and the altered cytokine production that follows. Adoptive transfer of inhibition of graft rejection is possible at early times after pv immunization, using plastic adherent cells obtained from the liver of treated mice. We show below that within 4 days of pv immunization, dendritic cells (NLDC-145+) isolated from the thymus, mesenteric lymph node (MLN), and.

Adoptive Transfer↗

PubMed1996

[Psoas abscess: diagnostic dilemma in childhood].

A series of 16 children diagnosed as having a psoas abscess or deep iliac lymphadenitis seen over a 25-year period (1970-1994) is presented. 10 were treated conservatively while 5 were drained surgically and 1 percutaneously under imaging guidance. The presenting signs and symptoms may mimic the frequently seen entities, acute appendicitis and acute hip arthritis. Lower abdominal and inguinal pain, limp, fever and increased white count are common in all of these conditions. Accurate differential diagnosis is necessary to avoid unnecessary surgery due to a wrong diagnosis. Ultrasonography is preferred for diagnosis. Antibiotic therapy should be instituted immediately, aimed primarily at Staphylococcus aureus, the most common causative agent, although other organisms may be implicated. When a psoas abscess has been diagnosed, surgery and drainage are indicated. One of the preferred approaches is percutaneous drainage under imaging guidance. Convalescence is usually rapid and without late sequelae.

Anti-Bacterial Agents↗

PubMed1996

[Thoracoscopic upper thoracic sympathectomy for primary palmar hyperhidrosis].

We report our initial experience, over the past 3 years, with thoracoscopic sympathectomy for severe, primary, palmar hyperhidrosis in children and adolescents. From 1992-1995, 179 thoracoscopic sympathectomies were performed in 61 girls and 35 boys, 5.5 to 18 years old (mean 14.8). During the first 2 years the procedures were performed bilaterally but not simultaneously. During the past years, 65 underwent bilateral, simultaneous sympathectomy, using a single 10 mm subaxillary port of entry. 94 (98%) had immediate and permanent relief of palmar sweating. The immediate postoperative course was uneventful in all except 2 who had residual pneumothorax that required 24-hour intercostal drainage. These results compare favorably with the open method and are actually better in terms of less pain, early discharge, quicker return to normal activity and a smaller and less conspicuous scar. We emphasize the benefits of early surgery in children with severe, palmer hyperhidrosis, to avoid the many years of psychological, social and physical discomfort during adolescent growth and development.

Adolescent↗

PubMed1996

Graft-infiltrating cells in rats receiving orthotopic semiallogeneic small intestine transplantation with portal or systemic venous drainage.

The effect of alterations in venous drainage, from either ivc to portal vein (pv), along with peritransplant systemic (ivc) or portal (pv) venous alloimmunization with irradiated semiallogenic cells, on cell subset recovery in lymphoid organs of Lewis rats receiving orthoptic small bowel allografts (from LewisXBrown Norway) F1, LBNF1) was examined. Combined portal, venous drainage and alloimmunization has been reported to increase graft/recipient survival in this model. FACS analysis using monoclonal antibodies specific for different lymphocyte subsets was performed on cell suspensions of peripheral (P) and mesenteric (M) lymph node (LN), small bowel intraepithelial lymphocytes (SBIEL), and Peyer's patch (PP) lymphocytes on days 2 and 8 posttransplantation. Donor cell contributions to these cellular analyses were estimated by comparison of FACS staining with polyclonal anti-Lewis or Lewis anti-LBNF1 antibodies. Control animals received syngeneic grafts. In both syngeneic and semi-allogenic transplants with pv or ivc drainage there was no consistent difference in cell subsets from in PLN compared with those of control nongrafted rats. Approximately 50% to 60% of these cells were alphabetaTcR+ with a CD4+/CD8+ ratio of 3-4:1 and a (CD4++CD8+)/alphabetaTcR+ ratio of 1:1. Some 5% to 12% ED3+ cells were also present. In IEL, MLN, and PP by contrast, there were significant differences in cells recovered from rats with ivc vs. pv drainage of grafts. The most striking changes reflected a decreased CD4+/CD8+ and alphabetaTcR+gammadeltaTcR+ cells in these tissues in rats predestined to show prolongation of allograft survival (ivc vs. pv injected IEL CD4/CD8+ ratios and alphabetaTcR+gammadeltaTcR+ ratios 1.0, 0.7 and 5.0, 1.0, respectively. These data are consistent with a proposed role for such gammadeltaTcR+ cells in the local regulation of graft rejection.

Animals↗

PubMed1996

A role for gamma(delta)TCR+ cells in regulation of rejection of small intestinal allografts in rats.

Lewis (LEW) rats received (Lewis x Brown Norway)F1 (LBNF1) small intestinal allografts (SIT) with graft venous drainage to either the portal vein (pv) or inferior vena cava (iv), along with immunization (pv or iv) with irradiated LBNF1 spleen cells. As reported earlier, in rats with pv drained grafts there was an increase in gammadeltaTCR+ cells infiltrating the Peyer's patches (PP) and mesenteric lymph node (MLN) compared with iv drained grafts. After restimulation in culture with irradiated LBNF1 spleen stimulator cells these PP and MLN cells from SIT rats with pv graft drainage were a prominent source of TGFbeta, IL-4, and IL-10. When subpopulations of cells from PP preparations were analyzed, an enriched (<2%betaTCR+) gammadeltaTCR+ population from SIT rats with pv graft drainage, but not iv drainage, was detected that suppressed in vitro type-1 cytokine production (IL-2, IFNgamma) from alphabetaTCR+ (<2%gammadeltaTCR+) cells derived from the MLN or peripheral lymph nodes (PLN) of these same animals. On adoptive transfer to naive LEW rats simultaneously receiving LBNF1 SIT, gammadeltaTCR+ enriched PP cells from these primary donors (pv immunized, SIT rats with pv graft drainage) produced prolonged graft/ animal survival compared with PP cells obtained from primary donors that had iv drained grafts. In addition, simultaneous infusion of anti-gammadeltaTCR monoclonal antibody into SIT rats with pv graft drainage blocked the graft enhancement normally seen in these animals. These data are consistent with an important role for type-2 cytokine producing gammadeltaTCR+ cells in the regulation of graft rejection in this model.

Animals↗

PubMed1996

Gamma delta TCR+ hybridomas derived from mice preimmunized via the portal vein adoptively transfer increased skin allograft survival in vivo.

C57BL/6 mice receiving pretransplant immunization with C3H.SW spleen cells via the portal vein, but not the vena cava, show Ag-specific delayed rejection of allogeneic C3H.SW skin grafts. This delayed rejection is not seen if preimmunization is performed in gamma delta TCR knockout (C57BL/6-Tcrdtm1Mom) mice. gamma delta TCR+ and alpha beta TCR+ hybridoma cells were prepared from Peyer's patch cells harvested from C57BL/6 mice 4 days following portal venous immunization with 100 x 10(6) irradiated C3H.SW spleen cells and skin grafting with C3H.SW tail skin. After recloning, these hybridoma cells were tested for cytokine production in vitro following restimulation with irradiated C3H.SW spleen cells and for their ability to delay rejection of C3H.SW skin grafts after adoptive transfer to C57BL/6 mice. Delayed graft rejection was a function of cells that showed preferential production of IL-10, not IFN-gamma, in vitro, independent of the source (vena cava or portal vein immunized mice) or the TCR phenotype of the hybridoma. Simultaneous infusion of anti-IL-10 mAb abolished this graft prolongation effect of transferred gamma delta TCR+ hybridomas. Hybridoma cells producing IL-10 on restimulation could polarize cytokine production from freshly stimulated mesenteric lymph node away from production of IL-2 and IFN-gamma, and toward IL-4, IL-10, and TGF-beta production. This immunoregulation by hybridoma cells in vivo and in vitro was observed even for third party Ag-stimulated mice/cells as long as the hybridoma cells themselves received stimulation with their specific Ag.

Adoptive Transfer↗

PubMed1996

A truncated hMSH2 transcript occurs as a common variant in the population: implications for genetic diagnosis.

Germline mutations of the hMSH2 gene are responsible for many cases of hereditary nonpolyposis colorectal cancer. While screening for hMSH2 gene mutations in hereditary nonpolyposis colorectal cancer kindreds, we observed that a previously reported germline mutation is in fact a common, alternatively spliced variant in the population. Using RT-PCR and the protein truncation test, the hMSH2 exon 13 deletion variant was found in more than 90% of individuals. The exon 13 deletion transcript was only present in lymphocyte RNA, no abnormalities were detected in genomic DNA flanking exon 13, and the deletion transcript is apparently not translated. These findings highlight further that caution should be exercised in providing genetic risk assessment on the basis of currently used germline mutation detection strategies.

Colorectal Neoplasms↗

PubMed1996

Ileal pouch-anal anastomosis: pregnancy, delivery and pouch function.

OBJECTIVE: To evaluate the pregnancies, deliveries and functional results of patients who have undergone and ileal pouch-anal anastomosis. DESIGN: A retrospective survey by questionnaire. SETTING: The study was conducted at a university hospital. SUBJECTS: Twelve women who had undergone an ileal pouch-anal anastomosis at the Inflammatory Bowel Disease Centre, Mount Sinai Hospital and who had subsequently become pregnant, were identified from the hospital records. A follow up questionnaire was completed by all subjects. RESULTS: Twelve patients had 16 deliveries. There were 10 vaginal deliveries and 6 caesarian sections. There were no pouch-related complication during the 16 pregnancies and there were two postpartum complications. CONCLUSIONS: Pregnancy is safe in women with an ileal pouch-anal anastomosis. Functional results are altered minimally. Vaginal delivery is safe and obstetric reasons should determine whether a caesarian section is performed.

Adolescent↗

PubMed1996

Changing causes of mortality in patients with familial adenomatous polyposis.

Widespread use of prophylactic colectomy has resulted in a reduction in the incidence of colorectal cancer in familial adenomatous polyposis (FAP) patients. A retrospective chart review of families registered at the Steve Atanas Stavro Familial Gastrointestinal Cancer Registry in Toronto was performed to determine whether the decrease in the number of patients developing colorectal cancer implies that causes of mortality in FAP patients are shifting to that of extracolonic manifestations of FAP. Information was available on 140 deaths within 158 families and among 461 individuals with FAP. When stratified by decade, from the 1930s to the 1990s, the ratio of deaths caused by extracolonic manifestations of FAP compared with deaths caused by colorectal cancer was noted to have risen. Even though most deaths in FAP patients are still from colorectal cancer, it appears that screening policies and prophylactic colectomy have resulted in a reduction in the number of FAP patients who develop colorectal cancer. Thus, in recent decades, a greater percentage of deaths in FAP patients appears to be attributable to extracolonic manifestations of the disease.

Adenomatous Polyposis Coli↗

PubMed1996

Biosynthesis of eicosapentaenoic acid in the microalga Porphyridium cruentum. I: The use of externally supplied fatty acids.

The biosynthetic pathways of eicosapentaenoic acid (20:5n-3) in microalgae, in general, and in Porphyridium cruentum, in particular, are not known. Some of the putative intermediates along the suggested pathways could not be detected probably due to their low endogenous level. In order to increase the endogenous levels of the intermediates, we provided various fatty acids in the growth medium. Exogenously supplied fatty acids were indeed incorporated into algal lipids and were further metabolized along the n-6 and n-3 pathways. In the n-6 pathway, 18:2 was desaturated to 18:3n-6, elongated to 20:3n-6, and subsequently desaturated to 20:4n-6 and then to 20:5n-3. In the n-3 pathway, 18:2 was first desaturated to 18:3n-3 which was then sequentially converted, apparently by the same enzymatic sequence of the n-6 pathway to 18:4n-3, 20:4n-3, and 20:5n-3.

Eicosapentaenoic Acid↗

PubMed1996

Altered serum cytokines in hepatic and portal blood of rats at early times following portal venous infusion of semi-allogeneic cells.

The liver of anaesthetized adult ( > 350 g) Lewis rats was perfused in vitro after cannulation of both the hepatic and portal vein, with clamping of the hepatic artery. Heparinized blood (400 microliters) was withdrawn at 0, 6, 12, 18, 24, 30 and 36 h from each site, and serum and peripheral blood lymphocytes (PBL) isolated after ficoll/hypaque separation. Serum was tested in bioassays for cytokines known to modulate lymphocyte:endothelial interactions in vivo and in vitro (IFN gamma, TGF beta, TNF alpha, IL-6, IL-1). In some experiments rats received, via portal venous infusion, a sterile inoculum of 150 x 10(6) semi-allogeneic (LBN F1) spleen cells immediately or 12 h after the start of the study. In animals which were unchallenged with cells via the portal vein, subtle differences in detectable cytokines were observed between hepatic and portal blood samples, as reported in earlier studies. Within 12 h the minor perturbations observed in cytokine profiles following surgical insult resolved, and the changes between hepatic and portal venous samples remained constant throughout the study in control rats. However, in rats treated with LBNF1 cells, changes in the cytokine profiles were seen compared with control animals, and as a function of time post F1 cell infusion. Changes in mRNAs for different cytokines were observed in PBL taken from portal/hepatic blood in these same animals. These data point to one possible mechanism whereby the liver may influence immunological processes following portal venous antigen challenge.

Adoptive Transfer↗