Human Tumor–infiltrating Lymphocytes Transfected with Tumor Necrosis Factor Gene Could Augment Cytotoxicity to Autologous Tumor Cells

Human tumor–infiltrating lymphocytes (TILs) derived from pleural or ascitic fluid were incubated with recombinant interleukin 2 and transfected with human tumor necrosis factor (TNF) a gene by the lipofection procedure. The resulting TILs secreted significant amounts of TNF in the culture supernatant and exhibited cytotoxicity against established cell lines, such as K562 and Daudi, and autologous tumor cells. The TNF gene–transfected TILs exhibited an augmented killing of autologous tumor cells.     

Reduction of Nitric Oxide with L–/Vc–Monomethyl Arginine in lnterleukin–2 and Anti–CD3 Monoclonal Antibody Combination Therapy

We evaluated nitric oxide induction in antitumor therapy consisting of anti–CD3 monoclonal antibody (anti–CD3) and interleukin–2 (IL–2), then determined the effect of nitric oxide reduction with L–N^G–monomethyl arginine (LNMA) on the therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK–resistant murine fibrosarcoma cell line), and 145–2C11 (hamster anti–murine–CD3 mAb) were utilized in an experimental hepatic metastasis model developed by injecting a tumor cell suspension into the spleen of mice. A marked increase in serum NO₂^–+ NO₁ was observed at 19 hours after anti–CD3 (10 μ, IV) and additional IL–2 administrations (40times10¹ U, twice, If) induced a further increase. The NO₂, + NO_3- elevation in spot urine in the combination therapy was not suppressed with LNMA at a dose of 100 μg/h but was significantly lowered at 300 μg/h. The efficacy of the anti–CD3 + IL–2 therapy was not diminished by LNMA administration either at 100 μg/h or at 300 μg/h.     

Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

Groove pancreatitis associated with true pancreatic cyst

We report a case of groove pancreatitis (GP) associated with a true pancreatic cyst. An 81-year-old man who had suffered epigastric pain for 4 months was referred to Saisekai Kure Hospital. Computed tomography and endoscopic retrograde pancreatography showed a cystic lesion in the groove area of the pancreas. Serum amylase elevation and imaging findings suggested GP due to the cyst. Six weeks of medical treatment did not improve the clinical symptoms. Therefore, pancreatoduodenectomy was performed. Histologic examination revealed a true cyst with intraluminal necrosis, which produced a protein plug that obstructed the Santorini duct. The parenchyma surrounding the groove area showed marked fibrosis and inflammatory cell infiltration. GP due to true pancreatic cyst was diagnosed. Although GP is usually caused by overconsumption of alcohol, which leads to changes in the pancreatic juice and the ultimate blockage of pancreatic outflow, the histologic features in our patient suggest that true pancreatic cyst stands as a secondary cause of GP.     

Changes in polyamine metabolism in rat liver after oral administration of alpha-naphthylisothiocyanate

Changes in the levels of urea cycle enzymes and polyamine metabolism in the liver of rats treated with alpha-naphthylisothiocyanate (ANIT), an inducer of experimental cholestasis, were studied. Activities of arginase increased approximately two-fold compared to the control values during the period of 24-72 hours after oral administration of ANIT (100 mg/kg), while activities of ornithine carbamyltransferase and ornithine aminotransferase decreased. The activity of ornithine decarboxylase was elevated by approximately 20- and 10-fold at 12 and 60 hours, respectively, after ANIT administration. Putrescine concentration doubled 24-48 hours after the ANIT administration, but spermidine level rose more slowly and reached the level of 1.5-fold of the control level in 36-72 hours. Spermine concentration decreased initially but increased in 96 hours. These results suggest that the increased activity of urea cycle accounts for the increase in the ornithine content and that the putrescine and spermidine acts as the initiator of recovery of the liver damaged by ANIT treatment.     

Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.     

Does operational diagnosis of schizophrenia significantly impact intellectual deficits in psychotic disorders?

Background Evidence suggests that, as a group, patients with schizophrenia have intellectual deficits that may precede the manifestation of psychotic symptoms; however, how successfully intelligence tests are able to discriminate schizophrenia from other psychotic disorders has yet to be investigated in detail. Methods Using Wechsler Adult Intelligence Scale – Revised (WAIS‐R) data for 55 inpatients with schizophrenia and 28 inpatients with non‐schizophrenic psychotic disorders (NSPD) (schizophreniform disorder, brief psychotic disorder, delusional disorder, psychotic disorder due to a general medical condition, and psychotic disorders not otherwise specified), intelligence performance was compared between schizophrenia and NSPD and among different subtypes of schizophrenia. Results There were no significant differences in intelligence quotient (IQ), verbal IQ (VIQ) and performance IQ (PIQ) discrepancy, and subtest scores of WAIS‐R between the patients with schizophrenia and those with NSPD. These diagnostic groups were not discriminated well by any WAIS‐R variables. Schizophrenia patients with prominent negative symptoms, on the other hand, had a significantly larger IQ discrepancy (VIQ > PIQ) than those without prominent negative symptoms and NSPD patients. Intelligence performance in schizophrenia did not differ with respect to diagnostic subtypes and longitudinal courses. Conclusions The current study failed to show diagnostic usefulness of WAIS‐R in discriminating schizophrenia and other psychoses. A diagnosis of schizophrenia does not significantly impact intellectual deficits in psychotic disorders.     

Effect of hypobaric hypoxia on fiber type composition of the soleus muscle in the developing rat.

The fiber type composition of the soleus muscle was investigated in male Sprague-Dawley rats exposed to hypobaric hypoxia of 460 mm Hg from 5 to 12 weeks of age. The muscle fibers were classified as fast-twitch oxidative (FO) and slow-twitch (S) on the basis of adenosine triphosphatase (ATPase) and succinate dehydrogenase (SDH) reactions. Intermediate fibers (INT) with intermediate ATPase and high SDH reaction intensities were also examined. A type shift of muscle fibers from FO to INT and S was found in the control group during development. After exposure to hypoxia, the hypoxia group had a significantly greater percentage of FO fibers than the age-matched control group. There was no significant change in the total number of fibers in the muscle during development and after exposure to hypoxia. These results indicate that the increased percentage of FO fibers found in the developing rat under hypoxic conditions is due to a hypoxia-induced inhibition of the type shift of muscle fibers from FO to S during development.     

Autoradiographic Analysis of Radiolabeled Anti-carcinoembryonic Antigen Monoclonal Antibody CEA102 in Colorectal Cancer Using Computed Radiography

Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with ¹³¹I-labeled intact CEA102 or its F(ab')₂. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of ¹³¹I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean G.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy.