Effect of conversion from cyclosporine A to mizoribine on transplant arteriosclerosis in rat aortic allograft models

Recent studies suggested that conversion from cyclosporine A (CsA) to antimetabolic agents protects allograft vasculopathy. However, the mechanism of this beneficial effect by the conversion therapy is not fully understood. In the present study, we investigated the effects of conversion from CsA to antimetabolic agent mizoribine (MZR) on the formation of transplant arteriosclerosis in rat aortic allografts. Conversion from CsA to MZR significantly prevented intimal hyperplasia and perivascular inflammatory cell infiltration at 28 days after aortic transplantation. These findings suggest that conversion therapy from CsA to antimetabolic agents might have therapeutic potential in transplant patients with chronic vascular rejection.     

A phase II clinical trial to evaluate the effect of paclitaxel in patients with ascites caused by advanced or recurrent gastric carcinoma: a new concept of clinical benefit response for non-measurable type of gastric cancer

A phase II clinical trial has started in the South West region of Japan to investigate the efficacy and safety of weekly paclitaxel chemotherapy for the treatment of patients with ascites-forming advanced gastric cancer. A novel trial design was created to assess more effectively prospective changes in symptomatology. The study design focuses on the typical features seen in patients with ascites-forming advanced gastric cancer, including girth of the abdomen and impaired performance status, which is evaluated in the endpoint of 'Clinical Benefit Response - Gastric Cancer'. The more traditional endpoints, objective tumor response and survival, are also included. As nearly 40% of patients with this disease are excluded from traditional phase II trials owing to the absence of 'measurable' disease, this study should more precisely illustrate the disease entity affecting patients with advanced gastric cancer.     

Mutations in the ST7/RAY1/HELG locus rarely occur in primary colorectal,gastric, and hepatocellular carcinomas

Human cancers frequently show a loss of heterozygosity on chromosome 7q31, which indicates the existence of broad-range tumour-suppressor gene(s) at this locus. Truncating mutations in the ST7 gene at this locus are seen frequently in primary colon cancer and breast cancer cell lines. Therefore, the ST7 gene represents a novel candidate gene for the tumour suppressor at this locus. However, more recent studies have reported that ST7 mutations are infrequent or absent in primary cancer and cell lines. To ascertain the frequency of mutations of the ST7 gene in cancer cells, we examined mutations in the ST7 coding sequence in 48 colorectal, 48 gastric, and 48 hepatocellular carcinomas using polymerase chain reaction-single-strand conformational polymorphism and direct sequencing. We detected somatic mutations, which were located near the exon-intron junction in intron 8, in only three out of 144 cases. We conclude that mutations in the ST7 gene are rare in primary colorectal, gastric, and hepatocellular carcinomas.     

Changes in serum alpha2u-globulin levels in castrated male rats treated with testosterone propionate in a Hershberger assay

The Hershberger assay has been proposed as a candidate screening test method for the detection of androgenic and anti-androgenic chemicals and is being validated presently under the test guideline programme of the Organization for Economic Cooperation and Development (OECD). Rat alpha2u-globulin is male rat-specific protein appearing in their serum and urine, and the protein is known to be induced by androgens. We investigated the usefulness of measuring serum alpha2u-globulin levels as a parameter for the androgenic activity of chemicals tested in the Hershberger assay. The serum alpha2u-globulin level was measured after the administration of testosterone propionate at dosages of 0, 20, 100 or 500 microg kg(-1) day(-1) for ten consecutive days in the castrated male rats. The ventral prostate, balbocavernosus/levator ani muscles, glans penis and Cowper's gland were collected and weighed. Although all the androgen-responsive organ weights were increased significantly at dosages of 100 and 500 microg kg(-1) day(-1), the serum alpha2u-globulin level was increased significantly only at a dosage of 500 microg kg(-1) day(-1). These results show that the serum alpha2u-globulin level may be a useful biomarker for detecting androgenic activity caused by test chemicals, but it is less sensitive than the organ weights of androgen-responsive tissues in the Hershberger assay.     

ARDS-like reactive respiratory failure after radical operation for esophageal cancer--with reference to PMN elastase and anaphylatoxin

In a study undertaken to elucidate the pathophysiology underlying reactive respiratory failure following surgery for esophageal cancer, postoperative esophageal cancer patients were divided into 2 groups, i.e. one with respiratory failure (defined as impairment of oxygenating capacity with a respiratory index (RI) value of 1.5 or above, lasting from more than 5 days after surgery) and the other without it, and between-group comparisons were made of respiratory & circulatory dynamics and biologic response system components, e.g., complement, anaphylatoxins and polymorphonuclear granulocytes (PMN) elastase. There were no differences between the two groups in patient's age at operation and pulmonary function test. The mean duration of endotracheal control was 5.1 days for the respiratory failure (+) group against 3.7 days for the respiratory failure (-) group. Assessments of respiratory & circulatory dynamics showed that the RI was significantly increase early in the postoperative course in the respiratory failure (+) group as compared with the respiratory failure (-) group, while the hydrostatic pressure of pulmonary circulation (pulmonary microvascular pressure (Pmv)-plasma colloid-osmotic pressure (COP] and pulmonary shunting rate (Qs/Qt) were also elevated in the former group. Among biologic response parameters, the leukocyte count, platelet count, CH5, C3, and C5 showed long-sustained decreases from the postoperative day 1 on in the repertory failure (+) group as compared to the respiratory failure (-) while PMN elastase activity and anaphylatoxin C3a were elevated from the postoperative day 1 on in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cloning and sequence of guinea pig interleukin 2 (IL-2)

Interleukin 2 (IL-2) is a T-cell proliferation factor released from TH0- and TH1-type helper T-cells and is an essential cytokine for certain immune responses. We reported here cloning and sequence of IL-2 cDNA in guinea pigs, which have been used for a long time in various immunological experiments and in vivo screening tests for skin sensitization potential of chemicals. Consequently, a cDNA clone was obtained encoding guinea pig IL-2 of 520 bp in length, which contained a complete open reading frame. Alignment of the amino acid sequence with human IL-2 indicates that guinea pig IL-2 is composed of 20 amino acids (aa) of a signal peptide and 132 aa of a mature peptide with a predicted molecular weight of 15 133. Guinea pig IL-2 has an amino acid homology of 62% with human IL-2, 52% with murine IL-2, and 55% with rat IL-2. In addition, guinea pig IL-2 has a possible N-linked glycosylation site as seen in bovine and porcine IL-2. Received: 8 April 1998 / Accepted: 1 July 1998     

Intraperitoneal administration of cisplatin (CDDP) for advanced or recurrent gastric cancer with peritoneal dissemination]

This study was undertaken in order to evaluate the effect of intraperitoneal administration of CDDP on fourteen patients with peritoneal dissemination of advanced or recurrent gastric cancer. The procedure was used together specific hydration transfusion and diuretics. Two patients showed a complete response and 5 patients a partial response. Following this therapy, 2 patients have survived for more than 6 months. Alimentary symptoms (nausea, vomiting) were found but renal toxicity and serious myelosuppression were not recognized in all patients.     

Development of Motion Analyzing System for Implanted Tilting Disk Valves

A motion-analyzing system was developed to quantitatively evaluate functions of the implanted tilting disk valve, e.g., an open angle and a duration of valve open and/or shut. In this system a picture of the valve on an x-ray cinefilm is displayed on the CRT screen by the TV camera for extraction of valve position. Data extracted are stored in the computer and are used to calculate parameters for motion analysis of the valve. The reliability of this system was confirmed within 3 degrees of error using the valve model prior to the evaluation of cinefilms clinically procured. With the aid of this motion analyzing system, complicated motions of the tilting disk valve were easily quantified and the useful information as given for clinical diagnosis and further valve development.     

Detection of antineutrophil antibodies in patients with neutropenia in infancy

Antineutrophil antibodies in the sera against peripheral blood neutrophils were examined in 8 infants (2 to 12 months of age) with neutropenia (absolute neutrophil count 0 to 480/microliter). The antibodies were detected by granulocyte indirect immunofluorescence test (GIIFT) and microleukocyte agglutination test (M-LAT). Three of the 6 serum samples with chronic benign-type neutropenia reacted in both GIIFT and M-LAT. In 2 of these 3 samples, the antibody was proved to be specific to neutrophil antigen NA1 by the absorption experiment. Neither the GIIFT nor the M-LAT showed the antibody in two patients with Kostmann-type neutropenia. These results suggest that the examination of antibodies against neutrophils is essential to the evaluation of the patients with chronic benign-type neutropenia in infancy.     

Gallium-67 citrate scintigraphy in the pre-operative evaluation of soft tissue tumors of the extremities

We conducted a study of 90 patients with soft tissue tumor in their arms or legs, in order to determine the usefulness of scintigraphy with gallium-67 citrate as a diagnostic means. All patients had adequate scan images, and tumor tissues had been histologically confirmed by surgical resection. The subjects consisted of 19 patients with malignant tumors, 55 patients with benign tumors, and 16 patients with other disorders in which soft tissue tumor-like lesions occurred. When the activity of the tumor was more than the activity of the normal region of the contralateral extremity, it was estimated to be positive. The positive rate was found in 78% (15/19) of patients with malignant tumors, in 25% (14/55) of patients with benign tumors and in 31% (5/16) of patients with other disorders. Classified by diseases, high positive rates were observed in liposarcoma, leiomyosarcoma, malignant lymphoma, neurinoma, extra-abdominal desmoid and sarcoidosis. Out of 7 patients in which the activity of the tumor was equal to, or higher than that of the liver, 6 patients had malignant tumors and one patient was diagnosed as having an abscess. It seemed possible to distinguish between liposarcoma and lipoma by means of a gallium-67 scan. Furthermore, the gallium-67 scan was useful in detecting lesions of sarcoidosis as well as in evaluating the response to treatment.