Biomedical subjects
Publications and source records attributed to K Kojima.
The synthesis and biological properties of new 3-phenoxymethylcephalosporins (1) are described. These compounds exhibited good antibacterial activity against Gram-positive and Gram-negative bacteria.
The irritable bowel syndrome (IBS) is characterized by alteration in bowel habits (i.e., constipation and/or diarrhea) and abdominal pain, and is most common gastrointestinal disorder in adults. The recurrent abdominal pain (RAP) in children is similar to IBS in adults except bowel habits, but there is no settled conception of IBS in children. In our department, diagnosis of pediatric IBS will be made if the child has; #1 functional gastrointestinal disorders without organic diseases, #2 abdominal pain and other gastrointestinal symptoms continuing more than 3 weeks, #3 psychogenic background factors. We experienced 63 cases of IBS (23.5% in all 268 cases) from April 1990 to March 1992 at our pediatric digestive outpatient clinic. They ranged from 4 to 15 years old and about 60% of them were elder than 13 years old. Psychogenic factors were usually related to environment of school life and home. Careful history taking and routine examination were most important for the diagnostic approach. Management of this disease included counseling and drug therapy. Almost all cases reached much better condition 1 to 6 weeks after the therapy started. The combination therapy with psychologist was required in a few cases.
The patient was a 64-year-old female who had been treated by a local doctor for rheumatoid arthritis and hypertension for 10 years. Malaise and edema developed since July, 1990, and as proteinuria and renal dysfunction were noted, the patient was admitted to our hospital on November 2. On admission, BUN was 33mg/dl, creatinine was 2.5mg/dl, and proteinuria was about 3g/day. Renal biopsy was performed after admission. Light microscopy revealed nodular lobulation of glomeruli and occlusion of loops. Dylon staining was negative. Immunofluorescent study showed granular deposition of IgG, IgM, C3, C4, Clq in the glomerular basement membrane and mesangial area. Electron microscopy showed a large amount of electron dense deposits in the subendothelium and mesangial area and dense aggregation of tubular structure in the deposit, part of which exhibited a profile of fingerprint deposit. The tubular structures were classified into three major types, which were 120, 100, and 50nm in diameter. From these findings, a diagnosis of immunotactoid glomerulopathy was made. After renal biopsy, plasmapheresis and prednisolone were administered, and the patient has been managed conservatively to date.
A 56-yr-old man had a solitary nodular mass in the right hepatic lobe. The nodule was clinically diagnosed as hepatocellular carcinoma, and a right hepatic lobectomy was performed. The nodule had a previously undescribed histological appearance, and was finally diagnosed as a Zahn infarct with the additional feature of fibrosis. We think that the mass was produced by occlusive phlebitis in a medium-size portal vein radicle and its smaller radicles. This is the case of a very unique Zahn infarct in two respects: 1) the histological appearance (fibrosis), and 2) the fact that it was due to occlusive phlebitis in portal vein radicles. The data obtained here indicate that a special type of Zahn infarct, as represented by this case, may present with clinical information (nodular mass and neovascularity) suggestive of hepatocellular carcinoma.
Pirarubicin (THP) is a derivative of adriamycin (ADM) which has been reported to have a lower cardiotoxicity than ADM. The authors investigated the in vivo antitumor effect of THP against human colon cancer cells (RPMI 4788) xenografted into nude mice. In the model of intra-abdominal carcinomatosis, intraperitoneal administration of THP (6 mg/kg) resulted in a significant prolongation of the survival compared with the saline control group (p less than 0.01). Intravenous administration of THP (8 mg/kg) significantly inhibited tumor growth compared with the saline control group. Labeling index with bromodeoxyuridine (BrdU) of RPMI 4788 tumors treated with THP was smaller than that in the control group. Mitotic index was also smaller in the group treated with THP. Labeling index with BrdU indicates the proportion of cells in the S phase. Thus, the tumor cells in both S and M phases have decreased after treatment with THP. This change in the cell cycle progression may be due to the accumulation of G2 phase similar to in vitro study. From these results, it was suggested that the change in cell cycle progression revealed in vitro might be caused by THP in vivo.
Inhibition mechanisms of 5'-triphosphates of 3'-azido-3'-deoxythymidine (AZT-TP) and 3'-deoxythymidine (ddTTP) on extensively purified DNA polymerase gamma from bovine testes were examined by analysis of the products synthesized on singly primed M13 single-stranded DNA or synthetic oligonucleotide template-primer in the presence of analogues. The results indicate that AZT-TP inhibits DNA polymerase gamma in competition with dTTP but is not incorporated into DNA, whereas ddTTP is incorporated into DNA and causes chain termination. In contrast, both analogues were used by reverse transcriptase and caused chain termination.
A lectin from Japanese jack bean (Canavalia gladiata agglutinin, CGA) was purified by affinity chromatography on a maltamyl-Sepharose column. On sodium dodecyl sulfate-poly(acrylamide) gel electrophoresis, CGA was shown to have a protein subunit with a mol. wt. of 30,000. CGA has an amino acid composition similar to that of Concanavalin A. The lectin activity of CGA could be detected not only by hemagglutination assay with trypsinized human erythrocytes but also by the binding assay with intact horseradish peroxidase. The binding method could determine CGA in a concentration ranging from 50 to 500 ng/mL. The quantitative-inhibition studies of the binding indicated that CGA has sugar-binding specificities similar to those of concanavalin A.
To know the possible relationships between nuclear phospholipids and cell proliferation, we have extensively analyzed phospholipids extracted from the nuclei of rat hepatic cells at various growth states. The content of phospholipid in nuclei as well as its composition was similar among liver cells tested, i.e., the regenerating rat livers (28 h, post-hepatectomy), sham-operated or non-treated control livers, and rat ascites hepatoma, AH7974 cells. In contrast, the fatty acid compositions of phospholipids differed from each other among these cells. At the 2-position of phospholipids in the regenerating liver nuclei at 28 h after partial hepatectomy, 18:1 (oleic acid) increased transiently at the expense of 20:4 (arachidonic acid) and 22:6 (docosahexaenoic acid), compared with those in the sham-operated control nuclei. This change in fatty acid composition was commonly observed throughout all phospholipids analyzed, i.e., phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS). On the other hand, the change at 1-position was rather limited: in the regenerating liver nuclei (28 h), 18:1 increased only in PC at the expense of 18:0 (stearic acid). The similar and more marked deviation at the 2-position was observed with AH7974 nuclei it contained approximately 2-times more of 18:1 in PC, PE and PI than regenerating liver nuclei (28 h), and the decreased levels of 20:4 and/or 22:6. It should be noted that there were significant differences in the fatty acid compositions of PE and PS between sham-operated and non-treated controls. So, the sham-operated rat is the appropriate control for proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate whether the proportion of activated T lymphocytes changes in an extracorporeal blood flow, we compared paired samples collected at the inlet and outlet lines of an artificial circuit for plasma separation, using a dual-immunofluorescence flow cytometric technique. In our series of materials from patients with rheumatoid arthritis or systemic lupus erythematosus, the percentages of HLA-DR-positive cells in both CD4+ (P less than 0.01, n = 6) and CD8+ (P less than 0.05, n = 10) subsets were significantly increased in the outlet lines compared with the inlet lines, suggesting that activated T lymphocytes pass through an extracorporeal blood circuit more easily than resting T lymphocytes.
Alveolar macrophages were obtained from 23 patients and the effects of phorbol myristate acetate (PMA), lipopolysaccharide (LPS), and dexamethasone (DEX) on the proportion of cells with intracellular alpha-1 antichymotrypsin (ACT), and concentrations of ACT in the culture medium were studied in vitro. The alveolar macrophages were obtained by bronchoalveolar lavage at autopsy or from resected lungs at operation and were cultured in suspension for 3 days in medium containing PMA, LPS, DEX, PMA+DEX, or LPS+DEX. Both PMA and LPS significantly increased the percentage of macrophages with intracellular ACT. Dexamethasone did not increase the number of ACT-positive cells and significantly suppressed the increase induced by PMA or LPS, releasing ACT into the culture medium. The release of ACT from macrophages may contribute to the anti-inflammatory effects of corticoids.
An adult female showed mild cerebellar ataxia and CSF pleocytosis following an acute infection of the upper respiratory tract, and was diagnosed as having acute cerebellar ataxia (ACA). CT and MR appearances in the acute stage revealed moderate swelling of the cerebellum and bilaterally increased signal intensity in the cerebellar cortex.
A case of omental torsion seen in a 16 year old male is reported herein. Abdominal pain in the right lower quadrant suddenly developed just after the patient twisted his waist and an emergency laparotomy revealed a hemorrhagic mass at the edge of the right omentum, which was excised. Histological examination of the resected specimen showed hemorrhage without any venous thrombosis or infarction, possibly suggestive of omental torsion with early spontaneous derotation. The patient was successfully treated as a case of omental torsion.
A female baby at two months old was diagnosed as having birth branchial palsy and was studied by magnetic resonance imaging (MRI) which is a non-invasive and safe method for assessing any brachial plexus injury in the infant. A traumatic meningocele involving a root avulsion injury was clearly demonstrated by the MRI findings.
Developmental changes of tomato (Lycopersicon esculentum) fruit tissues during maturation were analyzed by a physically defined method (stress-relaxation analysis). The tip of a conical probe connected to a load sensor was positioned on the cut surface of a sliced tomato fruit, and the decay of the imposed stress was monitored. Stress-relaxation data thus obtained were used for the calculation of three stress-relaxation parameters. Different zones within tomato fruit harvested at six different ripening stages were analyzed. One of the stress-relaxation parameters, minimum stress-relaxation time (T(0)), decreased as the fruits matured. The decrease in T(0) was first found in the core of the carpel junction within the endopericarp at the blossom end during the breaker stage. The decrease in T(0) progressed from the blossom end, through the equatorial region and finally throughout the shoulder, as the fruit matured. In mature green fruit, T(0) values within the placenta and the proximal carpel junction were lower than those by other parts of the fruit. For all measurements the maximum stress-relaxation time was not substantially changed during maturation, nor were their changes observed in different regions of the fruit. The observed relaxation rate was therefore correlated with softening. The results indicate that fruit softening may be physically associated with the stress-relaxation parameter, T(0), and the extent of softening is a function of position within the fruit. Decreases in T(0) value appear to be correlated with the reported regional variation in the appearance of polygalacturonase.
Obstructive jaundice, produced by ligating the common bile duct, induced a transient DNA replication followed by cell proliferation in rat liver. At 48 h after the operation, DNA polymerase alpha activity started to increase and reached its maximum level (more than twice the control) at day 4. At day 7, the enzyme level had decreased to the control level. Pulse-labeling experiment using radioactive thymidine showed that the rate of DNA synthesis increased approximately 2.5-fold in the same pattern as that of DNA polymerase alpha. The mitotic index in hepatocytes also increased 10-fold at day 4 and then decreased. The proliferation of liver cells induced by obstructive jaundice mimics the regeneration of partially hepatectomized liver, although the response was slightly delayed and the proliferation was transient.
We examined the mechanism of the inhibition of DNA synthesis by a new platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato+ ++)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis-diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase alpha were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase beta was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP.
The high-affinity interleukin-2 (IL-2) receptor (IL-2R) consists of the non-covalent association of at least two subunits, p55 and p70-75, capable of binding IL-2 with low and intermediate affinity, respectively. We studied the effects of cytokines on the IL-2R expressed on human peripheral blood B lymphocytes using monoclonal antibodies specific for IL-2R p55 and IL-2R p70-75, by means of two-colour flow cytometric analysis. In freshly isolated peripheral blood B lymphocytes, the p55 subunit was expressed only in a small population (7.0% of CD20+ cells), whereas the p70-75 subunit was expressed in a large population (89.0% of CD20+ cells). Of the cytokines studied, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were involved in the regulation of IL-2R on B cells. After a 2-day incubation with IL-4, expression of IL-2R p55 was markedly induced, but expression of IL2-R p70-75 was profoundly suppressed in a dose-dependent manner. These abilities of IL-4 to promote IL-2R p55 expression and suppress IL-2R p70-75 expression were inhibited by the presence of IFN-gamma. Other cytokines, including IL-1, IL-2, IL-5, and IL-6, had little effect on the expression of these two subunits. These findings suggest that IL-4 is a cytokine modulating B cell response through the regulation of IL-2R.