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Biomedical subjects

T Kitagawa

Publications and source records attributed to T Kitagawa.

At least 361 records · Page 20Linked to original sources

c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas.

Ductectatic-type mucinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K-ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT----GAT (Gly----Asp) with the remaining one, found in a cancer, being GGT----GTT (Gly----Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K-ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma-carcinoma sequence in the evolution of this type of neoplasm and we suggest that K-ras activation may be an important event in the phase of adenoma development.

Adenoma↗

Hepatocarcinogenesis in transgenic mice carrying albumin-promoted SV40 T antigen gene.

We have developed transgenic mice that inherit albumin promoter-regulated simian virus 40 (SV40) large T antigen gene, expressed specifically in hepatocytes. These mice all develop multifocal hepatocellular carcinomas at around 5 months and die of liver insufficiency by 7 months. Sequential morphological observation of hepatocarcinogenesis revealed 5 distinct stages: (I) newborn to 2 weeks of age, neither recognizable histological changes nor cellular replication in spite of T antigen expression; (II) between 3 and 7 weeks, diffuse cytomegalic change of hepatocytes with numerous abnormal mitoses, usually resulting in cell death; (III) from 7 weeks onwards, quasi-regenerative small hepatocyte foci with a decreased tendency for cytomegaly in spite of T antigen expression, rapidly replacing the hepatic tissue; (IV) 11 weeks of age and thereafter, neoplastic foci and nodules with enzymatic alteration; (V) 20 weeks of age and thereafter, gross hepatocellular carcinomas with occasional pulmonary metastases. Considerable variation existed both in morphological and enzymatic features and T antigen expression among neoplastic lesions, including carcinomas. Thus, these transgenic mice clearly show a multistep process in hepatocarcinogenesis with remarkable synchrony and provide a promising model for analyzing the essential events of carcinogenesis at different stages.

Animals↗

Establishment and characterization of an epithelial cell line with quasi-normal chromosomes from a tubular adenoma of a familial polyposis coli patient.

An epithelial cell line designated FPCK-1 has been established from a tubular adenoma developing in a male familial polyposis coli (FPC) patient. The FPCK-1 cells grow very slowly with abundant mucus production and have been maintained stably for 3 years in culture. No growth was evident either in soft agar or nude mice. FPCK-1 cells present a normal male karyotype and do not show loss of specific loci on chromosomes 5, 17, 18, and 22 which have been reported to be lost frequently in human colon carcinomas. The cells have neither a point mutation on codon 12 of K-ras gene nor gene amplification of myc, c-H-ras, and/or c-K-ras genes. These results thus suggest the existence of hitherto unknown causative event(s) underlying adenoma development in FPC patients. The FPCK-1 cell line should prove useful for further analytical investigation of the multiple steps involved in human colon carcinogenesis.

Adenoma↗

Alpha-fetoprotein-producing papillary adenocarcinoma originating from a uterine body. A case report.

A rare case of alpha-fetoprotein (AFP)-producing papillary adenocarcinoma originating from the uterine body of a 55-year-old Japanese woman is reported. The histologic appearance of the tumor was reminiscent of a serous papillary carcinoma of the ovary, in clear contrast to that of common endometrial adenocarcinomas. No features of embryonal carcinoma or yolk sac tumor were evident. Immunohistochemical examination demonstrated the production of AFP by the tumor cells. To our knowledge there are six reported cases of AFP-producing malignant tumors of the uterine body in the literature, four of them being yolk sac tumor, one mixed mesodermal tumor, and one endometrial adenocarcinoma. This is therefore the first case of an AFP-producing papillary adenocarcinoma that developed in the uterine body. This report should contribute to a better understanding of the histogenesis of AFP-producing tumors in this organ.

Adenocarcinoma, Papillary↗

Autosomal recessive polycystic kidney in rats.

We evaluated the characteristics of renal lesions in rat autosomal recessive polycystic kidney (ARPK). In rat ARPK, small cysts appeared primarily in the medulla 2 months after birth and gradually extended to the cortex, forming large cysts involving the entire layer after 8 months. By immunofluorescence microscopy, type IV collagen was more strongly stained in the epithelial basement membrane of the rat ARPK than in the normal rat tubular basement membrane (TBM). Electron microscopy demonstrated a marked thickening, slight splitting and lamination of the TBM in the ARPK. As peroxidase-labeled lectins, dolichos biflorus very strongly stained the cyst epithelium whereas lens culinaris did not. These findings indicate that cysts in rat ARPK originate in the collecting duct.

Age Factors↗

Clinical manifestation of human T-cell lymphotropic virus type-I-associated myelopathy and vesicopathy.

Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) sometimes have accompanying voiding disturbances. We performed clinical surveys and urodynamic examinations on 25 untreated patients with HAM. Although 4 cases (16%) were entirely aware of urinary symptoms, the onset of urinary symptoms preceded other pyramidal symptoms in 6 cases (24%). All cases suffered from dysuria. The cause of dysuria was thought mainly to be detrusor external sphincter dyssynergia, but in some cases an underactive detrusor and poor opening of the bladder neck at voiding were also the causes of dysuria. There was a tendency for urinary dysfunction to become worse as the primary disease progresses. Patients with HAM must be carefully followed up by urologists in order to prevent deterioration of the urinary tract.

Adult↗

A new enzyme immunoassay for a solid Chinese crude drug, pinellia tuber.

A new immunoassay for a solid Chinese crude drug was studied. An antiserum specific for Pinellia tuber was elicited in two rabbits. Using the antiserum and powdered Pinellia tuber-coated microtiter plate as the immunological reagents, and beta-D-galactosidase-labeled goat anti-rabbit immunoglobulin G (IgG) as the tracer, a new enzyme immunoassay for a solid Pinellia tuber with a working range between 0.1 and 1000 micrograms/ml was developed. The assay was specific for a solid Pinellia tuber and showed low cross-reaction values on other Chinese crude drugs and the extract of Pinellia tuber. The specificity of the assay was compared with the selected antibody enzyme immunoassay (SAEIA) for the extract of Pinellia tuber recently developed. Both methods utilized the same immunological reagents such as the serum and the enzyme-labeled goat anti-rabbit IgG, and the only difference between them was the solid-phase antigen used. The assay results of several antigens determined by them were quite different, showing that selective measurements of different antigens, either solid or the extract of Pinellia tuber, were possible using the same antiserum, when the tracing reaction in the immunoassay was adequately selected.

Drugs, Chinese Herbal↗

Fluorometric determination of an inverse agonist to benzodiazepine receptors S-135 in monkey plasma by high performance liquid chromatography.

A high performance liquid chromatographic method for the determination of an agent of benzodiazepine receptor inverse agonist (S-135) was developed. S-135 in monkey plasma, after its administration, was assayed using the method. S-135 is ionized in alkaline N,N-dimethylformamide (DMF), and fluoresces strongly at 490 nm on excitation at 290 nm. Extracted S-135 from a plasma sample was separated with an Asahipak GS-310H polyvinyl alcohol gel column and detected fluorometrically, with the eluate being mixed with a triethylamine-DMF mixture. S-135 in plasma is assayable with a coefficient of variation being less than 3.5% (n = 11). The lower limit of the determination is 2 ng/ml. This method was applied as a highly sensitive and simple method to pharmacokinetic studies of S-135 after oral administration to cynomolgus monkeys.

Animals↗

[Pathogenesis of human cancer].

The multistep aspects of carcinogenesis including initiation and promotion problems in both human and experimental hepatocarcinogenesis are discussed, especially in terms of oncogene and antioncogene changes. It is shown that the H-ras activation may be an event occurring in relatively late phase of carcinogenesis in the mouse systems, and that hepatitis B integration frequently causes host chromosomal rearrangement possibly leading to inactivation of cancer suppressor genes. In addition, significance of endogenously-produced nitrosamines in hepatocarcinogenesis is pointed out.

Animals↗

Multistep hepatocarcinogenesis in transgenic mice harboring SV40 T-antigen gene.

We have developed transgenic mice that inherit albumin promoter-regulated simian virus 40 (SV40) large T-antigen gene, expressed specifically in hepatocytes. These mice all develop multifocal hepatocellular carcinomas (HCCs) at around 5 months and die of liver insufficiency by 7 months in remarkable synchrony. The liver tissue appears normal in the initial 3 weeks, and thereafter rapid cytomegalic degeneration of original hepatocytes, proliferation of quasi-regenerative hepatocytes, neoplastic cell foci, nodules and finally HCCs develop in sequence. Considerable variation existed both in morphological and enzymatic features and in T-antigen expression among neoplastic lesions, including carcinomas. Oligonucleotide hybridization studies revealed activating point mutations of the c-H-ras oncogene in 40% (10/25) of tumors obtained at around 6 months. The positive signals were, however, considerably weaker in half of them suggesting that such tumors comprised cells both with and without ras mutation. Sequential observation of culture cell lines established from tumors also revealed the appearance of activated c-H-ras with time, which was associated with biological progression. Thus, in this model system, ras activation may be an event occurring in a relatively late phase of carcinogenesis associated with progression of tumors. Karyotype analysis of cell lines revealed remarkable chromosomal instability. In studies of sister chromatid exchange in hepatocytes, twice as frequent occurrence was demonstrated in transgenic mice as in their counterpart hepatocytes. Thus T-antigen may be contributing as a mutagen to the hepatocarcinogenesis, in addition to its cytotoxic and growth modifying activities.

Animals↗

[Clinical evaluation of intramuscular imipenem/cilastatin sodium in surgical infections].

A multi-center clinical study was carried out at the first Department of Surgery, Okayama University Medical School and its affiliated institutions to evaluate the efficacy and safety profiles of intramuscular imipenem/cilastatin sodium (IPM/CS) in surgical infections, which were mainly biliary tract infections and peritonitis. The following results were obtained: 1. The efficacy rate was 72.0% in a total of 25 evaluable patients and 81.8% in patients with cholecystitis. 2. The efficacy rates in patients with and without underlying diseases were 70.0% and 73.3%, respectively, and they were 71.4% in patients with mild or moderate infections and 75.0% in patients with severe infections. 3. Bacteriologically, the eradication rate was 100% for Gram-positive bacteria and 62.5% for Gram-negative bacteria, with an overall eradication rate of 78.6%. The eradication rate for monomicrobial infections was 71.4% and that for polymicrobial infections was 100%. 4. Out of 25 patients, one developed diarrhea as a drug-related adverse reaction, and laboratory abnormalities attributable to the treatment were observed in 5 patients. None of them was serious, however. 5. The overall usefulness rate was 60.0%, and the usefulness for cholecystitis (72.7%) was superior to that for cholangitis (33.3%).

Adult↗

Observation of the petropharyngeal muscle in Japanese.

The petropharyngeal muscles were observed in 7 cadavers, 8 cases (1.4%) [both side: one case (0.3%), one side: 6 cases (1.9%)] in 614 Japanese cadavers. All cases of this supernumerary muscles of the stylopharyngeal muscle took origin from the petrous part of the temporal bone to inserted to the outer surface of the middle constrictor pharyngeal muscles. And also of its muscle bundles were innervated by the glossopharyngeal nerve and supplied from the ascending pharyngeal artery. The appearance of the sex differences male was much higher than female in Japanese.

Aged↗

[The evaluation of the modified Blalock-Taussig shunt with a prosthesis of microknitted Dacron for tetralogy of Fallot in early infancy].

We evaluated the surgical results of the modified Blalock-Taussig shunt (MBTS), performed with a prosthesis of microknitted Dacron, for the ductus-dependent tetralogy of Fallot (TOF) in early infancy. Nine MBTSs for eight patients, 4 with and 4 without pulmonary atresia, were performed, and one patient died. The mean age was 30 +/- 27 days, and the mean weight was 3460 +/- 770 g at the initial MBTS. In the initial two cases, the patients experienced convulsions due to severe hypoxia on account of the troubles of the preoperative administration of Prostaglandin E1 (PGE1). Thereafter, in order to prevent brain damage, we performed the MBTS following short-term administration of PGE1 (2-13 days). Consequently, we did not experience brain damage in later cases. Half of the patients with the MBTS with a 5 mm diameter prosthesis experienced postoperative congestive heart failure due to excessive pulmonary flow, and one of them died. The patients with the MBTS with a 4 mm diameter prosthesis had good postoperative courses. The suitable shunt flow in these patients was estimated to be 70-90 ml/kg/min. The MBTS with a 4 mm prosthesis obtained the lower level of this suitable shunt flow, but that a 5 mm prosthesis induced excessive shunt flow. Observing the patients' weight gain and the progress of polycythemia until two years of age, there were no differences between the MBTS with a 4 mm prosthesis and that with a 5 mm prosthesis. From these results, we recommend a 4 mm microknitted Dacron prosthesis for the MBTS of the TOF in early infancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

[Duodenal varices treated successfully by percutaneous transhepatic obliteration: report of a case].

A 73-year-old female with bleeding from duodenal varices treated by percutaneous transhepatic obliteration (PTO) was reported. She was admitted to our hospital because of tarry stool and general malaise. Gastroduodenoscopy revealed tortous elevations in the descending part of the duodenum, and observed intermittent bleeding. Percutaneous transhepatic portography (PTP) was carried out. PTP revealed duodenal varices supplied via the inferior pancreaticoduodenal vein and drained to the inferior vena cava, and continuously obliterated by gelfoam. Duodenal varices disappeared after obliteration and we observed no recurrence of varices for a year endoscopically. In general, it is accepted that the causes of the upper gastrointestinal bleeding secondary to portal hypertension are esophagogastric varices, hemorrhagic gastritis, gastro-duodenal ulcer, and so on. However, we must keep in mind the case with duodenal varices in which bleedings are of unknown origin. We also reviewed duodenal varices reported in Japanese literature from 1968 to 1989.

Aged↗

The use of N-(aminobenzoyloxy) succinimide as a two-level heterobifunctional agent for the preparation of hapten-protein conjugates. Daunomycin as a model hapten with an amino group.

Three geometric ortho-, meta-, and para-isomers of N-(aminobenzoyloxy)succinimide (ABS) were synthesized, and their usefulness as a two-level heterobifunctional cross-linking agent in the preparation of hapten-protein conjugates was evaluated. The conjugation was based on the principle that ABS reacts immediately with an amino group of a hapten, and an aminobenzoyl group incorporated into the hapten is then activated by diazotization to a functional diazobenzoyl group acting on tyrosine or histidine residues of the protein. Using the anti-tumor antibiotic daunomycin (DM) as a model hapten, the three isomers of ABS were compared for their ability to conjugate DM with bovine serum albumin (BSA); DM incorporation onto a BSA molecular was found to occur to the highest degree with m-ABS, followed by p-ABS. while o-ABS completely failed to conjugate under the same coupling conditions. Using m-ABS it was possible to introduce more than 10 molecules of DM per BSA molecule. One of the DM-BSA samples was used as the immunogen for the production of anti-DM serum in a rabbit. The antibody specificity was shown to be direct to DM but not to other anti-cancer drugs (bleomycin, mitomycin C, actinomycin D and 5-fluorouracil) by the double antibody enzyme immunoassay (DEIA) using DM-beta-galactosidase conjugate as a label. An enzyme-linked immunosorbent assay (ELISA) for anti-DM IgG was developed using a DM-human serum albumin (DM-HSA) conjugate similarly prepared with m-ABS and horseradish peroxidase-conjugated goat anti-rabbit IgG as the solid-phase antigen and the labelled second antibody, respectively. This ELISA permitted us to measure accurately as little as 50 ng of anti-DM IgG per ml using a standard anti-DM IgG which had been purified from the anti-DM serum using an affinity column of Sepharose 4B with DM-HSA as the ligand. Using this ELISA as well as a sandwich enzyme immunoassay (SEIA) for total IgG, serum levels of anti-DM IgG and total IgG levels were easily monitored in a rabbit following immunization with DM-BSA. These results indicate that the use of DBS provides a novel method for preparing hapten-protein conjugates which will be useful in biochemistry and immunochemistry.

Acetylation↗

Determination of fluoride ion in animal bone by microdiffusion analysis.

A microdiffusion analysis method for the determination of fluoride ion in animal bone sample was established by using a new diffusion cell. The cell is equipped with a water jacket to control the temperature. The space inside the cell is divided by a crossed-beam stand into top and bottom parts. In the bottom part, derivatization of fluoride ion to trimethylfluorosilane (TMFS) by hexamethyldisiloxane as the reagent occurs, with the volatile TMFS being absorbed into alkali placed in an open-top cup supported by the stand. The cell is placed on a magnetic stirrer to rotate the stirring bars in both reaction and absorption solutions. Stirring and elevation of temperature increase the reaction rates. Maintaining the cell at 40 degrees C for 3 h is sufficient for complete extraction of fluoride ion from the bone and its recovery. With our method, more than 10 micrograms/g of fluoride ion in bone can be assayed with a coefficient of variation of less than 3%. The fluoride levels of various rat bones were clarified.

Animals↗