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Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 145 records · Page 8Linked to original sources

Absence of measles viral genomic sequence in intestinal tissues from Crohn's disease by nested polymerase chain reaction.

The aetiology of Crohn's disease remains unknown, although evidence for a viral cause has long been sought. Recent studies have shown inflammation of the submucosal microvascular endothelium and granulomata, and endothelial cell cytoplasmic inclusions, consistent with paramyxovirus, were identified by electron microscopy suggesting a persistent measles virus infection in Crohn's disease. Measles, mumps, and rubella viruses were tested for Crohn's disease by polymerase chain reaction (PCR). RNA was extracted from resected intestinal specimens from 15 patients with Crohn's disease, 14 with ulcerative colitis, and 14 controls without inflammatory bowel disease. This was used to perform nested PCR after reverse transcription (RT) of the RNA to cDNA with primer pairs directed against two regions in the genome of the measles virus and one region in the mumps and rubella viral genomes. Despite enhanced sensitivity of nested RT-PCR, measles, mumps, and rubella viral genomic sequences were not found in any intestinal specimen.

Adolescent↗

Endothelial constitutive nitric oxide synthase protein and mRNA increased in rabbit atherosclerotic aorta despite impaired endothelium-dependent vascular relaxation.

Atherosclerotic arteries are well known to exhibit impaired endothelium-dependent relaxation (EDR), but the exact mechanism of this impairment remains unclear. Recently, endothelial constitutive nitric oxide synthase (ECNOS), which generates nitric oxide and mediates EDR, was cloned, and ECNOS mRNA expression was reported to be modified by various cytokines, lipoproteins, and shear stress. To investigate the expression of ECNOS mRNA and protein in atherosclerotic arteries with impaired EDR, thoracic aortas isolated from Watanabe heritable hyperlipidemic (WHHL) rabbits were examined by using in situ hybridization and immunohistochemistry. Compared with thoracic aortas from Japanese White rabbits, WHHL aortas exhibited significantly impaired EDRs, although both in situ hybridization and immunohistochemistry exhibited enhanced expression of ECNOS mRNA and protein in WHHL aortas. There was no significant relationship between expression of ECNOS mRNA and protein of endothelial cells and age of the examined WHHL aortas. These data suggest that the mechanism of impaired EDR in atherosclerotic arteries is not due to the decrease in ECNOS mRNA and protein.

Acetylcholine↗

[Contingent negative variations associated with vocalization in humans].

We investigated the late negative components of the contingent negative variations (CNVs) in the verbalization task. Six subjects were instructed to perform three different motor tasks, jaw opening, vocalization of a meaningless sound and that of a word, in response to a sound stimulus following a visual warning stimulus with interstimulus interval of 4.0 sec. The electroencephalograms (EEGs) were recorded from the midline-central (Cz), left and right temporal areas (T3 and T4) and frontal areas (F7 and F8). EEGs were averaged 16 times using the visual stimulus pulse as a trigger to obtain the CNVs in each motor task. There was no significant difference between the tasks of the jaw opening and vocalization of the sound in the CNV amplitudes at bilateral electrodes. However, the amplitudes of the CNVs at the left frontal and temporal areas were significantly larger in the case of vocalization of the word than in that of jaw opening (p < 0.05). On the other hand, there was no significant difference between these two tasks in the CNV amplitudes at the right frontal and temporal areas. Our results suggested that the CNVs generated over the left hemisphere might reflect the brain activities involved in language production.

Adult↗

[Etoposide (VP-16) in gynecologic malignancy].

Clinical application of etoposide (VP-16) for gynecologic malignancy has been investigated in trophoblastic disease, ovarian, endometrial and cervical cancer. Etoposide has proved to be one of the most effective agents for trophoblastic disease. It is widely used in single or multiple drug regimens in chemotherapy of the disease. Furthermore, this drug is observed to be active in the combination of BLM with CDDP for germ cell tumor of the ovary. It is now playing an important role in chemotherapy of this tumor.

Antineoplastic Agents, Phytogenic↗

Prognostic value of cervical size and pelvic lymph node status assessed by computed tomography for patients with uterine cervical cancer treated by radical radiation therapy.

PURPOSE: To determine the prognostic impact of cervical size and pelvic lymph node status assessed by computed tomography (CT) in uterine cervical carcinoma treated with irradiation alone. METHODS AND MATERIALS: Seventy patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB and IIIB uterine cervical squamous cell carcinoma treated with a combination of external and high dose-rate intracavitary irradiation were entered into analyses. Univariate and multivariate analyses using the Cox regression model were performed to determine statistical significance of some tumor-related factors. RESULTS: There were no significant differences in pelvic control rate (PC), distant metastases-free rate (DMF), cause-specific disease-free survival rate (CSDFS) among subgroups with cervix < 60 mm in diameter. However, PC (p = 0.023), DMF (p = 0.000025), and CSDFS (p = 0.0023) were significantly lower for patients with cervix > or = 60 mm than < 60 mm. The 5-year CSDFS was 77.5% for < 60 mm, and 28.6% for > or = 60 mm. Pelvic node status assessed by CT scans had significant prognostic impact on outcome. the 5-year CSDFS rate was 84.9% for patients with no enlarged nodes, and 58.9% for those with enlarged nodes greater than 1 cm in minimum diameter (p = 0.023). Whereas PC was not significantly affected, the DMF was strongly correlated with nodal status (p = 0.00027). Pelvic node status was taken as an independent predictor for DMF (p = 0.019) on multivariate analysis. CONCLUSION: Although cervical size assessed by CT had limited prognostic value, pelvic node status assessed by CT is the significant prognostic factor for patients with uterine cervical carcinoma treated with radical irradiation.

Adult↗

Electrochemical determination for enzymic production of ultimate carcinogen from tryptophan pyrolysate by rat hepatic microsomes.

This study established a rapid and sensitive method of determining the level of the ultimate carcinogen from 3-amino-1-methyl-5H-prido[4,3-b]indole (Trp-P-2) produced by rat hepatic microsomes. An electrochemical detector (ECD) used with high-performance liquid chromatography (HPLC) gave a linear calibration curve for synthetic N-hydroxy-Trp-P-2 (the ultimate carcinogenic form) at concentrations ranging between 0.3 and 340 pmol. The enzymic production of N-hydroxy-Trp-P-2 from Trp-P-2 was also determined by the ECD with HPLC. Hepatic microsomes (0.2 mg as protein) from rats treated with methylcholanthrene (MC) and phenobarbital (PB) were incubated with Trp-P-2 for 5 min. The mixture was centrifuged with acetonitrile and the supernatant was then analyzed using HPLC. The ECD determined the level of N-hydroxy-Trp-P-2 to levels nearing 1 pmol, and the preparation before submission to the HPLC took such a short time (5 min) that N-hydroxy-Tr-P-2 did not have sufficient time to decompose. Then, the microsomal N-hydroxylation activity on Trp-P-2 was compared with five different sources of microsomes. The microsomes from rats treated with MC plus PB, MC, PB, or polychlorinated biphenyl showed an activity level (mol/min/mol P450 enzymes) of 2.41 +/- 0.19, 1.92 +/- 0.21, 0.048 +/- 0.017, and 1.79 +/- 0.15, respectively, and those from untreated rats showed no activity. This method was useful for evaluating the N-hydroxylation activity of P450 enzymes.

Animals↗

Sutureless anastomosis using a biofragmentable anastomosis ring.

The biofragmentable anastomosis ring (BAR) is composed of polyglycolic acid and barium sulfate. When used for intestinal anastomosis, the BAR fragments after the anastomosis is established. We used this device in 43 patients. In three patients, the anastomosis with BAR was abandoned due to technical difficulties. A total of 43 anastomoses with BAR were performed in 40 patients. The operations in which BAR was used included right hemicolectomy in 12 patients, transverse colectomy in 7, sigmoidectomy in 11, small bowel resection in 5 and other bowel resections in 8. The time spent for the BAR anastomsis ranged from 7 to 30 min with a mean of 15.2 min, which was significantly shorter than that of conventional hand-sutured anastomosis in 23 cases. The fragmentation and excretion of the BAR occurred from 14 to 49 days later with a mean of 21.8 days. There was only one instance of anastomotic leakage (1/40, 2.5%), which occurred in a patient with a cytomegaloviral infection of the intestine. A postoperative barium enema study in 28 patients showed no passage disturbance through the anastomosis. In conclusion, the anastomosis using BAR is considered to be a simple, safe, and fast method for performing either colonic or small intestinal anastomosis.

Adult↗

Rabbit granulomatous enterocolitis induced by injection of muramyl dipeptide emulsified with Freund's incomplete adjuvant.

We induced granulomatous enterocolitis in rabbits by injecting them with muramyl dipeptide (MDP), a subunit of the peptidoglycan polymers that endow the bacterial cell wall with structural rigidity, emulsified with Freund's incomplete adjuvant (FIA). Injections of 0.1 ml of a water-in-oil emulsion of MDP and FIA were given submucosally at six sites in the rectum and colon, 10 cm proximal to the anus, using a flexible endoscope. Four rabbits each were sacrificed 1, 2, and 4 weeks after a single injection of the emulsion. Another 4 rabbits each were injected six times at 1- and 2-week intervals, and were sacrificed 1 and 2 weeks after the last injection of the emulsion, respectively. In all 20 rabbits, injected with the MDP emulsion, histological findings of the colon consisted of cellular infiltrations of plasma cells and lymphocytes, granulomatous lesions, and granulomas, although the findings differed in degree. Cellular infiltration in hyperplastic villi and denuded epithelia of the small intestine were seen in 2 of 8 rabbits repeated that received MDP emulsion injections. The histological changes in this animal model may be useful for studying the pathogenesis of inflammatory bowel disease in humans.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Epidemiological study of tsutsugamushi disease in Gunma prefecture. A special field study and serotype].

An epidemiologically investigated of invasion of Rickettsia tsutsugamushi, inhabitant of mites and serum sample from patients with Tsutsugamushi disease in Gunma prefecture from 1984 to 1994 was made. Our data clearly indicated that Rickettsia tsutsugamushi was not located but widely spreaded throughout the Prefecture. Mites on rodents, were classified into 4 genus and 12 species and about 15% of them were Leptotrombidium pallidum and Leptotrombidium scuttellare, well known virulent vectors. The highest incidence rate of this disease was observed in the northwest area of the Prefecture from October to December, while a smaller number of patients occurred in other areas and in other months. About fifty percent of the serum samples from the patients were positive to the Karp strain. These results suggest that the major cause of this disease is the Karp strain and the disease could occur potentially in various areas of the Prefecture.

Animals↗

Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus.

The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta-methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin. SM-17466 had a broad spectrum of action against gram-positive bacteria, showing especially potent activity against methicillin-resistant staphylococci. The MICs of SM-17466, meropenem, imipenem, vancomycin, and arbekacin at which 90% of clinical isolates of methicillin-resistant Staphylococcus aureus were inhibited were 3.13, 50, 100, 1.56, and 3.13 micrograms/ml, respectively. This activity of SM-17466 was almost equivalent to those of the antibiotics used for the treatment of infections caused by this organism. SM-17466 also showed bactericidal activity against methicillin-resistant S. aureus. In contrast, SM-17466 was less active against gram-negative bacteria, especially against Pseudomonas aeruginosa, compared with the other carbapenems; however, of the carbapenems, SM-17466 exhibited the highest activity against Haemophilus influenzae and Bacteriodes fragilis. SM-17466, at a 50% inhibitory concentration of less than 1 microgram/ml, bound to penicillin-binding proteins 1 to 4 in methicillin-susceptible S. aureus and also had good binding to penicillin-binding protein 2' in a methicillin-resistant strain (50% inhibitory concentration, 5.9 micrograms/ml). This high affinity, which was 10 and 20 times greater than those for meropenem and imipenem, respectively, was reflected in the potent activity of SM-17466 against methicillin-resistant S. aureus. SM-17466 demonstrated excellent in vivo efficacy against methicillin-susceptible and -resistant S. aureus strains in a mouse peritoneal infection model: the efficacy of SM-17466 against methicillin-resistant strains was equal to or one-third that of vancomycin. This activity was comparable to the in vitro activity of SM-17466. The subcutaneous injection of SM-17466 in mice revealed that the half-life of SM-17466 in serum was about 18 min, intermediate between those of vancomycin and arbekacin and 1.5-fold that of imipenem-cilastatin. SM-17466 was resistant to hydrolysis by swine renal dehydropeptidase I, to an extent comparable to the resistance shown by meropenem.

Animals↗

Two cases of early gallbladder cancer incidentally discovered by laparoscopic cholecystectomy.

In case 1, a 68-year-old woman with asymptomatic gallstones underwent laparoscopic cholecystectomy after radical mastectomy for breast cancer. Histological examination revealed gallbladder carcinoma with involvement confined to the mucosa and positive margin at the cystic duct. We resected the remnant cystic duct with open laparotomy. In case 2, a 63-year-old woman with a diagnosis of early rectal cancer underwent laparoscopic cholecystectomy for silent gallstones following transanal resection of the rectal tumor. Pathologic analysis illustrated a gallbladder carcinoma with wide mucosal spread and minimal invasion into the subserosal layer. No additional treatment was warranted. As laparoscopic cholecystectomy has become widely used, an increase in the number of resected cases of early gallbladder cancer can be expected, especially among asymptomatic gallstone patients. Additional treatment should be determined through meticulous microscopic investigation of the specimen, with special attention to the depth of invasion and the range of mucosal spread.

Adenocarcinoma↗

[Neoadjuvant chemotherapy with tegafur suppository for rectal cancer--effects of tegafur on nuclear DNA content of cancer cells--Tochigi Colorectal Cancer Study Group].

To assess the significance of neoadjuvant chemotherapy for large bowel cancer, we investigated an effect of tegafur on cancer cell kinetics by DNA content flow cytometric analysis. The pathologic specimens analyzed in this study were obtained from 28 patients with rectal cancer who had received tegafur suppositories prior to surgery. Mean cumulative doses administered were 13.4 g, and mean duration was 12.7 days. In 24 of the 28 specimens, the DNA ploidy and DNA index of the cancer cells were essentially unchanged after the chemotherapy, and DNA aneuploidy was present in 67%. The proportion of cells in S-phase in DNA aneuploid tumors was significantly higher than in DNA diploid tumors. The proportion of cells in G0G1-phase was inversely correlated to that in S-phase. After the chemotherapy, the proportions of cells in S-phase increased both in DNA diploid and aneuploid tumors, although a significantly higher mean value was found only for the latter (p < 0.05). In the DNA aneuploid tumors, there was a higher frequency of responders confirmed by histological evaluation (44%) as compared to the DNA diploid tumors (25%), and a tendency for increases in S-phase fraction of the responders to be greater than in non-responders. These results suggest that DNA flow cytometry-derived parameters may conceivably be useful in predicting the antitumor effect of 5-FU and its derivatives against large bowel cancer.

Aged↗

Biological-clinical significance of selective loss of HLA-class-I allelic product expression in squamous-cell carcinoma of the uterine cervix.

To determine possible correlations between the selective loss of HLA-class-I allelic forms on neoplastic cells and their biological-clinical characteristics, 89 squamous-cell carcinomas of the uterine cervix were evaluated immunohistochemically using monomorphic and polymorphic antibodies against HLA-A, -B, and -C molecules and analyzed clinico-pathologically. Four of the carcinomas exhibited a lack of detectable class-I heavy-chain expression associated with beta 2-microglobulin. In 19 of 42 HLA-A2-positive patients, tumor cells revealed loss of the HLA-A2 allelic product. Loss of HLA-B7 and/or 40 (B7/40) allelic product(s) on tumor cells was observed in 12 of 25 HLA-B7/40-positive cases. These alterations did not correlate with patient age, clinical stage (FIGO) of the disease, histological sub-type (WHO) or depth of cervical invasion. However, a statistically significant correlation was observed between lymph-node metastases and selective loss of HLA-B7/40 allelic product(s), but not with HLA-A2 allelic product on cancer cells of the primary lesion. Our results indicate that selective loss of certain HLA-class-I alleles on neoplastic cells can influence the nodal metastatic potential and suggest that these 2 class-I molecules may have different immune functions as restriction elements in T-cell-mediated cytotoxicity.

Adult↗