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Biomedical subjects

H Kusano

Publications and source records attributed to H Kusano.

At least 19 recordsLinked to original sources

Opposite effects of isoniazid and fasting on the expression of CYP2E1 protein and mRNA in house musk shrew (Suncus murinus).

The effects of isoniazid and fasting on hepatic CYP2E1 in the suncus were investigated. Aniline hydroxylation and N-nitrosodimethylamine demethylation, which are known to be catalyzed by CYP2E1, in liver microsomes were induced and suppressed by the treatment with isoniazid and the fasting, respectively. Immunoblot analysis indicated that CYP2E1 protein in liver microsomes from isoniazid-treated suncus was increased in contrast to the result with the fasting of the suncus. Northern blot analysis showed that the treatment of suncus with isoniazid increased the expression of CYP2E1 mRNA in livers although the fasting of the suncus significantly decreased CYP2E1 mRNA. These results suggest that the regulation of hepatic CYP2E1 in the suncus by treatment with isoniazid and fasting was different from that in rats.

Amino Acid Sequence

Quantitative analysis of numerical chromosome aberrations in various morphological types of colorectal carcinomas.

Quantitative analysis by fluorescence in situ hybridization (FISH) on thin paraffin-embedded tissue sections, using specific probes for chromosomes 11, 17, and 18 was employed in various morphological types of early and advanced colorectal cancer to clarify tumor cytogenetics. The chromosome index (CI) was calculated as a quantitative measure of the chromosome copy number. Compared with the CI of normal epithelium, the CI of chromosome 11 in villous components of adenomas or polypoid early cancers was decreased, while the CI in flat type or advanced colorectal cancers, conversely, was increased (P < 0.05). The CI of chromosome 17 in villous components of adenomas and all cancers was higher than that of normal epithelium (P < 0.05), but the differences were not significant. In protruding advanced cancers, the CI of chromosome 18 was significantly decreased (P < 0.01) compared to the CI of normal epithelium. There was no significant chromosomal heterogeneity between the superficial and the deepest layer in each cancer. In mucosa adjacent to sessile and flat type cancers, the CI of chromosome 17 was significantly higher than the CI in normal epithelium or adenomas (P < 0.05). These results suggest that numerical chromosome aberrations are associated with the histological type of adenoma and the morphological diversity of cancer in the colorectum, and that chromosome 17 abnormality occurs in mucosa adjacent to sessile and flat cancers.

Adenocarcinoma

Chromosomal assignment of the Bcl2-related genes, Bcl2l and Bax, in the mouse and rat.

The Bcl2-related genes, Bax and Bcl2l (formerly called Bclx), are involved in the regulation of apoptotic cell death, and the chromosome location of these two genes was determined in the mouse and rat by fluorescence in situ hybridization. Bcl2l was localized to mouse chromosome 2H1 and rat chromosome 3q41.2, and Bax was localized to mouse chromosome 7B5 and rat chromosome 1q31.2. Both genes mapped in a region of conserved linkage homology between the two the species. Molecular linkage analysis using interspecific backcross mice revealed the murine Bcl2l locus at 0.7 cM terminal to D2Mit22, and the murine Bax locus at 0.8 cM terminal to D7Nds5.

Animals

[A case of solitary splenic metastasis from colon cancer].

A 58-year-old male who had a left hemicolectomy for descending colon cancer on July 1, 1993 was admitted to our hospital. A CT scan revealed a homogeneous low-density mass in the inferior portion of the spleen. Under the diagnosis of solitary splenic metastasis, a splenectomy was performed on August 10, 1995. Histologically, splenic tumor revealed moderately differentiated adenocarcinoma consistent with the primary tumor. Flow cytometric analysis revealed DNA diploidy in the primary tumor, and DNA aneuploidy (DNA index = 1.76) in the metastatic tumor. Using fluorescence in situ hybridization with p17 H8, numerical aerrations of chromosome 17 were observed in the primary tumor.

Adenocarcinoma

Evidence for the lack of hepatic N-acetyltransferase in suncus (Suncus murinus).

The abilities of liver cytosol fractions from the suncus and Sprague-Dawley (SD) rats to N-acetylate aniline, p-aminobenzoic acid, p-aminosalicylic acid and 2-aminofluorene (AF) were compared. The cytosol from rats N-acetylated these substrates at efficient rates, whereas the cytosol from the suncus did not N-acetylate these substrates at detectable rates. When AF was given to the suncus, 2-acetylaminofluorene (AAF), a metabolite of AF formed by N-acetyltransferase (NAT), was not detectable in serum, whereas the metabolite was seen clearly in rats. Northern blot and Southern blot analyses, using cDNAs coding for human NATs as probes, indicated that not only the transcripts but also the genes of the enzymes were undetectable in suncus. These results suggest that the suncus is among the few species known to lack NATs.

2-Acetylaminofluorene

Anal metastasis from carcinoma of the lung: report of a case.

We report herein the case of a 75-year-old man who developed anal canal metastasis from squamous cell carcinoma of the lung. Initially, he underwent a right middle and lower lobectomy combined with left atrial wall resection under cardiopulmonary bypass. He presented 3 months later with an anal polyp which had prolapsed and bled, for which he underwent a transanal polypectomy. Histologically, the polyp was classified as squamous cell carcinoma and considered to be a metastasis from the primary lung cancer. He is presently well with no signs of recurrence 9 months after his initial operation. To our knowledge, there has been no other case of anal metastasis from lung cancer ever reported.

Aged

An immunohistochemical study of the distribution of blood group substances and related antigens in primary colorectal carcinomas and metastatic lymph node and liver lesions, using monoclonal antibodies against A, B, H type 2, Le(a), and Le(x) antigens.

Using indirect immunoperoxidase staining, we examined the distribution of blood group substances and related antigens, including Le(a), A, B, H type 2, and Le(x), in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in metastatic lesions of 32 lymph nodes and 9 liver specimens. The compatible expression rate of A/B/H type 2 antigens was 33.3% (3/9) in proximal normal colon, but only 6.1% (2/33) in distal normal colon. Compatible expression was observed in 14 of 25 carcinomas in the proximal colon (56.0%), but these antigens in distal colon cancers reappeared with a high positive rate, 62.9% (39/62). The rate of H type 2 accumulation with the deletion of A and/or B antigens was 6.9% (6/87). Incompatible expression was not observed in colorectal cancer. Le(a) and Le(x) antigens were expressed in normal mucosa and primary carcinoma throughout the colon. Le(a) and Le(x) in primary carcinoma that showed A/B deletion with/without H type 2 accumulation was expressed more than in carcinoma with A/B/H type 2 compatible expression (88.2% vs 71.7% for Le(a); 94.1% vs 88.7% for Le(x), respectively). In 16 of 32 patients (50.0%), A/B/H type 2 antigen expression in metastatic lesions had disappeared or was decreased compared with that in primary carcinoma, followed by metastasis to regional lymph nodes. These results suggested that: (a) A/B/H type 2 blood group substances in the distal colon behave as tumor-associated antigens in colorectal carcinoma. (b) Most frequently, A/B/H type 2 antigens expressed in primary carcinoma were weakened or had disappeared in metastatic lymph nodes. Further investigation of the biological function of carbohydrate chains, such as those of blood group substances and related antigens on cancer cell surfaces may lead to a solution of the problem of the metastatic behavior of tumor cells.

Adenocarcinoma

An immunohistochemical employer monoclonal antibodies against Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens in primary colorectal, carcinomas and lymph node and hepatic lesions.

The immunohistochemical expression of sialylated and non-sialylated forms of both Le(x) and Le(a) were studied in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in 32 metastatic lymph nodes and 9 hepatic lesions, using an indirect immunoperoxidase staining. Their antigens were expressed in normal mucosa with the following frequencies: Le(a), 95.2% (40/42); sialyl Le(a), 88.1% (37/42); Le(x), 95.2% (40/42); and sialyl Le(x), 17.0% (7/42), whereas in carcinomas, the respective rate of frequency were: 78.2% (68/87); 78.2% (68/87); 90.8% (79/87); and 93.1% (81/87). Sialyl Le(x) antigen showed the highest tumor specificity compared to other antigens. In three normal mucosal specimens and four carcinomas with Le(a-b-) phenotype, the expression of type 1 antigens (Le(a) and sialyl Le(a)) was not consistent, whereas type 2 antigens (Le(x) and sialyl Le(x)) were consistently observed in carcinomas. The staining of type 1 antigens and Le(x) was decreased in metastatic lesions compared with primary carcinomas, whereas sialyl Le(x) antigen had the same positive-staining rate in both. Metastatic carcinoma expressed the sialylated form more predominantly than the non-sialylated form in type 2 antigens whereas the opposite result was observed in type 1 antigens. These results suggested that: (a) sialyl Le(x), defined by monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen in colorectal carcinoma, and (b) the alteration of Lewis-related carbohydrate antigens in cancer cell membranes, including sialylation and/or aberrant glycosylation, may be related to metastatic behavior.

Adenocarcinoma

Activities of drug-metabolizing enzymes in the liver of Suncus murinus: possible lack of N-acetyltransferase activity in liver cytosol.

The amounts of several drug-metabolizing enzymes in livers of Suncus murinus (suncus) were studied in comparison with rats. The content of cytochrome P450 in suncus was less than one third that seen in rats. Activities of glutathione S-transferase, UDP-glucuronyltransferase and arylhydroxycarbon hydroxylase in suncus were less than half those in rats. Activity of flavin-containing monooxygenase in suncus was 71% that of rats. Interestingly, N-acetyltransferase (NAT) activity in suncus liver cytosols was not detectable: no detectable activities were seen with aniline, p-aminobenzoic acid and p-amino-salicylic acid as substrates. We propose that suncus is a unique animal possibly lacking NAT in liver cytosol.

Animals

Clinical study of audiograms in the initial stage and fixed stage of sudden deafness.

Audiograms in the initial stage and the fixed stage of sudden deafness were analyzed in 79 cases using the following 5 criteria; i) the onset is sudden and time of onset definite, ii) hearing loss at 1 kH is more than 35 dB, iii) the course of hearing recovery is clear, iv) unaffected ear has normal hearing, and v) the first examination and treatment is within 15 days after onset. Consequently, at least in cases receiving treatment within 6-15 days after onset, it was considered that the prognosis of hearing recovery could be established rather than the pattern of hearing loss than by the period of treatment after onset.

Adolescent

Immunohistochemical expression of sialyl Lex antigen in relation to survival of patients with colorectal carcinoma.

BACKGROUND: The alterations of carbohydrate chains in cancer cell membrane can be related, not only to the formation of tumor-associated antigens, but also to cell biologic significance. There is, furthermore, a possibility of their relationship to tumor metastatic behavior and subsequent survival of patients with cancer. Recent clinical studies elucidated that a carbohydrate antigen, sialyl Lex, is a useful tumor marker in colorectal cancer. However, the sialyl Lex antigen immunoreactivity in colorectal carcinoma in relation to patient survival is unknown. The aim of the study was to elucidate whether sialyl Lex expression in tumors was correlated with patient survival. METHODS: Immunohistochemical expression of sialyl Lex antigen, as detected by monoclonal antibody CSLEX1, was studied in 175 specimens of primary colorectal carcinoma from 120 patients who received radical surgery. RESULTS: The positive expression of sialyl Lex was observed in 87 of 120 patients (72.5%). There was no statistically significant association between the negative or positive of sialyl Lex and clinicopathologic factors, excluding Dukes stage and histologic type. The difference between overall 5-year survival of patients with sialyl Lex-negative tumors and that of patients with sialyl Lex-positive tumors (81.2% versus 60.6%) was statistically significant (P = 0.0263). In proportion to staining intensity that was expressed as a score based on the percentage of the total field stained positive with CSLEX1, 5-year survival of patients indicated a worse outcome (P = 0.0113). The prognostic value was then studied in a Cox regression model. Dukes stage had the strongest association with patient survival, whereas sialyl Lex expression was found to be the second-ranking parameter. CONCLUSIONS: When examining the expression of sialyl Lex antigen, as detected by monoclonal antibody CSLEX1, clinically useful information for patient survival after radical resection of colorectal cancer is given.

Adenocarcinoma

Esophagectomy for metastatic carcinoma of the esophagus from lung cancer.

A patient with metastatic carcinoma of the esophagus from lung cancer is reported. The patient was a 54-year-old woman who underwent a left lower lobectomy for lung cancer 5 years previously. The authors performed a thoracic esophagectomy, dissection of mediastinal lymph nodes, and reconstruction of the esophagus; the surgery was followed by chemotherapy. Because the histologic pattern of the esophageal tumor was similar to that of lung cancer and mucosal involvement was not seen, the esophageal tumor was interpreted to be a metastasis from lung cancer. The patient is well without recurrence of disease 23 months after operation. This is the first report of a successful esophagectomy for metastatic carcinoma of the esophagus from lung cancer.

Adenocarcinoma

Surgical experience with 5 n3(+) early gastric carcinoma cases.

Of 370 patients who underwent a resection for early gastric carcinoma, 317 (85.6%) were N(-), 28 n1(+), 20 n2(+) and five (1.4%) n3 respectively. In this study, n3(+) early gastric cancers were clinicopathologically evaluated and sites of the metastatic nodes were also defined. In addition, a comparative study in DNA ploidy patterns between primary and metastatic node cell was performed according to Hedley's method using a FACS-IV scan of paraffin-embedded tissues. All n3(+) early gastric cancers showed an aneuploidy pattern. R2 or R3 operations are recommended for early gastric carcinomas with aneuploidy pattern and most of the metastatic nodes arise from the identical stem cell line of cancer cells.

Aged

[Continuous hyperthermic peritoneal perfusion (CHPP) for prevention or treatment of peritoneal dissemination].

We performed CHPP with concomitant use of CDDP and etoposide for prevention or treatment of peritoneal dissemination in gastric (10 cases) and colon (1 case) cancers with serosal invasion or peritoneal dissemination. The patients received intra-abdominal perfusion by saline heated to 41.5-42 degrees C dissolving CDDP and etoposide for 40-50 minutes. The blood concentrations of total CDDP and etoposide rapidly increased and reached maximum at the end of perfusion. Post-operative complications were more frequent in the group without STS than with STS. The prognosis of patients with peritoneal dissemination (P3) was poor, but ascites was observed to disappear in four of five cases. All patients with S (+) or P1 have been alive and free from disease for 1 to 12 months after CHPP. These results suggested that CHPP was effective for prevention and treatment of peritoneal dissemination.

Adult

[Study of combined hepatocellular and cholangiocarcinoma].

Four patients with combined hepatocellular and cholangiocarcinoma were studied. One case received hepatic arterial infusion therapy (HAIT), 2 hepatectomy and the case with extrahepatic cholangiocarcinoma underwent enucleation. According to Allen's classification, two were combined type and the others mixed type. Tumor ploidy patterns on flow cytometric DNA analysis were aneuploid in 2 cases with curative resection, of which one is still alive 6 years and 3 months after surgery. It suggested that the patient's survival was affected by the pathological factors more than the ploidy patterns of the tumor. A case treated by HAIT improved considerably in terms of symptoms and evidenced reduction in the size of the deposits. Selection of anticancer agents sensitive to both hepatocellular and cholangiocarcinoma is required.

Adenoma, Bile Duct

[Studies on tissue concentration of tegafur, 5-fluorouracil, uracil after UFT administration together with the study of microangiography of colorectal cancer].

In order to elucidate the effect of tumor vascularity on a various regimens concentration in tumor tissue, correlation among tegafur, 5-fluorouracil (5-FU), uracil concentrations in tissue and the microangiography were examined in 27 patients with colorectal cancer after preoperative administration of UFT (400 mg/day for 7 days). The concentrations of tegafur, 5-FU and uracil in tumor were higher than those in normal tissue (p < 0.01). There was no definite correlation between tissue concentration in each regimen and the extra or intramural vascular changes. A significant high concentration of 5-FU was found in the protuberant cancer and the ulcerative cancer with horizontal growth than that in the ulcerative cancer with vertical growth (p < 0.05). The present study indicates that the vascular changes within a tumor and the vascular pattern of tumor may be a contributing factor affecting the tissue concentration in the regimens.

Aged

Decrease in the content of cytochrome P450IIE by fasting in liver microsomes of house musk shrew (Suncus murinus).

The effects of fasting on hepatic cytochrome P450 in the mature male house musk shrew, Suncus murinus (suncus), were studied by Western blot analyses and enzyme assays. The content of P450IIE protein was decreased, by fasting, to 24% of the control level in contrast to the results with rats, in which P450IIE protein was increased to 172% by fasting. These changes reflected on catalytic activities, such as aniline hydroxylase and N-nitrosodimethylamine demethylase activities, which were decreased to about 45% and 28%, respectively, of the control levels by fasting, while in fasting rats, the catalytic activities of these enzymes were 2-3-fold higher than in controls.

Aniline Hydroxylase

[Pharmacokinetic study of tegafur in the hepatic tissue obtained from the patients with liver cancer].

SF-SP capsules, containing sustained release granules of tegafur, were given to 17 patients with liver cancer (5 primary and 12 metastatic), and tissue levels of tegafur and its metabolites, inhibition of thymidylate synthetase were examined. 5-FU and FdUMP, the active metabolites of tegafur, showed a good accumulation in hepatic lesion and their levels were found to be higher in patients with primary lesion than in metastatic one. In contrast, inhibitory rate of thymidylate synthetase in metastatic lesion was larger than in primary one, suggesting that the agent has stronger antitumor effect against metastatic lesion. This result is consistent with our clinical experiences. No clear relationship between tissue level of tegafur or its metabolites and inhibitory rate of thymidylate synthetase was found. Inhibition of DNA synthesis and/or RNA function are thought to be the action mechanisms of 5-FU and its derivatives. The present study suggests that measurement of the inhibition of thymidylate synthetase in malignant tissue together with the concentration of the drug and its metabolites may contribute for the elucidation of the antitumor effect of the drug.

Aged