Search PubMed⌕ Search

Biomedical subjects

K Hojo

Publications and source records attributed to K Hojo.

At least 73 records · Page 4Linked to original sources

Effects of amino acids on acute alcohol intoxication in mice--concentrations of ethanol, acetaldehyde, acetate and acetone in blood and tissues.

Condensation reactions between some SH-amino acids (L-and D-cysteine 1%) and acetaldehyde (50 microM) were studied in vitro experiment. In the aqueous solution, free acetaldehyde was reduced to 41.3% by L-cysteine and to 36.4% by D-cysteine. In the reaction with human blood medium, after the medium was deproteinized with perchloric acid reagent, acetaldehyde was reduced to 47.0% by L-cysteine and to 43.8% by D-cysteine. D-Cysteine appears to have great stability of reacting acetaldehyde. In vitro experiment reactability for D-cysteine exhibited 3-8% higher than that for L-cysteine. Next, effects of some amino acids on alcohol metabolism were studied in male ICR mice. The animals were given ethanol through a gastric catheter at a dose of 2 g/kg and they were intraperitoneally injected L-cysteine (300 mg/kg), D-cysteine (300 mg/kg), L-alanine (300 mg/kg) and control (saline), respectively in the period of one hour before the injection of ethanol. Blood and tissues samples were analyzed for ethanol, acetaldehyde, acetate and acetone during alcohol intoxication in mice by head space gas chromatography. In the groups administered D-cysteine and L-cysteine, the mice showed a definitely faster oxidation and disappearance of ethanol. Especially in the D-cysteine group, ethanol levels in blood, liver and brain remained lower than that in the other groups (p less than 0.01). Acetaldehyde levels in blood, liver and brain remained low by L-cysteine. Ethanol metabolites during alcohol oxidation by chemical reactabilities of L- and D-cysteine showed different distribution in the mice, respectively. In the mice received L-alanine, acetate and acetone levels in blood, liver and brain were distinctly reduced (p less than 0.01). L-Alanine is reported to supply an abundance of pyruvic acid that performs the NAD-generating system. NAD produced is introduced to alcohol metabolism and the TCA cycle. It was thus presumed that the L- or/and D-cysteine, and L-alanine was effective in acute alcohol intoxication by heavy drinking.

Acetaldehyde↗

Establishment of a murine thymic epithelial cell line capable of inducing both thymic nurse cell formation and thymocyte apoptosis.

A thymic epithelial cell (TEC) line (B/c. TEC-L1) was established from a normal thymus of a 4-week BALB/c mouse. The B/c. TEC-L1 had an epithelial morphology showing a contact-inhibited cobblestone-like arrangement with occasional desmosome-like structures at the adjacent cellular membranes. B/c.TEC-L1 cells showed positive staining for desmosomal glycoprotein, cytokeratin, thymosin alpha 1 beta 3, and I-Ad, and MHC class I antigens. The doubling time was 24 hours, and the chromosome number ranged from 52 to 78 with the mode of 70. Coculture of B/c.TEC-L1 cells with syngeneic, peanut agglutinin-agglutinated (PNA+) thymocytes in suspension at 37 degree C was followed by the formation of TEC thymocyte rosettes, after which the reconstitution of thymic nurse cells ensued. At 4 degrees C, PNA+ thymocytes bound to the B/c.TEC-L1 cell but did not form thymic nurse cells. PNA- thymocytes, although to a lesser degree than PNA+ cells, bound to the TECs at 37 degrees C, but at 4 degrees C few cells bound to the TECs. Allogeneic thymocytes also bound to the TECs at 37 degrees C. When the PNA+ thymocytes were cultured on the B/c.TEC-L1 monolayer, the small ones chiefly adhered on the surface of the TECs, while underneath the TECs the relatively large thymocytes (including cells in mitosis) predominated. Although the PNA- thymocytes bound to the surface of the monolayer within a few hours after coculture, by 24 hours nearly all cells disappeared. It is presumed that the thymocytes creeping underneath the B/c.TEC-L1 monolayer and those enveloped within the thymic nurse cell reconstituted in the suspension culture; both may be placed in circumstances analogous to the thymic microenvironment, wherein immature thymocytes appear to contact TECs directly and to be exposed to higher concentrations of thymic hormones and other soluble factors. Additionally, cell death in the PNA+ thymocytes was also observed in the coculture with B/c.TEC-L1 cells. The PNA+ cells revealed the morphological changes termed "apoptosis" characterized by chromatin condensation and nuclear fragmentation.

Animals↗

Significance of lateral node dissection for advanced rectal carcinoma at or below the peritoneal reflection.

Two hundred thirty two patients with rectal cancer at or below the peritoneal reflection, who underwent extended systematic lymphadenectomy, especially lateral node dissection, were reviewed with respect to survival rate, degree of surgical technique, and mode of recurrence. On the basis of the extent of lateral node spread, two types of lateral node dissection were performed, consisting of preservation of internal iliac vessels (conventional) and en bloc excision of these vessels (extended). The overall disease-free five-year survival rate was 69.4 percent in all patients--75.8 percent for those who underwent extended resection and 67.4 percent for those who underwent conventional resection an excellent survival rate of 49 percent of patients with lateral node metastasis was obtained. The analysis was carried out with regard to prognostic factors such as number of node metastases, obesity index, mode of recurrence, etc. We would recommend that systemic lymphadenectomy with lateral node dissection be performed for advanced rectal cancer at or below the peritoneal reflection.

Adenocarcinoma↗

An analysis of survival and voiding, sexual function after wide iliopelvic lymphadenectomy in patients with carcinoma of the rectum, compared with conventional lymphadenectomy.

Records of four hundred thirty-seven patients with lower and middle rectal cancer who underwent resection for cure at National Cancer Center Hospital from 1969 to 1983 were reviewed. There were significantly lower recurrence rates in the extended excision group compared with the conventional excision group. The recurrence rates between these two groups with Dukes' A were 0 percent (0 of 23) vs. 5.2 percent (5 of 96), those with Dukes' B were 6.3 percent (5 of 80) vs. 21.9 percent (14 of 64), Dukes' C were 23.6 percent (20 of 89) vs. 32.8 percent (28 of 85). The differences between the two groups with Dukes' B and C were statistically significant (P less than .05). The cumulative five-year survival rates in the extended excision group were 94 percent with Dukes' A stage, 88 percent with Dukes' B stage, and 61 percent with Dukes' C stage, compared with 91 percent (Dukes' A), 74 percent (Dukes' B), and 43 percent (Dukes' C) in the conventional excision group. There were also statistically significant differences between the two groups with Dukes' B and C stages (P less than .05). Although wide iliopelvic lymphadenectomy was successful as far as decreasing the incidence of local recurrence and also in prolonging survival, there were increased incidences of urine-voiding failure (loss of sense of bladder being full of urine detected in 39.4 percent of the extended excision group vs. 8.8 percent of the conventional excision group) and sexual impotency (76 percent vs. 37.5 percent).

Adolescent↗

Differential effect of cyclosporine in vivo on the distribution of T cell subsets in the thymus, spleen, and lymph nodes.

Cyclosporine treatment of BALB/c mice (at a dose of 20 mg/kg every other day for 3 weeks) caused a remarkable reduction in the PNA-, L3T4+Lyt-2- subset of thymocytes. A significant reduction of the L3T4+Lyt-2-subset was also observed in both the lymph node and spleen cells of CsA-treated mice, though the degree of the reduction was lower than that in thymocytes. Both lymph node and spleen cells from CsA-treated mice showed a significant increase in the percentage of Thy-1.2 negative, L3T4-Lyt-2- cells (perhaps B cells). Thymocytes from CsA-treated mice showed a reduction in the in vitro proliferative responses to Con A and PHA. On the other hand, there was a slight, but not significant, decrease in the responses of lymph node cells to Con A, PHA and LPS. Spleen cells from CsA-treated mice showed a significant reduction in the responses to Con A and PHA, though the degree of the reduction was lower than that of thymocytes. There was a significant decrease in the proliferative response of spleen cells to LPS. These results suggest that CsA affects both thymus and spleen cells in vivo, preferentially impairing the L3T4+Lyt-2- subset (helper T cells or their precursors) within the thymus. The lymph node cells seem to be relatively spared from the in vivo effect of CsA compared with cells in the thymus and spleen.

Animals↗

Enzyme-linked immunosorbent assay (ELISA) for detecting antisperm antibodies in mice with testicular autoimmunity.

We developed an ELISA for measuring antisperm antibodies in the mouse by using serum samples obtained from mice immunized with murine testicular antigens in complete Freund's adjuvant (CFA) as well as from mice rendered vasectomized. Sperm antigens used were syngeneic epididymal spermatozoa and two types of soluble, murine testicular antigens prepared in our laboratory. This study deals with a) the sequential changes of antisperm antibody levels following immunization; b) determination of immunoglobulin classes of these antibodies; c) a correlation between the absorbance values and the endpoint titers of antisperm antibodies; and d) comparison of endpoint titers of antisperm antibodies detected by ELISA with those by immunoperoxidase staining method in immune and nonimmune sera. It is suggested that serum dilution as high as 1/800 or more is required for detecting antibody titers of immune sera, because nonimmune mouse sera reveal a definite, although low, level of absorbance value at a serum dilution of 1/400 or less.

Animals↗

[Results of intra-arterial infusion chemotherapy of colorectal cancer in patients with metastatic liver cancer].

Fifty-nine colorectal cancer patients with metastatic liver cancer who underwent intra-arterial infusion chemotherapy (IAIC) at the National Cancer Center Hospital from May 1986 to February 1989 were reviewed. Excisions of metastatic liver cancer were performed in 36 patients and 23 had nonresectable metastatic liver cancer. Catheter troubles, including severe infection (8), extravasations (3), obstruction (1) and other problems (1) occurred in 13 (22.0%) patients, and 6 patients (10.2%) were unable to receive IAIC. Three patients did not undergo IAIC because of hepatitis or other reasons. Serious complications following IAIC, including sclerosing cholangitis (6), extravasations (6) and obstructions (3) were observed in 15 patients (30.0%). Results of IAIC were discussed in 21 patients undergoing hepatic resection and 17 patients with nonresectable metastatic liver cancer. 5-Fluorouracil (5-FU) (700 mg/m2) and mitomycin C (MMC) (7 mg/m2) were infused through implantable pumps every week or every two weeks. Total infused doses of 5-FU ranged from 500 to 15,000 mg (mean: 8,300 +/- 3,400 mg) and those of MMC were from 26 to 144 mg (mean: 58.8 +/- 32.7 mg) in 21 patients undergoing hepatic resections, whereas 1,500-26,250 mg (mean: 11,000 +/- 7,800 mg) of 5-FU and 0-130 mg of MMC (mean: 57.3 +/- 33.3) were infused in 17 patients with nonresectable liver cancer. Seven patients (33.3%) had recurrent liver cancer during 7-31 months (mean: 16.2 +/- 6.0 m) follow-up after hepatic resections, whilst only 3 of 13 patients (23.1%) with solitary liver metastasis had recurrent liver cancer. Three of these recurrent liver cancer patients (37.5%) underwent hepatic re-excision. Seven of 17 nonresectable patients (41.2%) were responders. Three patients completely responded (CR) and 4 responded partially (PR). Another study is needed to clarify the effect of IAIC in survival. IAIC should be undertaken as a treatment not only for patients with nonresectable metastatic liver cancer, but also for those with resectable metastatic liver cancer in order to prevent hepatic recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

[Complications of intra-arterial infusion chemotherapy in patients with colorectal cancer with liver metastasis, with special reference to IA-5-FU induced sclerosing cholangitis].

Fifty-nine colorectal cancer patients with metastatic liver cancer who underwent intra-arterial infusion chemotherapy (IAIC) at the National Cancer Center Hospital from May 1986 to February 1989 were reviewed. Excisions of metastatic liver cancer were performed in 36 patients and 23 had nonresectable metastatic liver cancer. Catheter troubles, including severe infections (8), extravasations (3), obstruction (1) and other (1) occurred in 13 (22.0%) patients, and 6 patients (10.2%) were unable to receive IAIC. Three patients did not undergo IAIC because of hepatitis or other reasons. Serious complications following IAIC, including sclerosing cholangitis (SC) (6), extravasations (6) and obstructions (3) were observed in 15 patients (30.0%). 5-Flourouracil (5-FU) (700 mg/m2) and mitomycin C (MMC) (7 mg/m2) were infused through implantable pumps weekly or every two weeks. Total infused doses of 5-FU ranged from 7,000 to 26,250 mg (mean: 11,800 + 7,700 mg) and those of MMC from 24 to 84 mg (mean: 45.3 + 25.8 mg) in 6 patients (12%) with SC, 4 resectable and 2 non-resectable cases. All six patients with SC had cholangiographic abnormalities of the biliary tract by endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), but serial CT examination of the liver did not show any progression of the tumor at the hilum in these patients. Segmental stricture at the common hepatic duct and bifurcation appeared specific to IA-5-FU induced SC. Obstructive jaundice occurred in 3 patients. Four patients had epigastralgia and 3 exhibited elevated alkaline phosphatase level prior to the cholangiographic examination. The elevated level of alkaline phosphatase was reversible in one patient without obstructive jaundice. Although the relation of the sclerosing process to IA-5-FU dose is not yet clear as well as IA-FUDR, it should be important to make an early detection of SC by ERCP and also to discontinue IAIC as soon as possible. In our opinion, SC may relate to the arterial delivery of 5-FU. In order to prevent SC, devascularization of the right hepatic artery via surgical procedures may well be effective, because retrograde flow from the right hepatic artery was confirmed by several clinical and anatomical studies.

Adult↗

[Surgery for far-advanced colorectal cancer--extension of surgical indication and its results].

The role of extended surgery for far advanced colorectal cancer (stage V, IV) was discussed. As the progression of colorectal cancer is relatively slow and small, as compared to cancers of other digestive organs, removal of the far advanced carcinoma by much extended operation was effective to enhance the survival or quality of life of patients. Combined resection of adjacent organ involved has given many patients chance of cure. Total pelvic eviscerations were performed for thirty eight patients with far-advanced rectal cancer which involved adjacent organs. The results were a 51.5% 5-year survival rate for curative resected group. For advanced rectal cancer with a high degree of lymph-node metastasis, extension of lymph-node dissection up to the para-aortic region or ileo-pelvic lateral dissection en bloc with the internal iliac vessels were effective for decreasing the incidence of local recurrence. For seventy two patients with liver metastasis, radical surgery with removal of liver metastatic lesions post removed intra arterial infusion therapy (5FU,MMC) was carried out and the resulting 5-year survival rate was 40% for patients with H1 liver metastasis. Removal of pulmonary metastatic lesions was also performed in sixty five patients and the 5-year survival rate was 40%. A complete removal of scattered tumors (P1,P2) and administration of anticancer drug-MMC (20-30mg) in the peritoneal cavity was conjugated to prolong the terms of survival of patients.

Colorectal Neoplasms↗

The effect of cyclosporine on murine thymic epithelial cells--an immunohistochemical study.

The authors recently demonstrated that cyclosporine (CsA) treatment of mice caused a remarkable reduction of L3T4+Lyt-2- subset in the thymocytes as well as the striking decrease in the size and cellularity of the thymic medulla. To elucidate the underlying mechanism of such thymic alterations, an immunohistochemical study on the thymic epithelial cells was made in mice receiving CsA. In the medulla, a marked reduction of Ia-positive, keratin positive and Ulex europeus agglutinin 1 (UEA 1) binding epithelial cells was observed. CsA also induced a reduction of anti-keratin stainability of cortical epithelial cells and of Ia antigen expression by them. The results of this study indicate that CsA is not only directly impair thymocyte function but also may act on epithelial cells in the thymus. It is suggestive that CsA may affect T cell differentiation and maturation via alteration of Ia-positive thymic epithelial cells.

Animals↗

Preoperative ultrasonography screening for liver metastases of patients with colorectal cancer.

The clinical value of preoperative ultrasonography in screening for synchronous liver metastases was prospectively evaluated in 338 patients with colorectal cancer. Synchronous liver metastases were observed at laparotomy in 11.5% (39/338) of the patients. The liver metastases had been found by preoperative ultrasonography in 30 patients and missed in nine. The overall accuracy rate, sensitivity and specificity, and the positive and negative predictive values of this modality were 0.970, 0.769, 0.997, 0.968 and 0.971, respectively. In detecting liver metastases, the results were superior to those of biochemical blood tests and measurements of carcinoembryonic antigen serum levels. The accuracy of the ultrasonography was also superior to that of these other tests combined. The results indicate ultrasonography to be an indispensable preoperative examination for patients with colorectal cancer.

Carcinoembryonic Antigen↗

[The value and limit of extended surgery in colorectal cancer].

Since the majority of colorectal cancers are well differentiated adenocarcinomas and grow rather slowly and well limited, surgery is the most available and favored treatment. The cancer-related 5-year survival rates of patients having undergone an extended operation versus those undergoing the conventional operation in our hospital (1969-1983) were 86% and 70% for Dukes B stage, and 60% and 38% for Dukes C stage. The survival superiority of the extended operation was confirmed as statistically significant (p less than 0.05). However, this survival advantage not true for patients with lateral lymphnode metastasis. A more extended operation with lateral dissection cutting the iliac internal vessels was performed for patients suspected of having lateral metastasis. Reduction of the incidence of local recurrence is really observed by this procedure. Urine-voiding and sexual dysfunction were observed more frequently in patients with the extended operation than the conventional one. By selectively preserving only 4th pelvic nerve, it becomes possible to preserve the urine voiding function without losing the benefits of the extended operation. In cases of far advanced cancer invading to adjacent organs, value of combined resection was also confirmed. Metastatic lesions to the liver or the lung should be removed by enucleation or partial resection of these organs, unless a multiple case. The 5-year survival of patients were 35% for liver metastasis and 40% for pulmonary metastasis.

Colorectal Neoplasms↗

En bloc excision of lower ureter and internal iliac vessels for locally advanced upper rectal and rectosigmoid cancer. Use of ileal segment for ureteral repair.

Eight patients who received en bloc excision of the ureter and internal iliac vessels for locally advanced upper rectal and rectosigmoid cancer were reported. Indications, techniques, functional results of the ileal ureter, and prognosis of these patients are discussed. Although three patients died of recurrent tumor--one of transperitoneal spread and two of liver metastasis--none of them developed local recurrent growth. As a replacement for the resected ureter, ileal substitution was applied in all eight patients--unilateral in six patients and bilateral in two. Serum creatinine and electrolyte patterns were within the normal range in all patients. A voiding cystogram showed no reflux to the anastomosed ureter, and a mild reflux to the ileal segment. The patients had excellent prognoses with regard to local control and also satisfactory functional results with the ileal ureter. The authors recommend that this procedure be applied to patients with locally advanced cancer such as those in this series.

Adult↗