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Biomedical subjects

K Okuno

Publications and source records attributed to K Okuno.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of a 7-tesla homogeneous magnetic field on mammalian cells.

When two types of mammalian cells, mouse leukemia cells, P388, and Chinese hamster fibroblast cells, V79, were grown under a 7-tesla (T) homogeneous magnetic field which was produced by a newly constructed superconducting magnet biosystem (SBS), the growth pattern of cells under 7 T magnetic field and the geomagnetic field control showed no differences. The DNA distribution of the two cells was compared by flow cytometry after exposure to 7 T for 3 and 24 h, but there was no significant differences between magnet-exposed cells and unexposed cells. When the two types of cells were exposed to different concentrations of the antitumor agent, bleomycin (BLM), for 3 h under 7 T, their viable cell numbers were almost the same as that of the control although sensitivity to BLM was different between the two cells. These results suggest that the 7 T homogeneous magnetic field exerts no adverse effects on mammalian cells.

Animals↗
PubMed1999

Comparison of controlled and Glisson's pedicle transections of hepatic hilum occlusion for hepatic resection.

BACKGROUND: For hepatic resection, intraoperative bleeding is reduced by clamping the afferent blood flow. Selective clamping at the hepatic hilum can be accomplished using the standard controlled method or Glisson's pedicle transection method. The safety and efficacy of these two methods have not previously been compared. STUDY DESIGN: The intraoperative findings and complications were retrospectively reviewed in 90 patients who underwent major hepatectomy with selective inflow clamping between 1988 and 1997. RESULTS: Blood loss and operative time did not differ between the two groups. Bile leakage was observed in 3 of 43 patients (7.0%) in the standard controlled method group and 11 of 47 patients (23.4%) in the Glisson's pedicle transection method group (p = 0.031). In the Glisson's pedicle transection method group, bile leakage occurred more frequently in patients who underwent left lobectomy than in those who underwent right lobectomy (p = 0.023). CONCLUSIONS: There were no differences in intraoperative findings and postoperative complications analyzed between the standard controlled method and Glisson's pedicle transection method for major hepatectomy except for the rate of bile leakage. In particular, attention must be paid to the bile duct injuries when the Glisson's pedicle is dissected.

Bile↗
PubMed1999

A simpler and more accurate equation to predict daily lithium dose.

Recently, the authors suggested that the lithium dose prediction equation created by Zetin and associates cannot always accurately predict a required lithium dose and that the inclusion of renal function data may improve the accuracy of the equation. The charts of 70 patients were reviewed to obtain data regarding factors thought to affect serum lithium concentrations, including renal function, and an equation to estimate the dose intended to achieve an expected concentration was derived by stepwise multiple linear regression. The equation was also applied to 30 other patients to evaluate its accuracy. The authors obtained the following equation: daily lithium carbonate dose (in milligrams) = 100.5 + 752.7 x (expected lithium concentration in millimoles per liter) - 3.6 x (age in years) + 7.2 x (weight in kilograms) - 13.7 x (blood urea nitrogen [BUN] in milligrams per deciliter). When the equation was applied to 30 patients, the mean +/- SD of deviations from the expected concentration was 0.15 +/- 0.30 mmol/L, and 19 patients (63%) had deviations of less than 0.20 mmol/L. On the other hand, when the equation set forth by Zetin and associates was applied to the same patients, the mean +/- SD of deviations from the expected concentration was 0.52 +/- 0.42 mmol/L, and only 6 patients (20%) had deviations of less than 0.20 mmol/L. Although it is necessary to measure BUN levels before starting lithium, this equation may be simpler and more accurate than that offered by Zetin and associates.

Adolescent↗
PubMed1999

Incidence and risk factors of benign creatine phosphokinase elevations in chronic psychiatric patients.

There have been few studies focusing on the creatine phosphokinase (CPK) elevations in chronic psychiatric patients. The survey was conducted prospectively to investigate the incidence and risk factors of CPK elevations in chronic psychiatric patients during a 2-year follow-up period. Sixteen of 32 (50%) patients had maximums of more than 230 U/l (upper limit of our normal range) and 7 (22%) patients had maximums of more than 500 U/l. Surprisingly, 4 (13%) patients had maximums of more than 1,000 U/l after exercises such as swimming and walking. Nonetheless, none of the 16 patients with the CPK elevations developed severe conditions such as rhabdomyolysis despite an absence of therapeutic intervention, and their CPK elevations were proven to be benign. According to the path analysis, usual physical activity and neuroleptic doses seemed to underlie CPK elevations directly. The present findings suggest that not a few chronic psychiatric inpatients may have at least one CPK elevation per 2 years. Patients engaging in more physical activity or receiving higher neuroleptic doses are at greater risk of developing such CPK elevations. However, most of these increases are benign, and it is not considered necessary to treat them.

Adult↗
PubMed1999

Geographical variation of the alleles at the two prolamin loci, Pro1 and Pro2, in foxtail millet, Setaria italica (L.) P. Beauv.

Allelic variation at the two prolamin loci (Pro1 and Pro2) and its geographical distribution in 560 local cultivars of foxtail millet (Setaria italica) mainly from Eurasia were studied using SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Genetic analysis of a newly detected polymorphic band, band 6, indicated that it is controlled by an allele at the Pro2 locus, which was designated as Pro2f. Two alleles (Pro1a and Pro1null) at the Pro1 locus and six alleles (Pro2a, Pro2b, Pro2c, Pro2d, Pro2e and Pro2f) at the Pro2 locus were detected among the cultivars examined. Although the frequency of the Pro1a allele varied from 0% in the Nansei islands of Japan and Africa to 66% in Afghanistan, no apparent trend was observed in geographical distribution. In contrast, two common alleles at the Pro2 locus, Pro2b and Pro2f, had clear differential geographical distribution. The Pro2b allele was most frequent in Europe and decreased in frequency eastwards. The Pro2f allele occurred frequently in subtropical and tropical regions including the Nansei islands of Japan, the Philippines, Nepal, India, Pakistan and Africa. All eight alleles at the Pro1 and Pro2 loci occurred in China, suggesting China is a center of diversity. The origin of geographical differentiation of local cultivars into a "tropical group" characterized by the Pro2f allele and other genes was discussed.

Africa↗
PubMed1999

N-terminal amino acid sequences of prolamins encoded by the alleles at the Pro1 and Pro2 loci in foxtail millet, Setaria italica (L.) P. Beauv.

N-terminal amino acid sequences of six prolamins encoded by seven alleles at two loci, Pro1 and Pro2, of foxtail millet (Setaria italica (L.) P. Beauv.) were analyzed and compared with other prolamins of subfamily Panicoideae. Based on the N-terminal amino acid sequences, band 3 (the prolamin purified from band 3) which is controlled by an allele at the Pro1 locus and bands 1, 2, 4, 5 and 6 which are controlled by alleles at the Pro2 locus could be classified into three groups. Band 3 was found to be homologous to the prolamin of pearl millet (Pennisetum americanum) and is designated as the "pennisetin-like prolamin". Bands 2 and 4, and bands 1, 5 and 6 were subdivided into "x-type prolamin" and "y-type prolamin". Both of the x-type and y-type prolamins showed homology with prolamin of Echinochloa crus-galli and alpha-zein-like prolamins of maize, sorghum and Job's tears. Therefore, these prolamins were designated as "alpha-zein-like prolamin". These results suggest that alleles at the Pro1 locus and those at the Pro2 locus have not arisen from an identical ancestral gene, and that the Pro2 locus comprise two tightly linked genes, which encode similar prolamins. Hypotheses on the diversification of alleles at the Pro2 locus are discussed based on the N-terminal amino acid sequences of the respective bands, combinations of bands controlled by the alleles, and frequencies of the alleles.

Alleles↗
PubMed1999

Genes controlling prolamin biosynthesis, Pro1 and Pro2, in foxtail millet, Setaria italica (L.) Beauv.

Variation and genetic control of seed protein in foxtail millet (Setaria italica) were studied using SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Variation in the electrophoregram of the total seed protein were detected in the range between 20 and 30 kDa which is derived from the polymorphism of five prolamin bands. The segregation for each of the bands in F2 seeds showed that these bands are governed by seven alleles at two loci, Pro1 and Pro2, which are not linked to one another. Among 271 local cultivars examined, eight out of ten possible genotypes were observed. With its level of diversity comparable to that of isozymes, the alleles conferring prolamin polymorphism are useful genetic markers.

Alleles↗
PubMed1998

Small bowel transplantation in rats using a venous cuff technique.

A venous cuff technique was applied only for venous drainage in orthotopic small bowel transplantation of rats. Rates of technical failure (death within 4 days) and in clinical signs were compared between the groups with (group A) and without (group B) venous cuff technique. Technical failures with and without venous cuff technique were 5% and 25%, respectively. Mean survival days, excluding deaths from technical failure, were 9.2 +/- 2.3 in group A and 8.1 +/- 2.6 days in group B. No significant differences were observed in mean survival days or in weight loss between the two groups. Acute rejection was the cause of death in both groups. Since the model with venous cuff technique showed low mortality, it could be widely employed in small bowel transplantation studies.

Anastomosis, Surgical↗
PubMed1998

Involvement of liver-associated immunity in hepatic metastasis formation.

AIMS: Hepatic metastasis formation and prevention were studied from the viewpoint of liver-associated immunity. METHODS: RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, in which the cancer is highly metastatic to the liver, were used. Fischer rats that were inoculated with parent RCN-9 colonic cancer cells (5 x 10(6)) via the portal vein showed liver metastasis in less than 60% of the animals. In contrast, all rats (100%) that received RCN-H4 produced multiple liver metastases. To investigate the difference of hepatic metastasis formation, we assessed the susceptibility of both cell lines against hepatic sinusoidal lymphocytes (HSL) by 51Cr-release assay, and the expression of MHC class I and class II of both cell lines by flow cytometry. In addition, we examined whether activation of HSL by interleukin-12 (IL-12) can prevent liver metastasis of highly metastatic clone RCN-H4. RESULTS: The RCN-H4 clone showed decreased susceptibility to lysis by natural cytotoxic cells in HSL. This decrease in cell susceptibility was attributable to an increase in cell surface expression of MHC class I antigen. Administration of IL-12, a potent NK/CTL stimulatory cytokine, augmented the cytotoxic activity against the RCN-H4 clone and prevented liver metastasis of RCN-H4 inoculated into the portal vein. CONCLUSIONS: Liver metastasis formation is positively correlated with the strength of the hepatic immune system which mainly consists of ontogenetically primitive T cells. As these effectors exert their cytotoxicity in a MHC-nonrestricted fashion, tumor cells that highly express MHC class I antigen can readily avoid hepatic surveillance and apt to cause liver metastasis. Augmentation of the hepatic immune system, for instance, with IL-12 administration, can prevent liver metastasis even in tumor cells with a high potential for liver metastasis.

Adenocarcinoma↗
PubMed1998

Hepatic immunopotentiation by galactose-entrapped liposomal IL-2 compound in the treatment of liver metastases.

To activate hepatic sinusoidal lymphocytes (HSL) and increase the local antitumor activity in the liver, we developed a liver-targeted interleukin-2 (IL-2) compound using a galactose residue-entrapped liposome. We prepared various kinds of IL-2-containing liposomes made by the hydration of powdered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 followed by the combination with galactose residues to facilitate the selective uptake by liver parenchymal cells bearing galactose receptors. The IL-2 liposomes were given to C3H/He mice followed by the determination of: (1) organ distribution by 125I-labeled IL-2, (2) antitumor activity of hepatic sinusoidal lymphocytes by 51Cr-release assay, and (3) in vivo antitumor efficacy by the measurement of hepatic metastases. When galactose-entrapped IL-2 liposomes (Gallip-IL-2) were administered, a significantly greater hepatic accumulation of IL-2 was seen for up to 2 weeks compared to IL-2 liposomes or free IL-2. According to these results, the antitumor activity of HSL was significantly augmented. Moreover, when mice with hepatic micrometastases were treated with Gal-lip-IL-2, the area of hepatic metastases was significantly reduced. These findings thus indicate that Gal-lip-IL-2 may enhance the therapeutic efficacy of IL-2 against hepatic metastases and thereby facilitate a more practical daily dosing regimen.

Animals↗
PubMed1998

Superiority of hepatic arterial infusion in preventing catabolism of 5-FU compared with portal vein infusion revealed by an in vivo 19F NMR study.

PURPOSE: The aim of this study was to identify the route of administration of 5-FU with the greatest pharmacological advantage in a rat model using non-invasive in vivo 19F nuclear magnetic resonance (NMR) spectroscopy. METHODS: 5-FU (50 mg/kg) was administered to anesthetized Wistar rats cannulated into the hepatic artery, portal vein or tail vein and 11 NMR spectra were acquired from the liver region to 60.5 min every 5.5 min. RESULTS: With systemic i.v. (tail vein) infusion, the 19F-NMR signal for 5-FU from the liver region peaked in the first spectrum (0-5.5 min), and then gradually decreased. The signal for the 5-FU catabolite alpha-fluoro-beta-alanine (FBAL) gradually increased to the sixth spectrum (0-33.0 min) and then plateaued. Following portal vein infusion the intensity of the first 5-FU spectrum was twice as high as that following i.v. infusion, but the intensity decreased and the FBAL signal increased gradually in the sixth spectrum as systemic i.v. infusion. In contrast, the intensity of the 5-FU signal following hepatic artery infusion was the same as that following portal vein infusion in the first spectrum, and maintained a strong intensity to the final spectrum (60.5 min). The FBAL signal was detected from the second spectrum following hepatic artery infusion, but its intensity was significantly weaker than that following i.v. or portal vein infusion. CONCLUSIONS: Hepatic arterial infusion resulted in the active form of 5-FU being present for a longer time and its degradation in the liver being suppressed compared with the results following portal vein infusion. This catabolic advantage of hepatic arterial infusion could lead to a more potent anti-tumor activity against liver metastases, but could also lead to significant host toxicity including biliary toxicity. We recommend that the dose/schedule of 5-FU administered via the hepatic artery should be adjusted carefully.

Animals↗
PubMed1998

An evaluation of neural invasion in esophageal cancer.

It is well known that the operative results for esophageal cancer, especially thoracic esophageal cancer, are not favorable. We analyzed the relationship between neural invasion (NI) and histopathologic factors and recurrence types in 104 patients who underwent resection of esophageal cancers with T2 or greater depth of invasion of the esophageal wall. The implications of NI as a prognostic indicator were also examined. Of the 104 patients, 48 (46.2%) were NI-positive (NI(+)) and 56 (53.8%) were NI-negative (NI(-)). The NI(+) patients had a higher ratio of type 3 cancer. Concerning the histopathologic factors, there was a significant relationship between NI and lymph node metastasis (N) and between NI and lymphatic vessel invasion (ly) (P < 0.05). Examining the types of recurrence, namely hematogenous, lymphogenous, and local/stump, as well as pleural or peritoneal dissemination, a relationship was observed between lymphogenous recurrence and N or ly, and between local/stump recurrence and NI. The prognosis of the NI(+) patients was significantly different from that of the NI(-) patients. According to a multivariate analysis, NI and N were significant prognostic factors. These findings demonstrate that NI is an important prognostic factor closely related to local recurrence in patients with esophageal cancer. Thus, when treating advanced esophageal cancer with T2 or greater depth of invasion, NI and lymph node excision should be considered.

Aged↗
PubMed1998

Longterm effects of hepatic arterial interleukin-2-based immunochemotherapy after potentially curative resection of colorectal liver metastases.

BACKGROUND: Our previous study of hepatic arterial infusion of interleukin-2 (IL-2)-based immunochemotherapy demonstrated a high response rate of patients with unresectable liver metastases. In this study, we applied this therapy to the prevention of liver recurrence in patients who underwent potentially curative resection of liver metastases. STUDY DESIGN: A pilot study was conducted of 18 patients with liver metastases from primary colorectal cancer who underwent potentially curative liver resection followed by adjuvant immunochemotherapy. The regimen consisted of a weekly hepatic arterial infusion of IL-2 (1.4-2.1 X 10(6) U) and 5-fluorouracil (250 mg) and a bolus of mitomycin C (2-4 mg) for 6 months. RESULTS: Among 18 patients, 14 are still alive with a median postoperative survival of 52 months (as of April 1998). The 5-year overall survival rate was 75%. Although recurrent cancer developed in 6 of the 18 patients, no patients had recurrence in the residual liver. This complete prevention of liver recurrence is believed to have contributed to the high 5-year survival rate (75%) as compared with the survival rate of patients treated with surgery alone (average, 30%-40%) or with several other forms of adjuvant therapy. CONCLUSIONS: Interleukin-2-based immunochemotherapy is useful in combination with liver resection for the prevention of liver recurrence in colorectal cancer patients with liver metastases. A multicenter randomized trial is recommended.

Adult↗
PubMed1998

Establishment and characterization of Epstein-Barr virus-specific human CD4+ T lymphocyte clones.

We developed a simple method for establishing Epstein-Barr virus (EBV)-specific, human CD4+ T cell clones. The method originates from our experience that the regression of cell growth in in vitro EBV transformation of B cells occurs when round lymphoid cells appear in the culture. Peripheral blood mononuclear cells (PBMCs) were cultured with EBV, and IL-2 (20 U/ml) was added to the culture on day 17 after the virus addition. The phenotype of the growing cells was CD3+, CD4+, and CD8-. The cells were cytotoxic for autologous lymphoblastoid B cell line (LCL) and EBV-superinfected autologous LCL. The cytotoxic T lymphocytes (CTLs) were confirmed to be CD4+ T cells but not CD8+ T cells in the culture. CTL clones were established by a limiting dilution method. All the CTL clones had the phenotype of CD3+, CD4+ and CD8-, and proliferated in response to autologous LCL. They produced interferon (IFN)-gamma, interleukin 2 (IL-2) and tumour necrosis factor (TNF)-beta but not IL-4. All but one clone responded to both autologous, EBV-superinfected and non-superinfected LCLs. Proliferative and cytotoxic responses to allogenic LCLs were heterogeneous. These results suggest that this method induces heterogeneous, EBV-specific CD4+ CTL clones and is useful for analysis of CD4+ T cells in EBV infections.

Adult↗
PubMed1998

[Multidisciplinary treatment for colorectal liver metastases].

The liver is an large immunologic organ with liver-associated macrophages (Kupffer cells) and natural killer-like primitive T cells. As these effectors are activated by interleukin-2 (IL-2), we have administered IL-2-based hepatic arterial infusion therapy in the treatment of patients with liver metastases of colorectal cancer. Patients with unresectable liver metastases were administered IL-2 7 x 10(5) U and 5-fluorouracil (5-FU) 250 mg/day as a continuous infusion, with a bolus injection of mitomycin C (MMC) 4 mg once weekly. Of 25 patients treated with this regimen, 19 achieved complete or partial responses (response rate: 76%). A multi-institutional randomized trial following the pilot study showed reproducible favorable results. For patients with resectable metastases, we have administered this infusion therapy for the prevention of cancer recurrence in the liver. Patients who had undergone curative hepatectomy received IL-2 1.4 to 2.1 x 10(6) U, 5-FU 250 mg and MMC 2 to 4 mg weekly for 6 months. Of 18 patients, 12 are alive disease-free, and the 5-year overall survival rate is 75%. Recurrent cancer has developed in 6 of the 18 patients; however, no patients had recurrence in the residual liver. We believe that liver metastases of colorectal can be controlled by this multimodal treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

The extent of lymph node dissection for colon carcinoma: the potential impact on laparoscopic surgery.

BACKGROUND: The surgeon is no longer able to palpate the mesocolon for lymph node metastases during laparoscopic colectomy. The extent of lymph node dissection should be determined beforehand for cancer control. METHODS: The distribution of lymph node metastases was obtained by the clearing method on colon carcinomas for 164 patients. RESULTS: For pericolic spread: for pT1 tumors, the distance from the primary tumor to a metastatic lymph node was 2.5 cm; for pT2, the distance was within 5 cm; for 97.0 % of pT3 tumors with lymph node metastases, the distance was within 7 cm; for 93.3 % of pT4 tumors with lymph node metastases, the distance was within 7 cm. For central spread: for pT1 tumors, the rate of metastasis to central lymph nodes was 0 %; for pT2, the rate of metastasis was 20.0 % to intermediate lymph nodes; for pT3, the rate of metastasis was 30.6 % to intermediate lymph nodes and 15.3 % to main lymph nodes; for pT4, the rate of metastasis was 44.4 % to intermediate lymph nodes and 22.2 % to main lymph nodes. CONCLUSIONS: Central lymph node dissection is not required for patients with T1 carcinomas, but proximal and distal 3-cm margins of resection are required. For T2, central lymph node dissection that includes the intermediate lymph node should be performed, as well as 5-cm proximal and distal margins of resection. For T3 and T4, central lymph node dissection including the main lymph node should be performed, as well as 7-cm proximal and distal margins of resection. [See editorial on pages 177-8, this issue.]

Colectomy↗
PubMed1997

The importance of neural invasion (NI) as a prognostic factor in diffuse invasive gastric cancer.

The relationship between histological factors, including neural invasion (NI), and survival rates in patients with Borrmann type IV diffuse invasive gastric cancer was examined to determine the significance of NI as a prognostic factor. NI was studied histochemically in 75 patients who underwent resection after 1982, 37 of whom underwent curative resection. The 3-year and 5-year survival rates of the 37 patients who underwent curative resection were 37.2% and 12.7%, respectively. Recurrence was detected as peritoneal dissemination in 19 of those patients (82.6%), and the most significant prognostic factor was the depth of wall invasion (P < 0.01). While NI (P = 0.06) and lymph node metastasis (P = 0.09) appeared to be prognostic factors, there were no significant differences. Therefore, the depth of wall invasion was classified as T2 and T3 or 4 to examine the association of NI and lymph node metastasis with prognosis, whereby NI was shown to be a significant prognostic factor in T2. In conclusion, NI may be a significant prognostic factor in patients with wall invasion of T2 without serosal invasion, as it provides a pathway for the progression to peritoneal dissemination.

Disease Progression↗