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Biomedical subjects

M Kanai

Publications and source records attributed to M Kanai.

At least 55 records · Page 3Linked to original sources
PubMed2001

Radical distal pancreatectomy with en bloc resection of the celiac artery, plexus, and ganglions for advanced cancer of the pancreatic body: a preliminary report on perfect pain relief.

OBJECTIVE: The purpose of this study was to report the effect of radical distal pancreatectomy with en bloc resection of the celiac artery, plexus, and ganglions for locally advanced cancer of the pancreatic body on intractable abdominal and/or back pain and to explore the histopathologic mechanism of this pain. PATIENTS: Five patients with pancreatic body cancer involving the celiac and/or common hepatic artery underwent this radical surgery intended to cure the cancer. DESIGN: A retrospective analysis was performed. MAIN OUTCOME MEASURES: Surgical magnitude, postoperative pain control, postoperative outcome, and histopathologic findings were studied. RESULTS: Arterial reconstruction, gastrointestinal reconstruction, and blood transfusions were unnecessary. The organ deficit was limited to the distal pancreas, spleen and left adrenal gland. There was no postoperative mortality. Postoperative complications occurred in four patients, who were successfully managed with medical treatment. This led to prolonged hospital stays. The intractable preoperative abdominal and/or back pain was completely relieved immediately after surgery in all patients. Perfect pain control has been maintained from surgery to the last follow-up. Histopathologic examination of the surgical specimens revealed cancer invasion of the celiac plexus in all patients. CONCLUSIONS: This operation offers not only disease radicality but also perfect pain relief. The survival benefit has not yet been fully defined.

Abdominal Pain↗
PubMed2000

Poly(ADP-ribose) polymerase localizes to the centrosomes and chromosomes.

Poly(ADP-ribose) polymerase (PARP) takes part mainly in regulation of DNA repair, thereby maintaining genomic stability in the nucleus. However, what role PARP plays in mitotic cells is not known. Centrosomes play an important role in maintaining the fidelity of chromosome distribution during cell division. Loss of these functions might cause chromosomal instability and aneuploidy. p53 and BRCA1 were recently found to localize to the centrosome at mitosis. We found that PARP is localized to the centrosomes and the chromosomes at cell-division phase and interphase by indirect immunofluorescence. Furthermore, by analysis of isolated centrosomes PARP protein was found to associate with the centrosomes during mitosis. These data suggest that PARP may be involved in maintenance of chromosomal stability.

Cell Line↗
PubMed2000

Selective photodynamic effects of the new photosensitizer ATX-S10(Na) on choroidal neovascularization in monkeys.

OBJECTIVE: To determine the optimal treatment variables for photodynamic therapy (PDT) with new photosensitizer ATX-S10(Na) (13,17-bis[1-carboxypropionyl] carbamoylethyl-8-etheny-2-hydroxy-3-hydroxyiminoethyliden e-2,7,12,18-tetranethyl 6 porphyrin sodium) to induce selective occlusion of choroidal neovascularization (CNV) in nonhuman primate eyes. METHODS: Experimental CNV was induced in monkey eyes by laser photocoagulation, and PDT was performed in neovascularized and healthy eyes with different treatment variables. At 0 to 150 minutes after 4-, 8-, and 12-mg/kg of body weight intravenous injections of ATX-S10(Na), a diode laser was irradiated at the dose of 1 to 127 J/cm2 (wavelength, 670 nm). Vascular occlusion induced by PDT was evaluated using fluorescein angiography, indocyanine green angiography, and histological examination at 1 day to 4 weeks after irradiation. RESULTS: Selective occlusion of CNV without damage to healthy retinal and choroidal capillaries was achieved in the following conditions: 30 to 74 J/cm2 irradiation at 30 to 74 minutes after the 8-mg/kg injection, and 1 to 29 J/cm2 irradiation at 30 to 74 minutes or 30 to 74 J/cm2 irradiation at 75 to 150 minutes after the 12-mg/kg dye injection. Regrowth of CNV often occurred when the retina was heavily injured by excessive PDT. CONCLUSION: By using optimal treatment variables, PDT using ATX-S10(Na) induces selective occlusion of CNV in nonhuman primate eyes, providing the possibility of therapeutic application to the clinical practice. CLINICAL RELEVANCE: Occlusion of CNV without direct damage to the sensory retina is useful to preserve visual acuity in patients with exudative age-related macular degeneration. A clinical trial of PDT using ATX-S10(Na) is desirable.

Animals↗
PubMed2000

Long-term effectiveness of photodynamic therapy by using a hydrophilic photosensitizer ATX-S10(Na) against experimental choroidal neovascularization in rats.

BACKGROUND AND OBJECTIVE: We previously demonstrated that a hydrophilic photosensitizer ATX-S10 had a potent photodynamic effect. This study was designed to reveal the long-term effectiveness of photodynamic therapy (PDT) with this agent in occluding choroidal neovascularization (CNV) and its selectivity in the neovascular tissue. STUDY DESIGN/MATERIALS AND METHODS: Experimental CNV was induced by intense photocoagulation in rat eyes. Immediately or 2 hours after intravenous injection of 8 mg/kg body weight of ATX-S10(Na), a cis isomer of ATX-S10, eyes were irradiated by a diode laser at the radiance of 3.25-65.3 J/cm(2) Vascular occlusion was identified by fundus photography, fluorescein angiography, and histology at 1, 3, 7, 14, and 28 days after PDT. As controls, non-neovascular eyes were subjected to PDT and similarly analyzed. RESULTS: By using the following treatment parameters, PDT with ATX-S10(Na) successfully occluded CNV without causing occlusion of retinal capillaries for 28 days; 7.4 and 19.6 J/cm(2) immediately after dye injection and 36.7 and 65.3 J/cm(2) 2 hours after injection. Although these conditions also caused occlusion of normal choriocapillaries and mild injuries of retinal vessels, retinal pigment epithelium, and photoreceptors at 1 day, retinal vessels and pigment epithelial cells recovered from damages by 28 days. No injuries were found in the inner retina. CONCLUSION: In optimal treatment conditions, PDT with ATX-S10(Na) can induce long-term, selective occlusion of CNV without causing irreversible damages in the inner retina.

Animals↗
PubMed2000

Age-related amyloid beta protein accumulation induces cellular death and macrophage activation in transgenic mice.

In view of the importance of amyloid beta protein accumulation in Alzheimer's disease, this paper examines age-related amyloid beta protein (Abeta) deposition and accompanying cellular changes in a mouse model in vivo. Transgenic mice were studied which expressed a gene encoding 18 residues of signal peptide and 99 residues of the carboxyl-terminal fragment (CTF) of the Abeta precursor, under the control of the cytomegalovirus enhancer/chicken beta-actin promoter. In the pancreas, Abeta accumulated in an age-dependent manner. Abeta deposits appeared as early as 3 weeks of age and increased in size and number from 4 to 16 months of age. The largest Abeta deposits were observed in the transgenic pancreas at 16 and 20 months of age. Haematoxylin and eosin staining, macrophage immunostaining, and electron microscopy showed that the Abeta fibril deposits closely correlated with degeneration of pancreatic acinar cells and macrophage activation. Abeta1-42 and Abetap3E-42 were predominant components of Abeta deposits among amino- and carboxyl-terminal modified Abeta species. These findings suggest that overproduction of Abeta causes age-related accumulation of Abeta fibrils, with accompanying cellular degeneration and macrophage activation in vivo.

Aging↗
PubMed2000

Inhibitory effect of TNP-470 on hepatic metastasis of mouse neuroblastoma.

PURPOSE: TNP-470 is a strong inhibitor of angiogenesis. The present study was designed to determine whether the angiogenesis inhibitor TNP-470 inhibits metastasis of mouse neuroblastoma cells to the liver and thus increases survival. METHODS: A murine neuroblastoma cell line, C1300, and A/J mice were used in this study. First, to demonstrate the inhibitory effects of TNP-470 on angiogenesis, we quantified the area of angiogenesis on images made with SP-500 image analyzer (Olympus) 7 days after implanting a millipore chamber and compared the areas for the TNP-470-treated mice and control mice. Next, to determine the inhibitory effect of TNP-470 on metastasis of neuroblastoma cells to the liver, we made a murine hepatic metastasis model by implanting C1300 cells (1 x 10(6)) in the spleen of the mice and compared histologic findings, sizes, and weights of the livers of treated mice and control mice 14 days after the beginning of a 7-day infusion of TNP-470 (60 mg/kg). We also compared survival rates using the Kaplan-Meier method. RESULTS: When the angiogenesis inhibitor TNP-470 was infused into mice that received tumor cells, the area of angiogenesis in the TNP-470-treated mice was smaller than that in the control mice (52.5 +/- 6.3 SD vs 94.1 +/- 27.6 mm(2), P < 0.001). After the same treatment in other mice, no histologic evidence of metastasis was found, whereas control mice had countless tumor cell masses. Similarly, the weight of the liver was less in TNP-470-treated mice (0.8 +/- 0.1 g vs 4.5 +/- 0.3 g, P < 0.001). Survival was longer in the TNP-470-treated mice than in controls (80% of treated mice were alive more than 60 days after treatment, whereas all control mice died by Day 20). CONCLUSION: TNP-470 inhibits metastasis of mouse C1300 neuroblastoma cells to the liver, and thus increases survival. TNP-470 inhibits metastasis by inhibiting angiogenesis.

Angiogenesis Inhibitors↗
PubMed2000

Pancreatoduodenectomy after hepato-biliary resection for recurrent metastatic rectal carcinoma.

Intrapancreatic bile duct metastasis from rectal carcinoma is rare. A 48-year-old man underwent extended left hepatic lobectomy and caudate lobectomy with extrahepatic bile duct resection for liver metastasis from a rectal carcinoma presenting with intrabiliary growth. A second recurrent tumor was successfully resected by pancreatoduodenectomy without injury to the jejunal loop for biliary reconstruction. Preservation of the previous bilio-enteric anastomosis was critical. Placing the jejunal limb of the hepaticojejunostomy through the retrogastric route was superior to placement through the common retrocolic and anteduodenal route, because the mesentery of the Roux-en Y jejunal limb did not obscure the pancreatic head. Histologic examination revealed a recurrent tumor growing into the remnant intrapancreatic bile duct. This suggested two possibilities: spontaneous shedding of cancer cells from the proximal metastasis, and implantation as a complication of percutaneous transhepatic biliary drainage. In both these circumstances, the metastatic lesion is not systemic, but is a local disease. An aggressive surgical approach for localized recurrence of this type may improve survival.

Bile Ducts, Extrahepatic↗
PubMed2000

Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis.

In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as > or = 75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (-2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis.

Adult↗
PubMed2000

Lung growth induced by tracheal occlusion in the sheep is augmented by airway pressurization.

BACKGROUND/PURPOSE: Prenatal tracheal occlusion (TO) has been shown to accelerate lung growth, yet the mechanism for this effect is poorly understood. Increased intratracheal pressure (ITP) with accumulation of lung fluid and secondary airway distension (stretch) may provide a mechanical stimulus for growth. In this study, ITP after TO is measured continuously, and the effect of altering ITP on lung growth is examined. METHODS: Fetal lambs of 115 to 120 days of gestation (term, 145 days) underwent placement of an intratracheal catheter and an amniotic fluid reference catheter. First, ITP was monitored continuously in normal controls (n = 4) and in fetuses undergoing TO (n = 6). In a subsequent study, 2 groups of fetuses were compared. In the TO group (n = 5) ITP was monitored after TO. In the pressurized group (n = 5) ITP was maintained at 7 to 8 mm Hg by a continuous servo regulated pump that maintains a preset pressure by lactated Ringers infusion. The animals were killed after 4 days, and lung growth was compared. RESULTS: In the control animals, ITP remained constant at 0.4 to 1.5 mm Hg. In the TO animals, ITP increased gradually during the initial 24 hours and plateaued at 4 to 5 mm Hg. In the second set of animals, ITP in the pressurized group was maintained at approximately 8 mm Hg using the infusion system. Lung volume (135.7+/-17.4 v. 95.2+/-14.8 mL/kg; P<.01), lung weight to body weight (6.70+/-0.73 v. 5.33+/-0.77%; P<.05), whole right lung dry weight (3.10+/-0.22 v. 2.63+/-0.20 mg/kg; P<.05), and right lung DNA and protein contents (87.3+/-6.0 v. 74.6+/-8.1 mg/kg, 2,310+/-248 v. 1,860+/-196 mg/kg, respectively; P<.05) were increased significantly in the pressurized group compared with the TO group. Morphometry confirmed greater volume of respiratory region and increased alveolar surface area in the pressurized lung. CONCLUSIONS: TO results in a gradual increase in ITP over 15 to 24 hours, which plateaus at 4 to 5 mm Hg. Further increasing ITP by infusion of crystalloid significantly augments lung growth beyond that observed with TO alone. These data support the hypothesis that airway pressure and secondary mechanical stretch are the primary stimuli of TO induced lung growth.

Animals↗
PubMed2000

Stromal cell-dependent ex vivo expansion of human cord blood progenitors and augmentation of transplantable stem cell activity.

In vitro maintenance and expansion of human hematopoietic stem cells is crucial for many clinical applications. Thrombopoietin (TPO) and flt3/flk2 ligand (FL) have been suggested to support the proliferation of primitive hematopoietic progenitors and the expansion of transplantable stem cells in culture. In this study, we examined the synergistic effects of the murine stromal cell line MS-5 and a combination of the two cytokines, TPO and FL, on the ex vivo expansion of human cord blood primitive progenitors and transplantable stem cells. A monolayer of MS-5 cells with TPO/FL synergistically supported a more than 600-fold expansion of human cord blood CD34+ cells and CD34+CD38- cells in 2 weeks of culture. Colony-forming unit in culture (CFU-C) and 5-week and 8-week cobblestone area-forming cells (CAFC) were also expanded approximately 300-, 4- and 13-fold, respectively. When MS-5 cells were physically separated from progenitors by a Transwell filter, the synergy was reduced to a quarter of the control, suggesting that direct cell-cell contact between MS-5 cells and progenitors is required for maximum expansion. The severe-combined immunodeficient (scid) mouse-reconstituting cell (SRC) assay demonstrated the slight augmentation of transplantable stem cell activity in culture. These results indicated that MS-5 cells provide a milieu that stimulates the proliferation of primitive progenitors including transplantable stem cells.

Animals↗
PubMed2000

Stromal cell-independent differentiation of human cord blood CD34+CD38- lymphohematopoietic progenitors toward B cell lineage.

To study the cytokine regulation of early stages of human B-lymphopoiesis, we developed a stroma-free two-step culture system. Single human cord blood CD34+CD38- cells were individually cultured by micromanipulation with interleukin (IL)-3, stem cell factor (SCF), fIt3 ligand (FL), IL-6 and granulocyte colony-stimulating factor (G-CSF). About 10% of the cells formed primary colonies, which were individually tested for myeloid and B-lymphoid potentials by reculturing aliquots of the primary colony cells into secondary myeloid and B-lymphoid cultures. One third of the primary colonies proved capable of differentiation into CD19+IgM+ cells, as well as into myeloid lineage cells. RT-PCR analyses revealed that some cells in the primary culture had already matured to express B cell-specific transcripts. Thus, the combination of IL-3, SCF, FL, IL-6 and G-CSF supported the differentiation of CD34+CD38- lymphohematopoietic progenitors toward B cell lineage in addition to myeloid lineages. Screening of cytokines to identify the minimum requirement of cytokines in the primary culture revealed that IL-3 and SCF were essential and that the addition of FL, and to a lesser extent IL-6 or G-CSF, to the combination of IL3 and SCF remarkably enhanced the primary colony formation and the generation of CD19+ cells in the secondary B-lymphoid culture.

Antigens, CD34↗
PubMed2000

A model of bacterial translocation in neuroblastoma-bearing mice.

PURPOSE: The aim of this study was to establish a model of bacterial translocation (BT) in neuroblastoma-bearing mice. METHODS: A suspension of 1 x 10(6) cells of the murine neuroblastoma cell line C1300 was injected subcutaneously into the thighs of 8-week-old female A/J mice, which were then killed after 7, 14, and 21 days. Some of the mice were given 1-microm or 2-microm fluorescein-labeled latex beads in their drinking water for 7 days before being killed. Mesenteric lymph nodes (MLNs) were aseptically removed and cultured for 72 hours at 37 degrees C. Segments of distal ileum were obtained for histologic examination. Samples of venous blood were obtained for laboratory tests. RESULTS: Tumors were found at the injection sites on days 14 and 21 after C1300 injection. Although tumors were not found in 7 days, significantly high number of 1-microm latex beads were detected in MLNs compared with the control, and the number increased with tumor growth. The number of 2-microm latex beads was significantly higher on days 14 and 21. The percentage of mice with MLN cultures positive were significantly higher on day 14, and the percentage increased along with tumor growth. On day 21 after C1300 injection, body weight loss and anemia were observed, and histologic findings of the terminal ileum showed mucosal edema and villous thinning. Serum levels of interleukin (IL)-6 were significantly higher in mice killed 14 and 21 days after injection. CONCLUSIONS: The results suggest that BT from the gut to MLNs may occur in neuroblastoma C1300-bearing mice, and it increases along with tumor growth. Even in the early stage of malignancy, particles as small as 1 microm may translocate from the gut to MLNs.

Animals↗
PubMed2000

Right trisegment portal vein embolization for biliary tract carcinoma: technique and clinical utility.

BACKGROUND: Right portal vein embolization has become popular in preparation for right hepatic lobectomy. However, right trisegment portal vein embolization (R3PE) is not well established. METHODS: We performed R3PE in 15 patients with biliary tract carcinoma and 1 patient with primary sclerosing cholangitis. We used 2 types of 5.5 F triple-lumen balloon catheters to embolize portal branches of the right trisegment (the left medial, the right anterior, and the right posterior segments). RESULTS: R3PE was successful in all patients without any complications. The calculated volume of the right lobe significantly (P < .01) decreased from 650 +/- 161 cm3 before embolization to 585 +/- 143 cm3 after embolization; the volume of the left lateral segment significantly (P < .0005) increased from 240 +/- 58 cm3 to 361 +/- 66 cm3. The volume of the left medial segment was unchanged. The volume gain of the left lateral segment was larger in patients with R3PE than in those patients (n = 41) with right portal vein embolization (122 +/- 39 cm3 vs 66 +/- 35 cm3; P < .0001). Two of the 16 patients underwent only laparotomy because of peritoneal dissemination, and the remaining 14 patients underwent right hepatic trisegmentectomy with caudate lobectomy. In addition, portal vein resection was also performed in 5 patients, and pancreatoduodenectomy and right hemicolectomy was performed in 3 patients. One patient died of posthepatectomy liver failure 87 days after surgery, a mortality rate of 7.1% (1/14 patients). CONCLUSIONS: R3PE is more useful than standard right portal vein embolization in preparation for right hepatic trisegmentectomy and has the potential to increase the safety of this high-risk surgery for patients with biliary tract carcinoma.

Adult↗
PubMed2000

Nitric oxide induces a decrease in the mitochondrial membrane potential of peripheral blood lymphocytes, especially in natural killer cells.

Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity of lymphoid cells. To investigate the effects of NO on the immune system, we measured the mitochondrial membrane potential (delta psi m) of the peripheral blood lymphocytes (PBL) cultured with a chemical NO donor. PBL from healthy volunteers were cultured with NOC18, a NO-generating compound, at various concentrations. The delta psi m of the PBL was measured by flow-cytometry using 3,3-dihexyloxacarbocyanine iodide (DiOC6(3)). NOC18 induced a decrease in the delta psi m of the PBL in a dose-dependent fashion, induced an increase in the levels of reactive oxygen species (ROS), and caused these cells to undergo apoptosis. Dual-color staining of the delta psi m and lymphocyte surface markers demonstrated that CD3-CD56+ natural killer (NK) cells were responsive to NO. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the delta psi m of the PBL. We showed that the delta psi m of peripheral NK cells were decreased by NO, which suggests that abundant NO at an inflammatory site may impair NK cell function.

Antioxidants↗
PubMed2000

Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience.

OBJECTIVE: To compare the experience and outcome in the management of hilar cholangiocarcinoma at one American and one Japanese medical center. SUMMARY BACKGROUND DATA: Controversies surround the issues of extent of resection for hilar cholangiocarcinoma and whether the histopathology of such cancers are similar between patients treated in America and in Japan. METHODS: Records were reviewed of 100 patients treated between 1980 and 1995 at the Lahey Clinic in the United States, and of 155 patients treated between 1977 and 1995 at Nagoya University Hospital in Japan. Selected pathologic slides of resected cancers were exchanged between the two institutions and reviewed for diagnostic concordance. RESULTS: In the Lahey cohort, there were 25 resections, 53 cases of surgical exploration with biliary bypass or intubation, and 22 cases of percutaneous transhepatic biliary drainage or endoscopic biliary drainage without surgery. In the Nagoya cohort, the respective figures were 122, 10, and 23. The overall 5-year survival rate of all patients treated (surgical and nonsurgical) during the study periods was 7% in the Lahey cohort and 16% in the Nagoya cohort. The overall 10-year survival rates were 0% and 12%, respectively. In patients who underwent resection with negative margins, the 5- and 10-year survival rates were 43% and 0% for the Lahey cohort and 25% and 18% for the Nagoya cohort. The surgical death rate for patients undergoing resection was 4% for Lahey patients and 8% for Nagoya patients. Of the patients who underwent resection, en bloc caudate lobectomy was performed in 8% of the Lahey patients and 89% of the Nagoya patients. Histopathologic examination of resected cancers showed that the Nagoya patients had a higher stage of disease than the Lahey patients. CONCLUSIONS: In both Lahey and Nagoya patients, survival was most favorable when resection of hilar cholangiocarcinoma was accomplished with margin-negative resections. Combined bile duct and liver resection with caudate lobectomy contributed to a higher margin-negative resection rate in the Nagoya cohort.

Adult↗
PubMed2000

Effect of optical purity on the critical heat capacity at the smectic-A-(chiral)-smectic-C transition in an antiferroelectric liquid crystal

High resolution ac calorimetric measurements have been carried out near the smectic-A-chiral-smectic-C phase transition in the antiferroelectric liquid crystal 4-(1-methylheptyloxycarbonyl)phenyl 4(')-octyloxybiphenyl-4-carboxylate (MHPOBC). Data on samples with different optical purities have been analyzed in detail using a renormalization-group expression with corrections-to-scaling terms. The chiral-smectic-C(alpha)-chiral-smectic-C phase transition is first order, while the smectic-A-chiral-smectic-C(alpha) phase transition is second order. A direct smectic-A-chiral-smectic-C phase transition, which occurs in near-racemic mixtures, was found to be quasitricritical and weakly first order. This implies that the smectic-A-smectic-C transition in the racemate locates at a special point where four critical lines intersect.

Journal Article↗