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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 91 records · Page 5Linked to original sources
PubMed2001

Caspase activity in newt spermatogonial apoptosis induced by prolactin and cycloheximide.

We previously showed in vivo and in vitro, that among the spermatogenic stages of the newt, prolactin (PRL) induces apoptosis specifically in the penultimate stage of secondary spermatogonia. In the current report, we demonstrate in vitro that cycloheximide (CHX), an inhibitor of protein synthesis, induces morphological apoptotic changes similar to those caused by PRL, such as chromatin condensation and apoptotic body formation. Next, we found that Z-VAD-fmk, an inhibitor of various caspases, suppressed the apoptosis induced by PRL and CHX, but ICE inhibitor Ac-YVAD-CHO or caspase-3 inhibitor Ac-DEVD-CHO did not. As high caspase activity was present in extracts of testes treated with CHX, we suggest that an unidentified caspase induces the morphological changes of apoptosis in newt spermatogonia.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Cold suppression of follicle-stimulating hormone activity on proliferation and survival of newt spermatogonia.

In newts elevated titers of plasma prolactin (PRL), induced by low temperature, cause apoptosis in the penultimatemitotic stage of spermatogonia, and this cell death is suppressed by antiserum against newt PRL, but only during the initial 3 days of exposure (Yazawa et al., 1999). Thus, factors other than PRL must be involved in spermatogonial death. Follicle-stimulating hormone (FSH) may be a plausible candidate. Accordingly, the current study examined the activityof FSH on the proliferation and survival of spermatogonia at low temperatures in vivo and in vitro. Porcine FSH (pFSH) administration in vivo inhibited spermatogonial death induced at 12 degrees C, but failed to do so at8 degrees C. Also pFSH promoted in vitro the proliferation of spermatogonia at 12 degrees C, but not at 8 degrees C. Furthermore,dibutyryl cyclic AMP stimulated in vitro DNA synthesis of secondary spermatogonia at 12 degrees C, but not at 8 degrees C. These different responses to temperatures were not caused by different levels of mRNA for the receptor of follicle-stimulating hormone, the numberof FSH binding sites, or FSH binding affinity to its receptors in the testicular cells. Thus, the results indicate that a temperature-sensitive period exists duringthe postreceptor process and is responsible for thelack of response of newt testis to FSH at 8 degrees C.

Animals↗
PubMed2001

Alternate venous drainage and return of warmed blood combined with continuous hypothermic visceral perfusion. A new adjunct of thoracoabdominal aortic aneurysm repair.

OBJECTIVE: As a new adjunct to surgical repair for a thoracoabdominal aortic aneurysm, we have devised and used visceral perfusion in combination with alternate venous drainage and return of warmed blood in 4 patients. METHODS: Surgical repair of a thoracoabdominal aortic aneurysm of Crawford type III (n = 1) or type IV (n = 3) was performed. During visceral branch reconstruction, hypothermic blood (30-32 degrees C) was perfused continuously to each visceral and renal artery at a total flow rate of 300 ml/min, in combination with alternate venous drainage and return of warmed blood to the inferior vena cava. RESULTS: The visceral and renal perfusion time was 115 +/- 55 (with a range from 52 to 190) minutes. All 4 patients recovered uneventfully. CONCLUSIONS: Alternate venous drainage and return of warmed blood combined with continuous hypothermic visceral perfusion were a useful adjunct to thoracoabdominal aneurysm repair during reconstruction of visceral and renal arteries.

Aged↗
PubMed2001

Aortic valve replacement in a heavily calcified "porcelain" aorta.

Although a heavily-calcified so-called "porcelain" aorta is encountered infrequently, its association presents a formidable problem in cardiac surgery. Here we describe a case of severe aortic stenosis and coronary artery disease combined with the circumferentially calcified aorta. The patient was a 63-year-old man who successfully underwent double coronary artery bypass grafting and aortic valve replacement during hypothermic perfusion through the right axillary artery with endoaortic balloon occlusion, followed by minimal endarterectomy of the calcified plate along the aortotomy, and closure of the aorta buttressed with bovine pericardium under circulatory arrest.

Aortic Diseases↗
PubMed2001

Wax ester biosynthesis in the liver of myctophid fishes.

The biosynthetic properties of wax esters in the liver were compared between two types of myctophid fishes having different body lipid composition, i.e., three triglyceride-rich species (Lampanyctus jordani, Diaphus theta, and Symbolophorus californiensis) and three wax ester-rich species (L. regalis, Stenobracius nannochir, and Stenobracius leucopsarus). n-Heptadecanol (17:0-ALC) and/or 10-cis-heptadecenoic acid (17:1-ACID) was incubated with liver homogenate of the six myctophid fishes and with co-factors such as NADPH and ATP for 2 to 5 h. Considerable amounts of wax esters with odd-numbered fatty acids and/or alcohols were produced in the liver homogenate of the wax ester-rich species. Stenobracius nannochir and L. regalis, which exclusively contained wax esters as neutral lipids, showed the highest activity of wax ester synthesis, followed by S. leucopsarus, which contained triglyceride as the minor constituent. Only trace amounts at most of odd-numbered fatty acids and alcohols were incorporated into the wax esters after incubation with the liver homogenates of the triglyceride-rich fishes. Active interchange between the fatty acids and the alcohols occurred during wax ester biosynthesis in the wax ester-rich fishes. The chain elongation and shortening of acyl moieties were also observed during incubation. These results suggested that the deposition of lipids in myctophid fishes is mainly due to their biosynthetic activities.

Adenosine Triphosphate↗
PubMed2001

Phase I trial of weekly docetaxel combined with cisplatin in patients with non-small cell lung cancer.

The phase I study was conducted to evaluate the maximum tolerated dose (MTD) and toxicity of weekly administered docetaxel combined with cisplatin in patients with non-small-cell lung cancer (NSCLC). In a dose escalation study, 22 patients, under 75 years old, with unresectable and metastatic untreated NSCLC with performance status (0-1) were enrolled. Patients were treated with cisplatin (day 1) and weekly docetaxel (days 1, 8, 15). Dose escalation levels in mg/m(2) were for cisplatin and docetaxel; 70 and 15 (level 1), 80 and 15 (level 2), 80 and 20 (level 3), 80 and 25 (level 4), 80 and 30 (level 5), respectively. Chemotherapy was repeated for at least two cycles every 28 days. All patients were assessable for toxicities. Although grade 3 neutropenia occurred in one case in level 4, there were no significant modifications of chemotherapy schedule until level 4. Grade 3 neutropenia occurred in all cases receiving level 5. One patient developed an infection, and two had incomplete recovery of neutropenia by the 28th day after the first cycle of chemotherapy. Nonhematological toxicities, including nephrotoxicity, nausea/vomiting, alopecia and hypersensitivity reaction, were tolerable. However, one case developed severe hyponatremia. Among 21 patients evaluable for response, eight cases achieved partial response, thus the overall response was 39%. Weekly administration of docetaxel at 25 mg/m(2) (days 1, 8, 15) combined with cisplatin 80 mg/m(2) (day 1) is recommended for phase II studies. The responses observed in the present study suggest an identical high degree of activity against NSCLC with less hematotoxicity compared with a standard schedule of cisplatin and docetaxel.

Adult↗
PubMed2001

Stem cell factor protects c-kit+ human primary erythroid cells from apoptosis.

OBJECTIVE: It has been reported that stem cell factor (SCF) promotes cell survival in primary cultured human erythroid colony-forming cells (ECFC). Given the heterogeneous nature of ECFC, which may affect interpretation of the data, we purified c-kit+ ECFC and investigated the specificity and mechanisms of the anti-apoptotic effects of SCF on these cells. MATERIALS AND METHODS: Glycophorin A+ (GPA+) c-kit+ cells were purified from primary cultured ECFC derived from purified human CD34+ cells. The GPA+c-kit- and nonerythroid cells were generated from the same CD34+ cells. Apoptosis of ECFC was investigated in the absence or presence of SCF and erythropoietin (EPO) in serum-free medium. DNA fragmentation was measured with enzyme linked immunosorbent assay for oligonucleosome-sized DNA, gel electrophoresis, and annexin V labeling. Characterization of expanded cells and enriched cells was performed using multiparameter flow cytometry. For Akt assay, cells were lysed and the cleared lysates subjected to SDS-PAGE followed by Western blotting. RESULTS: In GPA+c-kit+ cells, deprivation of cytokine caused rapid DNA fragmentation within 4 hours that reached a maximum at 6 hours. This was partially but clearly prevented by SCF or EPO. In contrast, no significant DNA fragmentation was seen in GPA+c-kit- and nonerythroid cells within 24 hours. PP2, a specific Src family kinase inhibitor, but not its inactive analogue PP3, reversed the anti-apoptotic effects of SCF. PP2 also inhibited SCF-induced phosphorylation of Akt. CONCLUSION: These data indicate that SCF protects purified human GPA+c-kit+ cells from apoptosis and suggest that kit-mediated Src kinase activation is involved in Akt activation and cell survival.

Apoptosis↗
PubMed2001

beta-Adrenergic blockade and emotional memory in PTSD.

Emotional arousal has been shown to enhance memory, an effect that is blocked by propranolol suggesting that the noradrenergic system is important in the mechanism action. Because PTSD has as prominent features heightened arousal and distressing memories, the current study was undertaken to examine whether PTSD subjects differed from controls in emotional enhancement of memory. Seventeen subjects with PTSD and 21 controls received either placebo or 40 mg of propranolol prior to exposure to either an emotionally arousing or emotionally neutral, narrated slide story. Recall, measured 1 wk later, for the arousing story was enhanced and this effect was reduced by propranolol. PTSD and control subjects did not differ in the acquisition and retention of memories under emotionally arousing or emotionally neutral conditions, nor were differential effects of propranolol observed between the two groups.

Adrenergic beta-Antagonists↗
PubMed2001

Expression of melanoma antigen-encoding gene-1 predicts lymph node involvement in early gastric carcinomas.

Our previous study suggested that melanoma antigen-encoding gene-1 may be activated in gastric carcinomas when the tumors develop or invade. In the present work we studied the gene as a preoperative indicator of lymph node involvement in early gastric carcinoma. We used a reverse transcription-polymerase chain reaction to analyze expression of the gene in 47 endoscopic biopsy specimens from early gastric carcinomas. Relationships between gene expression and histopathologic findings were analyzed statistically. Eight of 47 tumor samples (17.0%) expressed the gene. The gene was not expressed in adjacent nontumor samples from carcinoma patients or in tissues from patients with benign gastric diseases. Gene expression correlated with infiltrative tumor growth in contrast to tumors with expansive growth patterns (P = 0.018). Gene expression also correlated with expression of platelet-derived growth factor-A (P < 0.001). MAGE-1 gene expression in biopsy specimens was a preoperative indicator of nodal involvement (P = 0.013). In conclusion, melanoma antigen-encoding gene-1 expression in biopsy specimens from early gastric carcinoma may serve preoperatively as an indicator of lymph node involvement.

Aged↗
PubMed2001

Apoptosis induced by ischemia-reperfusion and fasting in gastric mucosa compared to small intestinal mucosa in rats.

The effect of ischemia-reperfusion and 48-hr fasting on apoptosis was characterized in rat gastric mucosa and compared to small intestinal mucosa. Under halothane anesthesia, the celiac artery or superior mesenteric artery in the rat was occluded for 60 min followed by reperfusion. Occlusion of the celiac artery reduced blood flow in the stomach and occlusion of the mesenteric artery reduced blood flow in the small intestine. Additional rats were fasted for 48 hr to evaluate the effect of fasting on mucosal apoptosis. The ratios of fragmented DNA to total DNA, electrophoresis, and immunohistochemical staining were examined after ischemia-reperfusion or fasting. Apoptosis was not induced significantly in the gastric mucosa after ischemia-reperfusion, although it increased dramatically in the intestinal mucosa after ischemia-reperfusion. Further, after 48 fasting, apoptosis was induced in the small intestine, but not in the stomach. These results indicate that rat gastric mucosa is not as sensitive as small intestinal mucosa to ischemia-reperfusion or fasting-induced apoptosis.

Animals↗
PubMed2001

A possible role for lamivudine as prophylaxis against hepatitis B reactivation in carriers of hepatitis B who undergo chemotherapy and autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Hepatitis B virus (HBV) reactivation, a well-known complication in immunosuppressed patients, can give rise to acute hepatitis and even fatal fulminant hepatitis. Three Japanese males with non-Hodgkin's lymphoma (NHL) who were carriers of HBV received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). To prevent HBV reactivation, all received oral lamivudine (150 mg/day), a nucleoside analogue, at the start of chemotherapy. All were treated at full-dose intensity, including corticosteroids, without modification of treatment regimens. All three patients completed the total course of chemotherapy and PBSCT, with no signs of HBV reactivation. Peripheral blood stem cell (PBSC) harvests and hematological recoveries after transplantation were not affected by lamivudine, which was continued for at least 16 weeks after transplantation. HBV-DNA and DNA polymerase levels remained negative/normal after discontinuation of lamivudine. Lamivudine effectively inhibits HBV replication and has few serious adverse effects, particularly those related to hematopoiesis. Thus, prophylactic use of lamivudine from initiation of chemotherapy deserves consideration in the treatment of HBV carriers who require immunosuppressive chemotherapy, and may prevent HBV reactivation.

Adult↗
PubMed2001

Successful non-myeloablative stem cell transplantation for a heavily transfused woman with severe aplastic anemia complicated by heart failure.

A 30-year-old Japanese woman weighing 35 kg with severe hemochromatosis due to multiple transfusions was referred to our clinic for treatment of severe aplastic anemia (SAA). The patient had heart failure with an ejection fraction of 36% requiring diuretics and a severe liver dysfunction with an indocyanine green clearance rate of 18%, as well as other transfusion-related complications such as chronic hepatitis due to hepatitis C virus and diabetes mellitus. She was treated with a non-myeloablative preparative regimen that included fludarabine monophosphate (Flu, 120 mg/m(2)), cyclophosphamide (CY, 1200 mg/m(2)) and antithymocyte globulin (ATG, 15 mg/kg) followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-matched sister. The regimen was well tolerated, and engraftment rapidly occurred without any therapy-related complications. Chimerism analysis on day 14 after transplant showed reconstitution with 100% donor cells. She no longer needed transfusion after day 23 and has been well in 90% Karnofsky status at 4 months post transplant. The clinical course of this patient indicates that this preparative regimen enables SAA patients with severe organ failure to safely undergo allogeneic stem cell transplantation.

Adult↗
PubMed2001

Localization of sphingomyelin during the development of dorsal and tail epidermis of mice.

BACKGROUND: The water permeability barrier of the stratum corneum seems to be regulated primarily by lamellar bodies situated between the corneocytes; the lamellar bodies originate largely from polar lipid precursors, mainly sphingomyelin (SM), provided by the cells of the stratum granulosum via exocytosis of their lamellar body content. OBJECTIVES: The aim of our study was to evaluate the cellular distribution of SM during development of the epidermis. Methods In this study, we investigated the expression and localization of SM in both adult and fetal mouse skin by a cytochemical detection method, immunofluorescence microscopy and immunoelectron microscopy, using anti-SM antibody, a specific binding protein to SM (lysenin), and Nile red stain. In addition, we measured transepidermal water loss to estimate the barrier function of the fetal skin. RESULTS: We observed that SM was widely distributed from the basal layer to the granular layer in the adult mouse epidermis. An intense cytochemical reaction for SM was observed on embryonic day E14.5 of gestation just before the differentiation of the granular and squamous cells from the intermediate cells. The immunofluorescence indicating SM was detected in two regions, i.e. the most superficial zone of the granular layer and the upper spinous layer after the cell differentiation at the late gestational age. This distribution was not detected by conventional lipid staining, such as with Nile red stain. Immunoelectron microscopy revealed that SM was mainly localized in the intercellular spaces of the adult mouse epidermis and in the intracellular vesicles without a complete lamellar structure in the cytoplasm of epidermal cells of E14.5 fetuses. It is well known that the formation of the structurally mature cornified cell envelope occurs at E15.5 of development. The skin of fetuses at E16.5 showed a definite barrier function. CONCLUSIONS: These findings suggest that SM dynamics is related to the formation of the lipid envelope, cell differentiation, and epidermal barrier function during development.

Animals↗
PubMed2001

Quantification of red blood cell fragmentation by automated haematology analyser XE-2100.

The extent of red blood cell fragmentation in peripheral blood is useful for diagnosis and follow-up in many diseases, e.g. haemolytic uremic syndrome, transplantation-associated thrombotic microangiopathy (BMT-TMA). However, this quantification still relies on manual counting of fragmented red cells on blood smears. We have developed a quantification system by gating a fixed area of fragmented red blood cells (Gate 1) on an automated haematology analyser (XE-2100, Sysmex Co., Kobe, Japan). The fragmented red cell percentage (FRC%) calculated with this system, from 100 samples, was highly correlated with the manual count (r=0.902, P < 0.0001). Because microcytic anaemia specimens usually occupy a lower position on the XE-2100 scattergram, with microcytic cells overlapping Gate 1 and causing a spuriously high FRC% calculation, a supplementary gate (Gate 2) was added. Using the particle number in this gate as well as in Gate 1, a revised method for such samples was developed and its validity confirmed (revised FRC% correlated with a manual count for 10 subjects (P < 0.001). Because this gating system can be programmed on any XE-2100, it is likely to prove useful for accurate quantification of red blood cell fragmentation and for the monitoring of the development of BMT-TMA.

Anemia, Iron-Deficiency↗
PubMed2001

Renal arteriovenous fistula developing after tumor enucleation using a microwave tissue coagulator.

With the increase in detection of incidental renal cell carcinoma, nephron-sparing surgery for small renal cell carcinomas is now recognized as one of the surgical options. We report a case of renal arteriovenous fistula developing after non-ischemic tumor enucleation of a small renal cell carcinoma using a microwave tissue coagulator. A 50-year-old Japanese man presented with right flank pain and gross hematuria. The patient had undergone non-ischemic tumor enucleation for right renal cell carcinoma, 2 cm in diameter, 1 month previously. Doppler ultrasound revealed the formation of an arteriovenous fistula at the enucleated portion. Transcatheter super-selective occlusion of the feeding artery was successfully performed with two metallic coils. The patient has been followed up with no sign of recanalization of the fistula. In this case, the tumor was located close to the renal hilus with thick arterial branches around the tumor. Additional microwave coagulations against arterial bleeding from the cutting surface might have been the cause of the fistula formation of this case. Non-ischemic tumor enucleation using a microwave tissue coagulator is a relatively easy and secure nephron-sparing surgical procedure. Excessive coagulation, however, should be avoided, since it might be the cause of unexpected postoperative vascular complications.

Arteriovenous Fistula↗