Biomedical subjects

K Sekine

Publications and source records attributed to K Sekine.

At least 55 records · Page 3Linked to original sources

PubMed1999

Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice.

In order to determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF), and related compounds on tumor growth and metastasis, bovine LF (bLF), and bLF hydrolysate and lactoferricin (bLFcin), active products generated by acid-pepsin hydrolysis were administered orally to BALB/c mice bearing subcutaneous (s.c.) implants of the highly metastatic colon carcinoma 26 (Co 26Lu). bLF and the bLF hydrolysate demonstrated significant inhibition of lung metastatic colony formation from s.c. implanted tumors without appreciable effects on tumor growth. bLFcin displayed a tendency for inhibition of lung metastasis. On the other hand, bLF did not exert marked anti-metastatic activity in athymic nude mice bearing Co 26Lu, though bLF had a tendency to inhibit the lung metastatic colony formation associated with anti-asialoGM1 antibody (Ab) treatment. AsialoGM1+ and CD8+ cells in white blood cells were increased after treatment with bLF. In vitro, the viability of Co 26Lu-F55 cells was markedly decreased when co-cultured with white blood cells from mice administrated bLF p.o., but recovered on treatment with anti-asialoGM1 Ab or anti-CD8 mAb and complement. The results suggest bLF and related compounds might find application as tools in the control of metastasis and that asialoGM1+ and CD8+ cells in the blood are important for their inhibitory effects.

Administration, Oral↗

PubMed1999

Fgf10 is essential for limb and lung formation.

The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis. In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development on the basis of its spatiotemporal expression pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10-deficient mice. Fgf10-/- mice died at birth due to the lack of lung development. Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted. In addition, mutant mice had complete truncation of the fore- and hindlimbs. In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected. Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation.

Animals↗

PubMed1999

Induction of apoptosis by bestatin (ubenimex) in human leukemic cell lines.

We investigated the growth inhibitory activity of bestatin, an inhibitor of aminopeptidase N (CD13), on six human leukemic cell lines. Proliferation of all the cell lines except KG1 was inhibited by bestatin. P39/TSU, HL60 and U937 were highly sensitive, with 50% growth inhibitory concentrations (IC50) close to the maximum serum concentration when bestatin was orally administered at 30 mg in clinical application. All cell lines except for K562 highly expressed CD13, but a clear correlation between the sensitivity to bestatin and expression of CD13 was not observed. Other aminopeptidase inhibitors such as amastatin A, arphamenine B and WM15 antibody showed no growth inhibitory effects. To confirm the growth inhibitory effects of bestatin, we quantitatively examined DNA fragmentation in five bestatin-sensitive cell lines. Bestatin dose-dependently induced DNA fragmentation in those cell lines. In case of U937, bestatin induced DNA fragmentation quantitatively and DNA ladder and enhanced caspase-3 activity. Furthermore, the growth inhibition by bestatin was reduced by the caspase inhibitor Z-Asp-CH2-DCB. These results suggested that bestatin exhibits direct antileukemic effects against human leukemic cell lines through the induction of apoptosis.

Aminopeptidases↗

PubMed1999

Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat.

A milk component, bovine lactoferrin (bLF), previously shown by us to be a strong chemopreventive of colon carcinoma development, was examined for its influence on other organs using a rat multi-organ carcinogenesis model. Male F344 rats, aged 6 weeks, were treated sequentially with diethylnitrosamine (DEN, i.p.), dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) and N-nitrosomethylbenzylamine (NMBA, s.c.) during the first 8 weeks (DDN treatment), and then bLF was administered in the basal diet, at a dose of 2, 0.2, 0.02 or 0.002%. Other groups were given DDN treatment or bLF alone as controls. All surviving animals were killed at week 41, and major organs were examined histopathologically for neoplastic lesions. In the esophagus, a tendency for reduction in development of papillomas was evident in the bLF-treated animals, along with a significant suppression of relatively large-sized papillomas (more than 50 mm3 volume) at the 0.2% dose (P<0.05, 11% of the control). The multiplicity of tumors (adenomas and carcinomas) in the lung was also decreased in animals fed 0.02% bLF (1.98+/-0.41 per cm2 lung tissue section, P<0.05) compared to the control group (3.48+/-0.33). No enhancing or inhibitory effects of bLF on tumor development in other organs were noted. The present results indicate that bLF exerts chemopreventive effects in the esophagus and lung in addition to the colon.

Adenoma↗

PubMed1999

Phase I study of cisplatin, ifosfamide and irinotecan with rhG-CSF support in advanced non-small cell lung cancer.

A phase I study was conducted in advanced non-small cell lung cancer to determine the maximum tolerated dose (MTD) of irinotecan combined with a fixed schedule of cisplatin and ifosfamide with rhG-CSF support. In addition, efficacy including survival time was evaluated at 2 years after the completion of patient registration. Cisplatin (20 mg/m2) and ifosfamide (1.5 g/m2) were administered at fixed doses on days 1-4, and irinotecan was given on days 1, 8 and 15 starting at 40 mg/m2, which was increased in 10 mg/m2 increments. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 microg/m2 on days 5-18 except on the day of irinotecan treatment. Forty-five patients were registered and 35 had received no prior chemotherapy. MTD or irinotecan was defined according to toxicity and the dose during three courses was increased up to 70 mg/m2. The dose 60 mg/m2 was recommended for phase II study. The dose-limiting factor was thrombocytopenia. The overall response rate was 57.8% and the median survival time was 492 days. In chemotherapy-naive patients, the response rate was 65.7% (95% CI; 50-81.4%), median response duration 161 days, median survival time 513 days, 1-year survival rate 62.4%, and 2-year survival rate 27.3%.

Adult↗

PubMed1999

Allergic bronchopulmonary aspergillosis due to Aspergillus niger without bronchial asthma.

A 65-year-old woman was admitted to our hospital with a dry cough and pulmonary infiltrates. Chest radiograph and CT revealed mucoid impaction and consolidations. Peripheral blood eosinophilia and elevated serum IgE were observed. Aspergillus niger was cultured repeatedly from her sputum, but A. fumigatus was not detected. Immediate skin test and specific IgE (RAST) to Aspergillus antigen were positive. Precipitating antibodies were confirmed against A. niger antigen, but not against A. fumigatus antigen. She had no asthmatic symptoms, and showed no bronchial hyperreactivity to methacholine. Thus, this case was diagnosed as allergic bronchopulmonary aspergillosis (ABPA) without bronchial asthma due to A. niger, an organism rarely found in ABPA. The administration of prednisone improved the symptoms and corrected the abnormal laboratory findings.

Aged↗

PubMed1999

Circadian variation in nasal reactivity in children with allergic rhinitis: correlation with the activity of eosinophils and basophilic cells.

BACKGROUND: In allergic rhinitis, the major symptoms of runny nose, sneezing, and stuffy nose tend to become worse upon waking up in the morning, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether the worsening of allergic rhinitis in the morning is associated with changes in the activity of inflammatory cells. METHODS: Nasal reactivity to methacholine was assessed twice in 8 children with allergic rhinitis and 8 healthy control subjects at 6.00 a.m. and 3.00 p.m. The amounts of eosinophil cationic protein (ECP), histamine and tryptase in induced nasal secretions and peripheral blood were also measured. RESULTS: Nasal reactivity to methacholine was higher at 6.00 a.m. not only in patients but also in healthy controls. Serum ECP and plasma histamine levels showed no circadian patterns. On the other hand, significantly higher levels of inflammatory activation products were found in nasal secretions at 6.00 a.m., thus showing a direct association with nasal reactivity. CONCLUSION: These results suggest that the circadian variation in nasal reactivity is associated with changes in the activity of eosinophils and basophilic cells in the nasal mucosa.

Adolescent↗

PubMed1999

Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice.

Previous studies have shown that 1,25-dihydroxyvitamin D [1,25(OH)2D] plays important roles in the formation of osteoclasts through its actions on osteoblastic cells. We have generated mice lacking vitamin D receptor (VDR) by gene targeting (VDR-/-). These mice had tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and exhibited similar levels of parameters for bone resorption to those in wild type mice. The present studies were undertaken to clarify whether effects of 1,25(OH)2D on osteoclast formation require VDR in osteoblasts, and to examine mechanisms of the formation of osteoclasts without VDR-mediated actions using VDR-/- mice. When wild-type calvarial osteoblasts and spleen cells were co-cultured with 1,25(OH)2D, TRAP-positive osteoclasts were formed regardless of the genotypes of spleen cells. In contrast, when osteoblasts from VDR-/- mice were co-cultured, no osteoclasts could be formed even with wild-type spleen cells. Parathyroid hormone and interleukin-1alpha stimulated osteoclast formation by co-cultures from VDR-/- mice, and the generated osteoclasts showed resorbing activity. These results demonstrate that VDR-mediated actions of 1,25(OH)2D in osteoblasts are essential for osteoclast formation by 1,25(OH)2D, and that functionally intact osteoclasts can be formed without 1,25(OH)2D actions under stimulations by other agents. It is suggested that osteoclastic bone resorption can be maintained without 1,25(OH)2D actions by other stimulatory agents.

Acid Phosphatase↗

PubMed1999

[Vasculo-Behcet's disease with fatal massive hemoptysis].

A 39-year-old man was admitted to our hospital because of hemoptysis. A chest X-ray film on admission showed a patchy shadow in the left lower lung field. Computed tomography revealed nodular opacities in the left pulmonary artery. The patient had history of oral ulcers, erythema nodosum, pustular lesions, and genital ulcers. Furthermore, the needle reaction was positive. Our diagnosis was an incomplete type of Behcet's disease. A radionuclide-venography and lung-perfusion study disclosed deep-vein thrombosis. Combined therapy with prednisolone, colchicine, and indomethacin farnesil was initiated, but the patient died of massive hemoptysis. Pathological examination revealed a ruptured aneurysm in the bronchus segmentalis apacalis and thrombotic angitis in the inferior vena cava. Behcet's disease is rarely a cause of hemoptysis. However, the prevalence of hemoptysis due to pulmonary vasculitis in patients with Behcet's disease has been reported to be 5 to 10% which is not so rare. Because of the poor prognosis, we want to emphasize Behcet's disease as a cause of hemoptysis.

Adult↗

PubMed1999

[Period of time patients with advanced non-small cell lung cancer could remain at home during CIC--therapy (cisplatin + ifosfamide + CPT-11)].

Two phase I studies (CIC-therapy) were conducted in advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerable dose (MTD) of CPT-11 combined with cisplatin and ifosfamide, and MTD of cisplatin combined with CPT-11 and ifosfamide with G-CSF support, respectively. Both regimens were repeated every 4 weeks. G-CSF was administered on days 5 to 18. Eighty-eight patients were registered in both studies. The overall response rate was 59.1%, and the median survival time was 393 days. In all patients enrolled, we examined retrospectively the period of time they could remain at home during chemotherapy. We examined this period divided into day 1-18 and day 18-28 until the third course. Although myelotoxicity occurring during the third course was the most severe, the mean time was 7.1 days (day 1-18 2.2, day 18-28 4.9) for the first course, 10.1 days (day 1-18 4.0, day 18-28 6.0) for the second course, and 11.0 days (day 1-18 4.7, day 18-28 6.3) for the third course. Only two patients came to the hospital because of acute upper respiratory tract infection. Although CIC-therapy was an aggressive chemotherapy with G-CSF support, most of the patients were able to stay at home during chemotherapy.

Adult↗

PubMed1999

[Benign clear cell tumor of the lung diagnosed by transbronchial biopsy].

A 26-year-old woman had an abnormal shadow on chest X-ray films during a general medical examination. A chest roentgenogram showed a nodular shadow 8 mm in diameter in the middle field of the right lung. Transbronchial biopsy specimens revealed that the coin lesion was a benign clear cell tumor. Benign clear cell tumors of the lung are rare; only 21 cases, including the present case, have been reported in Japan. Although the diagnosis in most of the cases reported required an open thoracotomy, for our patient the diagnosis was based solely on the findings of a transbronchial biopsy.

Adult↗

PubMed1999

FGF-FGFR signaling in vertebrate organogenesis.

Fibroblast growth factor and FGF receptor (FGFR) system play significant roles in many biological events including pattern formation in many tissues during vertebrate embryogenesis at early stages. The functions of each of FGFs and their receptors have recently been revealed by a variety of approaches among species. We have recently generated FGF10-deficient mice by gene targeting. This KO mice had complete truncation of the fore-and hindlimbs and with no lung. Analyses of the embryos and marker gene expression showed that FGF10 triggers sequential events, which are essential for formations of limb and lung. Focusing on FGF10 function, the FGF-FGFR system is discussed.

Animals↗

PubMed1999

[Compensatory increases in residual lobar volume following lung resection].

To investigate compensatory increases in residual lobar volume after lobectomy and pneumonectomy, we measured lung lobar volumes on the basis of pre- and postoperative computed tomographic (CT) images obtained on 40 patients (11 right upper, 7 right lower, 10 left upper, 8 left lower lobectomies and 4 left pneumonectomies). A personal computer image processing program was utilized to calculate lung lobar volumes from sequential CT images. Decreases in whole lung volume after lung resection averaged from 7.4% to 9.5% of preoperative whole lung volume in the lobectomy patients, and 30% in the patients who underwent left pneumonectomy. Those values were much smaller than the volumes of resected lobe, as measured on the basis of preoperative CT images. Increased residual lobar volume after lung resection averaged from 11% to 15% of preoperative whole lung volume in both the lobectomy and left pneumonectomy patient groups. Residual lobes compensated for approximately 60% of the resected lobar volume in the lobectomy patients, but only about 30% of resected lung volume in the left pneumonectomy patients. Increases in residual lobar volume tended to be larger in patients who underwent upper lobectomies, and on the operative side in patients other than those who underwent left lower lobectomies. We concluded that compensatory increases in residual lobar volume should be taken into full consideration when making predictions about postoperative pulmonary function.

Adult↗

PubMed1998

Inhibitory effects of bovine lactoferrin on intestinal polyposis in the Apc(Min) mouse.

Chemopreventive effects of bovine lactoferrin (bLF), previously shown to strongly inhibit intestinal carcinogenesis in rats (K. Sekine, E. Watanabe, J. Nakamura, N. Takasuka, D.J. Kim, M. Asamoto, V. Krutovskikh, T.H. Baba, T. Ota, M.A. Moore, M. Masuda, H. Sugimoto, H. Nishino, T. Kakizoe, H. Tsuda, Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats, Jpn. J. Cancer Res. 88 (1997) 523-526; K. Sekine, Y. Ushida, T. Kuhara, M. Iigo, H. Baba-Toriyama, M.A. Moore, M. Murakoshi, Y. Satomi, H. Nishino, T. Kakizoe, H. Tsuda, Inhibition of initiation and early stage development of aberrant crypt foci and enhanced natural killer activity in male rats administered bovine lactoferrin concomitantly with azoxymethane, Cancer Lett. 121 (1997) 211-216), on spontaneous intestinal polyp development were assessed in the ApcMin mouse, a model for both familial adenomatous polyposis and sporadic colon cancers. In the experiment, 54 mice at 6 weeks of age were given 2% bLF (15 mice), 0.2% bLF (15 mice) and AIN-93G (24 mice) as basal diet ad libitum for 8 weeks. An overall tendency for a reduction in the total number of polyps in the small intestine was evident in the bLF-treated animals, along with significant suppression in the jejunum at the 2% dose (P < 0.05, 68% of the control). In addition, body growth suppression, presumed to be due to anemia and/or intussusception as a consequence of numerous polyps in the intestine, was alleviated. No toxic effects were observed in the intestinal epithelium. Although not as obvious as observed for the rat case, the data suggest that bLF may be a chemopreventor of intestinal polyposis.

Animals↗

PubMed1998

Urinary excretion of aquaporin-2 in term and preterm infants.

Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel of the renal collecting duct and is excreted in human urine. We measured the urinary excretion of AQP-2 by radioimmunoassay in 14 term and 12 preterm infants aged 1 month. Excretion of AQP-2 was low compared with adults, and correlated significantly with urine osmolality in preterm infants. Our results demonstrate that AQP-2 water channels are expressed in the renal collecting duct of both term and preterm infants.

Aquaporin 2↗

PubMed1998

Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLf) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.

Animals↗

PubMed1998

Renal water channel expression in newborns: measurement of urinary excretion of aquaporin-2.

Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney.

Acetylglucosaminidase↗

PubMed1998

Abnormalities of the FHIT transcripts in osteosarcoma and Ewing sarcoma.

In a study of FHIT gene abnormalities by reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis of the PCR products, we found normal and abnormal PCR products in 11 osteosarcomas, one osteosarcoma cell line and 3 Ewing sarcomas, and a normal PCR product only in 5 osteosarcomas and 8 Ewing sarcomas. Sequence analysis of the abnormal PCR products revealed 7 osteosarcomas lacking exons 4 to 6, 7, 8 or 9, two lacking exons 5 to 7 or 10, and two lacking exons 6 to 8 or 10. In the aberrant transcripts of the 11 osteosarcomas, fusion had occurred in the exon/intron junctions in 2 tumors, between a segment within an exon and a complete exon in 3, and between segments within exons in 6. The 3 Ewing sarcomas had lost exon 4 or 5 to exon 6 or 10, and fusion had occurred in the exon/intron junction in one, and between segments within exons in 2. These findings suggest that both abnormal or variant splicing and other mechanisms such as genomic instabilities in the FHIT locus may have resulted in the expression of aberrant transcripts. One osteosarcoma and one cell line established from this osteosarcoma showed different abnormal FHIT transcripts, indicating that the tumor cells with the initial aberrant transcripts may not have had a selective advantage for proliferation. The FHIT abnormalities did not seem to be correlated with lung metastasis or a poor clinical outcome in our patients with osteosarcoma or Ewing sarcoma.

Acid Anhydride Hydrolases↗