Biomedical subjects

K Takenaka

Publications and source records attributed to K Takenaka.

At least 19 recordsLinked to original sources

PubMed2006

Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting.

BACKGROUND: Although the aetiology of moyamoya disease (MMD) has not been fully clarified, genetic analysis of familial MMD (F-MMD) has considerable potential to disclose it. OBJECTIVE: To determine the inheritance pattern and clinical characteristics of F-MMD to enable precise genetic analyses of the disease. METHODS: 15 highly aggregated Japanese families (52 patients; 38 women and 14 men) with three or more affected members were examined. The difference in categories of age at onset (child onset, adult onset and asymptomatic) between paternal and maternal transmission was compared by chi2 statistics. RESULTS: In all families there had been three or more generations without consanguinity, and all types of transmission, including father-to-son, were observed. Among a total of 135 offspring of affected people, 59 (43.7%) were patients with MMD or obligatory carriers. Affected mothers were more likely to produce late-onset (adult-onset or asymptomatic) female offspring (p = 0.007). CONCLUSIONS: The mode of inheritance of F-MMD is autosomal dominant with incomplete penetrance. Thus, in future genetic studies on F-MMD, parametric linkage analyses using large families with an autosomal dominant mode of inheritance are recommended. Genomic imprinting may be associated with the disease.

Adolescent↗

PubMed2006

Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms.

Neoplasms of natural killer (NK)-lineage are rare. Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma. The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998. Of 228 patients selected for analysis, 40 underwent HSCT (15 allografts and 25 autografts). The underlying diseases were myeloid/NK cell precursor acute leukemia (n = 4), blastic NK-cell lymphoma (n = 11), aggressive NK-cell leukemia (n = 3), and nasal-type extranodal NK-cell lymphoma (n = 22). At the time of HSCT, 22 patients were in complete remission (CR), 11 were in relapse, and seven were primary refractory. All patients received myeloablative conditioning regimens including total-body irradiation. Sixteen died of disease progression, and six of treatment-related causes. Overall, 4-year survival was 39% with a median follow-up of 50 months; this was significantly better than that of patients who did not undergo HSCT (21%, P = 0.0003). For patients transplanted in CR, the 4-year overall survival was 68%, which was significantly better than that of patients who went into CR but did not undergo HSCT (P = 0.03). These findings suggest that the HSCT is a promising treatment strategy for NK-cell lineage.

Adolescent↗

PubMed2005

Laparoscopic cholecystectomy using a newly developed laparoscope manipulator for 10 patients with cholelithiasis.

BACKGROUND: Laparoscopic surgery has continued to gain popularity in almost all fields of abdominal surgery, and robotic systems have been introduced in general surgery. Naviot is a new remote-controlled laparoscope manipulator system controlled by the operator's hand. This study assessed its introduction into clinical practice. METHODS: A group of 10 consecutive patients with cholelithiasis underwent laparoscopic cholecystectomy assisted by the Naviot system (Naviot group). Another group of 41 patients who underwent laparoscopic cholecystectomy with a conventional human camera holder (human camera group) were selected for a comparison of their operative results with those of the Naviot group. RESULTS: The operative time of 89.3 +/- 27.1 min for the Naviot group was significantly longer than that of 74.8 +/- 28.1 min for the human camera group (p < 0.05). However, when the setup time for the Naviot system was excluded, the operative time was not significantly different from that for the human camera group. Other operative results showed no significant difference between the two groups. CONCLUSIONS: The authors believe that the new Naviot system is feasible for clinical use, and that it enables surgeons to perform solo gastrointestinal surgery.

Aged↗

PubMed2005

Collapse of coherent quasiparticle states in theta-(BEDT-TTF)2I3 observed by optical spectroscopy.

Optical conductivity measurements on the organic metal theta-(BEDT-TTF)2I3 revealed that the system crosses over rapidly from a coherent quasiparticle state to an incoherent state with temperature. Despite the metallic temperature dependence of resistivity, a well-defined Drude peak at low temperatures turns into a far-infrared peak with temperature. The peak energy shifts to higher frequencies and, simultaneously, the spectral weight is transferred to high frequencies beyond the electron band width. These characteristics imply that theta-(BEDT-TTF)2I3, so far believed to be a typical metal, is in fact a strongly correlated electron system with "bad-metal" character.

Electric Conductivity↗

PubMed2005

Role of insulin-sensitizing property of telmisartan, a commercially available angiotensin II type 1 receptor blocker in preventing the development of atrial fibrillation.

Atrial fibrillation (Af) is the most common disorder of cardiac rhythm and is responsible for substantial morbidity and mortality in the general population. A recent community-based observational study revealed that diabetes and hypertension were associated with the development of Af. Since there is no definite evidence to show that type 1 diabetes is at increased risk for the development of Af, insulin resistance rather than hyperglycemia per se could explain the link between diabetes and Af. Several clinical trials suggest that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of insulin resistance. Indeed, interruption of the RAS with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been shown to prevent the onset of diabetes in hypertensive patients. Further, several experimental and clinical studies showed the beneficial role for the inhibition of the RAS in preventing Af as well. However, to what extent the insulin-sensitizing effects of ARBs could account for the prevention of Af remains to be clarified. Recently, telmisartan, an ARB, was found to act as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma influences the gene expression involved in carbohydrate metabolism. In animal study, telmisartan administration caused a significant attenuation of weight gain and reduced glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet, compared with treatments of losartan, another type of ARB. Furthermore, recently, some clinical papers also reported the insulin-sensitizing effects of telmisartan in hypertensive patients. In this paper, we would like to propose the possible ways of clarifying to what extent the insulin-sensitizing effects of ARBs could account for the prevention of Af. (1) Does telmisartan reduce the development of Af in insulin resistant hypertensive patients? (2) When adjusted for blood pressure, is the effect of telmisartan superior to other ARBs? (3) Does this beneficial effect of telmisartan correlate to its insulin-sensitizing properties? Ongoing clinical trial (ONTARGET) has been designed the efficacy of telmisartan with an ACEI, ramipril, alone or in combination. This randomized, double-blind, multicenter international studies will provide further information whether telmisartan can improve insulin resistance and subsequently reduce the development of Af in high-risk hypertensive patients.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Direct evidence for cooperating genetic events in the leukemic transformation of normal human hematopoietic cells.

Although genetic abnormalities associated with hematological malignancies are readily identified, the natural history of human leukemia cannot be observed because initiating and subsequent transforming events occur before clinical presentation. Furthermore, it has not been possible to study leukemogenesis in vitro as normal human cells do not spontaneously transform. Thus, the nature and sequence of genetic changes required to convert human hematopoietic cells into leukemia cells have never been directly examined. We have developed a system where the first step in the leukemogenic process is an engineered disruption of differentiation and self-renewal due to expression of the TLS-ERG oncogene, followed in some cases by overexpression of hTERT. In two of 13 experiments, transduced cells underwent step-wise transformation and immortalization through spontaneous acquisition of additional changes. The acquired karyotypic abnormalities and alterations including upregulation of Bmi-1 and telomerase all occur in acute myeloid leukemia (AML), establishing the relevance of this system. One resultant cell line studied in depth exhibits cellular properties characteristic of AML, notably a hierarchical organization initiated by leukemic stem cells that differentiate abnormally. These findings provide direct evidence for multiple cooperating events in human leukemogenesis, and provide a foundation for studying the genetic changes that occur during leukemic initiation and progression.

Blotting, Western↗

PubMed2005

Prevention of overlooked bullae during video-assisted thoracic surgery (VATS) with a combination of high frequency jet ventilation (HFJV) and positive end-expiratory pressure (PEEP) for spontaneous pneumothorax.

BACKGROUND: Overlooked bullae have been reported to contribute to the higher incidence of recurrence of pneumothorax following video-assisted thoracic surgery (VATS). In this study, we investigated whether high frequency jet ventilation (HFJV) + positive end-expiratory pressure (PEEP) prevented overlooking of bullae by blowing up the bullae and inflating the lungs moderately during VATS for spontaneous pneumothorax patients. METHODS: A total of 31 patients with spontaneous pneumothorax who underwent VATS were enrolled in this study. We examined the number, size, and location of bullae with and without HFJV+PEEP during VATS. RESULTS: More bullae were found with HFJV + PEEP than without HFJV + PEEP in 15 of the 31 patients. Significantly more bullae smaller than 2 cm in diameter were detected with HFJV + PEEP than without HFJV + PEEP. In the patients with 1 - 3 bullae, the detection rate was significantly higher with HFJV + PEEP than without HFJV + PEEP. All bullae confirmed with VATS were detected only in one case (3.2 %) on preoperative chest X-ray, and in two cases (6.5 %) on chest CT. The recurrence rate of pneumothorax following VATS with HFJV + PEEP was 3.3 % (1/31). CONCLUSION: Our results suggested that VATS combined with HFJV and PEEP might prevent the overlooking of bullae and reduce the postoperative recurrence of spontaneous pneumothorax.

Adolescent↗

PubMed2005

Ferromagnetic microstructure in double exchange manganites.

Ferromagnetic (FM) microstructures in double-exchange manganites, La0.825Sr0.175MnO3, were examined by low-temperature Lorentz microscopy. It was found that the FM domains with the stripe pattern were in the FM metallic phase of La0.825Sr0.175MnO3. The FM insulator phase induced by the substitution of Al ions for Mn in La0.825Sr0.175MnO3 was characterized as a complex mixture of the characteristic FM domains, which consists of three types of FM domains: the stripe domains, the plate-shaped domains and the complicated wavy domains. It is suggested that this mixture of different types of FM domains breaks the coherence of the electric conductivity and gives rise to the insulating character in Al doped La0.825Sr0.175MnO3.

Journal Article↗

PubMed2005

Molecular mechanisms for vascular injury in the metabolic syndrome.

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes and dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been shown to be associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. In the present article we review the molecular mechanisms by which the metabolic syndrome causes endothelial dysfunction and subsequently promotes atherosclerosis. We also discuss promising therapeutic strategies that specifically target the mechanisms responsible for vascular alterations in the metabolic syndrome.

Animals↗

PubMed2005

Blockade by nifedipine of advanced glycation end product-induced CD40-CD40 ligand interaction in endothelial cells.

Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of accelerated atherosclerosis. There is a growing body of evidence that CD40-CD40 ligand (CD40L) interaction also plays an important role in atherogenesis. However, the effects of AGEs on CD40-CD40L signaling in endothelial cells (ECs) remain to be elucidated. In this study, we investigated (i) whether injection of AGE-proteins to normal rats stimulates CD40L expression on circulating platelets and (ii) whether AGEs up-regulate CD40 mRNA levels in cultured ECs. We further examined the effects of nifedipine, one of the most popular dihydropyridine-based calcium antagonists, on CD40 gene expression in AGE-exposed ECs. Platelet surface CD40L expression was increased in AGE-bovine serum albumin (AGE-BSA)-injected rats, compared with nonglycated BSA administration. AGEs were found to induce up-regulation of CD40 mRNA levels in ECs, which were significantly blocked by nifedipine. These results suggest that AGEs could enhance CD40-CD40L interaction, thereby promoting atherosclerosis in diabetes. Blockade of CD40-CD40L signaling in ECs may be a molecular target for the vasculoprotective property of nifedipine.

Animals↗

PubMed2004

Clinical significance of VEGF-C status in tumour cells and stromal macrophages in non-small cell lung cancer patients.

Recent experimental studies have revealed that tumour-associated stromal macrophages as well as tumour cells express vascular endothelial growth factor C (VEGF-C), which plays important roles in lymphangiogenesis, which is a critical factor in the progression of many malignant tumours including non-small-cell lung cancer (NSCLC). However, no clinical study on VEGF-C expression in both stromal macrophages and tumour cells has been reported, and we conducted the present study to address the issue in resected NSCLC. A total of 206 patients with completely resected pathologic stage I-IIIA NSCLC were retrospectively reviewed. Expression of VEGF-C in primary lung tumour was assessed immunohistochemically. Expression of VEGF-C in tumour cells was high in 125 patients (60.7%), and that in stromal macrophages was positive in 136 patients (71.2%). The status of VEGF-C in tumour cells or in stromal macrophages was not correlated with nodal status or angiogenesis. The 5-year survival rate of high tumoral VEGF-C patients (60.7%) was significantly lower than that of low tumoral VEGF-C patients (39.3%) (P=0.046), and a multivariate analysis confirmed that tumoral VEGF-C status was a significant and independent prognostic factor. Moreover, tumour showing high VEGF-A and VEGF-C expression in tumour cells showed the poorest prognosis (5-year survival rate, 45.1%). The status of VEGF-C in stromal macrophages was not correlated with the prognosis. In conclusion, tumoral VEGF-C status, not stromal VEGF-C status, was a significant prognostic factor in resected NSCLC.

Aged↗

PubMed2003

Acute lymphoblastic leukemia with large molecular ACTH production.

Ectopic hormone production is very rare in hematological malignancy. Here, we describe an interesting case of acute lymphoblastic leukemia (ALL) with adrenocorticotropic hormone (ACTH) production. A 47-year-old man was admitted to our hospital with a 7-month history of hyperpigmentation. The plasma level of ACTH was markedly elevated without a circadian rhythm and the level of cortisol was normal. Examination of bone marrow aspiration revealed ALL, and no other disease as a cause of the elevated ACTH was detected. Sephadex G-75 chromatography of plasma ACTH extract revealed the existence of an abnormally large molecular ACTH (probably proopiomelanocortin) in addition to authentic 1-39 ACTH. Ectopic ACTH of low biological activity is considered to be the reason for a discrepancy in the plasma levels of ACTH and cortisol. Shortly after remission induction chemotherapy, blast cells in the peripheral blood disappeared, and the plasma level of ACTH became normal, leading to an improvement of skin pigmentation. These clinical findings and laboratory data suggested that leukemia cells in this case may produce the ACTH.

Adrenocorticotropic Hormone↗

PubMed2003

Somatic mutation of the Caspase-5 gene in human lung cancer.

Using cDNA array-based gene expression profiling, we previously found reduced expression of the Caspase-5 gene in highly metastatic subpopulations of a lung cancer cell line. The Caspase-5 gene contained poly(A) repeats in its coding region, an area that has been reported to be mutated in both endometrial and gastrointestinal tumors displaying evidence of microsatellite instability. In order to determine the contribution of Caspase-5 gene inactivation to lung cancer development and progression, the mutational status of the Caspase-5 poly(A) tract in 30 primary lung cancers with distant metastasis and 30 lung cancer cell lines was determined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. Three somatic mutations of the Caspase-5 gene were found in two out of 30 lung cancer tissues, although no mutations were found in other genes that also contain small nucleotide repeats, such as hMSH3, hMSH6 and BAX. The results of the present study, combined with our prior cDNA array-based gene expression profiling data, suggest that Caspase-5 might be a suppressor gene of highly metastatic potential in lung cancer.

Base Sequence↗

PubMed2002

Bilateral adrenal hemorrhage in essential thrombocythemia.

A 67-year-old woman with previously untreated essential thrombocythemia developed bilateral adrenal hemorrhage. She had no known vascular risk factors including smoking, diabetes mellitus, hypertension, and hypercholesterolemia. Her platelet count was 921 x 10(9)/l. She received preemptive steroid therapy to prevent the occurrence of adrenal crisis, but 5 weeks later the replacement therapy was discontinued because the patient fully recovered with a normal adrenocorticotropic hormone stimulation test. Thereafter, she remained well for more than 4 years with a platelet count ranging from 600 to 800 x 10(9)/l. Although adrenal hemorrhage is very rare, it can occur as a hemorrhagic complication of essential thrombocythemia.

Adrenal Gland Diseases↗

PubMed2002

Chaotic mixing generated by acoustic streaming.

The acoustic mixer presented in this paper is a closed cylinder containing chemical solutions. The ultrasound was generated in a water bath outside of the cylinder. The mixing efficiency was measured by using a laser-photodiode system and by mixing iodine and sodium thiosulfate. Iodine solution has a light brown color which becomes transparent if the solution is mixed with sodium thiosulfate. The unmixed regions of the solution in the container remain dark. Starch was used to make the solution darker. Considering the relative position between the cylinder and the transducer, it was shown that displacements parallel to the axes of the streaming have little effect on the mixing speed. Indeed, the distance of the cylinder from the center of the streaming is more important to obtain ideal mixing performances. The frequency and size of the transducers has been investigated too and little effect was found. In contrast, the wave amplitude seems to be the biggest factor in obtaining rapid mixing.

Journal Article↗

PubMed2002

Life-threatening bleeding and acquired factor V deficiency associated with primary systemic amyloidosis.

Acquired factor X deficiency has been described in patients with amyloidosis but acquired factor V deficiency is quite rare. We report here a case of life-threatening bleeding and acquired factor V deficiency associated with primary amyloidosis. A 50-year-old man who had no previous hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis, gingival bleeding and hemospermia. The laboratory examination revealed that both the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) were significantly prolonged, and factor V activities were markedly decreased to 14-39% of the normal value. Other coagulation factors such as fibrinogen, prothrombin, factor VII, factor VIII, factor IX and factor X were subnormal and normal. Transaminases were slightly elevated but serological tests of hepatitis B and hepatitis C were negative. Mild hepatosplenomegaly was noted without sign of liver cirrhosis. The PT and aPTT obtained 8 years ago when he received a cholecystectomy due to cholecystitis were both normal. Specific assays for the detection of factor V inhibitor were repeatedly performed but no factor V inhibitor was found. Furthermore, a significant recovery of the infused factor V was noted shortly after an intravenous administration of 5-10 U fresh frozen plasma, but it did not last more than 6 h. Melena, bleedings into the left shoulder and buttock, and finally mortal retroperitoneal hemorrhage developed despite repeated infusions of large amounts of fresh frozen plasma. Acquired factor V deficiency associated with primary amyloidosis was suspected but histological diagnosis was not obtained because of the severe bleeding tendency. Autopsy revealed hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart and other parenchymal organs. Perivascular amyloid deposition and factor V deficiency are both thought to be the cause of the severe hemorrhagic tendency seen in this patient.

Amyloidosis↗

PubMed2001

Aberrations in the fragile histidine triad (FHIT) gene in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) seems to be closely associated with lung carcinogenesis. To identify the genetic characteristics of precancerous IPF lesions in the peripheral lung, we performed PCR-based microsatellite analysis with DNA extracted from microdissected tissues; fluorescent in situ hybridization (FISH) analysis of the fragile histidine triad (FHIT) gene and immunohistochemical analysis of Fhit protein expression in samples of metaplasias and bronchiolar epithelia obtained from patients with IPF. We used four microsatellite markers of the FHIT gene within or flanking the FHIT gene on chromosome 3p for loss of heterozygosity (LOH) analysis. LOH of the FHIT locus was frequently found among the lesions of metaplasias and bronchiolar epithelia in the patients with IPF [62 (52%) of 119 informative lesions]. Fifty-four (73%) of the 74 lesions of metaplasias and bronchiolar epithelia obtained from the IPF patients with lung carcinoma and 8 (17%) of the 46 samples obtained from the IPF patients without lung carcinoma showed LOH at the FHIT gene (P < 0.0001). We confirmed allelic loss in the metaplasias and bronchiolar epithelia of IPF by FISH analysis of the FHIT gene. Additionally, the level of Fhit protein expression in the metaplastic cells of IPF was frequently reduced. Our findings suggest that allelic loss of the FHIT gene may be involved in carcinogenesis in the peripheral lung of patients with IPF.

Acid Anhydride Hydrolases↗

PubMed2001

Cytokine characteristics of jaundice in mouse liver.

OBJECTIVE: The aim of this study is to clarify the perioperative cytokine changes and their mechanism in jaundiced liver. MATERIALS AND METHODS: Obstructive jaundice was induced using a common bile duct ligation (CBDL) and a two-thirds hepatectomy (HEP) was performed in six- to seven-week-old male C3H/HeN mice. When hepatectomy was added to CBDL, it was carried out 2 to 5 days after CBDL. The serum interleukin 6 (IL-6) levels and heat shock protein (HSP)-70 expression were evaluated. One mg per mouse of methylprednisolone (MPL) was intraperitonealy administered in some mice of CBDL+HEP group. RESULTS: The post-hepatectomy IL-6 values at 2 and 3 days after CBDL were significantly lower than those in the HEP group, while those at 5 days after CBDL were significantly higher than those in HEP group. The serum IL-6 value of the steroid group was significantly lower than that of non-steroid group in HEP group. However, no steroid effects were recognized on post-hepatectomy IL-6 values at 3 days after CBDL, steroid inhibited post-hepatectomy IL-6 production at 5 days after CBDL. No expression of HSP70 protein was observed in the control group, but HSP70 protein was expressed in both the hepatocytes and Kupffer cells 3 days after CBDL, then at 5 days after CBDL, no HSP70 protein was expressed in the Kupffer cells. CONCLUSIONS: In the early period of obstructive jaundice, the IL-6 level after hepatectomy did not increase in comparison to HEP group, and steroid had no effect on IL-6 level. According to the progression of obstructive jaundice, the IL-6 level after hepatectomy increased to a higher level than before, and the effect of MPL was restored. HSP70 is thus suggested to have an important role in cytokine production.

Animals↗