Association study between a novel single nucleotide polymorphism of the promoter region of the prostacyclin synthase gene and essential hypertension.

The purpose of this study was to investigate whether an association exists between the promoter region of the prostacyclin synthase gene and essential hypertension (EH). Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a novel single nucleotide polymorphism (SNP), T-192G, in the 5'-flanking region. We performed an association study using the SNP in 200 patients and 200 controls. The allele frequency distribution in the two groups was not significantly different. Thus, this SNP in the PGIS gene is not associated with EH.     

A case of intractable hemoptysis originating from the branches of the right subclavian artery, successfully treated with arterial coil embolization]

A 30-year-old woman was admitted because of persistent and severe hemoptysis in November 2005. She had been given a diagnosis of interstitial pneumonia (IP) and pulmonary aspergilloma in 2001, and she was treated with oral prednisolone and itraconazole. However she had persistent and intractable hemoptysis. Multi-detector row computed tomography (MDCT) revealed that hemoptysis from the right upper lobe did not originate in bronchial arteries, but the abnormal branches of the right subclavian artery. Surgery was not performed because of her pulmonary function, but she was successfully treated by non-bronchial arterial coil embolization. At 10 months after the embolization, hemoptysis has not recurred. MDCT was very useful for diagnosing the cause of hemoptysis and selective nonbronchial arterial coil embolization might be helpful in treating intractable or refractory hemoptysis.     

Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry

OBJECTIVES: This study was designed to evaluate whether rapid endothelialization of stainless steel stents with a functional endothelium prevents stent thrombosis and reduces the restenotic process. BACKGROUND: A "pro-healing" approach for prevention of post-stenting restenosis is theoretically favored over the use of cytotoxic or cytostatic local pharmacologic therapies. It is believed that the central role of the vascular endothelium is to maintain quiescence of the underlying media and adventitia. METHODS: Sixteen patients with de novo coronary artery disease were successfully treated with implantation of endothelial progenitor cell (EPC) capture stents. RESULTS: Complete procedural and angiographic success was achieved in all 16 patients. The nine-month composite major adverse cardiac and cerebrovascular events (MACCE) rate was 6.3% as a result of a symptom-driven target vessel revascularization in a single patient. There were no other MACCE despite only one month of clopidogrel treatment. At six-month follow-up, mean angiographic late luminal loss was 0.63 +/- 0.52 mm, and percent stent volume obstruction by intravascular ultrasound analysis was 27.2 +/- 20.9%. CONCLUSIONS: This first human clinical investigation of this technology demonstrates that the EPC capture coronary stent is safe and feasible for the treatment of de novo coronary artery disease. Further developments in this technology are warranted to evaluate the efficacy of this device for the treatment of coronary artery disease.     

Time in range correlates glycated albumin measured immediately after 2 weeks of continuous glucose monitoring

AimsTime in range (TIR), an index of glycemic control and also blood glucose fluctuation, obtained from continuous glucose monitoring (CGM), has been increasing its importance along with the spread of CGM in recent years. For a while, glycated albumin (GA) has been also used as a glycemic control index during about 2-weeks in routine clinical practice. It has not yet been confirmed under optimal condition whether TIR and GA correlates. Clarification of the correlation between TIR and GA, which was measured immediately after 2-weeks of CGM, might be a finding that further supports the utility of TIR.MethodsGA was measured at the conclusion of 2-week CGM in 71 diabetes outpatients at our hospital, and the correlation between GA and indices such as TIR obtained from CGM was statistically analyzed.ResultsIt was found that TIR and time above range (TAR) were significantly correlated with GA. Upon performing multiple regression analysis, TIR, TAR and BMI. indicated a significant regression coefficient with respect to GA.ConclusionsThese findings further support the utility of TIR as a marker of glycemic control that it might also be correlated with GA, and also suggest a relation between GA and blood glucose fluctuation.     

Disruption of autosomal recessive hypercholesterolemia gene shows different phenotype in vitro and in vivo

We previously characterized the patients with autosomal recessive hypercholesterolemia (ARH) as having severe hypercholesterolemia and retarded plasma low-density lipoprotein (LDL) clearance despite normal LDL receptor (LDLR) function in their cultured fibroblasts, and we identified a mutation in the ARH locus in these patients. ARH protein is an adaptor protein of the LDL and reportedly modulates its internalization. We developed ARH knockout mice (ARH-/-) to study the function of this protein. Plasma total cholesterol level was higher in ARH-/- mice than that in wild-type mice (ARH+/+), being attributed to a 6-fold increase of LDL, whereas plasma lipoprotein was normal in the heterozygotes (ARH+/-). Clearance of 125I-LDL from plasma was retarded in ARH-/- mice, as much as that found in LDLR-/- mice. Fluorescence activity of the intravenously injected 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-LDL was recovered in the cytosol of the hepatocytes of ARH+/+ mice, but not in those of ARH-/- or LDLR-/- mice. Also, less radioactivity was recovered in the liver of ARH-/- or LDLR-/- mice when [3H]cholesteryl oleyl ether (CE)-labeled LDL was injected. In contrast, uptakes of [3H]CE-labeled LDL, 125I-LDL, and DiI-LDL were all normal or slightly subnormal when the ARH-/- hepatocytes were cultured. We thus concluded that the function of the hepatic LDLR is impaired in the ARH-/- mice in vivo, despite its normal function in vitro. These findings were consistent with the observations with the ARH homozygous patients and suggested that certain cellular environmental factors modulate the requirement of ARH for the LDLR function.     

Marked elevation of CA19-9 in a patient with idiopathic pulmonary fibrosis: CA19-9 as a bad prognostic factor

Abstract A 53-year-old Japanese female, who had been suffering from idiopathic pulmonary fibrosis (IPF) for 3 years, was admitted with dyspnoea. The important laboratory finding on admission was a serum CA19-9 level of 649 U/mL. Despite steroid treatment for IPF, her respiratory condition gradually deteriorated with the increase of serum CA19-9 level up to 3020 U/mL and she died of respiratory failure. Immunohistochemistry showed the positive stain of CA19-9 in bronchoepithelial cells. We also reviewed the Index Medics and picked up the cases who had elevation of CA19-9 more than 1000 U/mL, and six patients were listed. Five of these six patients died within 6 months, therefore the marked elevation of CA19-9 seemed to be a bad prognostic factor in patients with pulmonary fibrosis.     

Three cases of non-specific interstitial pneumonia associated with primary lung cancer

NSIP associated with primary lung cancer has been rarely reported. In the present report, three cases of histologically proven non-specific interstitial pneumonia (NSIP) associated with primary lung cancer are described. Importantly, in our 3 cases, interstitial pneumonia which is histologically proven to be NSIP was observed diffusely in both lungs. NSIP in these 3 cases responded to steroid therapy. However, 2 patients died from primary lung cancer and 1 patient died from progression of the interstitial pneumonia. Although the association between lung cancer and NSIP has been rarely documented, this combination was considered to be one of the paraneoplastic phenomena. The possible association between primary lung cancer and NSIP is discussed.     

Contribution of Bcl-2, but not Bcl-xL and Bax, to antiapoptotic actions of hepatocyte growth factor in hypoxia-conditioned human endothelial cells

Angiogenic growth factors play important roles in angiogenic responses, such as vasculogenesis and angiogenesis in response to hypoxia. A novel angiogenic growth factor, hepatocyte growth factor (HGF), has been reported to inhibit endothelial cell death. However, its molecular mechanisms are largely unknown. Thus, we studied (1) the effects of HGF on hypoxia-induced endothelial apoptosis and (2) the molecular mechanisms of the antiapoptotic actions of HGF in endothelial cells. Severe hypoxia increased the cell death rate in human aortic endothelial cells, whereas HGF significantly attenuated cell death. In addition, hypoxic treatment resulted in a significant increase in apoptotic cells, whereas HGF could attenuate apoptosis, accompanied by attenuation of the increase in caspase-3-like activity (P<0.01). Of importance, HGF significantly increased Bcl-2, an inhibitor of apoptosis, in a dose-dependent manner under normoxic and hypoxic conditions (P<0.01), whereas hypoxic conditions resulted in a significant decrease in Bcl-2. In contrast, HGF failed to affect Bcl-xL, which is also well known as an inhibitor of apoptosis under both normoxic and hypoxic conditions, whereas Bcl-xL was significantly decreased in endothelial cells exposed to hypoxia (P<0.01). No significant change in Bax, a promoter of apoptosis, was also observed in endothelial cells under hypoxia, whereas HGF did not affect BAX: Overall, this study demonstrated that HGF prevented endothelial cell death induced by hypoxia through its antiapoptotic action. The antiapoptotic mechanisms of HGF in hypoxia-induced endothelial cell death largely depend on Bcl-2, but not Bcl-xL and BAX:     

Effect of kihito extract granules on cognitive function in patients with Alzheimer's-type dementia

Background:   It has been recently suggested that Japanese herbal (kampo) medicines, such as kami-untan-to, may improve cognitive function in elderly subjects with Alzheimer's disease. Polygalae radix is thought to be a useful component of kami-untan-to because it enhances the activity of choline acetyltransferase in cultured neuronal cells. The purpose of the present study was to investigate the safety and usefulness of kihito extract granules, a commercially available Japanese herbal medicine that contains P. radix , for elderly patients with senile dementia.
Methods:   Seventy-five elderly subjects (84.4 ± 6.4 years) with senile dementia of Alzheimer type according to Diagnostic and Statistical Manual of Mental Disorders , 4th edition criteria were randomly assigned to the non-treatment, goshajinkigan (control kampo medicine) or kihito groups. Each medicine was given three times a day for 3 months.
Results:   There was no severe adverse event in any of the groups. We examined the Mini-Mental State Examination (MMSE), the activities of daily living (ADL) scale and cerebrovascular single photon emission computed tomography (SPECT) before and after treatment. MMSE scores were significantly improved only in the kihito group (+1.65 ± 0.53) but not in the non-treatment (−0.3 ± 0.67) and goshajinkigan (−0.58 ± 0.49) groups. ADL scores remained unchanged in all groups. Treatment with kihito was not associated with an increase in cerebral blood flow.
Conclusion:   These results propose that kihito may be useful and has potential to be tested as a medicine for Alzheimer's-type senile dementia, although further examination is required to clarify the mechanism of the improving effect of kihito on cognitive function.