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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 199 records · Page 11Linked to original sources

Hypertrophic cardiomyopathy as a manifestation of cardiac sarcoidosis.

The present study aimed to clarify whether cardiac sarcoidosis causes changes that mimic hypertrophic cardiomyopathy. Eighty-two consecutive patients (35 men, 47 women), who were referred to the Department of Cardiovascular Medicine, with a diagnosis of pulmonary and/or ocular sarcoidosis (average age, 49.5 years, range 20-74), underwent detailed clinical, electrocardiographic, and echocardiographic evaluations; in some patients, right and left heart catheterization, selective coronary artery cineangiography, and right and left endomyocardial biopsies were performed. Over a 15-month period of observation, 6 of these 82 patients (7.3%) were found to have echocardiographic abnormalities: increased thickness of the interventricular septum was found in 4 patients, asymmetric septal hypertrophy in 2, localized septal hypertrophy in 1 and apical hypertrophy in 1 patient. One patient had an 'ace-of-spades' deformity of the left ventricle. Cardiac sardoidosis can mimic, and even present as, hypertrophic cardiomyopathy.

Adult↗

Immunohistochemical demonstration of Cl- pump in type A intercalated cells of rat kidney.

In order to demonstrate the localization of an ethacrynic acid-sensitive Cl- pump in the rat kidney, immunohistochemical analysis was performed using an anti-Cl- pump antibody raised against rat brain Cl- pump protein with confocal laser scanning microscopy. The antibodies against Na+,K+-ATPase, aquaporin 2 and a type B intercalated cell marker, 43-kDa protein, were also used for comparison. Anti-Cl- pump antibody recognized a 51-kDa renal protein of the same size as that in the brain on Western blots. Cl- -pump-like immunoreactivity was observed on the basolateral membranes of 42+/-3% of cortical collecting duct (CCD) cells and of 38+/-1% of outer medullar collecting duct (OMCD) cells. Such immunoreactivity in CCD was sometimes co-localized with Na+,K+-ATPase, but in OMCD, the Cl- pump-like immunoreactivity co-existed with neither Na+,K+-ATPase, aquaporin 2 nor the type B intercalated cell marker 43-kDa protein. Thus, the Cl- pump was demonstrated to be localized on the basolateral membranes of type A intercalated cells of cortical and medullary collecting ducts in the rat kidney.

Animals↗

Preceding stimulus frequency-dependent potentiation of the postrest shortening of the action potential duration in rabbits.

Action potential duration (APD) in rabbit ventricular myocardium shortens after a rest period (postrest shortening). However, the effects of preceding stimulus frequency on the postrest shortening have not been elucidated. We recorded transmembrane action potentials (TAPs) and monophasic action potentials (MAPs) from the rabbit ventricle. In in vitro experiments. repetitive regular stimuli (S1) at cycle lengths ranging between 500 to 3000 ms were followed by a single extrastimulus (S2) at a coupling interval of 5000 ms. A decrease in S1S1 interval resulted in a progressive shortening of the duration of TAP (TAPD) elicited by S2 (S2-TAPD), which was potentiated by increasing extracellular calcium concentration ([Ca2+]o) or application of ouabain and was inhibited by lowering [Ca2+]o or verapamil. Application of ryanodine was most effective in lengthening S2-TAPD following a short S1S1 interval. 4-aminopyridine and E4031 caused marked lengthening of S2-TAPD when S1S1 was long. However, the lengthening effect was attenuated and disappeared with a shorter S1S1 interval. In in vivo experiments, regular ventricular pacing (S1) at cycle lengths ranging between 250 to 1000 ms was followed by a single extrastimulus (S2) with a coupling interval (S1S2) of 1500 ms. A decrease in the S1S1 interval also resulted in progressive shortening of the duration of MAP elicited by S2. Our results indicate that the postrest shortening is potentiated by an increase in the preceding stimulus frequency in the rabbit ventricle, in which the function of sarcoplasmic reticulum may play a significant role.

Action Potentials↗

Prevention of nephrotoxicity of cisplatin by repeated oral administration of ebselen in rats.

The ability of ebselen, which exhibits glutathione peroxidase (GSH-Px)-like activity, to prevent cisplatin (CDDP)-induced nephrotoxicity was examined in rats. CDDP (6 mg/kg [20 micromol/kg] body weight) was injected intraperitoneally. In subgroups, daily ebselen doses of 2.75 (10 micromol), 5.5 (20 micromol), or 11.0 mg (40 micromol)/kg body weight were administrated orally 1 hour prior to CDDP treatment. Treatment with CDDP alone resulted in significantly increased plasma creatinine (Cr) and blood urea nitrogen (BUN) levels. Repeated administration of 5.5 and 11.0 mg/kg ebselen prevented the CDDP-induced elevation of plasma Cr and BUN levels and protected against kidney damage. Relative to controls, rat that received CDDP treatment displayed a decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), an indicator directly related to oxidative stress, and elevated malondialdehyde (MDA) levels in the kidney. In comparison with controls, activity of GSH-Px activity, which antioxidant enzyme, was also reduced in the kidney of rats treated with CDDP. Repeated administration of 5.5 or 11.0 mg/kg ebselen prevented CDDP-induced alteration of GSH/GSSG ratios, MDA levels, and GSH-Px activity; however, no protection against CDDP was observed with administration of 2.75 mg/kg ebselen. Effective protection of CDDP-induced nephrotoxicity with ebselen was observed only when the molar amount of each daily ebselen treatment equaled or exceeded

Administration, Oral↗

Mechanism of liver-selective thyromimetic activity of SK&F L-94901: evidence for the presence of a cell-type-specific nuclear iodothyronine transport process.

The thyromimetic compound SK&F L-94901 shows more potent thyromimetic activity in the liver than in the pituitary gland or heart when administered to rats. The mechanisms of liver-selectivity of SK&F L-94901 were examined using cultured rat hepatoma cells (dRLH-84) and rat pituitary tumor cells (GH3), both of which showed saturable cellular uptake of tri-iodothyronine (T(3)). When isolated nuclei with partial disruption of the outer nuclear membrane were used, SK&F L-94901 competed for [(125)I]T(3) binding to nuclear receptors almost equally in dRLH-84 and GH3 cells. SK&F L-94901 also did not discriminate thyroid hormone receptors (TR) alpha1 and beta1 in terms of binding affinity and activation of the thyroid hormone responsive element. In intact cells, however, SK&F L-94901 was a more potent inhibitor of nuclear [(125)I]T(3) binding in dRLH-84 cells than in GH3 cells at an early phase of the nuclear uptake process and after binding equilibrium. These data suggest that SK&F L-94901 is more effectively transported to nuclear TRs in hepatic cells than in pituitary cells and therefore shows liver-selective thyromimetic activity. In conclusion, SK&F L-94901 discriminates hepatic cells and pituitary cells at the nuclear transport process. The cellular transporters responsible for this discrimination were not evident.

Animals↗

Dermatomyositis with splenic and renal infarctions during corticosteroid therapy.

A 60-year-old woman was admitted to our hospital with complaints of muscle weakness and erythema on her extremities. Gottron's sign, heliotrope rash, elevation of serum myogenic enzymes, electromyography and magnetic resonance imaging findings established a diagnosis of dermatomyositis (DM). She was treated with 60 mg of daily prednisolone. One week later, she suddenly developed splenic and renal infarctions, which were considered to have resulted from vasculopathy associated with DM. Cyclophosphamide and anticoagulants along with increasing the dosage of corticosteroid were effective. This is the first report describing splenic and renal infarctions in a patient with adult-onset DM.

Anti-Inflammatory Agents↗

Mutations in the genes for hepatocyte nuclear factor (HNF)-1alpha, -4alpha, -1beta, and -3beta; the dimerization cofactor of HNF-1; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in Pima Indians.

OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of type 2 diabetes characterized by an early age at onset and autosomal dominant inheritance. MODY can result from heterozygous mutations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset type 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS: The coding regions of the known MODY genes hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, HNF-1beta, and insulin promoter factor 1 and the coding regions of two MODY candidate genes, HNF-3beta and the dimerization cofactor of HNF-1, were sequenced in genomic DNA from Pima Indians. The primary "affected" study population consisted of 46 Pima Indians whose age at onset of type 2 diabetes was < or =20 years. DNA sequence variants identified in the affected group were then analyzed in a group of 80 "unaffected" Pima Indians who were at least 40 years old and had normal glucose tolerance. RESULTS: A total of 11 polymorphisms were detected in these genes. However, none of the polymorphisms differed in frequency among Pima Indians with an early age at onset of diabetes compared with older Pima Indians with normal glucose tolerance. CONCLUSIONS: Mutations in these known MODY or MODY candidate genes are not a common cause of early-onset diabetes in Pima Indians.

Adolescent↗

Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in patients in the early stage of diabetic nephropathy.

OBJECTIVE: To determine whether the antiplatelet drug dilazep dihydrochloride affects the number of urinary podocytes in diabetic patients with microalbuminuria. RESEARCH DESIGN AND METHODS: Fifty patients with type 2 diabetes and microalbuminuria (30 men and 20 women, mean age 48.6 years) and 30 age-matched control subjects (18 men and 12 women, mean age 49.2 years) were included in the study. No patients showed serum creatinine levels in excess of 2.0 mg/dl. Urinary podocytes were examined by immunofluorescence microscopy with monoclonal antibodies against podocalyxin. RESULTS: Urinary podocytes were detected in 18 of the 50 microalbuminuric diabetic patients (mean, 1.3 cells/ml). Urinary podocytes were not detected in the remaining 32 patients or in the 30 healthy control subjects. Diabetic patients positive for urinary podocytes were divided into 2 treatment groups: a dilazep dihydrochloride treatment group (300 mg/day; n = 9, group A) and a placebo group (n = 9, group B). Treatments were continued for 6 months. In group A, microalbuminuria decreased significantly from 146 +/- 42 to 86 +/- 28 microg/min (P < 0.01) and urinary podocytes also decreased from 1.3 +/- 0.8 to 0.4 +/- 0.2 cells/ml (P < 0.01). However, in group B, microalbuminuria and urinary podocytes changed little over the study period. CONCLUSIONS: Podocyte injury may occur in patients with early diabetic nephropathy, and dilazep dihydrochloride may be useful for preventing glomerular injury.

Albuminuria↗

A case of synchronous double cancers of the pancreas and stomach.

Pancreatic cancer carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. We present here the case of a 76-year-old man who developed synchronous double cancers of the stomach and pancreas. He was referred to our hospital in December, 1997, with a provisional diagnosis of carcinoma of the stomach. Laboratory data on admission showed normal levels except for the serum carcinoembryonic antigen level. Abdominal ultrasonography revealed a low echoic mass anterior to the pancreas, suggestive of a nodal metastasis. Intraoperative histological findings from the pancreatic nodule confirmed a primary pancreatic cancer. The diagnosis of double cancers of the stomach and pancreas was made, and subtotal gastrectomy and distal pancreatectomy with lymph nodes dissection were carried out. The histologic sections from the stomach showed a moderately differentiated tubular adenocarcinoma, whereas those from the pancreas showed a well to moderately differentiated tubular adenocarcinoma. Double carcinomas in this association are relatively rare.

Aged↗

Two cases of biliary hemorrhage after percutaneous transhepatic biliary drainage in which transcatheter arterial embolization was effective.

Patient No. 1 was a 66-year-old male who was diagnosed as having cancer of the caput pancreatis, and underwent percutaneous transhepatic biliary drainage (PTBD). Since the tube slipped out, percutaneous transhepatic gallbladder drainage (PTGBD) was performed. After PTGBD, biliary hemorrhage was observed for two to three days, then hemorrhage disappeared and bile flowed smoothly. Since the tube was likely to slip out, the tube was replaced. After replacement of the tube, biliary hemorrhage was noted for two to three days, then spontaneously subsided again. After icterus was reduced, pancreatoduodenectomy was performed. During surgery, a number of massive blood clots were noted in the bile duct. The PTGBD tube was removed, and a transjejunal tube was placed. On the 11th day after the surgery, hemorrhage occurred in the bile duct tube, and the patient went into shock. Emergency abdominal angiography was performed. A false aneurysm was detected in A6 and embolized using a microcoil. After transcatheter arterial embolization (TAE), hemorrhage stopped, and the patient was discharged. Patient No. 2 was a 68-year-old male who was diagnosed as having cholelithiasis and underwent PTBD. On the 21st day after PTBD, biliary hemorrhage occurred and the patient fell in shock status. Emergency abdominal angiography was performed. A false aneurysm was detected in A3 and embolized using a microcoil. After TAE, cholangioscopic lithectomy was performed and the disease alleviated. Thereafter the patient was discharged. It is necessary to consider false aneurysm when biliary hemorrhage occurs after PT(G)BD.

Aged↗

A case of duodenal papillary carcinoma complicated by repeated acute pancreatitis.

We present a patient with duodenal papillary carcinoma who repeatedly developed acute pancreatitis preoperatively. The patient was a 65-year-old male. In February 1997, the patient consulted a local hospital due to vomiting, high fever, and jaundice. With the diagnosis of obstructive jaundice, percutaneous transhepatic biliary drainage (PTBD) was performed, revealing a distal bile duct obstruction. Because duodenal papillary carcinoma was diagnosed based on endoscopic findings, the patient was admitted to Kurume University Hospital. Hypotonic duodenography (HDG) disclosed a protruding lesion with an irregular surface in the descending part of the duodenum, resulting in a diagnosis of positive duodenal invasion (du1). Because computed tomography (CT) demonstrated a protruding lesion on the medial side of the second portion of the duodenum, positive pancreatic invasion (panc2) was diagnosed. On March 18 and April 22, sudden abdominal pain, leukocytosis, and an increase in serum amylase were noted. CT revealed that the pancreas was diffusely enlarged, showing an ill-defined boundary between the pancreas and adipose tissue and fluid collection. On CT, the lesion was evaluated as Grade 3 and moderate. For treatment, pancreatic enzyme inhibitors and antibiotics were intravenously injected. Peritoneal perfusion was concomitantly performed during the second treatment. Because symptoms remitted thereafter, a pylorus preserving pancreatoduodenectomy (PpPD) was carried out. The postoperative histologic examination revealed negative pancreatic invasion. Concerning the etiology of acute pancreatitis, not pancreatic invasion, but impaction of the liberated tumor mass in the common canal was considered responsible for the repeated pancreatitis because the tumor showed a cauliflower-like shape.

Acute Disease↗

A case of intrahepatic gallstone formation around nylon suture for hepatectomy.

A 69-year-old female underwent left lobectomy for hepatolithiasis in February 1994. She was admitted to the Kurume University Hospital in December 1997 because computed tomography (CT) showed calcification in the porta hepatis. Ultrasonography (US) revealed a hyperechoic area with an acoustic shadow in the right hepatic duct. Dilated intrahepatic bile ducts and a mural lucent area in the right hepatic duct were noted on endoscopic retrograde cholangiography (ERC). Although the above findings suggested a diagnosis of recurrent hepatolithiasis, percutaneous transhepatic biliary drainage (PTBD) for biopsy was performed in order to rule out cancer. Biopsy showed no evidence of malignancy. Under a cholangioscope, a tip of a nylon suture was found to be protruding into the bile duct. Although a gallstone had already slipped off, the surface of the nylon suture was covered with biliary sludge. The protruding tip of the nylon suture was considered to be the nucleus of the stone. The tip was removed under cholangioscopy. Postoperative CT confirmed the absence of calcification in the porta hepatis. There has been no recurrence of hepatolithiasis after surgery. Although the formation of gallstones around the core of nylon sutures is very rare, absorbable sutures should be used during surgery of the bile duct because nonabsorbable sutures can become the nucleus of gallstones.

Aged↗

Human T-lymphotropic virus type I provirus and T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare type of post-thymic T-cell neoplasm, the etiology of which is unknown. Patients with T-PLL have been found to be seronegative for human T-lymphotropic virus type-I (HTLV-I), and their leukemia cells do not retain monoclonally integrated HTLV-I provirus. Recently, we have demonstrated the presence of defective HTLV-I provirus by polymerase chain reaction in the DNA extracted from peripheral blood cells or affected lymph nodes of T-PLL patients. Although there is a possibility, from our observation, that an alternative mechanism is operating in HTLV-associated leukemogenesis, it is still unknown whether and how HTLV-I can contribute to the leukemogenesis of T-PLL. In this review, we describe controversial issues and discuss a role of HTLV-I in the leukemogenesis of T-PLL.

Cell Transformation, Viral↗

Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats.

OBJECT: In Japan fasudil hydrochloride (HA1077), a protein kinase inhibitor, is widely administered to prevent vasospasm in patients after subarachnoid hemorrhage. The effects of fasudil on experimental spinal cord injury (SCI) were investigated and compared with those obtained using methylprednisolone. METHODS: Spinal cord contusion was induced in rats by applying an aneurysm clip extradurally to the spinal cord at T-3 for 1 minute. After injury three groups of rats were treated with intravenously administered saline (control), intraperitoneally administered fasudil (10 mg/kg), or intravenously administered methylprednisolone (four 30 mg/kg injections). Neurological recovery was evaluated periodically over 1 month by using a modified combined behavioral scale and histopathological examination. Leukocyte infiltration near the injury site was evaluated by measuring myeloperoxidase (MPO) activity at 24 hours. Spinal cord blood flow was measured at intervals up to 3 hours after injury by using laser Doppler flowmetry. In rats in the fasudil-treated group significant improvement in modified combined behavioral score was demonstrated at each time point, whereas in the methylprednisolone-treated rats no beneficial effects were shown. In the fasudil-treated group, reduction of traumatic spinal cord damage was evident histologically in the caudal portion of the injured areas, and tissue MPO activity in tissue samples was reduced. Spinal cord blood flow was not significantly different between fasudil-treated and control group rats. CONCLUSIONS: Fasudil hydrochloride showed promise of effectiveness in promoting neurological recovery after traumatic SCI. Possible mechanisms of this effect include protein kinase inhibition and decreased infiltration by neutrophils.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[A randomized trial of conventional dose vs reduced dose in BHAC-DM therapy for acute myelogenous leukemia in elderly patients].

Twenty-nine patients aged 60-75 years with newly diagnosed acute myelogenous leukemia (AML) were randomized to receive BHAC-DM either at a reduced dose (S-1 group, n = 13; BHAC 150 mg/m2 1-7 day, DNR 30 mg/m2 1-3 day, 6MP 70 mg/m2 1-7 day) or the conventional dose (S-2 group, n = 16; BHAC 200 mg/m2 1-7 day, DNR 40 mg/m2 1-3 day, 6MP 70 mg/m2 1-7 day). On day 7, patients were given therapy for 2 more days if the ratio of blasts in their bone marrow was more than 15%. Granulocyte-colony stimulating factor was injected when the leukocyte count decreased below 1,000/microliter. The rates of complete remission were 46.2% in the S-1 group and 43.8% in the S-2 group. No significant differences in response distinguished the 2 groups. The mortality rate during myelosuppression was 1/13 in the S-1 group and 1/16 in the S-2 group. The rate of treatment-related death was 10.1% for all patients. Grade-4 adverse effects were not seen in any of the patients. We concluded that the conventional dose of BHAC-DM was as acceptable as the reduced dose in elderly patients with AML.

Aged↗

Correlation between cardiac output and cerebral blood flow following subarachnoid hemorrhage.

The authors examined the correlations between cerebral blood flow (CBF) during the stage of vasospasm following subarachnoid hemorrhage and four parameters, namely, cardiac output (cardiac index), mean arterial blood pressure, age, and the Glasgow coma scale score. Forty-two patients who were diagnosed to have subarachnoid hemorrhage were included in this study, and 50 measurements were performed between day 5 and 12 following the subarachnoid hemorrhage. The CBF was measured by stable xenon-enhanced CT and the mean values of four CBF maps were corrected for a PaCO2 of 34 mm Hg (CBF34). The cardiac output and cardiac index were continuously monitored during the CBF measurement. The correlation coefficients of cardiac index, mean arterial blood pressure, age, and GCS against CBF34 were, respectively, 0.436, 0.227, 0.037, and 0.225, and the p values were, respectively, 0.002, 0.074, 0.789, and 0.087. The CBF34 was positively correlated with only the cardiac index and not with any of the other three parameters. Therefore, an increase in the cardiac output is apparently associated with an increase in the CBF during the stage of vasospasm following subarachnoid hemorrhage. Furthermore, we measured the CBF and cerebral perfusion pressure before and after increasing cardiac output in three patients during the stage of vasospasm. The CBF increased by 22.5% +/- 2.9 (SD), with a 42.0% +/- 16.4 increase in the cardiac index, however, no significant change in cerebral perfusion pressure was observed. Therefore, the increase in CBF associated with the increase in cardiac output seems to be attributable to a reduction in the cerebrovascular resistance.

Aged↗