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Biomedical subjects

M Kanai

Publications and source records attributed to M Kanai.

At least 73 records · Page 4Linked to original sources

Accumulation of NACP/alpha-synuclein in lewy body disease and multiple system atrophy.

OBJECTIVES: NACP/alpha-synuclein is an aetiological gene product in familial Parkinson's disease. To clarify the pathological role of NACP/alpha-synuclein in sporadic Parkinson's disease and other related disorders including diffuse Lewy body disease (DLBD) and multiple system atrophy (MSA), paraffin sections were examined immunocytochemically using anti-NACP/alpha-synuclein antibodies. METHODS: A total of 58 necropsied brains, from seven patients with Parkinson's disease, five with DLBD, six with MSA, 12 with Alzheimer's disease, one with Down's syndrome, one with amyotrophic lateral sclerosis (ALS), three with ALS and dementia, one with Huntington's disease, two with progressive supranuclear palsy (PSP), one with Pick's disease, one with myotonic dystrophy, and three with late cerebellar cortical atrophy (LCCA), and 15 elderly normal controls were examined. RESULTS: In addition to immunoreactive Lewy bodies, widespread accumulation of NACP/alpha-synuclein was found in neurons and astrocytes from the brainstem and basal ganglia to the cerebral cortices in Parkinson's disease/DLBD. NACP/alpha-synuclein accumulates in oligodendrocytes from the spinal cord, the brain stem to the cerebellar white matter, and inferior olivary neurons in MSA. These widespread accumulations were not seen in other types of dementia or spinocerebellar ataxia. CONCLUSION: Completely different types of NACP/alpha-synuclein accumulation in Parkinson's disease/DLBD and MSA suggest that accumulation is a major step in the pathological cascade of both diseases and provides novel strategies for the development of therapies.

Aged↗

Effect of erythromycin on ATP-induced intracellular calcium response in A549 cells.

ATP induced a biphasic increase in the intracellular Ca(2+)concentration ([Ca(2+)](i)), an initial spike, and a subsequent plateau in A549 cells. Erythromycin (EM) suppressed the ATP-induced [Ca(2+)](i) spike but only in the presence of extracellular calcium (Ca(2+)(o)). It was ineffective against ATP- and UTP-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] formation and UTP-induced [Ca(2+)](i) spike, implying that EM perturbs Ca(2+) influx from the extracellular space rather than Ca(2+)release from intracellular Ca(2+) stores via the G protein-phospholipase C-Ins(1,4,5)P(3) pathway. A verapamil-sensitive, KCl-induced increase in [Ca(2+)](i) and the Ca(2+) influx activated by Ca(2+) store depletion were insensitive to EM. 3'-O-(4-benzoylbenzoyl)-ATP evoked an Ca(2+)(o)-dependent [Ca(2+)](i) response even in the presence of verapamil or the absence of extracellular Na(+), and this response was almost completely abolished by EM pretreatment. RT-PCR analyses revealed that P2X(4) as well as P2Y(2), P2Y(4), and P2Y(6) are coexpressed in this cell line. These results suggest that in A549 cells 1) the coexpressed P2X(4) and P2Y(2)/P2Y(4) subtypes contribute to the ATP-induced [Ca(2+)](i) spike and 2) EM selectively inhibits Ca(2+) influx through the P2X channel. This action of EM may underlie its clinical efficacy in the treatment of airway inflammation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

A catalytic asymmetric strecker-type reaction promoted by Lewis acid-Lewis base bifunctional catalyst.

A general asymmetric Strecker-type reaction is reported, catalyzed by the Lewis acid-Lewis base bifunctional catalyst 1. The reaction of trimethylsilyl cyanide (TMSCN) with various fluorenyl imines, including n-aldimines and alpha,beta-unsaturated imines, proceeds with good to excellent enantioselectivities in the presence of a catalytic amount of phenol as additive (20 mol%) (catalytic system 1). The products were successfully converted to the corresponding amino acid derivatives in high yields without loss of enantiomeric purity. Furthermore, hydrogenation or dihydroxylation of the products from alpha,beta-unsaturated imines afforded saturated or functionalized aminonitriles also without loss of enantiomeric purity. The absolute configuration of the products and a control experiment using catalyst 2 supported the proposed dual activation of the imine and TMSCN by the Lewis acid (Al) and the Lewis base moiety (phosphine oxide) of 1. From the mechanistic studies including kinetic and NMR experiments of the catalytic species, the role of PhOH seems to be a proton source to protonate the anionic nitrogen of the intermediate. Specifically, we have found that TMSCN is more reactive than HCN in this catalytic system, probably due to the activation ability of the phosphine oxide moiety of 1 toward TMSCN. This fact prompted us to develop the novel catalytic system 2, consisting of 1 (9 mol%), TMSCN (20 mol%) and HCN (1.2 mol eq). This new system afforded comparable results with obtained by system 1 (1 (9 mol%)-TMSCN (2 mol eq)-PhOH (20 mol%)).

Acids↗

Experimental use of a transportable hyperbaric chamber durable for 15 psi at 3700 meters above sea level.

A transportable hyperbaric chamber durable for 15 psi of pressure was used to treat a patient suffering from moderate acute mountain sickness at 3700 m above sea level. The symptoms were ameliorated a few minutes after pressurization in the chamber. After a 20-minute stay in the chamber, the patient was completely free of symptoms. Since the chamber can be inflated by using compressed air from a cylinder, no strenuous work was required of the operators. This transportable chamber seems to be useful for the treatment of high-altitude disorders at around 3000 m above sea level.

Acute Disease↗

Dihydropyrimidine dehydrogenase activity and mRNA expression in advanced gastric cancer analyzed in relation to effectiveness of preoperative 5-fluorouracil-based chemotherapy.

Dihydroxypyrimidine dehydrogenase (DPD) is an enzyme involved in degradation and inactivation of 5-fluorouracil (5-FU). The amount of its expression in a tumor is thought to be a factor determining the response of the tumor to 5-FU therapy. We compared DPD activity and DPD mRNA expression in resected tumors between two groups of patients, i.e., a group of 14 patients with advanced gastric cancer who received preoperative chemotherapy (neoadjuvant chemotherapy; NAC) and surgery and a group of 24 patients with advanced gastric cancer who underwent surgery without preoperative chemotherapy. Tumor DPD activity was found to correlate well with tumor DPD mRNA expression. In the surgery alone group, DPD activity decreased significantly as the tumor stage advanced. This change was not observed in the NAC plus surgery group. Neither tumor depth (T factor) nor lymph node metastasis was found to correlate with DPD activity. Patients who responded to preoperative chemotherapy had lower DPD mRNA levels. Based on these results, we anticipate that measurement of DPD expression in clinical specimens may be clinically useful in managing advanced gastric cancer.

Adenocarcinoma↗

[Extended liver resection for hilar cholangiocarcinoma].

Liver resection for hilar cholangiocarcinoma should be designed for individual patients, based on both precise diagnosis of cancer extent and accurate evaluation of hepatic functional reserve. Therefore we have developed various types of hepatic segmentectomy. Combined caudate lobectomy is essential in every patient with separated hepatic confluence. So-called extensive hepatectomy, resection of 50% or more of the hepatic mass, includes right lobectomy and right or left trisegmentectomy. Right lobectomy with caudate lobectomy is indicated when the progression of cancer is predominant in the right anterior and posterior segmental bile ducts. The plane of liver transection is along the Cantlie line, and the left hepatic duct is divided just at the right side of the umbilical portion of the left portal vein. Right trisegmentectomy with caudate lobectomy is performed in carcinoma which involves the right hepatic ducts in continuity with the left medial segmental bile duct. The umbilical portion of the left portal vein is freed from the umbilical plate by dividing the small portal branches arising from the cranial side of the umbilical portion. Then the left lateral segmental bile ducts are exposed and divided at the left side of the umbilical portion of the left portal vein. Left trisegmentectomy with caudate lobectomy is suitable for carcinoma which involves the left intrahepatic bile duct in continuity with the right anterior segmental bile duct. Liver transection is advanced along the right portal fissure. The right posterior segmental bile duct is usually divided distal to the confluence of the inferior and superior branches.

Bile Duct Neoplasms↗

[Perioperative management of a patient with general lymph-congestion following total spondylectomy with posterior and anterior fusion for first thoracic vertebral hemangioma].

A 50-year-old healthy woman was scheduled for surgery of the first thoracic vertebral (T 1) hemangioma accompanying rapidly aggravated neurological deficit in three months. Anesthesia was induced with intravenous fentanyl and propofol and maintained with isoflurane-oxygen-air inhalation, followed by propofol infusion combined with sevoflurane inhalation. Following posterior decompression of T 1 with fusion of C 6-T 3, consecutive total spondylectomy of T 1 with anterior fusion of C 7-T 2 was carried out. At the end of surgery, marked edema was noticed on her face, neck and bilateral upper extremities, possibly due to long manipulation around the left jugular angle. Next morning the edema spread to her whole body and the elevation of both diaphragms and the mediastinal expansion were recognized. Mechanical ventilation in the mode of IMV was performed until subsiding of edema on the fifth postoperative day. During this period, hypoxemia was frequently observed in spite of appropriate respiratory support. On the third postoperative day, bronchoscopic bronchial toilet was performed which brought the improvement of blood oxygenation. The occasional administration of furosemide was not effective to reduce general edema, but served for the acceleration of lymphatic drainage after the release of the thoracic duct obstruction and the patient was extubated uneventfully on the sixth postoperative day.

Anesthesia, Intravenous↗

Apolipoprotein E4 accelerates dementia and increases cerebrospinal fluid tau levels in Alzheimer's disease.

To examine the effect of apolipoprotein E (ApoE) 4 on the progression of Alzheimer's disease (AD), the clinical course of 33 AD patients (17 cases with ApoE epsilon4 and 16 cases without ApoE epsilon4) was evaluated with the mini-mental state examination (MMSE) and cerebrospinal fluid (CSF) biological markers. The decline of MMSE scores to zero was shortened in the ApoE4 group. During a mean follow-up of 20 months, a significant increase of CSF tau levels was observed in the ApoE4 group. A lower level of CSF A beta1-42(43) was found in both the ApoE4 and non-ApoE4 groups than in age-matched normal controls. The ApoE epsilon4 allele accelerates the progression of dementia and increases the levels of CSF tau in AD patients.

Aged↗

Carboxyl-terminal fragments of presenilin-1 are closely related to cytoskeletal abnormalities in Alzheimer's brains.

To clarify the role of presenilin-1 (PS-1) in the pathology of Alzheimer's disease (AD), we tested four antisera to PS-1. The specific antisera to the N-terminus (HSN-2) and C-terminus (HS-C) of PS-1 detected a 44/40kD holoprotein, a 25kD N-terminal fragment (NTF) and a 16kD C-terminal fragment (CTF) of PS-1 in COS-7 cells. The 25kD NTF and 16kD CTF were observed in human brains, and their amounts were not significantly different between the control and AD brains. The antibody HS-C labeled extensive neurofibrillary tangles, dystrophic neurites and curly fibers in the AD brains. In the paired helical filament (PHF) fraction containing A68 protein from AD brains, a smear pattern of CTFs was revealed. Antisera (HS-L292 and HS-L300) to cleavage sites of PS-1 also revealed immunoreactive neurofibrillary tangles in the AD brain sections and the smear pattern of CTFs of A68 protein fraction. The CTFs of PS-1 accumulate with PHF tau, suggesting a close relationship between PS-1 and cytoskeletal abnormalities in AD brains.

Aged↗

A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy.

Many clinical and pathological discussions have been focused on the difficulty of differential diagnosis between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) in recent years. This study was conducted to evaluate the usefulness of tau proteins in cerebrospinal fluid (CSF) for the differentiation of these two diseases. Subjects consisted of 10 patients with CBD (four males and six females with a mean age of 67.9+/-5.8 years), 12 patients with PSP (eight males and four females with a mean age of 62.6+/-5.8 years) and 36 control subjects (CTL) (16 males and 20 females with a mean age of 65.8+/-9.9 years). The CBD group included patients with probable CBD, while all the patients in the PSP group satisfied the diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP). CSF tau proteins were measured with the sandwich ELISA method (Innogenetics, Belgium). The CSF tau protein level was 320.1+/-86.5 pg/ml in the CBD group, 151.5+/-52.7 pg/ml in the PSP group and 128.7+/-91.7 pg/ml in the CTL group. Significant differences were noted in tau protein levels between the CBD group and both the PSP group (P<0.001) and the CTL group (P<0.005). We suggested that the measurement of CSF tau proteins may be useful for the differentiation between CBD and PSP.

Aged↗

An extremely large solitary primary paraganglioma of the lung: report of a case.

We present herein the case of a 38-year-old woman found to have an extremely large solitary primary paraganglioma of the lung. The patient presented with chest pain on exertion and a mass was discovered in the left lower lobe of the lung by chest X-rays and computed tomography (CT). As no other neoplasms were detected elsewhere, a left lower lobectomy was performed. The patient has remained well without any evidence of recurrence for 5 years since her operation. The tumor, measuring 13 x 12 x 7 cm, was composed of ovoid cells (Zellballen), which were positive for Fontana-Masson and Grimelius stains, and sustentacular cells. Immunohistochemically, the ovoid cells were positive for neuron-specific enolase, S-100, CAM5.2, Leu7, and chromogranin A, and negative for carcinoembryonic antigen and epithelial membrane antigen. The sustentacular cells were positive for S-100 protein and CAM5.2, and negative for glial fibrillary acid protein. Therefore, the tumor was diagnosed as a paraganglioma. The tumor from our patient is the largest of the 17 solitary primary pulmonary paragangliomas reported thus far in the English-language literature.

Adult↗

Treatment strategy for mucin-producing intrahepatic cholangiocarcinoma: value of percutaneous transhepatic biliary drainage and cholangioscopy.

Intrahepatic cholangiocarcinomas that secrete macroscopically excessive mucin into the biliary system are rare, and few of the previously reported cases have achieved a curative resection. We defined these tumors as "mucin-producing intrahepatic cholangiocarcinomas" and clarify the optimal preoperative and surgical management for them. Eleven patients with mucin-producing intrahepatic cholangiocarcinomas underwent surgical resection in our department. The clinical, radiologic, surgical, and pathologic findings were studied. The clinical presentation of the 11 patients included repeated abdominal pain, jaundice, and fever. Conventional cholangiographies, such as percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography, could not offer precise information about tumor location and extension because of abundant mucin in the biliary system. Using percutaneous transhepatic biliary drainage (PTBD) and percutaneous transhepatic cholangioscopy (PTCS), we were able to drain the mucin and determine precisely the cancer extension into intrahepatic segmental bile ducts. Based on these findings, various types of liver resection with or without extrahepatic bile duct resection were planned, and 10 patients obtained curative resection. The cumulative 5-year survival rate after curative resection was 78%. In patients with mucin-producing intrahepatic cholangiocarcinoma, PTBD and PTCS are important for evaluating the cancer extension. Rational surgery based on accurate preoperative diagnosis improved the prognosis of patients with this disease.

Adult↗

Macroscopic classification and preoperative diagnosis of intrahepatic cholangiocarcinoma in Japan.

We reviewed the records of 64 patients with resected intrahepatic cholangiocarcinoma (ICC) according to the macroscopic classification proposed by the Liver Cancer Study Group of Japan, in which ICC is classified into three types based on the macroscopic appearance of the cut sur-face of the tumor: mass-forming, periductal-infiltrating, and intraductal growth types. There were 24 patients with the periductal-infiltrating type, 28 with the mass-forming type, and 12 with the intraductal growth type. The mass-forming type essentially showed expansive growth irrespective of hilar invasion. The periductal-infiltrating type of tumor exhibited diffuse infiltration along the portal pedicle, and preoperative planning of the resection procedure was similar to that for primary bile duct carcinoma of the hepatic confluence. Vascular resection and reconstruction was required in some patients with advanced disease. In the intraductal growth type of tumor, precise determination of tumor extent was difficult because of the ambiguity caused by abundant mucin secreted by the tumor and/or by the superficial mucosal spread of the tumor along the bile duct. Percutaneous transhepatic cholangioscopy provided the most reliable information for designing the operative procedure. The macroscopic classification is useful for preoperative diagnosis of tumor extent and for planning the surgical procedure.

Bile Duct Neoplasms↗

Right hepatic lobectomy for bile duct injury associated with major vascular occlusion after laparoscopic cholecystectomy.

A 57-year-old woman underwent laparoscopic cholecystectomy (LC) for cholelithiasis. Continuous bile leak was observed beginning on the first postoperative day. Postoperative endoscopic retrograde cholangiography revealed bile leak through the common hepatic duct, and severe stenosis of the hepatic confluence. A total of three percutaneous transhepatic biliary drainage (PTBD) catheters were inserted to treat obstructive jaundice and cholangitis. The patient was referred to our hospital for surgery 118 days after LC. Cholangiography through the PTBD catheters demonstrated a hilar biliary obstruction. Celiac arteriography revealed obstruction of the right hepatic artery, and transarterial portography showed occlusion of the right anterior portal branch. On the basis of the cholangiographic and angiographic findings, we performed a right hepatic lobectomy with hepaticojejunostomy to resolve the bile duct obstruction and address the problem of major vascular occlusion. The patient's postoperative recovery was uneventful and she remains well 25 months after hepatectomy. We discuss a treatment strategy for bile duct injury suspected after LC, involving early investigation of the biliary tree and prompt intervention.

Arterial Occlusive Diseases↗

Spontaneous rupture of splenic hamartoma: a case report.

Splenic hamartomas are rare. The authors report a case of spontaneously ruptured splenic hamartoma in a 5-month-old boy. This rupture led to the death of the child. If abdominal pain is present and a mass is palpated, the splenic hamartoma should be managed surgically in an expeditious manner. There have been only two known previous reports of spontaneous rupture of splenic hamartoma in adults, but none in children.

Hamartoma↗

Value of percutaneous transhepatic portography before hepatectomy for hilar cholangiocarcinoma.

BACKGROUND: The diagnostic value of percutaneous transhepatic portography (PTP) for assessing cancer invasion of the portal bifurcation in patients with hilar cholangiocarcinoma has not been studied previously. METHODS: From April 1977 to March 1998 combined hepatobiliary and portal vein resection was performed in 45 patients. In 25 patients, PTP was carried out before operation and the resected portal bifurcation was examined histologically. Correlation between portographic and microscopic findings at the portal bifurcation was studied retrospectively. RESULTS: Portographic and microscopic findings were classified into three groups (type A, B or C, and grade 0, I or II respectively) according to the findings at the portal bifurcation. There was a significant correlation between the portographic type and degree of cancer invasion (P = 0.0001). In seven of the eight patients with type A portograms, there was no microscopic cancer invasion of the portal bifurcation. In 15 of the 17 patients with type B or C portograms, cancer invasion was found microscopically. All patients with microscopic grade II invasion had type C portograms. CONCLUSION: PTP can be used to evaluate cancer invasion of the portal bifurcation with sufficient reliability for preoperative staging of hilar cholangiocarcinoma.

Adult↗