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Biomedical subjects

K Suda

Publications and source records attributed to K Suda.

At least 55 records · Page 3Linked to original sources
PubMed2000

Intracellular calcium and protein kinase C mediate expression of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in osteoblasts.

Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) produced by osteoblasts/stromal cells are involved as positive and negative regulators in osteoclast formation. Three independent signals have been proposed to induce RANKL expression in osteoblasts/stromal cells: vitamin D receptor-, cAMP-, and gp130-mediated signals. We previously reported that intracellular calcium-elevating compounds such as ionomycin, cyclopiazonic acid, and thapsigargin induced osteoclast formation in cocultures of mouse bone marrow cells and primary osteoblasts. Increases in calcium concentration in culture medium also induced osteoclast formation in cocultures. Treatment of primary osteoblasts with these compounds or with high calcium medium stimulated the expression of both RANKL and OPG messenger RNAs (mRNAs). 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)-tetra(acetoxymethyl)ester, an intracellular calcium chelator, suppressed both ionomycin-induced osteoclast formation in cocultures and expression of RANKL and OPG mRNAs in primary osteoblasts. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, also stimulated osteoclast formation in these cocultures and the expression of RANKL and OPG mRNAs in primary osteoblasts. Protein kinase C inhibitors such as calphostin and staurosporin suppressed ionomycin- and PMA-induced osteoclast formation in cocultures and expression of RANKL and OPG mRNAs in primary osteoblasts. Ionomycin stimulated RANKL mRNA expression in ST2 and MC3T3-G2/PA6 cells, but not in MC3T3-E1 or NIH-3T3 cells. These effects were closely correlated with osteoclast formation in response to ionomycin in cocultures with these stromal cell lines. OPG strongly inhibited osteoclast formation induced by calcium-elevating compounds and PMA in cocultures, suggesting that RANKL expression in osteoblasts is a rate-limiting step for osteoclast induction. Forskolin, an activator of cAMP signals, also stimulated osteoclast formation in cocultures. Forskolin enhanced RANKL mRNA expression but suppressed OPG mRNA expression in primary osteoblasts. These results suggest that the calcium/protein kinase C signal in osteoblasts/stromal cells is the fourth signal for inducing RANKL mRNA expression, which, in turn, stimulates osteoclast formation.

3T3 Cells↗
PubMed2000

Echocardiographic predictors of outcome in newborns with congenital diaphragmatic hernia.

OBJECTIVE: Despite new treatments, congenital diaphragmatic hernia (CDH) still has high mortality. The aim of this study was to identify echocardiographic predictors of outcome in newborns with an isolated CDH. METHODS: We reviewed medical charts and echocardiograms of 40 newborns who presented with CDH in the first 24 hours of life, from 1992 to 1996. We compared the cardiac valves and great arteries diameters, left-ventricular volume and mass, Apgar scores, and modified McGoon index (the combined diameter of hilar pulmonary arteries, indexed to the descending aorta) of survivors and nonsurvivors. We performed Student's t test and multiple logistic regression analysis between the 2 groups. RESULTS: Fourteen patients died 1 to 33 days after birth (median: 3 days), including 8 from progressive hypoxemia without operation; 26 have survived up to 5 years (median: 2 years) after successful operations. Nonsurvivors had significantly smaller diameters of right and left hilar pulmonary arteries, more frequent right-sided CDH, and lower mean Apgar scores at 1 and 5 minutes. The most significant prognostic factor was the modified McGoon index. A modified McGoon index </=1.3 predicted mortality with a sensitivity of 85% and specificity of 100%. CONCLUSION: Echocardiographic measurement of hilar pulmonary arteries, which may represent the adequacy of the pulmonary vascular bed, is a strong prognostic factor for newborns with congenital CDH.

Female↗
PubMed2000

Histopathologic and immunohistochemical studies on the mechanism of interlobular fibrosis of the pancreas.

OBJECTIVE: To elucidate the mechanism of interlobular fibrosis of the pancreas, which is categorized as chronic alcoholic pancreatitis. METHODS: Forty pancreatic tissue samples from patients with ampullary carcinomas, which cause various degrees of stricture of the main pancreatic duct, and 20 patients with chronic alcoholic pancreatitis were studied histopathologically and immunohistochemically. RESULTS: Fibrosis was observed in 23 of 40 patients with ampullary carcinomas and was classified into 3 categories: mild changes (10 cases), moderate changes (9 cases), and marked changes (4 cases). In the mild change cases, mild fibrosis was diffusely distributed in the interlobular areas, with scant immunoreactivity of anti-alpha-smooth muscle actin (alpha-SMA) and an expansive lobular appearance, whereas moderate and marked change cases showed interlobular and intralobular fibrosis with marked anti-alpha-SMA immunoreactivity and lobular atrophy. By quantitative analysis, the mild change cases showed both higher MIB1-positive and lower apoptotic acinar cell ratios than those of moderate and marked changes. Anti-alpha-SMA immunoreactivity in the patients with chronic alcoholic pancreatitis was found in interlobular fibrosis. Hence, mild changes in cases of ampullary carcinomas had histologic findings similar to chronic alcoholic pancreatitis, except for excessive fibrosis cases with patchy distribution. CONCLUSION: Incomplete obstruction of the main pancreatic duct caused the beginning of interlobular fibrosis, which is categorized as chronic alcoholic pancreatitis.

Actins↗
PubMed2000

[Histopathologic problems in the classification of pancreatic carcinoma].

The major differences between the third and fourth edition of the classification of pancreatic carcinoma are that tumors of ductal origin are divided into intraductal tumors and invasive ductal carcinoma, and atypical hyperplasia is mentioned. A low papillary or flat carcinoma in the pancreatic duct which is regarded as an early feature of ductal adenocarcinoma is classified as an intraductal tumor. However, usage of this term is not suitable from the standpoint of the outline of pathology. Minimally invasive intraductal papillary-mucinous carcinoma is classified as an intraductal tumor instead of invasive ductal carcinoma. It is often argued that minimally invasive intraductal papillary-mucinous carcinomas and invasive carcinomas derived from intraductal papillary adenocarcinoma should be distinguished. An intraductal papillary-mucinous tumor represents cystic dilatation of the pancreatic duct due to mucin secretion and papillary projection and is sometimes misdiagnosed as a mucinous cystic tumor. However, the two tumors are different. This point should be revised in the next edition. The pathologic description of the classification of pancreatic carcinoma should reflect the exact pathophysiology of these tumors and be simple.

Carcinoma, Ductal, Breast↗
PubMed2000

Mechanism-based inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil in the presence of NADPH.

Purified recombinant human dihydropyrimidine dehydrogenase (hDPD) was incubated with (14)C-labeled (E)-5-(2-bromovinyl)uracil ([(14)C]BVU) in the presence of NADPH to investigate a possible mechanism in the 18 patient deaths caused by interactions of 5-fluorouracil prodrugs with the new oral antiviral drug, sorivudine. BVU is formed from sorivudine by gut flora and absorbed through intestinal membrane. hDPD, a rate-limiting enzyme for the catabolism of 5-fluorouracil and endogenous pyrimidines in the human, was NADPH dependently radiolabeled and inactivated by [(14)C]BVU. Two radioactive tryptic fragments, I and II, isolated from radiolabeled hDPD were found by complete amino acid sequencing to originate from a common regional amino acid sequence located at positions 656 (Lys) to 678 (Arg) for I and positions 657 (Ser) to 678 (Arg) for II. However, only Cys(671), which should be present in the peptides, was not identified by amino acid sequencing. Mass spectrometric analysis of the tryptic fragments indicated that the sulfhydryl group of Cys(671) in the hDPD was modified with 5, 6-dihydro-5-(2-bromoethylydenyl)uracil (BEDU), a putative allyl bromide type of reactive molecule, to form a sulfide bond with loss of hydrogen bromide. The Cys(671) sulfide bearing the debrominated BEDU had a 5,6-dihydrouracil ring highly strained by the exocyclic double bond at the 5-position, so that it underwent facile hydrolytic ring fission with alkali and heated acid treatments. A new proposal is also made for the amino acid sequence of the pyrimidine-binding domain, including Cys(671), of DPD in the human and other species.

Amino Acid Sequence↗
PubMed2000

[Long-term effect of polystan monocusp ventricular outflow patch after right ventricular outflow tract reconstruction].

Forty-eight patients who underwent right ventricular outflow tract reconstruction with Monocusp Ventricular Outflow Patch (MVOP) fifty-five times and survived surgery, were reviewed in this study. Mean age at surgery was 6.4 years-old and mean follow-up interval was 75.2 months. There was no late death, however reoperation was performed 7 times. Freedom from reoperation rate was 97.2% and 80.7% after 5 and 10 years after surgery, respectively. The main cause for reoperation were right ventricular outflow obstruction RVOTO (5 cases). All of the RVOTO occurred at the distal end of the anastomosis. However, there was no RVOTO in patients who underwent RVOTR with MVOP during the past ten years. So, we considered the cause of RVOTO a technical problem. Pulmonary regurgitation was one to two degree early after surgery, and had worsened by almost two or three degrees more than 5 years after surgery. Moreover, five of six patients who underwent cardiac catheterization more than 10 years after surgery had three degrees of pulmonary regurgitation as well as a large CTR. In conclusion, according to long-term results, especially more than 10 years post operatively, pulmonary regurgitation was the most important problem.

Adolescent↗
PubMed2000

[A case report of chronic myelocytic leukemia with multiple brain metastases, which responded to the gamma-knife therapy].

We report a 78-year-old woman who had multiple leukemic cell tumors in the brain in the course of chronic myelocytic leukemia (CML). As far as we could survey, such brain tumors were extremely rare. She had been followed because of chronic phase of CML until October, 1998, when she noticed muscle weakness in her left upper and lower extremity. A head MRI revealed multiple masses in the brain, a biopsy of which revealed a tumor of CML cells. Although 40 Gy gamma-knife therapy had reduced the size and numbers of brain tumors, we found recurrence of left hemiparesis and tumors three months after the gamma-knife therapy. Whole brain irradiation therapy (total 30 Gy) was somewhat effective to the tumor and hemiparesis transiently subsided. Thereafter her general condition worsened again, and she died in June, 1999, eight months after the diagnosis of the brain tumors of leukemic cells. We had not seen any other clinical evidence of generalized blastic crisis in this patient. In our case, MRI of the brain showed two patterns of metastases, tumor forming and cortical invasive type. We thought that these two patterns of brain involvement might show different responses to the radiation therapy, and it was characteristic in this patient.

Aged↗
PubMed2000

[A 57-year-old woman with progressive disturbance of gait and mental deterioration].

We report a 57-year-old woman with progressive gait disturbance and mental deterioration. She was well until March 1995, when she was 54 years of the age. At that time she noted a gradual onset of tremor and difficulty using her hand. Similar symptoms appeared in her right hands, and she visited another hospital, where 300 mg of levodopa and 7.5 mg of bromocriptine were prescribed. These medication did not help her symptoms. In the summer of 1996, she became to fall down easily. In September of the same year, she started to repeat the same words many times. She was unable to stop it. She was hospitalized to our service on January 25, 1997. On admission, she was alert but demented moderately; her Hasegawa dementia scale was 15/30. She showed palilallia, logoclonia, and echolalia. She showed constructional apraxia and questionable left-right disorientation. She had marked vertical gaze palsy with preserved oculocephalic response. She had masked face and small voice. Her gait was wide based with small steps. No muscle atrophy or weakness was noted. She showed only mild rigidity in the neck, but no rigidity was noted in the limb. No tremor was noted. She was bradykinetic. Deep tendon reflexes were symmetric and within normal limits. Laboratory findings on admission was unremarkable. MRI showed atrophy of the brain stem as well as cerebral cortical areas, particularly in the fronto-temporal region. Her hospital course was complicated with paralytic ileus and septicemia. She developed hypotension and pronounced dead on July 28, 1998. She was discussed in the neurological CPC. The chief discussant arrived at a conclusion that the patient had progressive supranuclear palsy and died of septic shock. All the participants wondered between PSP and CBD, but majority agreed with this diagnosis of the chief discussant. Only one thought that she might have had corticobasal degeneration rather than PSP, because of dementia, cortical atrophy in MRI, and lack of limb rigidity. Postmortem examination revealed cortical and brain stem atrophy. In the premotor cortex, marked astrocytosis and ballooned neurons were seen. Furthermore, astrocytic plaques were seen; this is considered to be pathognomonic for CBD. The substantia nigra showed marked neuronal loss and gliosis, but no neurofibrillary tangles or Lewy bodies were seen. Gliosis was also seen in the globus pallidus and in the medial thalamus. The pathologic diagnosis was corticobasal degeneration. This patient was very interesting case, in that the clinical manifestations appeared to be consistent with PSP, yet pathologic diagnosis was CBD. Lack of limb rigidity may be atypical for advanced PSP. In addition, palilalia appears to be more associated with CBD.

Brain↗
PubMed2000

Beta-adrenergic receptors and adenylate cyclase activity in the parotid acinar cells from acute streptozotocin-induced diabetic rats.

The changes in beta-adrenergic receptors and in adenylate cyclase (AC) activity were investigated in parotid glands from rats with acute diabetic mellitus (DM) induced by a single injection of streptozotocin (STZ, 80 mg/kg). The animals were divided into three groups: control rats, DM rats, and insulin-treated DM rats. Experiments were performed 7 days after the injection of STZ. Amylase and norepinephrine (NE) contents in parotid glands were markedly decreased in DM rats in comparison with control rats. The density of beta-adrenergic receptor decreased in DM rats, but its affinity for ligand was unaffected. The effect of GTP on isoprenaline (ISO)-stimulated adenylate cyclase (AC) activity significantly decreased in DM rats, but forskolin-stimulated AC activity was unaltered. In addition, diabetes induced the blunted response of AC activity to ISO. The changes in AC activity and in amylase content induced by diabetes were restored by insulin, but those in NE content and receptor density could not. These observations indicate that diabetes decreases NE and amylase contents, receptor density, and receptor-AC coupling in parotid gland, and that these changes would occur in the earlier stage of acute STZ-induced diabetic state.

Adenylyl Cyclases↗
PubMed2000

Effect of exercise training on ANP receptors.

To clarify whether exercise-training affects ANP function, we trained male Wistar rats by treadmill running for nine weeks and measured ANP receptor number and affinity in the kidney, lung and adrenal. We also measured guanylate cyclase activity, by which second messenger cGMP accumulates. The number of adrenal ANP receptor significantly increased after exercise-training. There was no significant difference of affinity for all the organs examined between the training group and the control group. Guanylate cyclase activity tended to decrease in the kidney in the training group. A significant difference was found when the samples were stimulated by C-type natriuretic peptide (CNP). There was no significant difference in guanylate cyclase activity in the lung and adrenal. These findings are consistent with the exercise-induced hypervolemia, but not with the anti-hypertensive role of exercise-training.

Adrenal Glands↗
PubMed1999

Evidence for a novel Chlorella virus-encoded alginate lyase.

To clone the genes encoding lysis protein from a Chlorella virus, water samples were collected from 13 aquatic environments located in the Kanto area of Japan. Eight water samples contained plaque-forming viruses on Chlorella sp. NC64A, but no virus was detected in the other five samples. A novel Chlorella virus, CVN1, was isolated from the Inba-numa marsh sample. CVN1 genomic DNA was partially digested and shotgun cloned into pUC118 to identify the genomic region responsible for the lytic phenotype on Chlorella sp. NC64A. A DNA fragment which encoded two ORFs, ORF1 and ORF2, was obtained by antialgal assay. The ORF2 gene product, CL2, consisted of 333 amino acids showing antialgal activity not only on the original host of Chlorella sp. NC64A, but also on the heterogeneous hosts of Chlorella vulgaris C-27 and C. vulgaris C-207. CL2 showed a weak homology (19.8% amino acid identity) to mannuronate lyase SP2 from Turbo cornutus. CL2 in Escherichia coli cells was purified using a nickel chelate column. Lyase activity of purified CL2 on alginic acid was observed in an enzyme assay. The specific activity of purified CL2 was 2.1x10(-2) U mg(-1), the optimum pH for enzymatic activity was 10.5, and Ca(2+) was required for enzyme activity. This is the first report of a Chlorella virus protein with lyase activity.

Alginates↗
PubMed1999

Mitochondrial Lon of Saccharomyces cerevisiae is a ring-shaped protease with seven flexible subunits.

Lon (or La) is a soluble, homooligomeric ATP-dependent protease. Mass determination and cryoelectron microscopy of pure mitochondrial Lon from Saccharomyces cerevisiae identify Lon as a flexible ring-shaped heptamer. In the presence of ATP or 5'-adenylylimidodiphosphate, most of the rings are symmetric and resemble other ATP-driven machines that mediate folding and degradation of proteins. In the absence of nucleotides, most of the rings are distorted, with two adjacent subunits forming leg-like protrusions. These results suggest that asymmetric conformational changes serve to power processive unfolding and translocation of substrates to the active site of the Lon protease.

ATP-Dependent Proteases↗
PubMed1999

Two genetically distinct lineages of the sika deer, Cervus nippon, in Japanese islands: comparison of mitochondrial D-loop region sequences.

To investigate genetic diversity among populations of the sika deer, Cervus nippon, nucleotide sequences (705-824 bases) of the mitochondrial D-loop regions were determined in animals from 13 localities in the Japanese islands. Phylogenetic trees constructed by the sequences indicated that the Japanese sika deer is separated into two distinct lineages: the northern Japan group (the Hokkaido island and most of the Honshu mainland) and the southern Japan group (a part of the southern Honshu mainland, the Kyushu island, and small islands around the Kyushu island). All sika deer examined in this study shared four to seven units of repetitive sequences (37 to 40 bases each) within the D-loop sequences. The number of tandem repeats was different among the populations, and it was specific to each population. Six or seven repeats occurred in populations of the northern Japan group, while four or five repeats occurred in populations of the southern Japan group. Each repeat unit included several nucleotide substitutions, compared with others, and 26 types were identified from 31 animals. Sequences of the first, second, and third units in arrays were clearly different between the northern and the southern groups. Based on these D-loop data, colonization and separation of the sika deer populations in the Japanese islands were estimated to have occurred less than 0.5 million years before present. Our results provide an invaluable insight into better understanding the evolutionary history, phylogeny, taxonomy, and population genetics of the sika deer.

Animals↗
PubMed1999

Histopathological and biochemical studies on pancreatic fibrosis in WBN/Kob rats.

We investigated the time-course of changes in pancreatic fibrosis accompanied with pancreatitis in WBN/Kob rats. The areas of fibrosis and fatty replacement were analysed morphometrically, and biochemical measurements of pancreatic and plasma prolyl hydroxylase and of pancreatic collagenase were assessed. Male rats showed acute pancreatitis at 2-3 months of age, lesions that later underwent a transition to widespread fibrosis. The fibrosis then decreased, and the fibrotic tissue was replaced with adipose tissue. Morphometrically, the fibrotic area reached its maximal size when the rats were 4 months old, diminishing thereafter. The fibrosis occurred mainly in the intralobular space, and was principally attributable to type-III collagen. Type-I collagen scarcely appeared throughout the experimental period. Alpha-Smooth muscle actin appeared in and around myofibroblasts that developed in an early stage and diminished later in accordance with the progressive manner of fibrosis. The plasma prolyl hydroxylase level was higher in males than in females from 4 through 10 months of age. Pancreatic collagenase activity in the males also increased during the same period. These findings suggest that pancreatic fibrosis in male WBN/Kob rats is affected by the balance between prolyl hydroxylase and collagenase.

Actins↗
PubMed1999

Three-dimensional reconstruction of the ventral and dorsal pancreas: a new insight into anatomy and embryonic development.

The recent introduction of limited resections of the ventral pancreas for benign disease and for low-grade malignancies calls for a thorough understanding of its anatomy. The two embryonic anlagen were characterized and distinguished through a comprehensive study of their macroscopic, histologic, and immunohistochemical characteristics in 20 autopsy specimens before reconstruction. Sections were histologically stained with hematoxylin-eosin and Grimelius and immunohistochemically stained with antibodies to insulin, glucagon, somatostatin, and pancreatic polypeptide by the avidin biotin complex method. The ventral and dorsal anlagen of the pancreas were reconstructed from eight autopsy specimens, using the "macroserial" method, after serial sectioning and immunohistochemical staining with anti-pancreatic polypeptide antibodies. Compared with the dorsal pancreas, the ventral pancreas was characterized by the presence of smaller and more closely packed lobuli, irregular rather than uniform islets of Langerhans, and rich immunostaining with anti-pancreatic polypeptide. Construction of the two anlagen showed that the dorsal pancreas consisted of the anterior part of the head of the pancreas, and the body and tail of the pancreas, while the ventral pancreas consisted of the posterior part of the head of the gland and the upper two-thirds (62.5%) or all (37.5%) of the uncinate process. The ventral pancreas was related to the right lateral surface of the superior mesenteric vein extending to the back. However, it did not extend across the front surface of the superior mesenteric vein to the left as previously described. The uncinate process was also located posterior to but not anterior to the superior mesenteric vein. The contributions of the ventral and dorsal anlagen to the anatomy of the pancreas gland as demonstrated in this study differ, in some relevant features, from the classical descriptions in the medical literature. The current anatomical findings add essential knowledge for the pancreatic surgeon who contemplates tissue-preserving resections.

Adolescent↗
PubMed1999

Epithelial cell proliferation activity of the biliary ductal system with congenital biliary malformations.

Congenital biliary malformations such as anomalous arrangement of the pancreaticobiliary ductal system (AAPB), congenital cystic dilatation of the common bile duct (CCDB), and congenital biliary strictures at the hepatic hilum (CBSH) are newly designated disease entities and are frequently found in adult patients with biliary malignancy such as gallbladder carcinoma, common bile duct carcinoma, and intrahepatic bile duct carcinoma. In the present study, the relationship of these malformations and biliary malignancy was investigated. We studied 61 gallbladders of patients with AAPB and 56 gallbladders of patients without AAPB; 16 common bile ducts of patients with CCDB (12 with AAPB and 4 without AAPB) and 11 gallbladders of patients without CCDB; and 17 intrahepatic bile ducts of patients with CBSH and 6 intrahepatic bile ducts of patients without CBSH. Tissue sections from the mucosa of the gallbladder, common bile duct, and intrahepatic bile duct were stained for proliferating cell nuclear antigen (PCNA). The PCNA labeling indexes of patients with these malformations were significantly higher than those of patients without these malformations (P < 0.05). Cell proliferation of the epithelia in the biliary ductal system in patients with these congenital biliary malformations was accelerated. Consequently, these congenital malformations appear to be an important risk factor for the occurrence of biliary malignancy.

Adult↗