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Biomedical subjects

I Endo

Publications and source records attributed to I Endo.

At least 55 records · Page 3Linked to original sources
PubMed1998

Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

Age of Onset↗
PubMed1998

Novel non-heme iron center of nitrile hydratase with a claw setting of oxygen atoms.

The iron-containing nitrile hydratase (NHase) is a photoreactive enzyme that is inactivated in the dark because of persistent association with NO and activated by photo-dissociation of NO. The crystal structure at 1.7 A resolution and mass spectrometry revealed the structure of the non-heme iron catalytic center in the nitrosylated state. Two Cys residues coordinated to the iron were post-translationally modified to Cys-sulfenic and -sulfinic acids. Together with another oxygen atom of the Ser ligand, these modifications induced a claw setting of oxygen atoms capturing an NO molecule. This unprecedented structure is likely to enable the photo-regulation of NHase and will provide an excellent model for designing photo-controllable chelate complexes and, ultimately, proteins.

Bacterial Proteins↗
PubMed1998

Anisakidosis: a cause of intestinal obstruction from eating sushi.

We report a case of strangulating small bowel obstruction in a 60-yr-old Japanese woman caused by anisakidosis (previously known as anisakiasis). With the increasing popularity of Japanese cuisine such as sushi in the United States, the incidence of anisakidosis is expected to increase. Intestinal anisakidosis can now be treated temporarily, but this condition may cause a serious obstruction afterwards, as evidenced by this particular case. Over 13,500 cases were reviewed in both the Japanese and English literature, and we discuss the prevention of anisakidosis without negatively altering the taste of the raw fish.

Animals↗
PubMed1998

Usefulness of three-dimensional computed tomography for anatomic liver resection: sub-subsegmentectomy.

BACKGROUND: Precise subtotal hepatectomies based on the vascular anatomy revealed by preoperative three-dimensional computed tomography (3D-CT) were reviewed to examine the usefulness of 3D-CT. METHODS: The clinical records and 3D-CT images of 20 patients with 24 hepatomas less than 50 mm in diameter who underwent hepatectomy for hepatocellular carcinoma and metastatic tumors and the usefulness of 3D-CT were assessed. Couinaud's classification of liver subsegments and Takayasu's classification of sub-subsegments were used as the criteria for the anatomic division. RESULTS: The accuracy in localizing tumors in a small subsegment of the liver was 75% (18 of 24 tumors) for conventional CT and 100% (24 of 24 tumors) for 3D-CT (p < 0.05). 3D-CT images made it possible to perform complete resection confined to the portal unit containing the tumor in patients with poor liver function. This method allowed complete preservation of the circulation of the remnant liver, thus reducing complications. CONCLUSIONS: The 3D-CT technique provides more accurate diagnosis and a realistic virtual image of a tumor's location in the liver and so makes possible the anatomic resection of the liver. Because diagnostic errors could result in such clinical complications as postoperative bile leakage, this is a useful technique for hepatectomy, especially for sub-subsegmentectomy.

Aged↗
PubMed1998

[Inflammatory mediator and organ dysfunction syndrome].

Inflammatory mediators include endotoxin (ETX), cytokines (interleukins [ILs], tumor necrosis factors [TNFs], and interferons), eicosanoids (prostaglandins and thromboxanes), reactive oxygen species (O2-, NO, and ONOO-), complements (C3 and C4), and stress hormones (catecholamine, cortisol, vasopressin, and growth hormone). These mediators work to maintain homeostasis under stressful conditions through a complex chain reaction or cascade that results in transient tissue damage known as the inflammatory response. The inflammatory response is decreased by a negative feedback system, which consists not only of the self-inhibitory action of ETX, TNF-alpha, IL-1, and IL-8, but also of the production of antiinflammatory mediators such as IL-4, -10, -11, and -13, TGF-beta, IL-Ra, and sTNFR. If excessive stress or a second attack of stress results in a higher level of inflammation-producing mediators than of inflammation-inhibiting mediators, tissue destruction occurs due to activation and infiltration of inflammatory cells or necrosis due to endothelial injury is seen, followed by disruption of homeostasis, organ dysfunction, and organ failure (multiple organ dysfunction syndrome [MODS] or multiple organ failure [MOF] induced by SIRS). In experimental liver dysfunction after 95% hepatectomy, massive apoptosis of hepatocytes is induced by prolonged hypercytokinemia, ONOO- production, decreased mitochondrial membrane potential of hepatocytes, and decreased Bc12 levels. On the other hand, if the antiinflammatory response is greater than the inflammatory response (CARS) a compromised state and refractory infection are seen, followed by progressive, irreversible organ dysfunction (MODS or MOF induced by CARS).

Animals↗
PubMed1998

[Hepatic resection for advanced carcinoma of the gallbladder].

Hepatic resection for advanced carcinoma of the gallbladder must be decided upon based on the modes of cancer spread to the liver. The cystic vein through the liver bed is considered an important route of liver metastasis, because liver metastases of gallbladder carcinoma are found frequently around the liver bed. About 70% of early metastatic foci demonstrated microscopically occur in segments 4a and 5. Resection of segments 4a and 5 is considered to be an adequate range of hepatectomy for patients with subserosal invasion, because early metastatic foci are detected not only in patients with direct invasion of the liver but also in those without direct invasion. For patients with direct liver invasion, various degrees of hepatic resection are needed to comply with the depth of direct invasion. It is necessary to achieve negative surgical margins 2 cm from the tumor. Because cancer cells extend along the Glissonian sheath in patients with hilar invasion, extended right hepatectomy with caudate lobectomy is required in these patients. A future problem is to establish the safety of extended hepatectomy in these patients.

Gallbladder Neoplasms↗
PubMed1997

Structure of the photoreactive iron center of the nitrile hydratase from Rhodococcus sp. N-771. Evidence of a novel post-translational modification in the cysteine ligand.

Nitrile hydratase (NHase) from Rhodococcus sp. N-771 is a photoreactive enzyme that is inactivated by nitrosylation of the non-heme iron center and activated by photodissociation of nitric oxide (NO). To obtain structural information on the iron center, we isolated peptide complexes containing the iron center by proteolysis. When the tryptic digest of the alpha subunit isolated from the inactive form was analyzed by reversed-phase high performance liquid chromatography, the absorbance characteristic of the nitrosylated iron center was observed in the peptide fragment, Asn105-Val-Ile-Val-Cys-Ser-Leu-Cys-Ser-Cys-Thr-Ala-Trp-Pro-Ile-Leu - Gly-Leu-Pro-Pro-Thr-Trp-Tyr-Lys128. The peptide contained 0.79 mol of iron/mol of molecule as well as endogenous NO. Subsequently, by digesting the peptide with thermolysin, carboxypeptidase Y, and leucine aminopeptidase M, we found that the minimum peptide segment required for the nitrosylated iron center is the 11 amino acid residues from alphaIle107 to alphaTrp117. Furthermore, by using mass spectrometry, protein sequence, and amino acid composition analyses, we have shown that the 112th Cys residue of the alpha subunit is post-translationally oxidized to a cysteine-sulfinic acid (Cys-SO2H) in the NHase. These results indicate that the NHase from Rhodococcus sp. N-771 has a novel non-heme iron enzyme containing a cysteine-sulfinic acid in the iron center. Possible ligand residues of the iron center are discussed.

Amino Acid Sequence↗
PubMed1997

Structural and functional characterization of homo-oligomeric complexes of alpha and beta chaperonin subunits from the hyperthermophilic archaeum Thermococcus strain KS-1.

To elucidate the function of group II chaperonin, the gene for the chaperonin from the hyperthermophilic archaeum Thermococcus strain KS-1 was cloned and sequenced. Two distinct genes coding for chaperonin subunits, designated alpha and beta, were obtained, and their deduced amino acid sequences are highly homologous to those of group II chaperonins from other sources. The alpha and beta subunits were individually expressed in Escherichia coli. Both of the recombinant subunits assemble to constitute the homo-oligomeric double-ring complexes, which are prone to form large aggregates. The alpha aggregate is dissociated into the typical chaperonin ring complex by incubation in buffer containing 15% (v/v) methanol, while the beta aggregate cannot be dissociated. At high temperature, both of the recombinant complexes have weak ATPase activities. They are able to arrest refolding of a chemically denatured thermophilic enzyme in the absence of ATP, and refolding is resumed when ATP is supplemented. These results suggest that homo-oligomeric complexes of the archaeal chaperonin have activity.

3-Isopropylmalate Dehydrogenase↗
PubMed1997

Purification and molecular cloning of the group II chaperonin from the acidothermophilic archaeon, Sulfolobus sp. strain 7.

To elucidate the structure and functional mechanism of the group II chaperonin, molecular cloning of the gene for and purification of the group II chaperonin from the thermoacidophilic archaeon Sulfolobus sp. strain 7 were performed. The purified Sulfolobus chaperonin exhibited weak ATPase activity and arrested the spontaneous refolding of the thermophilic lactate dehydrogenase. However, the refolding could not be resumed by addition of ATP. The chaperonin consists of two kinds of subunits, alpha and beta, the deduced amino acid sequences of which were highly homologous to those of TF56 and TF55 from Sulfolobus shibatae, respectively.

Adenosine Triphosphate↗
PubMed1997

The role of lymph node dissection in the treatment of gallbladder carcinoma.

BACKGROUND: Lymph node involvement is an important prognostic factor in gallbladder carcinoma (GBC). The lymph node involvement pattern, extent, and indications for systematic lymph node dissection for patients with advanced GBC were investigated. METHODS: Forty-one patients with GBC who underwent radical resection with systematic regional lymph node dissection over the past 11 years were analyzed. RESULTS: The lymph node metastasis rate was 63.4% overall, 0% in pT1 disease, 61.9% in pT2 disease, and 81.3% in pT3/pT4 disease. When reviewed according to site, the rate was 41.5% in pericholedochal lymph nodes, 22.0% in the lymph nodes around the common hepatic artery and the portal vein, 36.6% in the posterior pancreaticoduodenal lymph nodes, 28% (5/18) in the celiac lymph nodes, 19% (3/ 16) in the superior mesenteric artery (SMA) lymph nodes, and 26% (7/27) in the aortocaval paraaortic lymph nodes. Patients with severe hepatoduodenal ligament invasion had high rates of paraaortic lymph node involvement. The mortality rate was 2.4% (1 of 41 patients) and the 5-year survival rate was 33.1% overall, 100% in patients with pT1 disease, 49.8% in patients with pT2 disease, and 0% in patients with pT3/pT4 disease. The 5-year survival rate for pT2 disease according to lymph node involvement was 72.7% in patients with pN0+ pN1+ positive posterior pancreaticoduodenal lymph nodes and positive lymph nodes around the common hepatic artery in the N2 patients and 0% in the patients with positive celiac and SMA lymph nodes in the N2 patient group or the positive paraaortic lymph node group (P < 0.05). CONCLUSIONS: These results suggest that systemic dissection of N1 lymph nodes, posterior pancreaticoduodenal lymph nodes, and lymph nodes around the common hepatic artery and the portal vein in N2 patients is necessary to improve the prognosis of those patients with pT2 disease without moderate or severe hepatoduodenal ligament invasion.

Adult↗
PubMed1997

Segmental pericholangial fibrosis: a peculiar benign fibrosing disease at the hepatic hilum.

The authors report on a 9-year-old child who underwent surgery to remove a tumor of the hepatic hilum with preoperative radiographic studies suggestive of malignancy, but whose surgical specimens showed a peculiar fibrosing disease. The lesion was localized to the bifurcation of the hepatic duct, where the bile duct wall and the surrounding tissue was markedly fibrotic. No malignant cells or epithelial destruction were seen. The patient's postoperative course was uneventful, and he is without any sign of recurrence 2 years after surgery. Because the histological features of this case do not correspond to any established disease, including primary sclerosing cholangitis, the authors believe it represents a new entity, segmental pericholangial fibrosis. Local resection resulted in a good outcome. A review of the literature disclosed a few similar cases with a benign clinical course.

Bile Duct Neoplasms↗
PubMed1997

[Mode of spreading and biological behavior in bile duct carcinoma].

There are three macroscopic types of hepatic bile duct carcinoma, such as papillary (P-), nodular (N-) and diffuse (D-) type. Immunohistochemical studies demonstrated that P-type expressed cadherin and catenin higher than N- and D-types. The expressions of both cadherin and catenin were found stronger in pap and tub1 than tub2. The nuclear area of cancer cell, correlated with both labeling index of Ki-67 and aberrant accumulation of p53, was significantly larger in the subserosal layer than in the mucosal layer. These may explain the differences in the biological behavior between P- and N, D-types. P-type grows within the mucosal layer, while N- and d-type are more invasive, developing into the subserosal layer. Our clinical data also demonstrates the poor prognosis of N-, D-type of hepatic bile duct carcinoma. On these basis of the biological malignancy of N, D-type, it is critical to remain the surgical margin free from cancer cells to cure this type of hepatic bile duct carcinoma.

Adenocarcinoma↗
PubMed1996

Resonance Raman evidence that photodissociation of nitric oxide from the non-heme iron center activates nitrile hydratase from Rhodococcus sp. N-771.

Nitrile hydratase (NHase) from Rhodococcus sp. N-771, which contains a non-heme iron center in the catalytic site, has been known to be activated by light illumination. Recently, endogenous nitric oxide (NO) was found in this enzyme by FTIR spectroscopy [Noguchi et al. (1995) FEBS Lett. 358, 9-12]. In order to directly detect the bonding between NO and the iron atom and the reaction of NO upon photoactivation, resonance Raman spectra of the NHase were measured with 413 nm excitation at 85 K. Two prominent bands at 592 and 570 cm-1 were observed in the inactive from, and both of them were completely lost upon photoactivation. Upon subsequent introduction of 15NO, the active NHase was converted to the inactive form again and the above two bands were restored with downshifts by 10 and 12 cm-1, respectively. Also, the excitation profiles of these bands in the 350-500 nm region mostly followed the absorption spectrum arising from the iron center. From these isotopic shifts and the excitation profiles, the two Raman bands were assigned to the Fe-NO stretching and bending vibrations that are probably coupled with each other. The results provided solid evidence that NO is bound to the non-heme iron in the inactive NHase and its photodissociation activates the enzyme.

Binding Sites↗
PubMed1996

Gene for aspartate racemase from the sulfur-dependent hyperthermophilic archaeum, Desulfurococcus strain SY.

Amino acid racemases are ubiquitous throughout eubacteria. However, no amino acid racemases have yet been found in eukaryotes and archaea. We cloned a gene highly homologous to that for the aspartate racemase from the sulfur-dependent hyperthermophilic archaeum, Desulfurococcus strain SY. The product of the gene showed 35.2% amino acid sequence identity with the aspartate racemase of Streptococcus thermophilus IAM10064, and was also homologous to glutamate racemases around the putative catalytic cysteine residues. The encoded protein was expressed in Escherichia coli. The recombinant protein had amino acid racemizing activity, which was highly specific for aspartate and increased with temperature from 37 degrees C to 90 degrees C. Therefore, this was identified as the first hyperthermophilic archaeal amino acid racemase. A little aspartate racemizing activity was also detected in the crude extract of Desulfurococcus strain SY. The function of this aspartate racemase might be the uptake of -aspartate formed at high temperature or the production of -aspartate as a cell component. The fact that the amino acid racemases are distributed among both eubacteria and archaea suggests that endogenous -amino acids in mammals are also synthesized by amino acid racemases.

Amino Acid Isomerases↗
PubMed1996

A novel factor required for the assembly of the DnaK and DnaJ chaperones of Thermus thermophilus.

We previously reported the isolation of T.DnaK.DnaJ chaperone complex from Thermus thermophilus. Here, we show that a novel factor is necessary for the assembly of T.DnaK and T.DnaJ into the complex. A dnaK gene cluster of T. thermophilus contained five genes, dnaK-grpE-dnaJ-orf4-clpB. Interestingly, T.DnaJ lacks the whole "cysteine-rich region" that has been postulated to be necessary to bind unfolded proteins. The orf4 gene encodes a novel 78-amino acid protein. Curiously, T.DnaK and T.DnaJ expressed in Escherichia coli did not form the complex. Careful reexamination of the T.DnaK.DnaJ complex revealed the presence of a small protein in the complex, which turned out to be a product of orf4. As expected, expression of three genes, dnaK-dnaJ-orf4, resulted in production of a T.DnaK.DnaJ complex in E. coli that was indistinguishable from the authentic complex in its ability to interact with nucleotide and denatured protein. The product of orf4 was also required for in vitro reconstitution of the complex and named T.DafA (T.DnaK.DnaJ assembly factor A). The complex comprises three copies each of T.DnaK, T.DnaJ, and T.DafA. Even though a definite homolog of T.DafA has not been found in the data base, this finding raises a possibility that interaction between DnaK and DnaJ chaperones in other organisms is also mediated by a small protein yet unnoticed.

Amino Acid Sequence↗
PubMed1996

Location of the non-heme iron center on the alpha subunit of photoreactive nitrile hydratase from Rhodococcus sp. N-771.

Nitrile hydratase (NHase) from Rhodococcus sp. N-771, which possesses a non-heme iron center binding nitric oxide (NO), is activated by light irradiation. To localize the iron center in the protein, we quantified Fe atoms and performed FTIR measurements of the isolated alpha and beta subunits. The native NHase and the isolated alpha subunit contained about 1.0 and 0.8 mol Fe per mol protein, respectively, whereas the beta subunit contained only a trace of Fe. An NO stretching band was observed at 1852 cm-1 in the FTIR spectrum of the alpha subunit, but not in that of the beta subunit. Upon light irradiation of the alpha subunit, the affinity of the Fe atom decreased and the NO band disappeared from the FTIR spectrum. These observations indicate that the non-heme iron center, which is responsible for the photoreaction, is present in the alpha subunit.

Amino Acid Sequence↗