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Biomedical subjects

J Kondo

Publications and source records attributed to J Kondo.

At least 37 records · Page 2Linked to original sources

New aspects of sterol carrier protein 2 (nonspecific lipid-transfer protein) in fusion proteins and in peroxisomes.

Sterol carrier protein 2 (SCP2) is a 13-kDa peroxisomal protein, identical to nonspecific lipid-transfer protein, and stimulates various steps of cholesterol metabolism in vitro. Although the name is reminiscent of acyl carrier protein, which is involved in fatty acid synthesis, SCP2 does not bind to lipids specifically or stoichiometrically. This protein is expressed either as a small precursor or as a large fusion (termed SCPx) that carries at its C-terminal the complete sequence of SCP2. SCPx exhibits 3-oxoacyl-CoA thiolase activity, as well as sterol-carrier and lipid-transfer activities. The N- and C-terminal parts of SCPx are similar to the nematode protein P-44 and the yeast protein PXP-18, respectively. P-44, which has no SCP2 sequence, thiolytically cleaved the side chain of bile acid intermediate at a rate comparable to that of SCPx. This, together with the properties of other fusions with SCP2-like sequence, suggests that the SCP2 part of SCPx does not play a direct role in thiolase reaction. PXP-18, located predominantly inside peroxisomes, is similar to SCP2 in primary structure and lipid-transfer activity, and protects peroxisomal acyl-CoA oxidase from thermal denaturation. PXP-18 dimerized at a high temperature, formed an equimolar complex with the oxidase subunit, and released the active enzyme from the complex when the temperature went down. This article attempts to gain insight into the role of SCP2, and to present a model in which PXP-18, a member of the SCP2 family, functions as a molecular chaperone in peroxisomes.

Animals↗

[Continuous monitoring of hepatic venous oxygen saturation (SHVO2) as a new diagnostic indicator of abdominal malperfusion in acute aortic dissection].

A 73-year-old woman was admitted with sudden-onset back and abdominal pain. Computed tomography scanning revealed type B acute aortic dissection with narrowing of the true lumen. We inserted an oximetric catheter into the right hepatic vein and started continuous measurement of ShvO2. The initial value was 20%. Consecutive aortograms showed an intimal tear in the thoracic descending aorta. Endovascular stent graft placement was performed to close the entry, and ShvO2 rose to more than 60% immediately after the stent graft expansion. ShvO2 is an excellent indicator of abdominal blood flow, not only for early diagnosis but also for the evaluation of treatment.

Abdomen↗

Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo.

Chondromodulin-I (ChM-I) was previously identified as an angiogenesis inhibitor in cartilage. Here, we demonstrated that the level of ChM-I transcripts was substantially reduced to 100 or even less in the lower-grade chondrosarcomas, in articular cartilage or other benign cartilage tumors. We implanted human chondrosarcoma OUMS-27 cells into nude mice that reproducibly produced tumors with cartilaginous matrix. Tumor-induced angiogenesis was evident when the tumors were excised 30 days after implantation. However, the local administration of recombinant human ChM-I almost completely blocked vascular invasion and tumor growth in vivo. Moreover, ChM-I also inhibited the growth of HT-29 colon adenocarcinoma in vivo, implying its therapeutic potential for solid tumors.

Animals↗

Characterization of DNA recognition by the human UV-damaged DNA-binding protein.

The UV-damaged DNA-binding (UV-DDB) protein is the major factor that binds DNA containing damage caused by UV radiation in mammalian cells. We have investigated the DNA recognition by this protein in vitro, using synthetic oligonucleotide duplexes and the protein purified from a HeLa cell extract. When a 32P-labeled 30-mer duplex containing the (6-4) photoproduct at a single site was used as a probe, only a single complex was detected in an electrophoretic mobility shift assay. It was demonstrated by Western blotting that both of the subunits (p48 and p127) were present in this complex. Electrophoretic mobility shift assays using various duplexes showed that the UV-DDB protein formed a specific, high affinity complex with the duplex containing an abasic site analog, in addition to the (6-4) photoproduct. By circular permutation analyses, these DNA duplexes were found to be bent at angles of 54 degrees and 57 degrees in the complexes with this protein. From the previously reported NMR studies and the fluorescence resonance energy transfer experiments in the present study, it can be concluded that the UV-DDB protein binds DNA that can be bent easily at the above angle.

Base Sequence↗

Intrathoracic omental herniation through the esophageal hiatus: report of a case.

We report herein an extremely rare case of intrathoracic omental herniation through the esophageal hiatus. In fact, according to our review of the literature, only eight other cases have been reported, most of which were misdiagnosed as mediastinal lipoma after being identified as an intrathoracic mass. We report herein the ninth case of intrathoracic omental herniation through the esophageal hiatus. A 54-year-old obese woman was admitted to our hospital for investigation of a chest roentgenographic abnormality. She was asymptomatic, and her physical examination and laboratory data were all within normal limits. Her chest X-ray demonstrated a large, sharply-defined mass, and a computed tomography scan of the thorax indicated a large mediastinal mass with fat density. A thoracotomy was performed under the diagnosis of a mediastinal lipoma which revealed an encapsulated fatty mass, 10x7.5x6 cm in size, that proved to be an omental herniation through the esophageal hiatus. There was no herniation of the stomach or intestines into the thorax. The esophageal hiatus was repaired after the omental mass and hernia sac had been resected. This case report serves to demonstrate that whenever a mass of fat density is recognized in the lower thorax, an omental herniation should be borne in mind as a possible differential diagnosis.

Diagnosis, Differential↗

Ku in the cytoplasm associates with CD40 in human B cells and translocates into the nucleus following incubation with IL-4 and anti-CD40 mAb.

CD40 plays a critical role in survival, growth, differentiation, and class switching of B lymphocytes. Although Ku is required for immunoglobulin class switching, how CD40 signal transduction is coupled to Ku is still unknown. Here, we show that CD40 directly interacts with Ku through the membrane-proximal region of cytoplasmic CD40. Ku was confined to the cytoplasm in human primary B cells, and the engagement of CD40 on the B cells cultured in the presence of IL-4 resulted in the dissociation of Ku from CD40, translocation of Ku into the nucleus, and increase in the activity of DNA-dependent protein kinase. These findings indicate that Ku is involved in the CD40 signal transduction pathway and may play an important role in the CD40-mediated events.

Antibodies, Monoclonal↗

Molecular cloning of human chondromodulin-I, a cartilage-derived growth modulating factor, and its expression in Chinese hamster ovary cells.

Bovine chondromodulin-I (ChM-I) purified from fetal cartilage stimulated the matrix synthesis of chondrocytes, and inhibited the growth of vascular endothelial cells in vitro. The human counterpart of this bovine growth regulating factor has not been identified. We report here the cloning of human ChM-I precursor cDNA and its functional expression in Chinese hamster ovary (CHO) cells. We first identified a genomic DNA fragment which encoded the N-terminus of the ChM-I precursor, and then isolated human ChM-I cDNA from chondrosarcoma tissue by PCR. The deduced amino acid sequence revealed that mature human ChM-I consists of 120 amino acids. In total, 16 amino acid residues were substituted in the human sequence, compared to the bovine counterpart. Almost of all the substitutions were found in the N-terminal hydrophilic domain. In the C-terminal hydrophobic domain (from Phe42 to Val120), the amino acid sequence was identical except for Tyr90, indicating a functional significance of the domain. Northern blotting and in situ hybridization indicated a specific expression of ChM-I mRNA in cartilage. We also successfully determined the cartilage-specific localization of ChM-I protein, using a specific antibody against recombinant human ChM-I. Multiple transfection of the precursor cDNA into CHO cells enabled us to isolate the mature form of human ChM-I from the culture supernatant. Purified recombinant human ChM-I stimulated proteoglycan synthesis in cultured chondrocytes. In contrast, it inhibited the tube morphogenesis of cultured vascular endothelial cells in vitro and angiogenesis in chick chorioallantoic membrane in vivo.

Amino Acid Sequence↗

Molecular cloning of mouse and bovine chondromodulin-II cDNAs and the growth-promoting actions of bovine recombinant protein.

We previously determined the complete primary sequence of a heparin-binding growth-promoting factor, chondromodulin-II (ChM-II), which stimulated the growth of chondrocytes and osteoblasts in culture. Bovine ChM-II was a 16-kDa basic protein with 133 amino acid residues and exhibited a significant sequence similarity to the repeats of the chicken mim-1 gene product. Here we report the nucleotide sequences of bovine and mouse ChM-II cDNAs. The cDNAs each contained an open-reading frame corresponding to the ChM-II precursor with 151 amino acid residues. The N-terminus of the precursor included a secretory signal sequence of 18 amino acids prior to the mature ChM-II sequence. Unlike MIM-1, there was no repeat structure in the precursor protein, indicating that ChM-II was encoded as a gene product distinct from MIM-1. We then expressed recombinant bovine ChM-II protein which was purified to homogeneity. The recombinant protein stimulated the growth of rabbit growth plate chondrocytes, mouse MC3T3-E1 cells and rat UMR-106 osteoblastic cells in vitro.

Amino Acid Sequence↗

[Clinical outcome of emergency coronary artery bypass grafting for acute myocardial infarction with cardiogenic shock].

From January 1993 through December 1998, Emergency Coronary Artery Bypass Grafting was Performed within 24 Hours after the Onset of Acute Myocardial Infarction (AMI) with Cardiogenic Shock in 22 Patients (17 men and 5 women; aged, 52-81 years). The incidence of AMI involving the left main coronary artery was 50%. The incidence of interventional therapy was 40.9% (PTCA 31.8%; PTCR 9.1%). The condition in 95.5% of the patients could be stabilized hemodynamically by preoperative intraaortic balloon pumping; 4 of the 5 patients suffered from cardiopulmonary arrest required percutaneous cardiopulmonary support. There were 4 (18.2%) deaths overall. Operative mortality was related to the intervals between AMI and operation (less than 6 hours, 25%; 6 to 24 hours, 10%). Three of the 4 patients who received cardiopulmonary support survived. We conclude that early revascularization and minimal reperfusion injury caused by mechanical devices are important determinants of survival in patients who have AMI with cardiogenic shock.

Aged↗

[Endovascular graft treatment of aortic aneurysms: future perspectives].

Endovascular graft treatment of aortic aneurysms, first clinically applied by Parodi et al., has gained popularity. Although it was initially limited to high-risk patients, its indications have been gradually expanded. From literature and our own experience, the future of this method is discussed. The concept of this method is to place the intravascular stent graft in the aneurysm, excluding the aneurysmal sac and maintaining the arterial blood flow, thus preventing further dilatation and possible rupture in the future. However, these were some cases in which aneurysms, excluded completely during surgery became patent due to endoleak years after the procedure. A prospective study of abdominal aortic aneurysms, which compared endovascular graft and conventional open repair, demonstrated less major morbidity with the former but no difference in mortality, Considering those and the fact that long-term results of conventional surgical treatment have been satisfactory, the current indications for stent grafting should be limited to high-risk patients. For thoracic aortic aneurysms, endovascular treatment may become a useful alternative for those with localized as well as dissecting aneurysms because of the high perioperative morbidity accompanying conventional open repair. In summary, most patients with aortic aneurysms are senile and may have concomitant multiple organ failure. Less invasive, intravascular stent grafting has a definite role in the management of some patients with aortic aneurysms.

Aged↗

Mouse MD-1, a molecule that is physically associated with RP105 and positively regulates its expression.

RP105 is a leucine-rich repeat molecule that is expressed on mouse B cells and transmits a growth-promoting signal. An anti-RP105 Ab precipitated additional molecules as well as RP105. These molecules were found to be a mouse homologue of chicken MD-1. Chicken MD-1 was previously isolated as a v-myb-regulated gene, since its transcription increases rapidly after v-myb induction. Mouse MD-1, when transiently expressed as an epitope-tagged protein, is secreted in culture fluid but tethered to the cell surface by coexpressed RP105. An association of these molecules was confirmed by immunoprecipitation with the anti-RP105 Ab and subsequent probing of the epitope tag on MD-1. Moreover, MD-1 has an effect on the expression of RP105. In transient transfection of RP105, the percentage of RP105-positive cells increased more than twice with the coexpression of MD-1. The stable expression of MD-1 conferred approximately a sevenfold increase in cell surface RP105 on a cell line that expresses RP105 alone. Thus, MD-1 is physically associated with RP105 and is important for efficient cell surface expression.

Amino Acid Sequence↗

Expression of the alpha 1 and alpha 2 chains of type IV collagen in the infarct zone of rat myocardial infarction.

Healing processes affect ventricular remodeling, an important prognostic factor in acute myocardial infarction (AMI). Type IV collagen, a major component of the basement membrane, has been demonstrated to appear in the infarct zone. Six type IV alpha chains, alpha 1 to alpha 6 [alpha 1(IV) to alpha 6(IV)], have been identified. We examined the expression of the alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 5(IV) in experimental rat AMI induced by permanent ligation of the left coronary artery in male Sprague-Dawley rats. Neonatal cardiac fibroblasts cultured to reach confluency were also used to examine the hypoxic induction of the expression of these chains. Northern blotting, in situ hybridization, and immunohistochemical staining were employed to examine the alpha chain expression. With the in situ hybridization, alpha 1(IV) and alpha 2(IV) mRNA signals were observed in spindle-shaped mesenchymal cells in the intercellular spaces, in the vascular endothelial cells and in some myocytes in the normal myocardium. Signals for both alpha 1(IV) and alpha 2(IV) mRNA appeared in the spindle-shaped mesenchymal cells located between the surviving myocytes in the infarct peripheral zone at 24 h after the ligation. These signals extended into the central zone and reached the center point of the infarct 5 days after the ligation. Neither alpha 3(IV) nor alpha 5(IV) mRNA signals were observed in the infarct zone. Northern blotting demonstrated increased expressions of alpha 1(IV) and alpha 2(IV) mRNA in the infarct zone compared to the sham-operated hearts. The expression of alpha 5(IV) mRNA was weak in the sham-operated hearts but was not detected in the infarct zone. alpha 3(IV) mRNA was not expressed in the infarct zones or sham-operated hearts. In the cultured cardiac fibroblasts, a hypoxic induction of the expression of both alpha 1(IV) and alpha 2(IV) mRNA was demonstrated by Northern hybridization. Immunohistochemistry revealed alpha 1(IV) and alpha 2(IV) staining in the infarct lesion. The findings demonstrate that among the type IV collagen alpha chains examined, alpha 1(IV) and alpha 2(IV) produced by mesenchymal cells appeared in the infarct zone, suggesting that type IV collagen composed by alpha 1 and alpha 2 chains contributes to the pathological course of myocardial infarction.

Animals↗

[A case of emergency surgery for acute mitral regurgitation due to complete papillary muscle rupture as complication of acute inferior myocardial infarction].

We experienced a case with acute mitral regurgitation caused by complete posterior papillary muscle rupture as complication of acute inferior myocardial infarction, who underwent successfully emergency operation of mital valve replacement and coronary revascularization in acute stage. A 64-year-old woman developed sudden cardiogenic shock shortly after the onset of acute inferior myocardial infarction. The diagnosis of acute inferior myocardial infarction was based on the electrocardiographic findings. Under IABP support, preoperative coronary angiography visualized total occlusion of segment 3 of the right coronary artery, and preoperative left ventriculography showed akinesis of inferior wall and severe mitral regurgitation. At 6 hours after onset of papillary muscle rupture, emergency operation was performed. At operation, posterior papillary muscle was found to be totally ruptured. Coronary artery revascularization and mitral valve replacement were performed. Postoperative course was uneventful, with 4 days of IABP and 5 days of ventilatory support. She was discharged on the twentieth postoperative day in NYHA class I. Reports of successful emergency operation for total papillary muscle rupture following acute myocardial infarction are rare. Early diagnosis and surgical treatment are mandatory to save this group of patients.

Emergencies↗

Sequential changes in the localization of the type IV collagen alpha chain in the infarct zone: immunohistochemical study of experimental myocardial infarction in the rat.

Collagen, as a component of the extracellular matrix, have a role in the healing process after myocardial infarction (MI). For type IV collagen, a major structural protein present in the basal membrane of myocytes, six alpha chains [alpha 1 (IV)-alpha 6(IV)] have been identified. We examined the sequential changes in the appearance and localization of the alpha 1 (IV)-alpha 5(IV) after experimental MI in rats. Hearts were excised from 1 day to 8 weeks after permanent left coronary artery ligation. Immunohistochemical staining with monoclonal antibodies was performed. On day 3, staining for both alpha 1(IV) and alpha 2(IV) first appeared, forming a wavy pattern in the infarct peripheral zone, and the staining was not restricted to the cell membrane. The staining intensity and distribution for both alpha 1(IV) and alpha 2(IV) in the peripheral zone then gradually increased, reaching a maximum around day 7. The distribution progressed from the peripheral to the central zone of the infarct for 1-2 days, reaching the center point after 2 weeks. The staining distribution gradually decreased after reaching the maximum, but the staining had not completely disappeared at 8 weeks. In contrast, no positive staining for alpha 3(IV), alpha 4(IV) or alpha 5(IV) was observed at any time during the 8-week observation period. Thus, the present results demonstrated that in rats, type IV collagen consisting of alpha 1 and alpha 2 chains appears in the infarct zone at a relatively early phase after MI, indicating that type IV collagen composed of alpha 1 and alpha 2 chains contributes to infarct healing.

Animals↗

Characteristics of prehospital cardiac arrest patients in Japan and determinant factors for survival.

Two hundred forty-seven consecutive patients who had prehospital cardiac arrest and were transferred to a municipal hospital were studied to elucidate the characteristics of these patients and to investigate factors for improving the survival rate among prehospital cardiac arrest patients. Detailed information on 130 patients with cardiac etiology was analyzed: 110 were confirmed dead in the emergency department (group A); 14 survived less than 1 week (group B); 6 survived longer than 1 week (group C). Only one patient received cardiopulmonary resuscitation (CPR) from a bystander, and none received electrical defibrillation before arriving at hospital because, at the time, emergency personnel were not allowed to perform advanced life support (ALS) in Japan. The three characteristics for better prognosis after prehospital cardiac arrest were found to be as follows: being witnessed on collapse, receiving prompt ALS, and ventricular fibrillation on arrival at hospital. The survival rate would have been higher if more lay people could have performed CPR and if emergency unit personnel had been allowed to perform ALS.

Aged↗

A case of malignant peritoneal mesothelioma showed complete remission with chemotherapy.

A 71-year-old woman presented with an abdominal mass and ascites and was subsequently admitted to our hospital in June 1995. Further examination revealed that the mass was malignant and, as a result, surgery was indicated. However, the mass demonstrated widespread peritoneal dissemination, which therefore could not be resected, and pathological findings suggested a malignant peritoneal mesothelioma. The patient showed a remarkable response to combined chemotherapy with an accompanying intraperitoneal injection of cisplatin and etoposide and an intravenous injection of caffeine. However, owing to side effects, this regimen was discontinued. The patient was administered a combination drug of uracil and tegafur (UFT) in addition to intraperitoneal injection of cisplatin as an outpatient. By the 223rd day after surgery, the tumor mass and ascites had completely disappeared according to the CT. Hence chemotherapy was judged to have resulted in complete remission. Such a marked response to chemotherapy is rare in an advanced malignant peritoneal mesothelioma such as the present case. Eight months later, the tumor recurred in the pleura. Another regimen of chemotherapy with cisplatin and CPT-11 was performed. However, this treatment proved ineffective. The patient subsequently died of respiratory failure in January 1997 due to the mesothelioma. This is a case report of complete remission of malignant peritoneal mesothelioma by combined chemotherapy.

Aged↗

Prevalence of hepatitis B and C virus markers in outpatients of Mongolian general hospitals.

In East Asian countries, the prevalence of viral hepatitis has been reported to be high, but precise data for each country remained to be investigated. Here we report the prevalence of viral markers of hepatitis B and hepatitis C in outpatient volunteers visiting two general hospitals in Ulaanbaatar, Mongolia. One hundred fifty sera were tested for HBs antigen (HBsAg), anti-HBs, and anti-HCV by Counting Immunoassay. The backgrounds of groups of patients positive for HBsAg and negative for anti-HCV (group 1; n = 18), negative for HBsAg and positive for anti-HCV (group 2; n = 47), positive for both HBsAg and anti-HCV (group 3; n = 25), and negative for both HBsAg and anti-HCV (group 4; n = 60) were compared. The prevalence of HBsAg, anti-HBs, and anti-HCV in this study group was 28.7%, 39.3% and 48.0%, respectively. Subjects of group 1 (mean +/- SD; 31.3 +/- 12.4 years old) were younger than those of group 4 (39.2 +/- 14.3; p < 0.05), while patients of group 2 (48.7 +/- 15.5) were older than those of group 4 (p < 0.01). More group 2 subjects had histories of jaundice (23/47) than those of group 4 (15/60; p < 0.05). Transaminase levels were higher in group 1 (median (range) IU/l of AST, ALT; 29 (13-95), 32 (9-144) and group 3 (25 (15-187), 22 (8-185)) than in group 4 (18 (9-13), 15 (6-133); p < 0.05, p < 0.005 vs. group 1, and p < 0.005, p < 0.001 vs. group 3, respectively). In HBsAg-negative subjects, those with higher titers of anti-HCV (cut-off index > 15) were older, and had more histories of jaundice and higher levels of AST and ALT than anti-HCV negative subjects (50.3 +/- 14.8 vs. 39.1 +/- 14.3, p < 0.01; 15/28 vs. 15/60, p < 0.01; 22.5 (12-127) vs. 18 (9-93), p < 0.05; 20.5 (7-362) vs. 15 (6-133), p < 0.05; respectively). In conclusion, this preliminary surveillance for hepatitis B and C viral markers showed that both hepatitis viruses are prevalent and may cause liver diseases in Mongolia. A nation-wide survey for these viruses should be urged and preventive measures should be taken to suppress the spread and development of liver diseases in this country.

Adult↗

Expression of type XVII collagen alpha 1 chain mRNA in the mouse heart.

The type XVII collagen alpha 1 chain has been identified as a component of the type I hemidesmosome, and is thus thought to play a role in extracellular matrix (ECM) maintenance and signal transduction between the cell and the ECM. We examined the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart by Northern blot analysis and determined the sequential changes of its expression in different developmental stages of the heart using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Northern blotting: Total RNA was extracted from 10 adult mouse hearts by the guanidine/cesium method. Hybridization was performed with mouse cDNA for alpha 1 (XVII) collagen. RT-PCR: Total RNA was extracted from 7 embryos, 4 neonates and 8 adult mice. Reverse transcription was performed using oligo-dT primer and MMLV. Amplification was carried out in alpha 1 (XVII) collagen and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH served as an internal control. Northern blotting revealed a 5.6 kb signal that was identical to that of the alpha 1 (XVII) of skin and transformed keratinocyte reported previously. The sequences of the PCR products were also identical to those reported. The normalized expression ratios of alpha 1 (XVII) were 0.91 +/- 0.20 in the embryonic heart, 0.36 +/- 0.20 in the neonatal heart and 0.96 +/- 0.21 in the adult heart. In conclusion, we identified the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart, suggesting that the type I hemidesmosome is located in the heart. The results of the RT-PCR at different developmental stages of the heart suggest that type XVII collagen contributes not only to cardiogenesis in the embryonic stage but also to maintenance of architecture and function in the adult heart.

Angiotensin-Converting Enzyme Inhibitors↗