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Biomedical subjects

J Kondo

Publications and source records attributed to J Kondo.

At least 109 records · Page 6Linked to original sources

Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease.

A neuropathological hallmark of Alzheimer disease (AD) is a widespread amyloid deposition. We analyzed the entire amino acid sequences in an amyloid preparation and found, in addition to the major beta/A4-protein (A beta) fragment, two unknown peptides. We raised antibodies against synthetic peptides using subsequences of these peptides. These antibodies immunostained amyloid in neuritic and diffuse plaques as well as vascular amyloid. Electron microscopic analysis demonstrated that the immunostaining was localized on amyloid fibrils. We have isolated an apparently full-length cDNA encoding a 140-amino-acid protein within which two previously unreported amyloid sequences are encoded in tandem in the most hydrophobic domain. We tentatively named this 35-amino acid peptide NAC (non-A beta component of AD amyloid) and its precursor NACP. NAC is the second component, after A beta, identified chemically in the purified AD amyloid preparation. Secondary structure predictions indicate that the NAC peptide sequence has a strong tendency to form beta-structures consistent with its association with amyloid. NACP is detected as a M(r) 19,000 protein in the cytosolic fraction of brain homogenates and comigrates on immunoblots with NACP synthesized in Escherichia coli from NACP cDNA. NACP mRNA is expressed principally in brain but is also expressed in low concentrations in all tissues examined except in liver, suggesting its ubiquitous and brain-specific functions. The availability of the cDNA encoding full-length NACP should help to elucidate the mechanisms of amyloidosis in AD.

Alzheimer Disease↗

Activation of the zymogen of hepatocyte growth factor activator by thrombin.

Hepatocyte growth factor activator (HGF activator) is a serine protease which converts single-chain HGF to the active two-chain form. HGF activator purified from human serum has a molecular mass of 34 kDa and consists of two chains held together by a disulfide bond. The nucleotide sequence of HGF activator cDNA shows that HGF activator is derived from the COOH-terminal region of a precursor of 655 amino acids by proteolytic cleavage of the bonds between Arg372 and Val373 and between Arg407 and Ile408 and that the precursor consists of multiple domains homologous to those observed in blood coagulation factor XII. In this study, we identified the precursor of HGF activator in human plasma using an enzyme-linked immunosorbent assay system. The precursor was purified from plasma by a five-step procedure. The purified precursor did not activate single-chain HGF. The precursor was efficiently cleaved in vitro by thrombin, at the bond between Arg407 and Ile408, in the presence of negatively charged substances. The cleaved precursor activated single-chain HGF. These findings led us to conclude that HGF activator is present in plasma as an inactive zymogen and that the zymogen is activated by the cleavage of the bond between Arg407 and Ile408 by thrombin. Characteristic structural domains in the NH2-terminal region of the zymogen may be involved in the binding of the zymogen to negatively charged substances, which stimulates the activation of the zymogen by thrombin.

Amino Acid Sequence↗

Haemopoietic activity associated with biglycan like proteoglycan.

One of the monocytic cell colony stimulating factors produced by thymic myoid cells, a 100 kDa factor, was purified by reversed phase HPLC and found to be homologous to the secreted form of proteoglycan 1 (biglycan) core protein. This biglycan associated colony stimulating factor did not carry an immunological motif of macrophage colony stimulating factor (M-CSF), but predominantly stimulated the proliferation and differentiation of monocytic lineage cells from bone marrow cells, nonadherent thymic cells and peritoneal exudate cells.

Amino Acid Sequence↗

Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII.

Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver cells, epithelial cells, and endothelial cells and may play an important role in liver regeneration following hepatic injury. HGF is homologous to plasminogen and is first synthesized and secreted as an inactive single-chain precursor and then activated to a heterodimeric form by endoproteolytic processing. Recently, a novel serine protease responsible for this processing (HGF activator) has been purified from fetal bovine serum (Shimomura, T., Ochiai, M., Kondo, J., and Morimoto, Y. (1992) Cytotechnology 8, 219-229). In this study, we purified HGF activator from human serum and determined its partial amino acid sequence. Based on the amino acid sequence, we have molecularly cloned the cDNA for human HGF activator. The nucleotide sequence of the cDNA revealed that HGF activator is derived from the COOH-terminal half region of a precursor protein of 655 amino acids and that the precursor consists of multiple putative domains homologous to those observed in blood coagulation factor XII. These domains may be involved in the conversion of the precursor to the active form of HGF activator.

Amino Acid Sequence↗

Parotid swelling. Does it affect serum isoamylase level?

Serum levels of total amylase and P-type, and S-type isoamylase were measured in 57 patients with chronic parotid swelling (41 men and 16 women; mean age 60.4) and the same number of age- and sex-matched control individuals without parotid swelling (41 men and 16 women; mean age 60.3). None of the three enzyme measurements differed significantly between patients with parotid swelling and control subjects. It is concluded that chronic enlargement of parotid glands does not affect serum isoamylase level.

Adult↗

Percutaneous insertion of a jacketed stent to close the entry of dissecting aortic aneurysms of DeBakey types I and II.

As a treatment for dissecting aortic aneurysms of DeBakey Types I and II, a percutaneous insertion method using a new jacketed stent was developed. The efficacy of the method was evaluated in an animal study. We developed a special stent prepared by modifying the original Gianturco self-expandable metallic stent and a fabric patch. A model of a dissecting aortic aneurysm of DeBakey Type I was created in dogs. The device was inserted into the ascending aorta from the left carotid artery through a sheath-introducer system. The aortogram showed the bloodstream through the false lumen before the insertion, but no bloodstream after the stent insertion. The autopsy showed that the entry, the reentry, and the false lumen were completely filled with fresh thrombus. By using this stent, we successfully achieved an interventional treatment for dissecting aortic aneurysms of DeBakey Types I and II.

Aortic Dissection↗

Unusual inflammatory responses around a collagen-impregnated vascular prosthesis.

A collagen-impregnated graft, called Hemashield, has been used clinically; however, some complications such as pyrexia, fluid accumulation, and unusual scar formation around the graft have been reported. To understand the cause of these problems, the graft was examined both in vivo and in vitro. Endotoxin and (1-3)beta-D-glucan were detected in the extract from Hemashield by special quantitative methods called Toxicolor and Endospecy. In an animal study, the grafts were implanted in the thoracic descending aorta of 9 dogs and were designed to explant at 2 weeks. Macroscopic evaluation of the explants showed that the graft had no infection, but fluid accumulation was found in the pleural cavity and around the graft-like seroma. Microscopical observations revealed that neither fibroblasts nor capillary blood vessels had infiltrated in the adventitial side of the graft, but numerous plasma cells, lymphocytes, and macrophages were noticed. The impregnated collagen was partially absorbed. These results indicate that the graft had some contaminants which contained a certain amount of endotoxin and (1-3)beta-D-glucan, resulting in noninfective inflammatory responses around the graft.

Animals↗

Hibernation-associated gene regulation of plasma proteins with a collagen-like domain in mammalian hibernators.

In mammals, hibernation is expressed by only a limited number of species, and the molecular mechanisms underlying hibernation are not well understood. Recently, we have found plasma proteins which disappear from blood specifically during hibernation in a mammalian hibernator, the chipmunk. Here, we report the cDNA cloning of these chipmunk hibernation-related proteins, HP-20, -25, and -27, and analyses of their expression. All three proteins contain a collagen-like domain near the N terminus and are highly homologous to each other. Their mRNAs were detected only in liver in nonhibernating chipmunks, and in hibernating chipmunks, the amounts were reduced to less than 1/10 of those in nonhibernating chipmunks, indicating that HP-20, -25, and -27 mRNA expression is regulated similarly in association with hibernation. Southern blot analyses of the squirrel family with each of chipmunk HP-20, -25, and -27 cDNA revealed that a nonhibernating species (tree squirrel) as well as another hibernating species (ground squirrel) retained the corresponding genes. However, their transcripts were detected only with the hibernating species, and in hibernating ground squirrels, their levels were greatly reduced compared with those in nonhibernating animals, as were the cases with the chipmunk. These observations are the first line of evidence for occurrence of hibernation-associated gene regulation. The results would indicate the commitment of HP-20, -25, and -27 to hibernation and support the idea that genetic controls are involved in mammalian hibernation.

Amino Acid Sequence↗

Acute left main coronary artery obstruction with myocardial infarction--reperfusion strategies, and the clinical and angiographic outcome.

We studied the clinical and angiographic outcomes in 8 patients with acute left main coronary artery obstruction. Intracoronary thrombolysis with 1.2 x 10(5) units of urokinase was performed in 3 patients during preparation for percutaneous transluminal coronary angioplasty (PTCA), and failed in all 3 cases. In 2 patients, the left main coronary artery was recanalized by intracoronary thrombolysis with 3.6 and 4.8 x 10(5) units of urokinase, respectively. PTCA was attempted either before or after intracoronary thrombolysis in 5 patients and achieved reperfusion in all 5 cases. However, 2 of the 8 patients had persistent high-grade residual stenosis 69% and 89% luminal reduction, respectively. Emergency coronary artery bypass grafting was successfully performed in these 2 patients, and both are currently alive. Although intraaortic balloon counterpulsation was performed in all 8 patients, 2 died acutely from pump failure in the catheterization laboratory. One patient died later due to congestive heart failure. The factors favoring survival were right coronary artery dominance and a well-developed collateral circulation. Our findings suggest that PTCA is a useful strategy for reperfusion following acute left main coronary artery occlusion. When PTCA cannot achieve sufficient revascularization, emergency coronary artery bypass grafting should be performed. To control pump failure, intraaortic balloon counterpulsation is insufficient in some cases and more aggressive measures may be required.

Aged↗

Evaluation of antibody against AR142, a synthetic peptide derived from the core sequence of hepatitis C virus, in the diagnosis of non-A, non-B chronic liver disease.

We evaluated serum anti-hepatitis C virus (HCV) using a synthetic peptide (AR142) which includes an epitope in the core region of HCV. The incidence of anti-AR142 in 98 patients with type non-A, non-B chronic liver diseases (NANB-CLD) was 89.8%, while all the 28 patients with non-type C chronic liver diseases were negative for anti-AR142. Among 98 NANB-CLD patients, 74 were positive for both anti-AR142 and anti-C100-3, 23 showed discordant results, and one was positive for neither. Eighty-one NANB-CLD patients underwent reverse transcription-polymerase chain reaction assay to detect viremia and 76 (93.8%) had a detectable level of HCV-RNA. Titers of anti-AR142 were not different among groups of different disease activities, genotypes of HCV, nor amount of serum HCV-RNA. These observations suggest that anti-AR142 could be a useful marker for chronic HCV infection.

Adult↗

[Unusual non-infective inflammatory responses around a collagen impregnated vascular prosthesis].

Causes of some complications such as pyrexia, fluid accumulation and unusual scar formation around the graft in "Hemashield" implantation were examined both in vivo and in vitro. In an animal study, the grafts were implanted in the thoracic descending aorta of 9 dogs, and were explanted at 2 weeks after implantation. Macroscopic evaluation of the explants revealed that the graft had no infection, but fluid accumulation and a thick scar layer formation were noticed in the pleural cavity and around the graft. Microscopical observations demonstrated that the impregnated collagen was almost absorbed and numerous plasma cells, lymphocytes and macrophages had infiltrated in the interstices of the Dacron fibers, but neither fibroblasts nor capillary blood vessels. Numerous erythrocyte were also noticed in the graft wall. In vivo experiment of the extract from Hemashield, endotoxin and/or (1-3) beta-D-glucan were detected by the special quantitative methods; Toxicolor and Endospecy. These results indicated that the graft had some contaminants which contained a certain amount of endotoxin, (1-3) beta-D-glucan, resulting in non-infective inflammatory responses around the graft.

Animals↗

[External work of canine latissimus dorsi muscle after vascular delay].

The first purpose of this study was to estimate physiological performance of skeletal muscle for circulatory assist. External work in the form of linear dynamic contraction was studied in canine latissimus dorsi muscle (LDM). The second purpose was to relate the effect of vascular delay of the LDM to the physiological performance. The left LDM with vascular delay (VD) were compared to the right control LDM (CTR) without vascular delay. Simultaneous dynamic contraction of both VD and CTR LDM were studied under various settings of the preloads and the afterloads. Maximal external work per single contraction were 136 +/- 38 mJ in VD and 81 +/- 21 mJ in CTR. Maximal total work, which includes external work and preload work, were 578 +/- 195 mJ in VD and 407 +/- 146 mJ in CTR. Maximal fractional shortenings of the LDMs were 22.8 +/- 4.7% in VD and 17.5 +/- 2.6% in CTR. The maximal external work of VD was 81% of canine LV stroke work and 620% of canine RV stroke work. The maximal total work of VD was 340% of canine LV stroke work. The fractional shortenings, external work and total work of VD were higher than those of CTR under all loading conditions. The physiologic performance of canine LDM was improved after vascular delay.

Animals↗

[A successful case of emergency coronary artery bypass grafting for a patient with cardiopulmonary arrest on arrival at our hospital due to acute myocardial infarction].

A successful case of emergency coronary artery bypass grafting for a 62-year-old man with cardiopulmonary arrest due to acute myocardial infarction was reported. He developed cardiopulmonary arrest 4 minutes before arrival at Critical care and Emergency Department of our hospital. The ECG of the patient showed ventricular fibrillation. He was resuscitated successfully 26 minutes after cardiopulmonary arrest. Emergency coronary angiography revealed that LAD just proximal was totally occluded and LCx just proximal was 90% stenosed. As he was still in the state of shock after resuscitation, emergency CABG was performed to LAD and LCx using saphenous vein grafts. The post operative course was uneventful. The patient has resumed a normal and active life-style as a deput principal of a high school one year after operation.

Cardiopulmonary Resuscitation↗

[Disadvantages of "Gelseal graft" as a vascular prosthesis].

In clinical use, the Gelseal Triaxial graft have been shown to have several problems, such as pyrexia, pleural effusion and seroma formation around the graft. To investigate the cause of these complications, we examined mechanical and biological properties of the graft. The water permeability was found to be 0 ml at 120 mmHg in an in vitro study. Scanning electron microscopical observation revealed that gelatin in the graft wall was not uniform and easily detached from the luminal surface. The amount of impregnated gelatin in the graft was found to be 6.73 mg/cm2. In addition, this graft contained 297 and 73 pg endotoxin in extract/g of graft wt at 25 degrees C 72 hrs as assessed by Toxicolor and Endospecy pyrogen tests, respectively. The grafts were implanted in the descending aorta of 8 dogs for 2 weeks in an animal study. Three out of 8 animals died of graft occlusion. Both macroscopic and microscopic evaluations of the explants from 5 dogs showed that neither fibroblasts nor capillary blood vessels had infiltrated in some area of the graft wall. Serous fluid was found to be retained between the graft and the surrounding host tissue in three cases. These results indicated that the Gelseal graft was easy to implant due to zero porosity, but the coated gelatin was not clean and gelatin was easily detachable. Hence, the graft would be prone to some complications such as pyrexia, immune response, thromboembolism, seroma, and pleural effusion. One must be aware of the potential disadvantages of the Gelseal grafts before using it in patients.

Animals↗

[A case of endocarditis caused by Candida glabrata].

A 45-year-old diabetic man had aortic valve replacement for Candida glabrata endocarditis. Postoperatively he was treated with fluconazole and amphotericin B. Despite therapy, C. glabrata was isolated from his blood. He collapsed suddenly and died of heart failure 70 days after operation. Autopsy revealed suture line insufficiency and perivalvular leakage. On histologic examination many colonies of fungi were found in the aortic valvular annulus and an embolus to the mesenteric artery.

Aortic Valve↗

[Long-term results of closed mitral commissurotomy--comparative study of closed mitral commissurotomy (CMC), open mitral commissurotomy (OMC) and mitral valve replacement (MVR)].

As the technique of open heart surgery has improved, CMC has been abandoned in favor of OMC and MVR. We evaluated and compared the results of CMC, OMC and MVR. METHOD. Between 1965 and 1978, 141 patients with mitral stenosis (MS) underwent CMC, and late follow-up obtained in 117 (83%) of them (CMC group). Between 1980 and 1989, 72 patients and 37 patients underwent OMC (OMC group) and MVR (MVR group), respectively. Cumulative follow-up periods were 1982, 632 and 200 patient-years in the CMC, OMC and MVR groups, respectively. RESULTS. (1) Survival rate; In the CMC group there were 2 operative deaths due to severe mitral regurgitation (MR). There were 17 late deaths, due to reoperations in 4 patients, cerebral infarction in 4 patients, congestive heart failure in 3 patients, myocardial infarction in 2 patients and unknown causes in 4 patients. The survival rate was 95%, 91% and 86% at 5, 10 and 15 years, respectively, in the CMC group. In the OMC and MVR groups there was no death. (2) The event free rate was 89%, 79% and 58% at 5, 10 and 15 years, respectively, in the CMC group, 97% and 97% at 5 and 10 years in the OMC group, and 95% and 90% at 4 and 5 years in the MVR group. (3) Reoperations; In the CMC group of 40 patients (34%) required reoperations in an average of 10.4 years after the initial operation, due to re-MS in 22 patients, MR in 10 patients and MRS in the 8 patients. Reoperative findings consisted of clefts in the mitral leaflets in 7 patients. There were pulmonary hypertension in 15 patients and tricuspid regurgitation in 22 patients. Fourteen patients underwent tricuspid anuloplasty and one patient underwent a tricuspid valve replacement. In the OMC group one patient required a reoperation due to MR; in the MVR group one patient required a reoperation due to a thrombosed valve. CONCLUSION. In the CMC group the survival rate and the event free rate were lower, and the rate of reoperation was higher than in the other two groups.

Adult↗

[A case of mitral regurgitation caused by total rupture of the posterior papillary muscle after acute myocardial infarction].

We observed a case of severe mitral regurgitation caused by total rupture of the posterior papillary muscle 13 days after acute myocardial infarction. The patient was a 76-year-old man who suddenly felt anterior chest pain. He was admitted to another hospital with the diagnosis of acute myocardial infarction. Electrocardiogram suggested a posterior infarction. He did well during the first 12 days of hospitalization, but at noon on the 13th day he developed anterior chest pain and dyspnea. Echocardiography demonstrated rupture of the posterior papillary muscle. He was subsequently transferred to our hospital with acute heart failure. He was initially treated with an intra-aortic balloon pump. Cardiac catheterization demonstrated 99% stenosis of segment 2 of the right coronary artery and mitral regurgitation, Sellers' stage IV. Intraoperative findings included total rupture of the posterior papillary muscle. Mitral valve replacement was performed using a Carbomedics prosthetic valve. The patient was discharged 53 days after surgery without heart failure or angina pectoris. This case represents the 6th successful operation of total papillary muscle rupture in Japan.

Aged↗