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Biomedical subjects

M Hayakawa

Publications and source records attributed to M Hayakawa.

At least 145 records · Page 8Linked to original sources

[A case of renal cell carcinoma with synchronous contralateral adrenal metastasis].

A 73-year-old female visited our department with right incidentally-found renal tumor, which was revealed by follow-up computed tomography (CT) on an annual physical check-up. CT also showed a left adrenal mass that was 4 cm. Further evaluation suggested right renal cell carcinoma and left adrenal metastasis. The patient, therefore, underwent right-adrenal-gland-sparing radical nephrectomy and left adrenalectomy. The pathology report indicated renal cell carcinoma with contralateral adrenal metastasis. A case of contralateral adrenal metastasis from renal cell carcinoma is not common clinically. Furthermore, whether ipsilateral adrenalectomy should be performed in such a case is still controversial at this stage.

Adrenal Gland Neoplasms↗

Hemofiltration removes bradykinin generated in the priming blood in cardiopulmonary bypass during circulation.

After induction of hemofiltration for the hemic prime of a cardiopulmonary bypass, the initial drop in blood pressure disappears, and postoperative edema rarely occurs. We have suspected that bradykinin, a strong vasodilator generated through the activation of factor XII, prekallikrein, and high molecular weight kininogen was removed by ultrafiltration. We examined the changes in the activities of plasma-factor XII, prekallikrein, high molecular weight kininogen and in the levels of bradykinin in the priming blood using red cell concentrates before and after hemofiltration, and evaluated the effectiveness of hemofiltration. Ten circuits were used, and ten sets of blood samples were collected from red cell concentrates, the priming blood before hemofiltration, after hemofiltration, and the filtrate. During circulation in the circuit, factor XII, prekallikrein and high molecular weight kininogen were completely consumed and a large amount of bradykinin was generated, but it was filtered well by ultrafiltration. Factor XII, prekallikrein and high molecular weight kininogen could be activated through the dilution of red cell concentrates during the priming and contact with the circuits. Because bradykinin is the most potent vasodilator, increasing microvascular permeability and relating to several other inflammatory mediators, the removal of bradykinin generated from factor XII, prekallikrein and high molecular weight kininogen is very significant in the prevention of non-specific inflammatory reactions during and after open-heart surgery.

Bradykinin↗

[Severe pulmonary hypertension due to mitral regurgitation without overt sign of congestive heart failure: a case report].

A 49-year-old man was found to have a heart murmur at a local hospital and was referred to our hospital for further examination. Although he had no signs of congestive heart failure, echocardiography and cardiac catheterization showed severe pulmonary hypertension caused by severe mitral regurgitation. Mitral valve replacement was performed, followed by reduction of pulmonary artery pressure. This patient had an unusual combination of no signs of lung congestion despite severe mitral regurgitation with pulmonary hypertension.

Echocardiography↗

[Intraperitoneal dissemination of testicular tumor: a case report].

A 42-year-old male presented with bilateral scrotal swelling and sense of abdominal fullness. Ultrasonography and computed tomographic (CT) scan showed right testicular tumor, left scrotal hydrocele and excessive ascites, but no distant metastases. The serum lactic acid dehydrogenase (LDH) value was as high as 4,060 IU/L and beta human chorionic gonadotropin (hCG) value was 4.0 ng/ml while alpha fetoprotein (AFP) value was within the normal range. Right high orchiectomy was performed as well as the ascites and the left scrotal fluid sampling. Histological examinations revealed anaplastic seminoma in the right testis, and similar cells were found in the ascites and the left scrotal fluid. The patient received three courses of BEP chemotherapy consisting of bleomycin, VP-16 and cisplatin. The ascites and tumor markers (LDH and beta hCG) decreased markedly. Intraperitoneal dissemination of the tumor cells seems to be caused by invasion along the right spermatic cord, but the route of dissemination into the left hydrocele fluid is not known. To the best of our knowledge, this is the first case report of testicular tumor that showed intraperitoneal dissemination without any evidence of metastasis to the lymph nodes or distant organs.

Adult↗

[Outcomes of 50 leukemia patients who received bone marrow transplants from unrelated donors].

Fifty leukemia patients were given bone marrow transplants (BMTs) from unrelated donors at Meitetsu Hospital. We studied the outcomes of their transplants from two perspectives: leukemia disease stage and acute graft versus host disease (GVHD). The probability of disease-free survival for standard-risk, high-risk, and super-high risk patients was 65%, 29%, and 8%, respectively. The main causes of death were septicemia, cardiac and renal failure, and relapse of leukemia in the high- and super-high risk patients, and grade III-IV acute GVHD in the standard-risk patients. The incidence of grade II-IV and grade III-IV acute GVHD was 32% and 17%, respectively. All 7 patients in whom grade III-IV severe acute GVHD developed died. We conclude that better control of acute GVHD and treatment of early stage complications are clearly important to improving the outcome of BMTs from unrelated donors, especially for high and super-high risk patients.

Acute Disease↗

Purification and characterization of agarases from a marine bacterium, Vibrio sp. PO-303.

A marine bacterium, Vibrio sp. PO-303, produced three kinds of extracellular agarases. These enzymes were purified to homogeneity by ammonium sulfate precipitation and successive column chromatographies. The molecular masses of agarase-a, -b, and -c were estimated to be 87.5, 115, and 57 kDa by SDS-PAGE with isoelectric point of 6.6, 3.4, and 8.4, respectively. These enzymes had maximal activity at pH 6.5-7.5 and at around 38-55 degreesC. They differed in their sequences at the amino termini of the protein chains. All enzymes were inhibited completely by Hg2+. Ag+, Cu2+, and Zn2+ strongly inhibited agarase-a and -c compared with agarase-b, and the activity of agarase-c fell wide by Al3+, Fe3+, and EDTA. Agarase-a hydrolyzed agarose to give neoagarotetraose and -hexaose as predominant products, but could not cleave neoagarotetraose. The main hydrolysis products of agarase-b were neoagarobiose from agarose and neoagarooligosaccharides more than dimer. Agarase-c could not cleave neoagarohexaose.

Journal Article↗

Migration activity of microglia and macrophages into rat brain.

We examined the entry of intra-arterially injected microglia and macrophages into the brain using a rat muscle graft model to compare their respective abilities to invade the brain parenchyma. Isolated microglia without any activation treatment entered into the brain with or without the muscle graft, while macrophages activated by phorbol 12-myristate-13-acetate (PMA) entered the brain only in the presence of the muscle graft. These results suggest that microglia have a higher affinity for the brain than macrophages.

Animals↗

The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation.

Recently we purified a 900 kDa cytokine-responsive IkappaB kinase complex (IKK) and molecularly cloned one of its subunits, IKKalpha, a serine kinase. We now describe the molecular cloning and characterization of IKKbeta, a second subunit of the IKK complex. IKKbeta is 50% identical to IKKalpha and like it contains a kinase domain, a leucine zipper, and a helix-loop-helix. Although IKKalpha and IKKbeta can undergo homotypic interaction, they also interact with each other and the functional IKK complex contains both subunits. The catalytic activities of both IKKalpha and IKKbeta make essential contributions to IkappaB phosphorylation and NF-kappaB activation. While the interactions between IKKalpha and IKKbeta may be mediated through their leucine zipper motifs, their helix-loop-helix motifs may be involved in interactions with essential regulatory subunits.

Amino Acid Sequence↗

A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB.

Nuclear transcription factors of the NF-kappaB/Rel family are inhibited by IkappaB proteins, which inactivate NF-kappaB by trapping it in the cell cytoplasm. Phosphorylation of IkappaBs marks them out for destruction, thereby relieving their inhibitory effect on NF-kappaB. A cytokine-activated protein kinase complex, IKK (for IkappaB kinase), has now been purified that phosphorylates IkappaBs on the sites that trigger their degradation. A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation.

Amino Acid Sequence↗

Phospholipase A2 is necessary for tumor necrosis factor alpha-induced ceramide generation in L929 cells.

The role of cytosolic phospholipase A2 (cPLA2) in the regulation of ceramide formation was examined in a cell line (L929) responsive to the cytotoxic action of tumor necrosis factor alpha (TNFalpha). In L929 cells, the addition of TNFalpha resulted in the release of arachidonate, which was followed by a prolonged accumulation of ceramide occurring over 5-12 h and reaching 250% over base line. The formation of ceramide was accompanied by the hydrolysis of sphingomyelin and the activation of three distinct sphingomyelinases (neutral Mg2+-dependent, neutral Mg2+-independent, and acidic enzymes). The variant cell line C12, which lacks cPLA2, is resistant to the cytotoxic action of TNFalpha. TNFalpha was able to activate nuclear factor kappaB in both the wild-type L929 cells and the C12 cells. However, TNFalpha was unable to cause the release of arachidonate or the accumulation of ceramide in C12 cells. C6-ceramide overcame the resistance to TNFalpha and caused cell death in C12 cells to a level similar to that in L929 cells. The introduction of the cPLA2 gene into C12 cells resulted in partial restoration of TNFalpha-induced arachidonate release, ceramide accumulation, and cytotoxicity. This study suggests that cPLA2 is a necessary component in the pathways leading to ceramide accumulation and cell death.

Animals↗

B7-1-transfected tumor vaccine counteracts chemotherapy-induced immunosuppression and prolongs the survival of rats bearing highly metastatic osteosarcoma cells.

To investigate the therapeutic efficacy of B7-1-expressing tumor vaccine on metastatic osteosarcoma, we introduced mouse B7-1 cDNA into a rat osteosarcoma cell line, MSK-8G. Flow cytometric analysis confirmed that the transfectants designated as B7-1-8G 10-1 and B7-1-8G 15-5 stably expressed B7-1 molecules on the cell surface. B7-1 transfectants were not only rejected by immunocompetent F344 rats but also conferred systemic immunity that protected against challenge with B7-negative parental osteosarcoma cells. In contrast, T-cell-deficient nude rats failed to reject B7-1 transfectants, indicating that T cells play a major role in the development of systemic immunity. We then conducted experimental therapies using irradiated B7-1-transfected tumor vaccine and methotrexate in an orthotopic implantation model. B7-1-transfected tumor vaccine significantly reduced the number of pulmonary metastatic nodules. Moreover, the combination of methotrexate and tumor vaccine further decreased the number of pulmonary metastatic nodules. Most important, the combined therapy with methotrexate and tumor vaccine resulted in a tumor-free condition as judged by the histopathological absence of tumors and survival of rats for more than 180 days. Furthermore, B7-1-transfected tumor vaccine could counteract the immunosuppressive effect of methotrexate. These findings strongly suggest that the B7-1-transfected tumor vaccine may be of clinical value for patients with metastatic osteosarcoma who exhibit immunosuppression due to chemotherapy.

Animals↗

Fragile mitochondrial DNA: the missing link in the apoptotic neuronal cell death in Parkinson's disease.

The oxidative stress theory, the mitochondrial (mt) hypothesis, and the apoptosis hypothesis are proposed as the cause of neuronal cell death in Parkinson's disease (PD). However, the direct link between them has remained unknown. Recently, the mt control of nuclear apoptosis is documented that collapse of mt transmembrane potential due to energy crisis leads to release of apoptotic protease activating-factors into cytosol and subsequently nuclear DNA fragmentation. However, an endogenous factor responsible for the energy crisis under physiological conditions is missing. Here we report the missing factor as that mtDNA in the striatum of a parkinsonian patient fragments into 134 types of deleted pieces, being detected by the total detection system for mtDNA deletion. The system has documented that the mtDNA is extremely susceptible to hydroxyl radical damage, hence to oxidative stress, enough to cause the cellular energy crisis. The extensive fragility of mtDNA in brain stem could link the oxidative stress up with the apoptotic neuronal cell-death of PD.

Adolescent↗

A hemizygous A to CC base change of the CHM gene causing choroideremia associated with pinealoma.

BACKGROUND: Although mutations of the CHM gene have been reported in the Caucasian patients with choroideremia, there have been no such reports in non-Caucasian patients. We analyzed the CHM gene in a Japanese patient with choroideremia associated with pinealoma. METHODS: The method for screening was a nonradioisotopic modification of single-strand conformation polymorphism (SSCP) analysis. The PCR products from the patient and the carrier were screened and directly sequenced using an automated DNA sequencer. The PCR product of the carrier was also subcloned into a vector and the subcloned products were sequenced. RESULTS: SSCP analysis showed an identical abnormal band shift in the patient and the carrier. Direct sequence analysis showed a hemizygous A to CC mutation at nucleotide 1608 of the CHM gene in the patient, suspected to result in the absence or truncation of the predicted CHM protein. The sequence using both the PCR product and the subcloned DNA of the carrier showed both wild-type and mutant bands indicating a heterozygote. CONCLUSION: The hemizygous mutation was detected in a patient and the heterozygous pattern in his mother, the carrier, suggesting that this mutation caused the disease.

Adaptor Proteins, Signal Transducing↗

A transcrista galli, translamina terminalis approach for highly placed basilar bifurcation aneurysms.

Surgery for highly placed basilar bifurcation aneurysms is one of the most difficult operations in neurosurgery. Specific surgical techniques have been developed including the temporopolar, zygomatic, transzygomatic subtemporal, transclinoid trans-seller transcavernous, and trans third ventricular approaches. The authors present some technical advances which have been developed for the transcristagalli translamina terminalis approach for the treatment of this aneurysm.

Aged↗

Budd-Chiari syndrome resulting from intrahepatic IVC compression secondary to blunt hepatic trauma.

Hepatic venous outflow obstruction (Budd-Chiari syndrome)is a rare sequel of abdominal trauma. Three cases of Budd-Chiari syndrome resulting from obstruction to the intrahepatic IVC by liver injury are reported. The CT findings include extrinsic compression of the intrahepatic inferior vena cava (IVC) by intraparenchymal and/or subcapsular hepatic haematoma, non-visualization or narrowing of one or more main hepatic veins with intravenous contrast-enhanced CT, and accumulation of low attenuation ascites. This entity should be distinguished from intraperitoneal bile leak or hemoperitoneum associated with major liver injury with which it could be confused. Decompression of the IVC and hepatic veins by surgical or percutaneous drainage of intrahepatic or subcapsular hematoma was curative in two of the three patients.

Adult↗

H2O2-derived free radicals treated fibronectin substratum reduces the bone nodule formation of rat calvarial osteoblast.

Fibronectin (FN) is involved in various cellular activities such as adhesion, proliferation and migration as a substratum. Since the metabolic turnover of FN is much slower than other cellular components, it may be affected by the oxygen free radicals produced in the aging process. However, the effect of oxygen free radicals on FN as substratum in bone formation has not been well characterized. The objective of this study was to examine the effect on the bone forming activity of osteoblasts using an oxygen free radical treated FN substratum in vitro (H2O2-Cu2+system). SDS-PAGE, Western blotting and immuno-blotting analysis revealed that FN was degradated and/or modified by H2O2-Cu2+ (.OH) treatment. Bone nodule formation per well was examined for total number, total area and area per nodule, which data were then compared between non-coated and FN-coated, and between FN-coated and .OH treated FN-coated. Bone nodule formation in the FN-coated was significantly greater than in the non-coated. Furthermore, bone nodule formation in .OH treated FN-coated was significantly less than that of FN-coated. These findings suggested that FN plays important roles in osteoblast activity and that FN substratum damaged by the oxygen free radicals produced by the aging process may cause decline of bone nodule formation through inhibition of the proliferation, differentiation and calcification processes.

Aging↗

Operation on high-lying basilar bifurcation aneurysms.

BACKGROUND: The surgical approach to basilar bifurcation aneurysms is a complicated procedure, especially with those located high in the interpeduncular cistern. We have developed a surgical approach to these aneurysms involving only a small anterior temporal craniotomy and detachment of the zygomatic arch. METHODS: The skin incision is placed 5 mm below the inferior border of the zygomatic arch and 5 mm anterior to the tragus, extending on towards the eyebrow but well within the hairline. The zygomatic arch is detached on either side followed by a small temporal craniotomy exposing the anterior temporal lobe. The temporal lobe is retracted and the internal carotid artery, posterior cerebral artery, posterior communicating artery, and inferior aspect of the optic chiasma are exposed. RESULTS: We have performed a transzygomatic anterior subtemporal approach in 12 patients with high-lying basilar bifurcation aneurysm. Eight patients demonstrated a good recovery as per the Glasgow outcome scale and four patients had a moderate disability that correlated with a poor WFNS grade preoperatively. One patient had an oculomotor palsy and another experienced a small infarction postoperatively. CONCLUSIONS: This approach is a suitable procedure for high-lying basilar bifurcation aneurysms in the interpeduncular cistern and 1.2 cm above the clinoid process.

Aged↗

The level of erythrocyte aldose reductase is associated with the severity of diabetic retinopathy.

To examine whether the level of erythrocyte aldose reductase is a risk factor for the severity of diabetic retinopathy, the enzyme level in 97 non-insulin-dependent diabetes mellitus (NIDDM) patients was measured by the two-site enzyme-linked immunosorbent assay. Based on the results of fundus photography and biomicroscopy, the severity of retinopathy was classified among NIDDM patients of more than 10 years. The level of erythrocyte aldose reductase was significantly higher in the patients with active proliferative retinopathy than in those with nonproliferative or quiescent proliferative retinopathy. Multivariate logistic regression analysis demonstrated that the level of erythrocyte aldose reductase was an independent risk factor for active proliferative retinopathy (odds ratio, 1.28; 95% confidence interval, 1.01-1.61). The results suggest that a high level of erythrocyte aldose reductase in NIDDM patients may affect the prognosis of diabetic retinopathy. Patients with high enzyme levels would need to be closely followed up in the management of the retinal complication.

Adult↗