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Biomedical subjects

H Osawa

Publications and source records attributed to H Osawa.

At least 73 records · Page 4Linked to original sources

Identification of proteins that interact with NF-YA.

We used the yeast two-hybrid system to show that the serum response factor (SRF) and zinc-fingers and homeobox 1 (ZHXI) proteins interact with the A subunit of nuclear factor-Y (NF-YA). GST pulldown assays revealed that both proteins interact specifically with NF-YA in vitro. Amino acids located between 272 and 564, a region that contains two homeodomains, are required for the interaction of ZHX1 with NF-YA. Two different domains of NF-YA, a glutamine-rich region and a serine/threonine-rich region, are necessary for the interactions with ZHX1 and SRF, respectively.

CCAAT-Binding Factor↗

Human ZHX1: cloning, chromosomal location, and interaction with transcription factor NF-Y.

NF-YA, B, and C comprise the heterotrimeric transcription factor known as nuclear factor Y (NF-Y) or CCAAT-binding protein (CBF). NF-Y binds many CCAAT and Y box (an inverted CCAAT box, ATTGG) elements. Mutations of these elements that disrupt the binding of NF-Y result in decreased transcription from various tissue-specific and inducible promoters. We employed a yeast two-hybrid system to screen a human liver cDNA library in an effort to isolate proteins that interact with NF-Y and that may play a role in tissue-specific or hormone-inducible promoter activity. Using a fragment of the NF-YA subunit as bait we isolated a cDNA that encodes most of the open reading frame of the human zinc fingers and homeobox 1 (ZHX1) protein. The complete open reading frame was subsequently isolated and found to encode a protein of 873 amino acids that contains two zinc fingers and five homeodomain motifs. Northern blot analysis of poly(A)(+) RNA isolated from various tissues revealed two major ZHX1 transcripts of about 4.5 and 5 kilobases. Both transcripts were expressed ubiquitously, although the 5-kilobase transcript is of greater abundance in most tissues examined. The human ZHX1 gene is located on chromosome 8q, between markers CHCL.GATA50B06 and CHLC. GATA7G07.

Amino Acid Sequence↗

Saccular descending thoracic aortic aneurysm with dysphagia.

A 76 year old woman had suffered from chest pain, back pain, and dysphagia for 8 months. She was diagnosed as having a thoracic aortic aneurysm by chest X-ray and chest enhanced computed tomography. Simultaneously, severe dysphagia developed. Chest enhanced computed tomography and chest aortic aortography at our hospital demonstrated a saccular descending thoracic aortic aneurysm. Esophagography demonstrated that the esophagus was compressed by the aneurysm; therefore, a graft replacement for the saccular descending thoracic aortic aneurysm was performed on February 17th, 1998. A left sided 6th intercostal approach was made, and graft replacement for the aneurysm using a 22 mm Hemashield prosthetic graft was performed under temporary bypass from the thoracic aorta just distal to the left subclavian artery and to the left femoral artery. The postoperative course was uneventful, the severe dysphagia improved dramatically, but a pleural effusion of 1000 ml collected 3 weeks after the operation. Surgical cases of saccular descending thoracic aortic aneurysm with dysphagia are rare, and with this in mind, we report this case to the the medical literature.

Aged↗

Involvement of the serotonergic neuronal system in phencyclidine-induced place aversion in rats.

The possible involvement of the serotonergic neuronal system in aversive motivation produced by phencyclidine [1-(1-phenylcyclohexyl)piperidine; PCP] was investigated using a place-conditioning paradigm in rats. PCP (4 mg/kg, i.p.) produced place aversion in this task as reported previously (Kitaichi K, Noda Y, Hasegawa T, Furukawa H, Nabeshima T. Acute phencyclidine induces aversion, but repeated phencyclidine induces preference in the place conditioning test in rats. Eur J Pharmacol 1996;318:7-9). The blockade of serotonin2A (5-HT2A) receptors using the antagonist ritanserin (3 and 10 mg/kg, p.o.) significantly attenuated this aversive property of PCP whereas lesions of serotonergic neurons using 5,7-dihydroxytryptamine (5,7-DHT, 100 microg/animal, i.c.v.) failed to affect it. Repeated PCP treatment (10 mg/kg, i.p. for 14 days), which is enough to diminish the stereotyped 5-HT2A receptor-mediated head-twitch behavior, also decreased the place aversion. These results suggest that the serotonergic neuronal system, specifically the 5-HT2A receptor, may play a critical role in producing PCP-induced place aversion.

5,7-Dihydroxytryptamine↗

A complete deficiency of coagulation factor XIII A-subunit due to a novel compound heterozygote of Ser 413 Leu missense and an nt 389 (ins G) frameshift mutation.

Coagulation factor XIII consists of two A- and two B-subunits, and either gene mutation can cause a complete deficiency. In a newborn patient with persistent bleeding from the umbilical cord stump, the plasma A-subunit protein was not detectable. Direct PCR sequencing revealed an nt 389 (ins G) frameshift mutation in exon 4 resulting in a new stop codon and a Ser 413 Leu missense mutation in exon 10 in either allele. His mother and father were heterozygous for the nt 389 (ins G) and the Ser 413 Leu, respectively, with about 50% reduction of the plasma A-subunit proteins. In all family members examined only those with either mutation showed the reduced subunit A protein levels. Thus, this complete deficiency of factor XIII was due to a novel compound heterozygous mutation in the A-subunit gene.

DNA Transposable Elements↗

Thrombin stimulates synthesis of type IV collagen and tissue inhibitor of metalloproteinases-1 by cultured human mesangial cells.

Glomerular accumulation of extracellular matrix (ECM) is the common pathologic feature following glomerular injury, and the alteration in the synthesis and degradation of ECM may be involved in the glomerular accumulation of ECM. Glomerular fibrin formation occurs in various forms of human and experimental glomerulonephritis, and it may play an important role in progressive glomerular injury. Thrombin, a multifunctional serine proteinase that is generated at the site of vascular injury, has central functions in hemostasis and it also shows various biologic effects. In this study, it is hypothesized that thrombin may alter the production and the degradation of type IV collagen, which is an important component of ECM in the glomeruli. Human mesangial cells (HMC) were cultured, and the levels of type IV collagen, tissue inhibitor of metalloproteinase-1 (TIMP-1), and matrix metalloproteinase-2 (MMP-2) in the culture supernatants were measured by enzyme immunoassay using specific antibodies. MMP-2 activity was also evaluated by zymography using polyacrylamide/ sodium dodecyl sulfate gel-containing gelatin. Thrombin increased the production of type IV collagen and TIMP-1 in a dose-and time-dependent manner, but it did not increase MMP-2. Thrombin also stimulated the gene expressions of the type IV collagen and TIMP-1 in HMC in a dose- and time-dependent manner. Thrombin treated with diisopropylfluorophosphate, a serine proteinase inhibitor, did not show any of these effects. Hirudin, a natural thrombin inhibitor, and anti-transforming growth factor-beta-neutralizing antibody inhibited the stimulating effect of thrombin. These findings suggest that thrombin may contribute to the excessive accumulation of ECM and progression of glomerulosclerosis through an increase of type IV collagen production and a decreased matrix degradation presumably via a transforming growth factor-beta-dependent mechanism.

Cells, Cultured↗

Improvement in insulin resistance and the restoration of reduced phosphodiesterase 3B gene expression by pioglitazone in adipose tissue of obese diabetic KKAy mice.

Phosphodiesterase (PDE) 3B is a key enzyme in the mediation of the antilipolytic action of insulin in adipocytes, and activation of this molecule results in a reduced output of free fatty acids (FFAs). An elevation of serum FFAs is known to cause insulin resistance in skeletal muscle and liver, which could be the primary cause of type 2 diabetes. To elucidate whether PDE3B is involved in this disease, we examined the PDE3B gene expression in epididymal fat tissues of obese insulin-resistant diabetic KKAy mice. We also examined the effect of an insulin-sensitizing drug, pioglitazone, on this gene expression. In adipose tissue of KKAy mice, PDE3B mRNA and its corresponding protein were reduced to 48 and 43% of those in C57BL/6J control mice. Basal and insulin-stimulated membrane-bound PDE activities were also decreased to 50 and 36% of those in the controls, respectively. Pioglitazone increased both PDE3B mRNA and protein levels by 1.8-fold of those in untreated KKAy mice. Basal and insulin-induced membrane-bound PDE activities were also increased by 1.6- and 2.0-fold, respectively. Pioglitazone reduced the elevated levels of serum insulin, glucose, FFAs, and triglyceride in KKAy mice. Thus, the reduced PDE3B gene expression in adipose tissues could be the primary event in the development of insulin resistance in KKAy mice, which was improved by pioglitazone possibly because of the restoration of the reduced PDE3B gene expression.

3',5'-Cyclic-AMP Phosphodiesterases↗

Ruptured distal aortic arch aneurysm associated with arteriosclerosis obliterans.

A 73-year-old man with a ruptured distal aortic arch aneurysm into the pericardial space, mediastinum and right pleural space is described. The patient underwent a successful total aortic arch replacement using deep hypothermia, systemic circulatory arrest and selective cerebral perfusion. Extracorporeal circulation was established with right axillar arterial perfusion due to arteriosclerosis obliterans (ASO). Presentation and management are discussed.

Aged↗

[Mitral valve annuloplasty with U-shaped flexible band using Duran ring].

To preserve the physiologic function and correct annular dilatation, U-shaped flexible band was applied for mitral valve annuloplasty in 6 cases. U-shaped flexible band was made by cutting Duran ring to the proper length of posterior annulus using Carpentier-Edwards ring sizer. Echocardiographic mitral regurgitation decreased from 3.8 +/- 0.4 to 0.7 +/- 0.5 after repair. All patients discharged without any complications. This annuloplasty method is effective for mitral insufficiency.

Aged↗

[Complete disruption of thoracic descending aorta without widening of the pseudoaneurysm].

A 41-year-old male was transported to our emergency room 25 minutes after blunt chest trauma. The chest X-ray film and CT scanning demonstrated left pulmonary atelectasis, hemothorax, and widening of mediastinum possibly due to hematoma. Hundred and fifty minutes after arrival to the hospital, we were rush to bring him to the operation theater suspecting serious injury of the thoracic organs in association with bleeding from left thoracic drainage tube without detection of the aortic rupture. The left standard thoracotomy disclosed no injury of the left lung, good continuity and no dilatation of the thoracic descending aorta. But visual blood flow observed through the adventitia of the aortic isthmus led us to the final diagnosis of the aortic rupture. After aortic clamping, the intima of the injured aorta was found to be completely disrupted for a length of 6 cm and was repaired with a vascular prosthesis under the partial cardiopulmonary bypass using a centrifugal pump. His postoperative course was uneventful. We reported a case of complete circumferential aortic rupture without widening of the pseudoaneurysm in the acute stage of the disease.

Adult↗

[Development of a serum lipoprotein A-I immunoassay method].

We developed an immunoturbidimetric assay method for lipoprotein A-I by treating sera with an anti-apo lipoprotein A-II and A-I antibody sequentially. The assay is sensitive to detect lipoprotein A-I as little as 155 mg/l with good precision. There was a good correlation in the level of serum lipoprotein A-I between the present assay and a conventional differential electroimmunoassay on ready-to-use plates (r = 0.947; p < 0.001). Reference intervals in normal healthy adults (n = 109) ranged from 284 to 736 mg/l. The values were significantly lower in patients with coronary artery disease than in normal subjects (p < 0.001). The present assay can be useful to analyze patho-physiologic events in various lipid disorders.

Adult↗

[Multi-drug resistant breast cancer responding to chemotherapy with docetaxel (taxotere: TXT)].

The patient was a fifty-five year old female who had stage IVb advanced breast cancer with hypoxia due to bilateral pulmonary metastases and lymphangitis. The cancer was adriamycin (ADM) and multi-drug resistant. We administered docetaxel (taxotere: TXT) 60 mg/m2 every 3 weeks. After 2 courses, the pulmonary metastases had become remarkably reduced in size and hypoxia was reduced and performance status (PS) improved. Major toxic defects were grade-4 neutropenia and hair loss. The patient could be discharged from the hospital without O2 inhalation and enjoyed a better quality of life (QOL). This chemotherapy is thought to be effective against ADM and multi-drug resistant breast cancer.

Antineoplastic Agents, Phytogenic↗

[Surgical treatment of 2 cases of irradiation induced constrictive pericarditis].

A 72-years-old man underwent radiation therapy (62 Gy) for esophageal carcinoma. Twelve months later, symptoms of heart failure such as syncope, cough and hepatomegaly manifested. On catheter study, a dip and plateau pattern of right ventricular pressure curve was evident. Pericardiectomy without extracorporeal circulation was performed. Operative findings and pathological results were compatible with radiation-induced constrictive pericarditis. He recovered from the heart failure, and has been doing well 3 months after the surgery. A 54-years-old man underwent thymectomy for malignant thymoma. He underwent a radiation therapy (52 Gy) postoperatively. After 12 months from the irradiation, syncope and dyspnea manifested. On catheter study, a dip and plateau pattern of right ventricular pressure curve was observed. Pericardiectomy with extracorporeal circulation was performed. He recovered from the heart failure after pericardiectomy, however he died of radiation-induced pneumonitis 6 months later.

Aged↗

Mitogen-activated protein kinase and p70 ribosomal protein S6 kinase are not involved in the insulin-dependent stimulation of cAMP phosphodiesterase kinase in rat adipocytes.

To elucidate the mechanism of anti-lipolytic action of insulin in rat epididymal adipocytes, we explored the potential mechanism that might be involved in the hormone-dependent stimulation of cAMP phosphodiesterase (PDE) kinase. PDE kinase was assayed in a cell-free system. Both wortmannin and LY294002, highly specific inhibitors of phosphatidylinositol 3-kinase, almost completely blocked the hormonal effect not only on PDE kinase but also on mitogen-activated protein (MAP) kinase. Neither PD98059, a specific inhibitor of MAP kinase, nor rapamycin, a potent inhibitor of insulin-dependent stimulation of p70 ribosomal protein S6 kinase (p70S6K), had inhibitory effect on that of PDE kinase. These results are consistent with the view that (i) insulin-activated PDE kinase as well as MAP kinase and p70S6K are localized downstream of phosphatidylinositol 3-kinase, (ii) PDE kinase is distinct from either MAP kinase or p70S6K and (iii) PDE kinase does not exist downstream of either MAP kinase or p70S6K. It is suggested that PDE kinase and MAP kinase or p70S6K may be localized in separate branches of the cascade of insulin action. The branching point of the cascade could be either at or below the level of phosphatidylinositol 3-kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Surgical stabilization of multiple rib fractures successfully achieved with the use of long metalic plates].

Surgical stabilization of multiple rib fractures in 5 male patients was successfully achieved with the use of orthopedic A-O metalic plates, which are called reconstruction plates. In each patient, we prevented deformity of the rib cage and flail chest which frequently occurs after multiple rib fractures. Three of these patients received emergency operations because of severe hemopneumothorax and flail chest due to crushing injuries to the chest. They were treated by the standard thoracotomy, hemostasis of intrapleural bleeding, and stabilization of fractured ribs with reconstruction plates, in addition two of the patients underwent a single lobectomy to control the pulmonary hemorrhage. Another two patients were treated with mechanical ventilation and closed-tube thoracotomy following the chest trauma because their thoracic bleeding from drainage tubes was tolerable. But flail chest and respiratory insufficiency did not improve, in spite of positive controlled ventilation as a mode of internal pneumatic stabilization. Then surgical stabilization of the fractured ribs with these plates was carried out ten to twelve days after the accidents in each case. All patients tolerated the surgical procedures well and were successfully removed from the respirator, demonstrating complete stability of the chest wall. The long metal reconstruction plates with many perforations were very useful for the external fixation of segmentary fractured ribs as an external brace. This was because they were long enough to cover the whole length of the fractured ribs and moderately soft enough to be appropriately bent or twisted by hand at the time of operation. Moreover a number of holes in it allowed the suture to pass through the plate and rib, avoiding displacement of the prosthesis. This is the first report which describes the usefulness of orthopedic reconstruction plates for the stabilization of multiple rib fractures.

Adult↗

Cimetidine reduces impairment of cellular immunity after cardiac operations with cardiopulmonary bypass.

OBJECTIVE: Depressive effects of cardiopulmonary bypass on cell-mediated immune responses may lead to postoperative infectious complications. We previously reported that cimetidine reduced postbypass depression of the cytotoxic activity of natural killer cells. This study evaluated cimetidine as an agent to preserve cellular immunity after cardiac operations. METHODS: In a prospective randomized study, 20 patients were divided into two groups of equal size. Cimetidine-group patients received 400 mg of cimetidine intravenously before bypass and a 33 mg/hr intravenous infusion of cimetidine after the operation, continuing until the fifth postoperative day. Control-group patients received conventional perioperative therapy. Lymphocyte subsets, natural killer cell activity, percentage of CD56+CD16+ (percentage of natural killer cells), and percentage of CD11b+CD8+ (percentage of suppressor T lymphocytes) were measured perioperatively. RESULTS: Although temporary postoperative reductions in percentages of CD3+, CD4+, and CD56+CD16+ cells were observed in both groups, CD8+ percentages on postoperative day 1 and CD11b+CD8+ percentages on postoperative days 1 and 3 in the cimetidine group were significantly lower compared with those in the control group (p = 0.01,p = 0.004, andp = 0.02, respectively). Temporary postoperative reduction of natural killer cell activity was also observed in both groups, but the natural killer cell activity on postoperative day 1 in the cimetidine group (17.1%) was significantly higher (p = 0.02) than that in the control group (8.20%). CONCLUSIONS: Cimetidine counteracts depressive effects of cardiopulmonary bypass on cell-mediated immunity and may possibly reduce postoperative susceptibility to infection.

Antigens, CD↗