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Biomedical subjects

H Mohri

Publications and source records attributed to H Mohri.

At least 163 records · Page 9Linked to original sources

Changes in myocardial beta-adrenergic receptors during acute rejection of heterotopically transplanted rat hearts.

To evaluate changes of the myocardial beta-adrenergic receptors in acute cardiac graft rejection, the density and binding affinity value of the myocardial beta-adrenergic receptors in heterotopically transplanted rat isografts and allografts were analyzed. Hearts from Fisher rat donors were transplanted either to the Fisher rats (isografts) or to Lewis rats (allografts). Histologic examination of the allografts showed mild to moderate rejection on the seventh and fourteenth days and showed severe rejection on the twenty-first day after transplantation. The density values in the allografts and isografts similarly increased significantly (p < 0.05) above the normal level on the seventh and fourteenth days after transplantation. The density in allografts on the twenty-first day decreased significantly (p < 0.05) below the normal level, while that in isografts remained at the normal level. In contrast, the binding affinity value of myocardial beta-adrenergic receptors in both isografts and allografts did not change after transplantation. These results demonstrated that myocardial beta-adrenergic receptors presented upregulation in mild to moderate rejection, whereas these receptors presented downregulation in severe rejection. The data suggested that downregulation of myocardial beta-adrenergic receptors plays a major role in decreased cardiac contractility during severe rejection, but not during mild and moderate rejection.

Abdomen↗

[Adult T-cell leukemia with various pulmonary complications].

A 59-year-old male, born in Wakayama prefecture, was admitted to our hospital because of cervical lymph node swelling, huge mass lesions in both liver and head of the pancreas, and multiple nodular shadows in the left lung. Lymph node biopsy revealed a necrotic lesion containing tuberculous bacilli with no epithelioid cells or giant cells. Adult T-cell leukemia (ATL) was diagnosed by the presence of atypical lymphocytes with a convoluted nucleus and positive anti-ATL antibody. During successful treatment of Mycobacterium tuberculosis with ethambutol, isoniazid and rifampicin, ATL transformed to the blastic phase. The new pulmonary infiltrates improved after treatment with both combination chemotherapy for ATL and antibiotics. However, new infiltrative shadows appeared in both lungs, and were resistant to treatment and the patient died of acute respiratory failure. Histological examination of the lung at autopsy showed interstitial fibrosis with infiltration of leukemic cells and cytomegalovirus infection.

Cytomegalovirus Infections↗

Separation of X- and Y-chromosome-bearing murine sperm by free-flow electrophoresis: evaluation of separation using PCR.

The effectiveness of separation of murine X- and Y-bearing sperm by free-flow electrophoresis was evaluated by the polymerase chain reaction (PCR). The ratio of X- and Y-bearing sperm from cauda epididymis was analyzed before and after free-flow electrophoresis. A Y-chromosome-specific sequence (pY353/B) and an autosomal sequence (myogenin) were used to estimate the ratio between X- and Y-sperm in the separated fractions. Cauda epididymal mice sperm were separated into two peak fractions under the electric field. Each peak fraction contained sperm of normal shape, however, the motility of the sperm was extremely diminished after separation by electrophoresis. DNA was extracted from 10(4) sperm from each fraction and from the unseparated sperm, and Y-chromosome specific PCR was performed. The PCR experiment revealed that fraction No. 16 (the peak near the cathode) was a Y-sperm rich fraction, whereas fraction No. 22 (the peak near the anode) was a Y-sperm poor one. These results suggested that murine X- and Y-sperm could be successfully separated by free-flow electrophoresis. Analysis of the chromosome-specific sequence by PCR was demonstrated to be a direct and adequate method to evaluate the separation of X- and Y-sperm.

Animals↗

[Malignant histiocytosis associated with central neurological symptoms and cerebrospinal fluid involvement].

A 53-year-old woman was admitted with fever and general fatigue in December, 1988. A diagnosis of malignant histiocytosis (MH) was made based on her high level of LDH, thrombocytopenia, mild splenomegaly without systemic lymphadenopathy. There was also bone marrow infiltration large atypical cells and erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual disturbance and left lagophthalmos were recognized in March 1990. These signs indicated central nervous system (CNS) relapse which disappeared after intrathecal methotrexate injection. The same symptoms and signs appeared after another, 5 months. Tumor cells were found not only in the central spinal fluid but also in bone marrow. CNS and bone marrow recurrence were treated with intrathecal methotrexate injection VEPA therapy and cranial irradiation. We diagnosed this case as MH, based on the clinical features which did not include systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement was observed in bone marrow cells. Only one case of CNS infiltration diagnosed when alive has previously been reported in Japan. We report here a very rare case in which by medical treatment CNS infiltrations was improved twice.

Facial Nerve Diseases↗

[Malfunction of prosthetic valves: pathogenesis and diagnostic measure].

Modality of the malfunction of prosthetic valve often reflects the specific features of its design and materials of the prosthesis. During past 17 years, a total of 499 cases of valve replacements were performed in our institute and among them, 50 cases received redo surgery, in which 52 prosthetic valves were replaced due to their malfunctions. Those replaced prosthetic valves were analyzed in terms of their pathogenesis, onset durations and diagnostic methods of each type of malfunction. The malfunctions included hemolytic anemia, thrombosis or tissue overgrowth and tissue failure of bioprostheses. Hemolytic anemia was experienced in 8 cases with Starr-Edwards (S-E) 2320 (n = 7) and Omni-Science (n = 1) both in the aortic position and those prostheses were replaced at 1-9.6 (mean 4.5) postoperative years (POY). The linearized rate of the complication with the S-E 2320 was 3.0%/patient-years (p-y) and its actuarial event free rate was 62% at 11 POY. Operative findings disclosed cloth wear in 5 and perivalvular leakage in 5 cases. Fourteen Hancock (H) and 3 Angell-Shiley (A-S) bioprostheses experienced tissue failure of valves and they were subjected to reoperation at 3.2-10.0 (mean 6.5) POY. The linearized rates were 4.1%/p-y for H and 4.5%/p-y for A-S with actuarial event free rates at 12 POY of 59 and 56%, respectively. Prosthetic valve thrombosis and/or tissue overgrowth were seen in 17 valves at 1.6-15.1 (mean 9.1) POY.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients].

The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered.

Adenocarcinoma↗

[Result of surgical treatment of true or dissected thoracic aneurysm: determinants analysis in operative mortality and morbidity].

Between 1986 and 1990, 69 patients underwent surgery either for thoracic aneurysm (27 patients) or aortic dissection (42 patients). Sixty one patients (88%) survived and 8 patients (12%) died after surgery. Main determinants of deaths in 4 patients with true arch aneurysm were bleeding from the sites of aortic clamping or anastomosis and intraoperative severe LOS. Three patients with acute type A dissection died from bleeding due to clamp injury or myocardial ischemia. The cause of death in the patient with chronic type B dissection was associated with brain damage due to hypoxia developed during left heart bypass. Postoperative cardiac, pulmonary, hepatic and renal functions were analyzed in the operative survivors. Cardiac functions were maintained well in all patients except two patients with chronic type A dissection. Four patients, one with true arch aneurysm, 2 with chronic type A and one with chronic type B dissection, required tracheostomy. The mean of maximum total serum bilirubin exceeded 4 mg/dl in the patients with true arch aneurysm, acute and chronic type A dissection. The level of serum creatinine showed slight increase in all patients but prophylactic peritoneal dialysis was performed in one patient with chronic type A dissection. In conclusion, the cause of deaths in most patients with thoracic aneurysm was due to inappropriate operative techniques and circulatory supports during surgery. Without the complication described above, the patients could tolerate surgery well.

Aged↗

[Further evaluation of GPIb binding domain of vWf by synthetic peptides].

We have already demonstrated that the GPIb binding domain of vWf resided at the regions corresponding to residues 474-488(G10) and 694-708(D5). Moreover, conformational change of vWf was suggested to be important for binding to GPIb. The effect of newly synthetized peptide combining G10 and D5 with lysin(G10-D5) on vWf binding to GPIb and platelet aggregation was studied. All synthetic peptides inhibited both vWf binding to GPIb, ristocetin-induced platelet aggregation and asialo vWf-induced platelet aggregation. G10-D5 possessed the most potent inhibitory activity in the interaction of vWf with GPIb. Only G10-D5 reacted with NMC-4 which recognized the epitope in appropriate conformation of vWf. These results indicate that G10-D5 retains some conformational structure and might be a good tool for anti-thrombotic agent.

Humans↗

Quantitative analysis of pulmonary vascular disease in total anomalous pulmonary venous connection in sixty infants.

A quantitative analysis of small pulmonary arteries, pulmonary veins, and lymphatic vessels was conducted in autopsy cases of total anomalous pulmonary venous connection. The materials were obtained from 60 cases of total anomalous pulmonary venous connection without asplenia or pulmonary stenosis, ages ranging from 2 days to 19 months at the time of death (mean age 2.2 months). Pulmonary arterial pressure had been measured in 32 of these patients before death. Twenty cases of ventricular septal defect with pulmonary hypertension and 15 normal individuals were used as the control group. The mean thickness of the media of small pulmonary arteries and veins was 12.7 and 7.6 microns, respectively, in the total anomalous pulmonary venous connection cases, both values being significantly larger than those for normal and ventricular septal defect cases. No changes in thickness with aging were found. Medial thickness in the arteries and veins was greater in the cases of pulmonary venous obstruction than in those without such obstruction. The medial thickness of small pulmonary arteries in total anomalous pulmonary venous connection cases correlated with increased pulmonary arterial pressure. When the patients with the same pulmonary arterial pressure levels were compared, the medial thickness was always greater in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect. The medial thickness of pulmonary veins was also highly correlated with increased pulmonary arterial pressure in total anomalous pulmonary venous connection. The severity of the intimal lesions was milder in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect, suggesting the protective role of the thickened pulmonary arterial media against development of intimal lesions. Intimal fibrous thickening of pulmonary veins was not seen in the cases of ventricular septal defect, but it was present in 45% of the total anomalous pulmonary venous connection cases. Lymphangiectasia was characteristically present in 62% of the total anomalous pulmonary venous connection cases. Interstitial emphysema was often a complication of lymphangiectasia, and it led to eight postoperative deaths.

Age Factors↗

[Postoperative respiratory dysfunction in patients with Stanford type A aortic dissection].

Between 1986 and 1990, 24 patients with Stanford type A dissection (acute; 14, chronic; 10) underwent surgery through median sternotomy. The patients were divided into two groups by a duration of postoperative ICU stay for respiratory care. Six patients in the long-period group stayed in ICU for more than 15 days and 18 patients in the short-period group stayed for less than 15 days after surgery. Acuity of disease, age, sex, operation time, pump time, aortic clamp time, lowest esophageal temperature, amount of blood transfusion, arch manipulation for cerebral perfusion with or without arch reconstruction, occurrence of phrenic nerve palsy and other postoperative complications, postoperative cardiac, hepatic and renal functions were compared between two groups. Conclusions are as follows: 1) Arch manipulation for cerebral perfusion with or without arch reconstruction, phrenic nerve palsy, other complications (pericardial and pleural fluid accumulation, recurrent nerve palsy, postoperative bleeding and coronary spasm) and high serum creatinine level were main factors for prolonged postoperative ICU stay for respiratory care and 2) arch manipulation in the patients with chronic type A aortic dissection induced high incidence of phrenic nerve palsy.

Adult↗

[Three M-components (IgG kappa, IgA kappa, IgM kappa) in a patient with non-Hodgkin's lymphoma].

Co-existence of three M-components in the serum or urine is rare. A case of non-Hodgkin's lymphoma was associated with three M-components. A 64-year-old woman was referred to our hospital because of M-proteinemia in June, 1989. On admission, serum electrophoresis on cellulose acetate membrane disclosed a triple M-peak. Immunoelectrophoresis showed M-bows for anti-IgG, anti-IgA, anti-IgM and anti-kappa simultaneously. In the urine, kappa type only Bence Jones protein was found. Scanning computed tomography revealed bulky masses in the lower abdomen, and the tumor masses were removed and diagnosed as non-Hodgkin's lymphoma. Immunohistochemical staining with antibodies to each immunoglobulins revealed the cells producing single M-component of each isotype of immunoglobulins. Although surgical removal of tumor caused a marked decrease in M-component especially IgA kappa, consistent presence of plasmacytoid lymphocyte was observed in peripheral blood. Combination therapy with melphalan and procarbazine resulted in disappearance of IgG kappa and IgA kappa from the serum. In January 1990, she achieved partial remission and was discharged. The patient has remained in remission for 16 months.

Antineoplastic Combined Chemotherapy Protocols↗

[Surgical repair of coarctation of the aorta during infancy].

Fourty-six infants less than 1 year of age underwent repair of coarctation of the aorta in our institution between 1972 and 1991. Pathologic types and numbers of patients were simple coarctation (Group 1) in 7 patients, with ventricular septal defects (Group 2) in 22 patients and with complex cardiac anomalies (Group 3) with 17 patients. A patent ductus arteriosus was present in 43 of these patients. Operative technique used were resection and end-to-end anastomosis (RETE) in 30 patients, subclavian flap angioplasty (SFA) in 15 and Blalock-Park operation in one patient. RETE procedures were employed from 1972 until 1980 and SFA procedures were employed between 1981 and 1985. After 1986 RETE procedures were employed again. The operative mortality rates were 0% (0/7) in Group 1, 9.1% (2/22) in Group 2 and 82.3% (14/17) in Group 3. The high mortality rate in Group 3 are thought to be related to severe associated cardiac anomalies. There were no significant differences in the operative mortality and recurrent coarctation rates between RETE and SFA procedures in Group 1 and 2. In patient with a large associated intracardiac shunt (Group 2 and 3) banding of the main pulmonary artery (PAB) was performed with coarctectomy simultaneously. In Group 2 VSD closure and debanding could be done a few months later with excellent results, but in Group 3 primary repair of cardiac anomalies may be worth to try since results of coarctectomy with palliative procedures in these group of patients were poor.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

[Separate perfusion of upper and lower body for ruptured thoracoabdominal aortic aneurysm--a case report].

A case of ruptured thoracoabdominal aortic aneurysm was presented. The patient had emergent replacement of thoracoabdominal aorta with an aid of separate perfusion of upper and lower body. The postoperative course was uneventful. It was suggested that separate perfusion of upper and lower body was useful in the patients who require extensive aortic replacement and who are at substantial risk for spinal cord injury.

Aorta, Abdominal↗

[Myelodysplastic syndrome associated with marked eosinophilia and basophilia].

Myelodysplastic syndrome (refractory anemia with excess of blasts; RAEB) with marked basophilia and eosinophilia is described. An 82-year-old male was admitted to our hospital because of severe normocytic normochromic anemia (Hb 5.6 g/dl). The white cell count was 9,200/microliters with marked basophilia (34.5%) and eosinophilia (19.5%). The bone marrow aspiration also revealed both basophilia and eosinophilia, with blast contents of 9%. Diagnosis of RAEB was established. Although the treatment with red cell transfusion and ubenimex (Bastatin) was started, anemia was not improved. A karyotype of the bone marrow cells from this patient showed 47, XY, +8, i (17q), which has been observed as additional chromosomal abnormalities in blastic crisis of chronic myelogenous leukemia. The diagnosis of CML was not compatible with this case, because Ph1 chromosome and bcr gene rearrangement were negative. It is concluded that eosinophilia and basophilia might be derived from clonal abnormalities associated with MDS.

Aged↗

Identification of discontinuous von Willebrand factor sequences involved in complex formation with botrocetin. A model for the regulation of von Willebrand factor binding to platelet glycoprotein Ib.

We have used proteolytic fragments and overlapping synthetic peptides to define the domain of von Willebrand factor (vWF) that forms a complex with botrocetin and modulates binding to platelet glycoprotein (GP) Ib. Both functions were inhibited by the dimeric 116-kDa tryptic fragment and by its constituent 52/48-kDa subunit, comprising residues 449-728 of mature vWF, but not by the dimeric fragment III-T2 which lacks amino acid residues 512-673. Three synthetic peptides, representing discrete discontinuous sequences within the region lacking in fragment III-T2, inhibited vWF-botrocetin complex formation; they corresponded to residues 539-553, 569-583, and 629-643. The 116-kDa domain, with intact disulfide bonds, exhibited greater affinity for botrocetin than did the reduced and alkylated 52/48-kDa molecule, and both fragments had significantly greater affinity than any of the inhibitory peptides. Thus, conformational attributes, though not strictly required for the interaction, contribute to the optimal functional assembly of the botrocetin-binding site. Accordingly, 125I-labeled botrocetin bound to vWF and to the 116-kDa fragment immobilized onto nitrocellulose but not to equivalent amounts of the reduced and alkylated 52/48-kDa fragment; it also bound to the peptide 539-553, but only when the peptide was immobilized onto nitrocellulose at a much greater concentration than vWF or the proteolytic fragments. These studies demonstrate that vWF interaction with GP Ib may be modulated by botrocetin binding to a discontinuous site located within residues 539-643. The finding that single point mutations in Type IIB von Willebrand disease are located in the same region of the molecule supports the concept that this domain may contain regulatory elements that modulate vWF affinity for platelets at sites of vascular injury.

Amino Acid Sequence↗

Inner arm dynein ATPase fraction of sea urchin sperm flagella causes active sliding of axonemal outer doublet microtubule.

In order to clarify the role of the inner arms of the axoneme in sperm flagellar movement, we prepared an ATPase fraction (12S) from the outer arm-depleted axonemes of sea urchin sperm flagella. When both arm-depleted axonemes were incubated with the 12S ATPase, they exhibited the sliding disintegration of outer doublet microtubules. Electron microscopy revealed that the ATPase rebound to the original inner arm sites of the axoneme. Therefore, it is quite likely that the 12S ATPase is one of the components of the inner arms. We referred to it as "inner arm dynein".

Animals↗

Novel effect of cyclicization of the Arg-Gly-Asp-containing peptide on vitronectin binding to platelets.

Vitronectin is one of the glycoproteins that mediate cell adhesion and spreading of a variety of cells through the RGD(S) sequence. Vitronectin is demonstrated to bind to glycoprotein IIb-IIIa and play a role in platelet aggregation. Synthetic peptides containing the RGD(S) sequence can inhibit vitronectin binding to platelets, but the affinity of these peptides is less than 1/100th that of native vitronectin. The present study thus examined the ability of modified RGD(S)-containing peptide to inhibit vitronectin binding to thrombin-stimulated platelets. The cyclicization of GRGDSPA peptide was done by the linkage of NH2-terminal glycin and the COOH-terminal alanin. The circular dichroism spectrum of cyclic GRGDSPA peptide only showed negative minimum at approximately 220 nm, but those of other linear peptides such as GRGDSPA and GRGESPA had no effect. This result indicated that only the cyclic GRGDSPA peptide retained some conformational structure to restrict its flexibility. Inhibition experiments revealed that the affinities of the ligands for the receptor decreased in the order of vitronectin = fibronectin = fibrinogen = von Willebrand factor (vWF) greater than cyclic GRGDSPA peptide greater than GRGDSPA peptide. GRGESPA peptide had no effect. These results demonstrate that the conformational structure of the RGD(S) sequence plays the important role for the affinity of vitronectin binding to activated platelets and the increased affinity of the modified peptide is a prerequisite for the potential antithrombotic use.

Amino Acid Sequence↗

How vitronectin binds to activated glycoprotein IIb-IIIa complex and its function in platelet aggregation.

Vitronectin, which is present in both plasma and extracellular matrix, inhibits the complement cascade and promotes the growth and attachment of cells in vitro. Like other adhesive proteins such as fibrinogen, von Willebrand factor, and fibronectin, vitronectin contains the sequence Arg-Gly-Asp and binds to some members of the family of receptors called integrins. Platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa) is well known as a member of integrins that bind to vitronectin as well as to fibrinogen, von Willebrand factor, and fibronectin. The interaction of vitronectin with GPIIb-IIIa was studied. Vitronectin bound to thrombin-stimulated platelets in a calcium-dependent, specific, and saturable manner with a molecular weight of 290 nmol/L and 9,100 sites per platelet. The binding was inhibited by the other adhesive proteins with IC50s of 0.078-0.15 mumol/L. The binding also was inhibited by the tetrapeptide Arg-Gly-Asp-Ser and the monoclonal antibody to GPIIb-IIIa (LJ-CP8). Vitronectin inhibited thrombin-induced platelet aggregation in a dose-dependent manner and fibrinogen enhanced platelet aggregation. These results suggest that vitronectin might modulate platelet aggregates by interfering with the interaction of fibrinogen with thrombin-activated GPIIb-IIIa.

Amino Acids↗