Biomedical subjects
Publications and source records attributed to A Hori.
The authors correlated neurologic features of rostral lateral pontine infarct (rLPI) with lesion location on MRI. rLPI is a motor-sensory stroke presenting as crural monoparesis or crural dominant hemiparesis and segmental superficial or deep sensory disturbances. The dorsolateral pontine base causes crural paresis without supranuclear facial palsy.
A 67-year-old man with AML, who had a 21-year history of psoriasis without remission, received a reduced-intensity transplantation from an HLA-identical sibling. The preparative regimen consisted of busulfan and fludarabine. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine and methotrexate. Psoriasis was completely resolved on day 18. The subsequent clinical course was uneventful until day 42, when psoriasis recurred at the same sites as before RIST. Peripheral blood examined on day 63 showed mixed chimerism with 54% recipient type. Cyclosporine was rapidly tapered off over the next 2 weeks. On day 90, 100% donor-type chimerism was confirmed. Subsequently, psoriasis improved simultaneously with the occurrence of mucositis and rash as a manifestation of GVHD. Scattered erythematous patches of psoriasis disappeared again by day 105. We initiated 0.5 mg/kg prednisolone on day 119, and resumed cyclosporine on day 133. At 7 months after RIST, he still suffers from chronic GVHD, but his psoriasis remains in remission for the first time in 21 years. The anti-psoriasis effect of the conditioning is mild and transient, while the graft-versus-autoimmunity effect, related to the induction of complete donor-type chimerism and GVHD, is more profound and persisting. A graft-versus-autoimmunity effect lies in the delicate balance between alloimmunity and immunosuppressant used for GVHD prophylaxis/treatment.
Explore the source record for details and available documents.
This is the first neuropathological documentation of a less known variant of Chiari anomaly type II without cerebellar herniation. It should be established that Chiari anomalies type II and type I belong to the same category of the basicranio-cervical hypoplasia and are not a primary CNS malformation.
The authors report a new murine model for myotonia congenita designated as B6MT. This line spontaneously arose from breeding of transgenic C57BL/6CrSlc mice, irrelevant of the transgene. The B6MT mouse showed moderate to severe action myotonia, and electromyography revealed myotonic discharge. The phenotype was transmitted with autosomal recessive inheritance. Molecular genetic study of the ClC-1 and the SCN4A genes revealed polymorphism with no functional consequences.
A 19-year-old woman with myelodysplastic syndrome underwent reduced-intensity stem cell transplantation [RIST: (cladribine 0.11 mg/kg for 6 days, busulfan 4 mg/kg for 2 days, and rabbit antithymocyte globulin)] from her one HLA-mismatched mother. Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A (CSA) alone. Severe acute GVHD in the skin, gut, and liver developed concurrently with stable engraftment, and methylprednisolone was administered (1-2 mg/kg per day, then pulse therapy with 1 g/day for 3 days) until day 40 of transplant, when a necrotic lesion of 10 mm in diameter appeared on the right cheek. The initial skin biopsy of the affected area showed a nonspecific inflammatory change. Routine X-ray and computed tomography examinations of the sinuses, chest, and abdomen disclosed no particular abnormalities. Despite intensive antibiotic therapy, the lesion rapidly extended to form an ulcer. A second biopsy specimen obtained from the lesion showed massive septa hyphae, suggesting mold infection. Although we immediately started amphotericin B, she died of multiorgan failure on day 68. Postmortem DNA sequence analysis of the specimen using the polymerase chain reaction identified Aspergillus ustus. Although this is an extremely rare complication after transplantation, this case highlights that we should pay more attention to primary cutaneous aspergillosis in severely immunosuppressed patients.
Explore the source record for details and available documents.
Disseminated aspergillus infection has a poor prognosis, but few reports have been published on extra-pulmonary involvement in aspergillosis. We reviewed 107 autopsy records of patients with invasive aspergillosis. Fifty-five patients had extra-pulmonary aspergillosis. Organs involved included heart, kidney, central nervous system, gastrointestinal tract, spleen, liver, thyroid gland and pancreas. Extra-pulmonary aspergillosis produces different manifestations according to involved organs. Risk factors associated with dissemination included cytotoxic chemotherapy within a month of death (P=0.0087). Lack of response to empiric or preemptive treatment of amphotericin B predicted IA dissemination (P=0.0328). To improve prognosis of IA, it is important to recognize clinical features of extra-pulmonary aspergillosis and to institute the aggressive anti-fungal treatment.
Synthesis of [2]catenane 6 has been successfully achieved by the combination of Pd complex 1 and pyridines 2 and 3 at a molar ratio of 2:1:1 in D20. A mixture of square molecule 4 (prepared from 1 and 2) and macrocycle 5 (obtained from 1 and 3), in which the final ratio of 1, 2, and 3 was kept 2:1:1 reorganizes in D2O/CD3OD (1:1) to form 6 within one day. However, the same mixture in D2O shows the formation of novel [3]catenane 7 along with the [2]catenane. In order to make 7, the theoretical ratio of components 1, 2, and 3 should be 3:1:2. Thus, deliberately maintaining such ratio of the above-mentioned molecules, a higher proportion of the [3]catenane is observed in D2O as found from 1H NMR spectra of the system. Reorganization of the twelve components to form [3]catenane is supported by studies with the DOSY method. This method is a first attempt to separate, from a mixture, either catenanes or any other supramolecular self-assembly structures. CSI-MS studies further support the assigned catenane super structures 6 and 7. All the results indicate that the [2]catenane is thermodynamically the most stable structure, while the [3]catenane is a meta-stable self-assembly.
We recently reported having identified of the ligand for an orphan G-protein-coupled receptor, hOT7T175, as the gene product (68-121)-amide of the metastasis suppressor gene KiSS-1. We further showed that the ligand, which we named "metastin," inhibits chemotaxis and invasion of Chinese hamster ovary (CHO) cells transfected with hOT7T175 cDNA (CHO/h175) in vitro, and pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. In the present study, we investigated the activity of metastin in CHO/h175 cells in greater detail. Metastin significantly suppressed motility in a chemotaxis assay and wound healing assay at 10-100 nM order concentrations. Two N-terminally truncated peptides, metastin(40-54) and metastin(45-54) inhibited the migration of CHO/h175 cells as potently as metastin itself. Metastin also inhibited the spreading, monolayer growth and colony formation in agar (0.8%) of CHO/h175 cells at 10-100 nM concentrations. These results indicate that metastin is a potent inhibitor of cell motility, leading to suppression of cell growth and antimetastatic activity, and suggest that low molecular chemical compounds could replace its activity as a novel antimetastatic agent.
Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.
Diagnosis of thrombotic thrombocytopenic purpura (TTP) is usually based upon the clinical features, and does not always involve histopathological evidence. We recently had experience with a patient who developed the five signs characteristic for TTP. He had been treated for liver cirrhosis associated with chronic hepatitis B infection, and the hepatic function was severely impaired at admission. Blood levels of vWF (von Willebrand factor) and factor VIII were highly elevated to 506% and 632%, respectively. These findings suggested severe endothelial damage. Thus, the patient was diagnosed as having TTP secondary to severe hepatic damage, and plasma exchanges were initiated immediately. He responded poorly to the treatment, and finally died of pulmonary hemorrhage. At autopsy, hepatocellular carcinoma was identified in the cirrhotic liver, but it was surprising that thorough postmortem examination failed to show any evidence of thrombotic lesions. Our experience suggests that secondary TTP does not always involve pathological evidence of the thrombotic lesions, and that the formation of thrombi causing vessel occlusion might not be essential in the pathogenesis of some secondary TTP.
Explore the source record for details and available documents.
We studied the causes of death in 295 patients (mean (+/- SD) age 70.5 +/- 13.2 y.o.) with active non-MDR pulmonary tuberculosis who died in our hospital between 1991 and 1999. A hundred and twenty eight patients (43.4%, group A) died of tuberculosis, while 167 patients (56.6%) of other accompanying diseases. In 46 patients of the latter (15.6%, group B), pulmonary tuberculosis gave an unfavorable impact on their clinical course. In these patients the extent of pulmonary tuberculosis on chest roentgenograph was similar with the remaining 121 patients who also died of the accompanying diseases (41.0%, group C) and was less severe than those of the group A patients. Their nutritional conditions measured by serum albumin and choline-esterase level on admission, however, were as low as those of the group A patients and distinctly worse than those of the group C patients. Most patients of groups A and B died within 3 months after admission, while less than half patients of group C died during the same period. The age frequency distribution of the patients in groups B and C had a single peak in the age group 70 to 89, while that in group A showed two peaks, one similar peak as in groups B and C, and another peak in the age group 50 to 59. The numbers of homeless patients, of the patients with extensive cavitary lesions, and of the patients who died of ARDS (Adult Respiratory Distress Syndrome) or severe pneumothorax in group A were the most also in the age group 50 to 59, indicating that the patients' delay in admitting to hospitals was the major cause of high motality in this age group. As to detailed causes of death in group A, patients died of respiratory failure (32 cases), emaciation (28 cases), progression of pulmonary tuberculosis (20 cases), ARDS (15 cases), tuberculosis-related diseases such as pneumothorax, hemoptysis, and DIC (24 cases). In groups B and C patients died of organ failure (36 cases), infectious diseases (33 cases) and malignancy (30 cases). The total number of died patients has increased, and the proportion of cases dying of ARDS and infectious diseases has increased statistically significantly recently.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The number of patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB) in our hospital is increasing year after year. Although most patients were HIV tested because of miliary tuberculosis or extra-pulmonary tuberculosis, some patients were found HIV seropositive by chance. In order to determine the incidence of HIV seropositivity among TB patients, HIV testing was carried out in TB patients for two years from January 1998 with the consent of patients. TB patients who received anti-HIV antibody examination were 164 in 1998, and 149 in 1999 and among them HIV seropositive TB patients were 4 in 1998 and 6 in 1999. The incidence of HIV seropositivity was 3.2% in all TB patients, 28.6% in miliary TB patients, and 1.0% in typical TB patients. The number of patients co-infected with HIV and TB in Tokyo was estimated by using these HIV seropositivity, it was 23 cases/year among miliary TB patients and 16 cases/year among typical TB patients. As there were many HIV-infected persons and many TB patients in Tokyo, it was thought that HIV testing in TB patients was important for the early detection of HIV infection and the early initiation of HIV treatment.
To clarify the sequence of alterations in the thrombotic and fibrinolytic systems after acute brain infarction, we prospectively examined sequential changes in coagulatory markers in 38 patients suffering from cardioembolic infarcts (CEI), 41 patients with atherothrombotic infarcts (ATI), 58 patients with lacunar infarcts (LI), and 32 age-matched controls. The plasma level of thrombin-antithrombin III complex (TAT), fibrinopeptide A (FpA), D-dimer, fibrin degradation products-E (FDP-E), fibrinogen, alpha2-plasmin inhibitor-plasmin complex (PIC), and percent activity of antithrombin III (AT-III) were measured within 48 h, at 1 week, and at 3 weeks after the stroke onset. Significantly elevated levels of TAT and FpA, which are both markers of thrombin formation, were observed in CEI patients, and these elevated levels were associated with increasing D-dimer levels for 3 weeks (P<0.0001). D-Dimer in CEI patients was significantly elevated compared to control, LI and ATI levels within 48 h (P<0.001). Percent activity of AT-III was significantly decreased in CEI patients for 3 weeks compared to this activity in controls, LI and ATI (P<0.001). TAT and FpA also increased significantly within 48 h in ATI subjects and declined thereafter. A significant elevation of FDP-E (P<0.001) and D-dimer (P<0.05, P<0.01) was detected in parallel with increasing fibrinogen for 3 weeks. However, there was no significant depletion of percent activity of AT-III in ATI. In LI subjects, no significant elevation of TAT, D-dimer or FDP-E were observed within 1 week. PIC increased significantly in three subtypes of brain infarcts, but did not differ significantly among the three subtypes for 3 weeks. An accurate assessment of sequential alterations in thrombotic and fibrinolytic markers in the acute stage of brain infarct should contribute to the clinical diagnosis of brain infarct subtype. Alterations in these markers in response to activation of the coagulatory system are attributable to the different pathogenesis of ischemic stroke.