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Biomedical subjects

Y Sudo

Publications and source records attributed to Y Sudo.

At least 73 records · Page 4Linked to original sources

Aneurysm of the left sinus of Valsalva producing aortic valve regurgitation and myocardial ischemia.

An aneurysm of the left sinus of Valsalva producing aortic valve regurgitation was treated by excising the aortic root including the aneurysm but leaving the aortic valve leaflets. The aortic valve was reimplanted inside a graft. Postoperative examinations revealed normal aortic valve function. In this case, the cause of aortic valve regurgitation was due to deformity of the aortic annulus. An aortic valve-sparing operation is an appropriate method for such a case.

Aged↗

Flow cytometric analysis of Thy-1 expression in myelodysplastic syndrome.

We analyzed the expression of Thy-1 (CD90) antigen on CD34+ bone marrow mononuclear cells (BMMNC) obtained from 25 patients with myelodysplastic syndrome (MDS) by two-color flow cytometry. Five of nine patients (55.6%) with refractory anemia with excess of blasts (RAEB) and two of 16 (12.5%) with RAEB in transformation (RAEB-t) showed more than 20% of Thy-1 expression of their CD34+ BMMNC. Regarding chromosomal abnormalities, -5/5q- or -18 might be correlated with the expression of Thy-1 on CD34+ BMMNC in MDS. Nine patients were analyzed twice, once before and once after leukemic transformation and showed no significant change in Thy-1 expression. These results show that Thy-1 was expressed on CD34+ BMMNC in certain patients with MDS before leukemic transformation and that it was maintained during the disease progression. In contrast, expression of Thy-1 did not seem essential to the leukemic transformation in MDS though the patients with high Thy-1 expression might have poorer prognosis compared with those with low Thy-1 expression.

Adolescent↗

The accuracy of endometrial cytology in the diagnosis of endometrial adenocarcinoma.

We have examined 62,234 cytological samples of endometrium to establish the accuracy and false-positive rate for the diagnosis of endometrial adenocarcinoma. The patients were either attending the gynaecological out-patients clinic with symptoms or were asymptomatic women attending for routine population screening as part of our cancer detection programme, the numbers from these two sources being equal. Out of 138 cases identified as endometrial adenocarcinoma by cytology 126 (91.3%) were confirmed histologically in our hospital. Twelve cases (8.7%) were shown to be false-positives. Reexamination of these led to the same false-positive diagnosis in all 12 cases. This was attributable to similarities of nucleo-cytoplasmic ratio, irregular arrangement of nuclei, variation in nuclear shape and in the numbers of nucleoli in repair cells and hyperplastic cells compared with the carcinoma cases. Most of the false-negative reports were due to insufficient material, pale staining in malignant cells or diagnostic error. Refraction measurement of the density of nuclei of cancer cells using equipment for which the patent is pending enabled objective measurement of nuclear density which indicated that the nuclei were not stained darkly enough in false-negative cases.

Adenocarcinoma↗

High level expression and secretion of Fc-X fusion proteins in mammalian cells.

We have developed a general expression system that enhances the production and secretion of proteins in mammalian cells. The protein of interest is expressed as a fusion to a signal peptide and the Fc fragment of immunoglobulin as the N-terminal fusion partner, which can direct the cellular processes into expressing and secreting high levels of many different types of proteins. These include secretory proteins, enzymes and soluble domains of membrane proteins, as well as nuclear and regulatory proteins. Typical expression levels of these proteins from stable cell lines ranged from several to 100 microg/ml in conditioned media. The Fc domain helps to solubilize hydrophobic proteins and provides a handle for easy detection and purification of the fusion proteins; and it can be cleaved off by treatment with protease if desired.

Animals↗

FLT-3 ligand mobilizes hematopoietic primitive and committed progenitor cells into blood in mice.

We investigated the effects of the administration of FLT-3 ligand (FL) on mobilization of primitive and committed progenitor cells in mice. C57bl/6J mice were injected subcutaneously with FL once a day for 5 d at doses of 20, 100 and 200 microg/kg. After the collection of peripheral blood, we determined the number of white blood cells (WBCs) with the differential counts. The formation of colony-forming cells (CFCs) in peripheral blood, bone marrow and spleen was evaluated. Although the administration of FL, 20 microg/kg, did not stimulate leukocytosis, its administration at doses of 100 and 200 microg/kg increased the number of WBC up to 1.7- and 2.4-fold, respectively. Committed progenitor cells were mobilized into the peripheral blood dose-dependently and the number of CFCs was increased up to 5.5-fold by the administration of FL at 200 microg/kg on d 5. The number of CFCs in the bone marrow increased, but not dose-dependently. The number of CFCs in the spleen also increased up to 32-fold at a dose of 200 microg/kg FL. Mobilized peripheral blood mononuclear cells were transplanted into lethally irradiated mice and the number of CFU-S (d 12) was scored. A dose-dependent mobilization of CFU-S (d 12) into peripheral blood was also observed. These observations suggest that FL can mobilize hematopoietic primitive and committed progenitor cells into the peripheral blood of mice and those cells mobilized by FL may be applicable to peripheral blood stem cell transplantation.

Animals↗

Muscarinic cholinergic receptors in human narcolepsy: a PET study.

OBJECTIVES: To investigate the function of the muscarinic cholinergic receptor (mAchR) in narcolepsy and the effects of pharmacotherapy on mAchRs. BACKGROUND: Muscarinic neural transmission serves as the main executive system in REM sleep. Studies in canine narcolepsy reported an increase in mAchRs in the pons. METHODS: The mAchRs of 11 drug naive/free patients with narcolepsy and 21 normal controls were investigated using PET with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB). Measurements were done in the pons, thalamus, striatum, and cerebral cortex. Seven of the 11 patients also underwent additional PET scans after the alleviation of symptoms by pharmacotherapy. RESULTS: There were no differences in [11C]NMPB binding between the control and drug naive/free patients in all areas analyzed. At the time of on-medication PET scan, [11C]NMPB binding in the thalamus was decreased, but only to a small degree compared with that by anticholinergic drugs. CONCLUSION: The present results do not support the notion that the mAchR is the main site of action of pharmacotherapy in the marked clinical improvement of human cataplexy.

Adult↗

[Myelodysplastic syndrome (RAEB in T) developed in a renal allograft recipient].

A 46-year-old man who had been treated with azathioprine (150 mg/day) and prednisolone (7.5-10 mg/day) for 16 years after allogeneic renal transplantation was admitted to our hospital in July 1996 for evaluation of pancytopenia. Three years earlier he had been given a diagnosis of renal pelvic and ureteral cancer, and underwent left nephrectomy with total uretectomy. His bone marrow was normocellular with excess of blasts (27.6%), and displayed trilineage myelodysplasia. A chromosomal analysis of the bone marrow revealed 43-45, XY with del (1) (p13), -5, del (7) (q22), -17, -18, and -19. The patient was given a diagnosis of refractory anemia with excess of blasts in transformation (RAEB in T), and treated with idarubicin and cytosine arabinoside. Two months later, overt acute leukemia developed and reinduction chemotherpay was started, but the patient died of cerebral hemorrhage in October. This case suggests that immunosuppressive agents such as azathioprine might play an important role in the pathogenesis of MDS (RAEB in T) and renal pelvic and ureteral cancer after renal transplantation.

Anemia, Refractory, with Excess of Blasts↗

[Effects of brovincamine fumarate on choroidal blood volume in rabbits].

We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits.

Animals↗

Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer's disease.

BACKGROUND: Acetylcholinesterase activity, a marker for degeneration of the central cholinergic system, has consistently been reported, in necropsy brain studies, to be reduced in the cerebral cortex of patients with Alzheimer's disease. We have shown regional acetylcholinesterase activity in vivo in rodent and primate brains with radioactive acetylcholine analogues. In the present study, we used one of the analogues to map acetylcholinesterase activity in the brains of living people. METHODS: Positron emission tomography (PET) and a radiolabelled acetylcholine analogue with high hydrolytic specificity to acetylcholinesterase [11C]N-methyl-4-piperidyl acetate (MP4A), was used in eight elderly healthy controls and five patients with Alzheimer's disease who had mild dementia. All participants were given an intravenous injection of [11C]MP4A and then sequential patterns of radioactivity in various brain regions were obtained by PET. Time courses of [11C]MP4A concentration in arterial blood were also measured to obtain an input function. A three-compartment model was used to estimate regional acetylcholinesterase activity in the brain. FINDINGS: The estimated acetylcholinesterase distribution in the brain of the control participants agreed with the acetylcholinesterase distribution at necropsy. All patients with Alzheimer's disease had multiple cortical regions with a reduced estimated acetylcholinesterase activity in comparison with control participants. The reduction was more pronounced in the parietotemporal cortex, with an average reduction rate of 31% in temporal and 38% in parietal cortex, and less pronounced in other cortical lesions (19% in frontal, 24% in occipital, and 20% in sensorimotor cortex). Each patient was found to have at least two cortical regions with significantly reduced acetylcholinesterase activity. INTERPRETATION: The method we describe for non-invasive in-vivo detection of regional acetylcholinesterase changes in the living human brain that is feasible for biochemical assessment of Alzheimer's disease.

Acetylcholinesterase↗

Synergistic effect of FLT-3 ligand on the granulocyte colony-stimulating factor-induced mobilization of hematopoietic stem cells and progenitor cells into blood in mice.

We have previously shown that FLT-3 ligand (FL) mobilizes murine hematopoietic primitive and committed progenitor cells into blood dose-dependently. Whether FL also acts synergistically with granulocyte colony-stimulating factor (G-CSF) to induce such mobilization has now been investigated. Five- to 6-week-old C57BL/6J mice were injected subcutaneously with recombinant human G-CSF (250 microg/kg), Chinese hamster ovarian cell-derived FL (20 microg/kg), or both cytokines daily for 5 days. The number of colony-forming cells (CFCs) in peripheral blood increased approximately 2-, 21-, or 480-fold after administration of FL, G-CSF, or the two cytokines together, respectively, for 5 days. The number of CFCs in bone marrow decreased after 3 days but was increased approximately twofold after 5 days of treatment with G-CSF. The number of CFCs in the bone marrow of mice treated with both FL and G-CSF showed a 3.4-fold increase after 3 days and subsequently decreased to below control values. The number of CFCs in spleen was increased 24.2- and 93.7-fold after 5 days of treatment with G-CSF alone or in combination with FL, respectively. The number of colony-forming unit-spleen (CFU-S) (day 12) in peripheral blood was increased 13.2-fold by G-CSF alone and 182-fold by G-CSF and FL used together after 5 days of treatment. Finally, the number of preCFU-S mobilized into peripheral blood was also increased by the administration of FL and G-CSF. These observations show that FL synergistically enhances the G-CSF-induced mobilization of hematopoietic stem cells and progenitor cells into blood in mice, and that this combination of growth factors may prove useful for obtaining such cells in humans for transplantation.

Animals↗

Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET.

Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R). D2R is expressed most highly in the striatum, but most of the recent positron emission tomography (PET) studies have failed to show any change in D2R densities in the striatum of schizophrenics, raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex, has been implicated in the control of working memory, and working memory dysfunction is a prominent feature of schizophrenia. We have therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of the negative symptoms (for instance, emotional withdrawal) and to poor performance in the Wisconsin Card Sorting Test. We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.

Adult↗

Aortic valve replacement via left thoracotomy after an esophageal operation.

Aortic valve replacement was performed through a left anterolateral thoracotomy using cardiopulmonary bypass in a 59-year-old man who had previously received esophageal resection with substernal reconstruction by gastric tube. Through this approach, injury of the reconstructed tube was avoided and the valve replacement operation was safely performed. We conclude that the lateral thoracotomy approach remains a valuable alternative for certain exceptional cases.

Aortic Valve↗

A translocation between 3q21 and 12q24 in a patient with minimally differentiated acute myeloid leukemia (AML-M0).

Only a small number of reports have described the cytogenetic analysis of minimally differentiated acute myeloid leukemia (AML, M0). We performed a cytogenetic analysis on a patient with AML (M0) with a normal platelet count. It revealed a chromosomal translocation between chromosome bands 3q21 and 12q24. 3q. Abnormalities in AML are known to be associated with normal or elevated platelet counts. 3q21 and 12q24 are common translocation sites in AML patients, but this is the first report of translocation t(3;12)(q21;q24) in an AML patient.

Cell Differentiation↗

Flow cytometric analysis of Thy-1 expression in CD34-positive acute leukemia.

We analyzed the expression of the Thy-1 antigen (CD90) in CD34+ acute leukemia using two-color flow cytometry. Leukemic cells were obtained from the bone marrow (BM) and/or the peripheral blood (PB) of 57 patients: 37 with acute myelogenous leukemia (AML) including nine with secondary AML following myelodysplastic syndrome (MDS/AML), and 20 with acute lymphoblastic leukemia (ALL) including three with chronic myelogenous leukemia in blast crisis (CML-BC) of the lymphoid type. Among these patients, one (3.6%) with de novo AML, two (22.2%) with MDS/AML, three (17.6%) with de novo ALL, and two (66.7%) with CML-BC coexpressed CD34 and Thy-1 (CD34+ Thy-1+) on more than 20% of the mononuclear cells within 'lymph' plus 'blast' window. Thy-1 was rarely expressed in de novo acute leukemia especially in AML. Interestingly, in 1 patient with CML-BC, the leukemic cells in BM were divided into two subpopulations (CD34+ Thy-1low and CD34+ Thy-1high), whereas most of the CD34+ leukemic cells in PB were Thy-1high. However, the mechanism for the mobilization of CD34+ Thy-1high leukemic cells into the PB is unknown.

Acute Disease↗

Serum thrombopoietin levels in patients undergoing autologous peripheral blood stem cell transplantation.

Recently, the ligand for c-mpl has been cloned and initial studies have shown it to be the platelet regulatory factor, thrombopoietin (TPO). To elucidate the role of TPO in the reconstitution of megakaryopoiesis and platelet production after stem cell transplantation, we measured serum TPO levels in nine patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) and in healthy volunteers. Serum TPO levels significantly correlated with the degree of peripheral thrombocytopenia and a strong inverse correlation between serum TPO level and platelet count was observed (r = -0.700, P < 0.001). Serum TPO levels began to rise as the platelet count decreased after chemotherapy, TPO levels peaked at over 25.00 fmoles/ml between days 0 and 10; TPO levels then decreased gradually as the platelet count began to rise. One patient with multiple myeloma received purified CD34+ peripheral blood stem cells. No difference was observed in the kinetics of serum TPO levels between unfractionated and purified PBSCT. These observations suggest that TPO plays a critical role in the reconstitution of megakaryopoiesis and platelet production after PBSCT.

Adolescent↗

Effects of thrombopoietin (c-mpl ligand) on growth of blast cells from patients with transient abnormal myelopoiesis and acute myeloblastic leukemia.

Thrombopoietin (TPO) is a ligand for c-mpl that promotes both proliferation and differentiation of megakaryocytes in vivo and in vitro. We investigated the expression of c-mpl transcripts and the effects of recombinant human TPO (rhTPO) on the proliferation and differentiation of human leukemic cell lines or fresh samples obtained from 32 patients with transient abnormal myelopoiesis (TAM) or acute myeloblastic leukemia (AML). Cells were cultured with TPO alone or combined with rh interleukin-3 (IL-3) or stem cell factor (SCF). Expression of c-mpl was verified in 6 of 13 cases tested. All but one of the cases that showed c-mpl expression responded to TPO. Blasts from all cases of TAM or French-American-British (FAB) subtype M7 showed growth responses to TPO with higher sensitivity than cells of other FAB subtypes and these responses were increased by addition of rhIL-3 or rhSCF in some cases. Responses of cells of other FAB subtypes varied. In addition, increased expression of platelet-specific surface antigens on MO7E cells after incubation with rhTPO was observed. These data suggest that TPO may be involved in the abnormal proliferation and differentiation of human leukemic cells, especially of M7 and TAM cells, considered to be of megakaryocytic lineage.

Adult↗