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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 667 records · Page 37Linked to original sources

Predominance of myeloid antigens in CD34-positive peripheral blood stem cells over those in bone marrow after administration of granulocyte colony-stimulating factor.

We analyzed the surface phenotype of CD34-positive (CD34+) cells in peripheral blood (PB) during the period of hematopoietic recovery following myelosuppressive chemotherapy. A significantly higher proportion of PB CD34+ cells coexpressed the CD13 and CD33 myeloid antigens (80.8%, 78.1%, respectively) than did BM CD34+ cells (45.8%, 37.8%, respectively) (both p < 0.01). In particular, the CD13 positivity of PB CD34+ cells harvested with granulocyte colony-stimulating factor (G-CSF) was significantly higher than that of those without G-CSF. Most of the PB CD34+ cells possessed the HLA-DR antigen, and less than 10% of the CD34+ cells coexpressed a mature cell antigen, such as CD14, GPA or Plt-1. The administration of G-CSF enhanced the appearance of significantly larger amounts of CD13+ 34+ and CD33+ 34+ cells (both p < 0.01). This G-CSF mobilization also resulted in an increased number of CD13- 34+ and CD33- 34+ cells and all types of colony-forming cells. On the other hand, macrophage colony-stimulating factor administration exerted little influence on the mobilization of PB CD34+ cells. Thus, G-CSF seemed to induce not only an expansion of circulating hematopoietic stem cells but also the myeloid differentiation of stem cells.

Adolescent↗

Analysis of the partial nucleotide sequences and deduced primary structures of the protease domains of mammalian blood coagulation factors VII and X.

In order to obtain sequence data for the blood coagulation factor VII and factor X in several mammalian species, we amplified and sequenced the DNA segments of exon VIII from each gene by means of the polymerase chain reaction (PCR) method. The DNA segments from the following species were successfully amplified: factor VII from the rhesus monkey and dog, and factor X from the rhesus monkey, Syrian hamster and rat. In each factor, the nucleotide sequences and predicted primary structures of the protease domain showed a high degree of homology among species; amino acid identities of approximately 68%-92% and 80%-98% were demonstrated among species in factor VII and factor X, respectively. The locations of the active site residues and five Cys residues were evolutionarily conserved in both factors. Interestingly, the amino acids involved in the human genetic variants, both factor VII 304-Arg and factor X 326-Arg, were always conserved across species. The data presented here will be helpful for investigating human genetic variants of factor VII or X, and will provide considerable information for constructing in vitro site-specific mutants of these factors.

Amino Acid Sequence↗

Value of phase-shift gradient-echo MR imaging in the differentiation of pelvic lesions with high signal intensity at T1-weighted imaging.

PURPOSE: To assess the value of phase-shift gradient-echo magnetic resonance (MR) imaging with the fast low-angle shot (FLASH) technique in the differentiation of hemorrhagic tumors and teratomas. MATERIALS AND METHODS: T1- and T2-weighted spin-echo imaging and phase-shift MR imaging were performed in 60 patients. On T1-weighted images, the signal intensity of lesions was compared with that of intraperitoneal fat. Findings at MR imaging were compared with the surgical findings. The diagnostic performance of each pulse sequence was analyzed with receiver operating characteristic curves. RESULTS: Sixty high-signal-intensity lesions were identified in 45 patients at T1-weighted imaging. Hemorrhagic lesions and teratomas had similar signal intensities on both T1- and T2-weighted images. Lesions were detected more decisively with FLASH imaging than with T1- and T2-weighted imaging. CONCLUSIONS: Phase-shift gradient-echo imaging is a readily available method for the differential diagnosis of lesions with high signal intensity at T1-weighted MR imaging.

Adolescent↗

Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system.

BACKGROUND: Prostacyclin elicits a potent vasodilation and inhibition of platelet aggregation through binding to its membrane receptor. The impairment of prostacyclin receptor activity is implicated in various human cardiovascular diseases. In the present study, we succeeded in the isolation and characterization of human prostacyclin receptor cDNA and elucidated its gene expression in human tissues. METHODS AND RESULTS: We isolated a cDNA clone encoding the human prostacyclin receptor from a human lung cDNA library. The isolated cDNA clone encodes a 386-amino acid protein with seven putative transmembrane domains, which belongs to the G protein-coupled receptor superfamily. [3H]iloprost, a prostacyclin receptor agonist, specifically bound to the receptor transiently expressed in COS-7 cells. The binding was inhibited in the rank order of iloprost = cicaprost, another prostacyclin receptor agonist, > prostaglandin E1 (PGE1) >> PGE2, PGF2 alpha, PGD2, STA2. In addition, iloprost dose-dependently stimulated cAMP generation in these COS-7 cells. These results are consistent with the characteristics of the human prostacyclin receptor. Northern blotting analysis on human tissues revealed that prostacyclin receptor mRNA is abundantly expressed in the aorta, lung, atrium, ventricle, and kidney. CONCLUSIONS: We cloned human prostacyclin receptor cDNA and elucidated its abundant gene expression in the human cardiovascular system. The present study will lead to better understanding of the significance of prostacyclin in humans and further facilitate the clinical application of prostacyclin.

Amino Acid Sequence↗

The effect of the partial pressure of oxygen on blood glucose concentration examined using glucose oxidase with ferricyan ion.

Glucose oxidase with ferricyan ion (GOD-F) is widely applied in clinical settings as a glucose sensor. However, blood oxygen concentration affects this blood glucose value because oxygen, at increased concentrations, consumes blood glucose, which cannot then be measured by this sensor. We investigated the effect of PO2 on blood glucose concentration in 48 patients who were breathing high concentrations of oxygen. Arterial and pulmonary arterial blood glucose values were analyzed using the GOD-F method and, as a control, the hexokinase method. The respective PO2 values were also measured. The blood glucose concentrations measured by the GOD-F method show a significant linear relation with that measured by the hexokinase method in both arterial (y = -24.4 + 1.01x, r = 0.99) and pulmonary arterial blood (y = -3.4 + 1.01x, r = 0.96). The difference of intercepts is statistically significant, but because of the relatively large limits of agreement indicating any hidden extraneous variabilities, the error of the GOD-F method could not be assessed just by the difference. The equation defining the effect of PO2 on the percent change between blood glucose measured by the GOD-F method and that measured by the hexokinase method is -19.8/(1 + 203900/PO2(2.68) (r = 0.62). This formula generally follows our measured materials and introduces the relationship among blood glucose value, PO2, and the error of the GOD-F method. We hesitate to suggest that the arterial blood glucose concentration when measured by the GOD-F method could be underestimated by as much as 20% in patients with high arterial oxygen pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesiology↗

Transcatheter arterial embolization of obstetric and gynaecological bleeding: efficacy and clinical outcome.

32 patients with uncontrollable genital bleeding resulting from postpartum haemorrhage (n = 15) or malignant neoplasms (n = 17) were treated by arterial embolization therapy on an emergency basis. The 15 patients with postpartum haemorrhage responded dramatically to treatment by embolization. Follow-up computed tomography or magnetic resonance studies in 12 cases showed haematomas in the pelvic extraperitoneal space, but most then reduced in size or disappeared spontaneously. In two patients with large haematomas, laparotomy was required. No serious complications developed and normal menstruation resumed in the women who did not undergo hysterectomy. In the 17 patients with malignant neoplasms, bleeding was temporally controlled in all, but recurred in seven and required re-embolization in three. One patient experienced slight numbness of the leg and another had a skin ulcer. All patients underwent subsequent treatment including radiation therapy (n = 10), operation (n = 5) or chemotherapy (n = 2). We conclude that arterial embolization has significant merits in the management of patients with uncontrollable genital bleeding.

Adult↗

Lymphocutaneous nocardiosis with multiple subcutaneous nodules distributed over the extensor aspect of the forearm. Report of a case.

We report a case of lymphocutaneous nocardiosis due to Nocardia brasiliensis, marked by multiple subcutaneous nodules and abscesses on the extensor aspect of the left forearm in a 53-year-old woman with systemic lupus erythematosus. Nine months before she was first examined, she had fallen on a concrete surface. A nodule had appeared 2 months later at the same site and had expanded and been followed by others, which finally covered most of the extensor aspect of the forearm. We speculated that the bacteria may have been conveyed retrogradely via the lymph vessels in a distal direction, perhaps as a result of the trauma and the subsequent development of an intradermal lesion.

Abscess↗

Asialoglycoprotein receptor function of hepatocytes in patients with autoimmune hepatitis.

To assess whether the hepatocyte asialoglycoprotein receptors are affected in patients with autoimmune hepatitis, the function of the hepatocyte asialoglycoprotein receptor was investigated in patients with autoimmune hepatitis or chronic hepatitis C. A new radionuclide liver imaging technique, Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was applied to evaluate the function of the receptor. A Receptor Index (LHL 15) was calculated by dividing the radioactivity of the liver region-of-interest (ROI) by that of the liver plus heart ROI 15 min after radiolabeled ligand injection. Serum albumin, prothrombin time, hepaplastin test and plasma retention rate of indocyanine green at 15 min were not significantly different between patients in the autoimmune hepatitis group and chronic hepatitis C group. In addition, the Receptor Index of patients with autoimmune hepatitis, in whom the asialoglycoprotein receptor is a candidate target antigen for autoimmune response, was similar to that of patients with chronic hepatitis C. These results indicate that the hepatocyte receptor for asialoglycoproteins is not affected in patients with autoimmune hepatitis.

Adult↗

Function of asialoglycoprotein receptor of hepatocytes in patients with Wilson's disease.

The function of hepatocyte asialoglycoprotein receptors was analyzed in normal subjects, in patients with Wilson's disease and in patients with chronic hepatitis C. A new radionuclide liver imaging, using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was applied to evaluate the function of the receptor, and a Receptor Index, LHL 15, which was calculated by dividing the radioactivity of the liver region-of-interest (ROI) by that of the liver plus heart ROI at 15 min after the radiolabeled ligand injection, was evaluated. The values were similar between the patients with Wilson's disease and patients with chronic hepatitis C. Hepatocyte receptors for asialoglycoproteins were not affected specifically in patients with Wilson's disease, suggesting that the defect in patients with Wilson's disease involves steps other than receptor-mediated endocytosis of asialoceruloplasmin via asialoglycoprotein receptor.

Adult↗

The c-kit molecule and the surface immunophenotype of human acute leukemia.

The proto-oncogene c-kit encodes the receptor for a stem cell factor (c-kit molecule). Expression of the c-kit molecule on the gated leukemic blast cells from newly diagnosed patients with leukemia was analysed by flow cytometry using the monoclonal antibody (17F11). Among 35 myeloid leukemia cases examined, significant c-kit-positive blast cells were detected in 24 cases (69%), even though the percentage of positive cells was widely variable. The correlation between the percentage of cells positive for the c-kit molecule and the percentage of cells positive for CD34 was found to be statistically significant (rs = 0.36, p < 0.05). Fifteen cases of myeloid leukemia were positive for lymphoid markers. The mean percentage of the cells expressing c-kit molecule among the lymphoid marker-positive cases was significantly larger than that among the lymphoid marker-negative cases (p < 0.05). All 19 lymphoid leukemia cases were c-kit-negative, including 8 cases which were positive for some myeloid markers. Stem cell factor enhanced the colony growth in five out of six acute myeloblastic leukemia cases expressing the c-kit molecule. On the other hand, SCF did not stimulate colony growth in any of the four cases which were not positive for the c-kit molecule. These findings indicated that the distribution of flow cytometrically detectable c-kit molecules on leukemic cells is related to the morphologic and immunologic classification of these leukemic cells and to the expression of the CD34 cell surface molecule on some myeloid leukemic cells. On such cells, expression of the c-kit molecule may have a functional role and be related to the maturation process.

Adult↗

[Small cell carcinoma of the prostate].

Small cell carcinoma of the prostate is a rare disease, since only about 50 cases in the English literature and two cases in Japanese literature have been reported. Here we report a case that is the youngest ever described in the literature. A 24-year-old man was referred to our hospital with right dull lumbago and dysuria. He had the same symptom for one and half year before referral. IVP showed right non-visualizing kidney and left hydronephrosis. Form abdominal CT scans and cystoscopic findings a retrovesical tumor was highly suspicious. Transperineal needle biopsy specimens revealed an undifferentiated malignant tumor. His serum Neuron Specific Enolase (NSE) and LDH were remarkably high and whole body CT scan and upper GI tract examination demonstrated no lesion. He developed ileus and underwent exploratory laparotomy and colostomy was constructed. There was a large mass arising from the prostate which invaded into the peritoneal cavity, and multiple metastases were seen on the omentum and mesenteric lymph nodes. Specimens from the mass arising from the prostate and lymph nodes revealed small cell carcinoma pathologically. A panel of antibodies were used to seek potential tumor markers and to identify substances produced by the tumor cells including enzymes, cytoskeletal components and hormones. And stains were positive for the NSE and chronogranin. An intensive anti-cancer chemotherapy with VP-16 and CDDP was done with minor response (MR) and the serum tumor marker, LDH and NSE, decreased markedly. However, he had expired on the 58th hospital day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Successful second autologous blood stem cell transplantation after G-CSF-combined conditioning for the treatment of high-risk acute myelogenous leukemia.

We describe a patient with acute myelogenous leukemia (AML) who received his second autologous blood stem cell transplantation (ABSCT) following a G-CSF-combined pre-transplant conditioning regimen. The patient underwent ABSCT during first remission but suffered a relapse 8 months later. After achieving second remission, he was prepared for his second ABSCT; recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered in combination with Ara C, in addition to the same conditioning regimen as that used before the first ABSCT. There was no increase in regimen-related toxicity after this second G-CSF-combined conditioning regimen when compared with that observed after the first ABSCT. To date, the patient's second remission following the second ABSCT has lasted 26 months, which has exceeded that following the first ABSCT. The G-CSF-combined pretransplant conditioning regimen for ABSCT may be effective in the treatment of high-risk AML by increasing the chemosensitivity of the residual leukemic cells.

Adult↗

[CD7 positive acute myelogenous leukemia exhibiting pleural involvement as an initial manifestation].

A 51-year-old man had suffered from massive pleural effusion due to invasion of malignant cells. The analysis of bone marrow aspiration showed the proliferation of myeloperoxidase-positive blasts. The surface marker analysis of the blasts revealed the positivities for CD7 and CD19 as well as CD13, CD33 and CD34, while the karyotypes of 20 cells were normal. Therefore, CD7 positive AML was diagnosed. The patient was treated with araC and daunorubicin as a remission induction therapy. Peripheral blood stem cells were harvested by leukapheresis after first and second consolidation therapies. Then, 3 x 10(4) cells/kg of CFU-GM were infused. Complete remission has been maintained for 8 months after autologous blood stem cell transplantation. Pleural involvement as an initial manifestation is rare in AML. Extramedullary growth of AML cells may be related to their immaturity, indicated by the expression of the cell surface antigens.

Antigens, CD↗

[Development of the brainstem and cerebellum in autistic children].

Studies of magnetic resonance images have revealed morphological disorders of the brainstem and cerebellum in autistic children and adults. When we studied development of the brainstem and cerebellum in autistic patients, these structures were significantly smaller in autistic patients than in controls. Although the brainstem and cerebellum significantly increased in size with age in both groups, the development of the pons, cerebellar vermis I-V and cerebellar vermis VI-VII was significantly more rapid in autistic patients than in controls. However, the development of the other brain structures in the posterior fossa did not differ between autistic patients and controls. The regression intercepts of the brainstem and cerebellum as well as those of their components were significantly smaller in autistic patients than in controls. These results suggested that significant anatomical changes took place in the posterior fossa brain structures in the prenatal period in autistic children, but were not progressive.

Adolescent↗

Differences in metabolism between 26,26,26,27,27,27-hexafluoro-1 alpha, 25-dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3 in cultured neonatal mouse calvaria.

We investigated the metabolism of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3, ST-630) and 1 alpha,25-dihydroxyvitamin (1,25(OH)2D3) in cultured neonatal mouse calvaria to elucidate why ST-630 is more potent than 1,25(OH)2D3 in stimulating bone resorption in organ culture. The metabolites were extracted with ethyl acetate or chloroform/methanol (1:1) from cultured calvaria or medium incubated with [3H]-ST-630 or [3H]-1,25(OH)2D3 for various periods, and separated by high performance liquid chromatography. [3H]-ST-630 in cultured calvaria was converted to [3H]-26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3(26,27-F6-1,23,25(OH)3D3,ST-232), which stimulated bone resorption equipotently as 1,25(OH)2D3. The amount of [3H]-ST-232 produced in the bone increased with passage of the culture period. In contrast, the amount of [3H]-ST-630 in the bones decreased in the 2 day cultures. In the medium, [3H]-ST-630 was hardly detectable for 2 days. This suggests that ST-630 is metabolized to ST-232 which is retained in the bones. On the other hand, some [3H]-1,25(OH)2D3 was metabolized to inactive forms detectable in the medium. Therefore, the high potency of ST-630 in stimulating bone resorption in organ culture may be associated with a difference between ST-630 and 1,25(OH)2D3 in the mode of metabolism in the cultured bones.

Animals↗

Changes in muscle and liver lactate concentrations after endotoxin infusion in rats.

The interstitial lactate concentration in rat skeletal muscle and liver was measured using a microdialysis method during the early stage of endotoxemia and during lactic acid infusion. The lactate concentration in the muscle and liver interstitium never exceeded the blood lactate concentration throughout the 180 min period after endotoxin administration. The present findings also showed that the muscle and liver interstitial lactate concentration gradually increased in endotoxin-infused animals compared to that in lactic-acid infused animals, although the blood lactate concentration in lactic acid-infused animals was the same as that in endotoxin-infused animals. These findings suggest that the skeletal muscle and liver may consume lactate in an endotoxemic condition. However, the capacity of lactate consumption in the skeletal muscle might gradually decrease after endotoxin administration, although that in liver might be well preserved.

Animals↗

[A randomized controlled trail of intensive and usual community-based education for blood pressure control].

A 1.5 year community-based hypertension education program was conducted and evaluated for the feasibility and effectiveness as a program for primary prevention of cardiovascular disease. The subjects were determined to be hypertensive from cardiovascular examinations and composed of 104 untreated men and women aged 35-69 whose blood pressure levels were between 140 and 179 mmHg for systolic and/or between 90 and 109 mmHg for diastolic and who had no evidence of hypertensive end organ effects in the 1990 examination. They were randomly assigned to either an intensive education (IE) group (n = 53) or a usual education (UE) group (n = 51) and invited to education classes six months later. The IE consisted of four education classes in the first six months and another 4 classes in the next 12 months. For the UE, one class in the first 6 months and another class in the next 12 months were held. Health education was focused on reduction of sodium intake, a 30 minutes of walking, and if necessary, reduction of alcohol and sugar intake. Mean (SD) values of systolic blood pressure at the start of the education program were 144.8 (11.7) mmHg in IE and 144.5 (12.2) mmHg in UE. The respective diastolic means (SD) were 80.6 (7.8) mmHg and 80.3 (8.6) mmHg. The proportion of persons who started to receive antihypertensive medication was 8-9% in both groups at six months, and 13% in IE and 29% in UE at 1.5 years. IE showed a 6 mmHg greater reduction in mean systolic blood pressure than UE at both six months and 1.5 years. No significant difference was found in diastolic blood pressure levels over time between the two groups. Dietary improvements related to reduction of salt intake were more evident in IE than in UE. There was no significant changes in means and distributions of relative weight index and alcohol intake in either group. Subgroup analysis according to antihypertensive medication use indicated that reduction of systolic blood pressure levels was significantly larger in IE than in UE for both no medication and medication subgroups at 6 months and 1.5 years. While it was difficult to evaluate an effect of the program at 1.5 years because of the difference in the proportion of medication use between IE and UE, the results at 6 months suggest that this community-based program was effective in reducing systolic blood pressure levels.

Adult↗

Myasthenia gravis after allogeneic bone marrow transplantation.

A 37-year-old Japanese man with chronic myeloid leukemia (CML) developed myasthenia gravis 29 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched brother. Proximal muscle weakness and bilateral ptosis occurred along with the exacerbation of chronic GVHD shortly after sudden cessation of cyclosporine (CYA) and prednisolone. The diagnosis of myasthenia gravis was made based on clinical symptoms and elevation of an anti-acetylcholine receptor antibody titer and all symptoms related to myasthenia gravis promptly diminished with the start of treatment for chronic GVHD. In most previously reported cases, the underlying disease was aplastic anemia (6 of 7 cases) and donors were of the opposite sex (6 of 7 cases). The haplotypes HLA B7 (3 of 5 cases), B35 (3 of 5 cases), and DR2 (3 of 3 cases) were common. All cases suffered from chronic GVHD. The present case had only chronic GVHD and HLA B7 as a background for myasthenia gravis after BMT. The abrupt cessation of immunosuppressive therapy may also be related to the development of myasthenia gravis after BMT.

Adult↗