Search PubMed⌕ Search

Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 901 records · Page 50Linked to original sources
PubMed1990

26,27-Hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) prevents osteoporosis induced by immobilization combined with ovariectomy in the rat.

The effect of 26,27-hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) on experimental osteoporosis in the rat induced by a combination of immobilization and ovariectomy was evaluated. F6-1,25(OH)2D3 increased the femur score and the photo-density. The administration of F6-1,25(OH)2D3 also significantly increased the dry weight, the ash weight and the ash content of the bone. Both F6-1,25(OH)2D3 and 1 alpha(OH)D3 showed a nearly dose-dependent effect and significant inhibition of the decrease of bone mass. Histomorphometry revealed a significant decrease of resorption by the administration of F6-1,25(OH)2D3. Bone formation rate in the F6-1,25(OH)2D3 treated group significantly decreased compared with the vehicle group. In conclusion, the pharmacological effective dose of F6-1,25(OH)2D3 was considered to prevent the osteoporotic decrease of bone mass by suppressing the elevated bone turnover.

Animals↗
PubMed1990

Effects of a new bisphosphonate (AHBuBP) on osteolysis induced by human prostate cancer cells in nude mice.

A new bisphosphonate, 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) assessing their effects on tumor induced osteolysis using human prostate adenocarcinoma cells in nude mice. The method consisted of inoculating transplantable human prostate cancer cells subcutaneously over the calvaria in nude mice resulting in a local tumor causing fragmentation of the bone. The parameters included assessing the extent of decreased osteolysis in bone as judged by X-ray and histological examination. The results showed the following sequence of potency: AHBuBP greater than AHPrBP greater than HEBP. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumor. This inhibition was obtained with no apparent effect on the growth of the tumor. AHBuBP appears to be an interesting new bisphosphonate for future clinical use.

Adenocarcinoma↗
PubMed1990

Selective IgG deficiency with a transcriptional disorder of the gamma switching region gene and the IL-4 gene.

A primary immunodeficiency patient was analysed whose serum IgG and IgE were extremely low but whose IgM and IgA levels were within the normal range or elevated. Southern blot analysis indicated no deletion of structural genes coding for C gamma, C epsilon, or C alpha. The majority of the patient's peripheral B cells expressed IgM and IgD on the surface yet IgG-positive B cells were not detected, suggesting that the defect is in a switch-recombination process from IgM to IgG. The RFLP pattern detected with the S mu and S gamma DNA regions revealed that there was no deletion or large mutation in the switch region DNA. An in vitro IgG production system with pokeweed mitogen showed an abnormality at the transcriptional level and the defects were in both the patient's T and B cells. Addition of recombinant IL-4 (rIL-4) to the normal B cells enhanced IgG production but the patient's B cells did not respond to rIL-4, although the IL-4 receptor was present at the normal level. Messenger RNA and IL-4 protein were not produced in the patient's T cells upon stimulation with phorbol ester and calcium ionophore, whereas IL-2 was normally produced. The patient's lymphocytes showed a proliferative response to various mitogens, including phorbol ester. The transcripts of unrearranged C gamma region genes were not detected in the patient's lymphocytes, suggesting that the chromatin structure of the S gamma region may not be open. These results suggest that the transcriptional defects at the S gamma region gene in B cells and at the IL-4 gene in the T cells may be responsible for the present IgG immunodeficiency. There might be a common transcriptional system operating in a certain step in the activation of both genes.

Adult↗
PubMed1990

Acute 'bilineal-biphenotypic' leukaemia.

We describe a unique case of hybrid leukaemia with bilineal and biphenotypic features. The coexistence of lymphoblasts and monoblasts was determined morphologically and cytochemically. Immunofluorescence and immunohistochemical analysis revealed that each blast population had both T lymphoid (CD2, cytoplasmic CD3) and myeloid (CD11, CD13, CD15) markers. Southern blot analysis of DNA extracted from the lymph node biopsy demonstrated the presence of monoclonal rearrangement of the TcR-C beta gene. Cytogenetic analysis of the bone marrow cells showed a karyotype of 48, XY, 7q+ in all of the metaphases examined. These observations are suggestive of a monoclonal origin for these two distinct blast populations.

Acute Disease↗
PubMed1990

Double-blind test of human urinary macrophage colony-stimulating factor for allogeneic and syngeneic bone marrow transplantation: effectiveness of treatment and 2-year follow-up for relapse of leukaemia.

A randomized, double-blind placebo-controlled phase III clinical trial was performed to study the effects of human urinary macrophage colony-stimulating factor (hM-CSF) after allogeneic and syngeneic bone marrow transplantation (BMT) in 60 hM-CSF treated and 59 placebo control patients. HM-CSF was administered at a daily dose of 2 x 10(5) units/kg from day 1 to day 14 after BMT. Significant differences between hM-CSF and control patient were found in the recovery time to greater than 0.5 x 10(9) granulocytes/l and the survival rate during the initial 120 d without retransplantation. There was no difference in the incidence or grade of graft-versus-host disease (GVHD). There was no difference in the rate of leukaemic relapse at 24-36 months after BMT in patients with acute lymphocytic, acute nonlymphocytic, or monocytic leukaemia. The results of this trial show that human M-CSF improves the outcome of BMT without any influence on the occurrence of leukaemic relapse or GVHD.

Adolescent↗
PubMed1990

Estimation of growth fraction in situ in human bladder cancer with bromodeoxyuridine labelling.

A group of 8 patients with invasive bladder cancer received fractionated intra-arterial infusions of the thymidine analogue bromodeoxyuridine (BrdU), 150 mg, every 6 to 10 h for 3 days before endoscopic cold cup biopsy to label tumour cells in the proliferative pool (growth fraction). The tumour specimens were fixed and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody. There was an area which could not be stained with anti-BrdU monoclonal antibody surrounding the stained area where diffusion effects could be excluded. This indicates a growth fraction less than 1 and implies that a proportion of the tumour cells in bladder tumours are cycling and contributing to growth. The BrdU labelling index (growth fraction) was determined by counting the number of BrdU labelled cells in the well labelled tissue sections. The average growth fraction of invasive bladder cancer was 38.4 +/- 7.7% (range 26.9-48.1%). Grade 3 tumours averaged 42.8 +/- 5.4% labelling versus 31.0 +/- 4.4% in grade 2. The higher growth fraction may indicate greater biological malignancy. These results indicate that immunohistochemical studies of cell kinetics using BrdU monoclonal antibodies may provide information about the biological characteristics of bladder tumours in situ.

Aged↗
PubMed1990

Effect of N-methionine-free, bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in a primate model.

We demonstrate the in vivo effects of bacterially synthesized, N-methionine-free recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) using a crab-eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM-CSF (30 micrograms/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (greater than 15.0 x 10(9)/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (greater than 8 x 10(9)/l) on d 10. Readministration of rh GM-CSF (30 micrograms/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two-fold increase of granulocyte/macrophage colony-forming units was also seen in the bone marrow, while the number of burst-forming units-erythroid was not affected. These data indicate that rh GM-CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.

Animals↗
PubMed1990

[Studies on the giardiasis as the zoonosis].

To obtain basic data on the route of Giardia infection as zoonosis, we examined feces from 80 dogs and 16 cats for Giardia cysts and evaluated the detection rates. In addition, familial infection was studied in 3 family members of the patient with giardiasis. Giardia cysts were detected in 10 of the 80 dogs (12.5%) but none of the cats. Of the 10 dogs from which Giardia cysts were isolated, 6 had been maintained by the breeders. Tow other dogs were for examination in the research institutions. None of the family members of the patient with giardiasis had this infection. Since the detection rates of Giardia cysts in the dogs and cats were low, the possibility that human infection is acquired from dogs or cats seemed to be low. However, some of patients with giardiasis we encountered had never been abroad. This fact together with the presence of Giardia cysts in the dogs despite the low detection rates suggest that attention should be paid to the possible association between human giardiasis and pets since the number of people keeping pets is increasing.

Animals↗
PubMed1990

[A case of sepsis caused by Edwardsiella tarda complicated panophthalmitis and pyogenic spondylitis].

Edwardsiella tarda (E. tarda) is gram negative enterobacteriaceae which has been found generally in animal hosts and occasionally in human feces. We have reported a case of sepsis caused by E. tarda, complicated panophthalmitis and pyogenic spondylitis. A 39-year old patient suffered from fever, polyarthralgia and lumbago. We performed blood culture, from which E. tarda was isolated. Spinal CT scan showed destruction and osteogenesis of the fourth and fifth lumbar vertebral body and cranial CT scan showed destruction of the right lens. So we diagnosed sepsis with pyogenic spondylitis and panophthalmitis. We suspected that chronic ethanol administration reduced the resistance to infection of E. tarda which caused sepsis.

Adult↗
PubMed1990

Acute leukemia during pregnancy. Association with immune-mediated thrombocytopenia in mother and infant.

A 29-year-old female in the 20th week of pregnancy was admitted because of a change in the ABO blood group and bleeding tendency. Acute myelogenous leukemia was diagnosed with a weak reaction of red blood cells with anti-A antibody and a decreased level of A-transferase activity. Though the patient tolerated intensive chemotherapy and achieved complete remission, thrombocytopenia persisted after consolidation chemotherapy. Since platelet-associated IgG was elevated, thrombocytopenia was considered to be immune-mediated. In the third trimester, premature separation of the normally implanted placenta developed and cesarean section was performed. The male baby was also thrombocytopenic, but successfully treated with gamma-globulin.

Abruptio Placentae↗
PubMed1990

pH-sensitive liposomes composed of phosphatidylethanolamine and fatty acid.

pH-induced destabilization, aggregation and fusion of liposomes composed of phosphatidylethanolamine (PE) and various fatty acid were studied. Destabilization was examined as a fluorescent change caused by leakage of coencapsulated aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and N,N-p-xylylenebispyridinium bromide (DPX). Fusion was monitored by two different methods, that is, intermixing assay of internal aqueous contents of liposomes, and lipid dilution assay of liposomes labeled with fluorescent phospholipids. Contents leakage from liposomes was observed by lowering the pH, and pH where the leakage began depended on fatty acid used. Fifty percent leakage of contents from PE liposomes containing alpha-hydroxypalmitic acid or alpha-hydroxy-stearic acid was observed at pH 5.5, that from liposomes containing stearic acid or palmitic acid was observed at pH 6.5-6.7, and that from ricinoleic acid at pH 7.2. Aggregation and fusion of the respective liposomes also occurred at a similar pH region. These results were interpreted by the notion that the protonation of the fatty acid triggers a series of pH-sensitive events. The liposomes developed in this study may be useful as a drug carrier which could release the contents in response to pH changes in their environment.

Chemical Phenomena↗
PubMed1990

[Studies on concentration of glycyrrhizin in plasma and its absorption after oral administration of licorice extract and glycyrrhizin].

The present study was carried out to elucidate the difference in the concentration of glycyrrhizin (G) in the rat plasma and in its absorption after oral administration of licorice extract and G. The concentration of G in the plasma was determined by high performance liquid chromatography. It was found that the time required for a maximum concentration (Tmax) of G was 8 h after administration of licorice extract. On the other hand, G reached a maximum plasma concentration at less than 6 h after administration of G. The plasma level of G fell slowly within 24 h after their oral administration, and it was still detected in the plasma even after 24 h. The maximum concentration (Cmax) of G in the plasma after oral administration of licorice extract was somewhat lower than that of G. On the other hand, the area under the plasma-time curve (AUC24h) of G after oral administration of licorice extract was almost the same as that of G. The effects of licorice extract and G on excretive urine volume was also investigated in rats. Licorice extract and G, at the dose used in this experiment, did not show any effect as compared with a control group.

Administration, Oral↗
PubMed1990

[Evaluation on equivalence of pharmacological properties between natural crude drugs and their cultured cells based on their components. Accelerative effect of lithospermi radix and inhibitory effect of coptidis rhizoma on proliferation of granulation tissue].

The present study was carried out to evaluate an equivalence of pharmacological properties between natural crude drugs and their cultured cells. The effects of ether extract of Lithospermi Radix and cultured cells of Lithospermum erythrorhizon Sieb. et Zucc. and aqueous extract of Coptidis Rizoma and cultured cells of Coptis japonica Makino var. dissecta Nakai on proliferation of granulation tissue in rats were compared. The ether extracts of Lithospermi Radix and the cultured cells enhanced proliferation of granulation tissue by the cotton pellet method. The potency of both extract was about the same, if results were compared with the corresponding doses which contained the same quantity of shikonin derivatives. On the other hand, the aqueous extracts of Coptidis Rhizoma and the cultured cells inhibited it. The potency of both extract was about the same, if results were compared with the corresponding doses which contained the same quantity of berberine-type alkaloids. From these results, to evaluate an equivalence of pharmacological properties between natural crude drugs and their cultured cells, it is concluded that their qualities and quantities are not so different each other and the almost same pharmacological effect expected on the basis of their uses is required.

Alkaloids↗
PubMed1990

Active and passive cutaneous anaphylaxis in WBB6F1 mouse, a mast cell-deficient strain.

WBB6F1 mouse, a mast cell-deficient strain, was tested for active and passive cutaneous anaphylactic reactions. Active cutaneous anaphylaxis was not produced in mice which had been immunized for 1 to 2 weeks by an intraperitoneal injection of bovine serum albumin with either adjuvant, Freund's complete adjuvant or Bordetella pertussis organisms, even though circulatory IgE and IgG1 antibodies were raised. Passive cutaneous anaphylaxis (PCA) was also absent, when the mice had been sensitized with allogeneic IgE or IgG1 monoclonal antibodies. However, obvious PCA was produced when allogeneic or xenogeneic hyperimmune serum was employed. These findings indicate that mast cells are not necessarily needed for the production of PCA. Some mechanism quite different from the well-elucidated mechanism, i.e., IgE- or IgG1 antibody-triggered histamine release from mast cells, seems to be operative.

Animals↗
PubMed1990

Immune deficiency of the CTS mouse. I. Deficiency of in vitro T cell-mediated immune response.

The cataract Shionogi (CTS) mouse characterized by cataracts and microphthalmia is a sister strain of the NOD mouse. We have made the immunological characterization of the CTS mouse by means of in vitro assays. Splenocytes of the CTS mouse were very low in the responsiveness to T cell mitogens such as Con A and PHA but not to a B cell mitogen, LPS. The production of IL 2 and expression of IL 2-receptor of spleen cells after in vitro stimulation with Con A decreased in the CTS mouse, when compared with those in the NOD and the other reference strains. In mixed lymphocyte culture, CTS splenocytes did not proliferate and did not generate cytotoxic T lymphocytes when cocultured with splenocytes of the C3H/He mouse. The NK activity against YAC-1 target cells was lower in the CTS mouse than in the C3H/He mouse, an NK high responder, but higher than in the NOD mouse, a low responder. These results suggest that the CTS mouse is deficient in T cells. Subset analysis of splenic lymphocytes of the CTS mouse using flow cytometry revealed that the percentage of T cells in the CTS mouse was significantly lower than those in the reference strains, which was consistent with the reduced responsiveness to T cell mitogens in the CTS mouse. The deficiency in the Ly-2+ T cell subset was particularly striking. However, the response to PHA of the splenocytes of the CTS mouse was normalized when T cells were enriched by nylon wool-passing and cell-sorting. Therefore, it seems that decreased T cell activity is due to a decrease in T cell number and not to dysfunction of individual T cells.

Animals↗
PubMed1990

[Identification of nutmeg by thin-layer chromatography and its introduction to Japanese standards for non-pharmacopoeial crude drugs].

When nutmeg was extracted with hot methanol and cooled, much precipitate was produced. The colorless crystals, obtained on recrystallization, were identified as trimyristin by spectroscopic means and by direct comparison with the standard. Then, the identification of nutmeg was established by using the same extraction as above and subjecting the precipitate to thin-layer chromatography. This method was newly introduced to the Standards for Non-pharmacopoeial Crude Drugs.

Chromatography, Thin Layer↗
PubMed1990

Granulocyte-macrophage colony-stimulating factor suppresses induction of neutrophil alkaline phosphatase synthesis by granulocyte colony-stimulating factor.

We evaluated the in vitro effects of recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) and rh granulocyte-macrophage CSF (GM-CSF) on neutrophil alkaline phosphatase (NAP) activity and the incorporation of amino acids into polymorphonuclear leukocytes (PMN) from normal individuals and patients with chronic myelogenous leukemia (CML). Both the NAP activity and incorporation of amino acids into PMN were enhanced by the addition of G-CSF in a dose-dependent manner. NAP activity induced by G-CSF in PMN from CML patients showed a greater increase than that in PMN from normal controls. In contrast to G-CSF, GM-CSF did not affect the NAP activity in PMN in spite of the enhanced incorporation of amino acids into PMN by GM-CSF. Interestingly, both the NAP-inducing ability of G-CSF and its enhancing ability for amino acid incorporation were suppressed by GM-CSF in a dose-dependent manner when PMN were incubated with various concentrations of GM-CSF in addition to 100 ng/ml of G-CSF. These observations suggest that G-CSF and GM-CSF act differently: G-CSF induces NAP synthesis in PMN, whereas GM-CSF negatively modulates the effect of G-CSF. Further, it is suggested that protein synthesis induced by G-CSF is negatively modulated by GM-CSF in a general fashion.

Alkaline Phosphatase↗