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T Hagiwara

Publications and source records attributed to T Hagiwara.

At least 73 records · Page 4Linked to original sources
PubMed1996

GpIIb/IIIa+ subpopulation of rat megakaryocyte progenitor cells exhibits high responsiveness to human thrombopoietin.

The recently cloned factor thrombopoietin (TPO) has been shown to exhibit megakaryocyte colony-stimulating activity in vitro. In this investigation, to further evaluate the action of TPO on megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]), GpIIb/IIIa+ and GpIIb/IIIa- populations of CFU-MK were prepared from rat bone marrow cells based on their reactivity with P55 antibody, a monoclonal antibody against rat GpIIb/IIIa, and their responsiveness to recombinant human TPO (rhTPO) and recombinant rat interleukin-3 (rrIL-3) was examined using a megakaryocyte colony-forming assay (Meg-CSA). rhTPO supported only megakaryocyte colony growth from both fractions in a dose-dependent fashion. The mean colony size observed with the GpIIb/IIIa+ population was smaller than that seen with the GpIIb/IIIa- population. With the optimal concentration of either rhTPO or rrIL-3, similar numbers of megakaryocyte colonies were formed from the GpIIb/IIIa+ population previously shown to be highly enriched for CFU-MK. In contrast, the maximum number of megakaryocyte colonies from the GpIIb/IIIa- population stimulated by rhTPO was only 24.2% of that achieved with rrIL-3. Morphologic analysis of rhTPO-promoted megakaryocyte colonies from the GpIIb/IIIa+ population showed that the average colony size was smaller but that the mean diameter of individual megakaryocytes was larger than in megakaryocyte colonies promoted with rrIL-3. rhTPO plus rrIL-3, each at suboptimal concentrations, had an additive effect on proliferation of CFU-MK in the GpIIb/IIIa+ fraction, whereas rhTPO plus murine IL-6 or murine granulocyte-macrophage colony-stimulating factor (mG-M-CSF) modestly but significantly reduced megakaryocyte colony growth. These results indicate that TPO preferentially acts on GpIIb/IIIa+ late CFU-MK with lower proliferative capacity and interacts with some other cytokines in CFU-MK development.

Animals↗
PubMed1996

A novel mutation Gly 1672-->Arg in type 2A and a homozygous mutation in type 2B von Willebrand disease.

Genetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEII.

Arginine↗
PubMed1995

Molecular cloning of two glutamate transporter subtypes from mouse brain.

The physiological action of glutamate is terminated by diffusional processes with its subsequent removal by high-affinity transport systems localized to glial and/or neuronal elements. Several cDNAs encoding glutamate transporters have been isolated from mammalian tissues. Here, we screened a cDNA library derived from mouse cerebellum and isolated the two glutamate transporters, termed MGLT1 and MEAAC1. The MGLT1 and MEAAC1 cDNAs encode proteins of 572 and 523 amino acids, respectively. MGLT1 has 93.9% amino acid sequence identity with the rat GLT1 and MEAAC1 has 89.3% identity with the rabbit EAAC1. MEAAC1 mRNA was expressed in brain, lung, kidney and skeletal muscle, whereas expression of MGLT1 was restricted to brain.

ATP-Binding Cassette Transporters↗
PubMed1995

Inhibition by folded isomers of L-2-(carboxycyclopropyl)glycine of glutamate uptake via the human glutamate transporter hGluT-1.

The effects of isomers of 2-(carboxycyclopropyl)glycine (CCG) on uptake of L-glutamate were investigated in COS-7 cells that expressed a cloned human glutamate transporter (hGluT-1). The (2S, 3S, 4R)-isomer (L-CCG-III) and the (2S, 3R, 4S)-isomer (L-CCG-IV) markedly inhibited glutamate uptake with a 50% inhibitory concentration of 290 nM and 1.1 microM, respectively. The (2S, 3S, 4S)-isomer (L-CCG-I) and the (2S, 3R, 4R)-isomer (L-CCG-II) did not inhibit glutamate uptake at concentrations of < or = 10 microM. Thus, hGluT-1 showed a markedly higher affinity for L-CCG-III and L-CCG-IV with a folded conformation of the glutamate skeleton, than for L-CCG-I or L-CCG-II with an extended conformation.

ATP-Binding Cassette Transporters↗
PubMed1995

Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats.

In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats. CPT-11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicity.

Animals↗
PubMed1995

Effects of lactoferrin and its peptides on proliferation of rat intestinal epithelial cell line, IEC-18, in the presence of epidermal growth factor.

The cell growth-stimulating activity of lactoferrin (LF) in combination with epidermal growth factor (EGF) was evaluated by using a rat intestinal epithelial cell line, IEC-18. LF was found to be more effective than EGF for inducing an increase in cell numbers when cultured for over 6 days using a medium containing 0.2% fetal calf serum (FCS), although the 3H-thymidine incorporation-stimulating activity of EGF was more potent than that of LF. A synergistic effect of LF and EGF was observed in both cell proliferation and DNA synthesis assays. The increase in cell numbers when stimulated with LF plus EGF corresponded to about 5 times that of the control. Iron was not required for manifestation of these effects of LF. On the other hand, iron-saturated transferrin (TF) had cell-growth-stimulating activity, but iron-free TF did not, either in the presence or absence of EGF. These results indicate that LF induces cell proliferation by a mechanism distinct from that of TF. A pepsin-generated hydrolysate of LF (LFH) had an activity similar to that of undigested LF, and a peptide with cell-growth-stimulating activity from bovine LFH was isolated by monitoring its effects in combination with EGF on DNA synthesis in IEC-18 cells. Sequence analysis indicated that the peptide has the structure Ala-Glu-Ile-Tyr-Gly-Thr-Lys-Glu-Ser-Pro-Gln-Thr-His-Tyr-Tyr, corresponding to residues 79-93 of bovine LF.

Amino Acid Sequence↗
PubMed1995

[General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium].

The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.

Animals↗
PubMed1995

[Massive and progressive hepatosplenomegaly caused by disseminated nontuberculous mycobacteriosis in a patient with acquired immunodeficiency syndrome].

A 28-year-old hemophilia A patient was admitted to our hospital in July, 1991 because of high fever, chronic diarrhea and anemia. The patient had been recognized as a asymptomatic carrier of human immunodeficiency virus (HIV) in 1985 and had developed Pneumocystis carinii pneumonia and had been diagnosed as acquired immunodeficiency syndrome (AIDS) in 1990. Hematologic laboratory examinations on admission revealed pancytopenia and a CD4+ cell count of 3/mm3. X-ray findings of chest and abdomen were normal and bacterial cultures of sputum, urine, blood, stool, cerebrospinal fluid and bone marrow yielded no pathogenic microorganisms. Microscopical examination of the stained specimens showed no acid-fast bacilli. On his fifth hospital day, his liver and spleen enlarged markedly and an abdominal CT scan obtained on the 13th day revealed high-grade hepatosplenomegaly. Administration of several kinds of antibiotics, antifungal agents, antiviral agents, antituberculous agents and gamma-globulin medicines did not relieve the symptoms. On the 28th day the patient had developed a subarachnoid hemorrhage and died five days later. Retrospectively all cultures for acid-fast bacilli of the specimens on his admission yielded nontuberculous mycobacteria. The bacteria were identified as Mycobacterium avium by polymerase chain reaction and his disease was eventually diagnosed as disseminated Mycobacterium avium complex (MAC) infection. The liver and spleen weighed 2,660 g and 1,840 g respectively at autopsy. Although hepatosplenomegaly is commonly recognized in AIDS patients with disseminated MAC infection, such massive and rapid enlargement has been rarely observed. This case study emphasize the importance of diagnosis and rapid treatment at the early stage of MAC infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

Mutation of low affinity nerve growth factor receptor gene in spontaneously hypertensive and stroke-prone spontaneously hypertensive rats: one of the promising candidate genes for hypertension.

There is evidence that abnormal formation of the sympathetic nervous system might be important for pathogenesis of hypertension. In the present study we analyzed nucleotide sequences of low affinity nerve growth factor receptor (LNGFR) genes in the spontaneously hypertensive rat and its stroke-prone substrain. There was a point mutation generating an amino acid substitution in signal peptide of these LNGFRs. This result suggested that the mutated LNGFR gene is one of the promising candidate genes for hypertension.

Amino Acid Sequence↗
PubMed1994

Disseminated pagetoid reticulosis: need for long-term follow-up.

A 54-year-old woman had an erythematous plaque on the left index finger for 2 years. Histologically there was a dense infiltrate of atypical mononuclear cells in the epidermis that produced a pagetoid appearance. A diagnosis of localized pagetoid reticulosis was made. Three years after total removal of the finger lesion, erythematous plaques appeared on her left thigh, followed by the development of similar plaques on the right thigh and lower abdomen. Histologically these skin lesions had the same pagetoid appearance as the plaque on the finger. This suggested development of the disseminated type of pagetoid reticulosis, long after removal of the initial skin lesion.

Diagnosis, Differential↗
PubMed1994

[A case of pediatric Chlamydia pneumoniae infection and properties of the isolate].

Chlamydia pneumoniae was isolated from the throat of a 2-year-old girl with upper respiratory illness. The isolate, Shizuoka-37, was stained with C. pneumoniae specific monoclonal antibody (RR402), as well as the genus specific antibody (Cultureset), but not with C. trachomatis specific monoclonal antibody (Micro-Trak). C. pneumoniae genome was amplified by polymerase chain reaction in the isolate. Elementary bodies (EB) of the isolate was round shaped by electron micrograph.

Child, Preschool↗
PubMed1994

[Multiple cooperative study of UFT-adjuvant chemotherapy for malignant tumor in the jaw and oral cavities. The Oral Surgery Malignant Tumor Research Association in Kanto Kohshinetsu District].

We studied the usefulness and safety of long-term administration of uracil and tegafur (UFT) after primary therapy of the malignant tumor in jaw and oral cavity regions randomized controlled trial. 112 cases were totallized 6 institutes belonging to the Oral Surgery Malignant Tumor Research Association in Kanto Kohshinetsu District during 2 years and 10 months, beginning in September 1986. After completing the primary therapy, treatment was not performed in group A and 400 mg/day of UFT was orally administered in group B for 1 year. A variation was observed in the stages of background factors such as sex and age (more than 30 years old and less than 80 years old), while no such discrepancy was observed in other stages. No significant difference of 1-year-survival ratio and non-recurrence ratio was noted in either group, while the non-recurrence ratio was more favorable in group B than group A, and the usefulness of UFT for adjuvant chemotherapy was suggested. The incidence of side effects in group B was 42.6%, and no serious side effect was observed.

Adenocarcinoma↗
PubMed1994

[Analysis of factors for the development of pulmonary tuberculosis in persons with collagenosis].

Recently, the annual reduction in the incidence rate of tuberculosis has slowed in Japan. One reason for this trend is believed to be due to an increase in the number of immunocompromised hosts. In our department, we discovered 10 cases of pulmonary tuberculosis among 962 cases of collagenosis, and have analyzed the factors for the development of pulmonary tuberculosis in these patients. A total of 29 patients wer involved in the study: 22 with systemic lupus erythematosus (SLE) (active disease, 10; inactive disease, 12) and having no pulmonary complications, and seven with pulmonary tuberculosis and no concomitant diseases. Our findings were as follows: 1. Seven of the 10 patients with pulmonary tuberculosis also suffered from SLE. 2. Nine of the 10 patients had been treated with a corticosteroid or immunosuppressant. 3. Serum CH50 and erythrocyte sedimentation rate (ESR) were valuable indicators for diagnosing pulmonary tuberculosis in the patients with SLE. 4. Patients with SLE and pulmonary tuberculosis tended to show lymphopenia in peripheral blood, which was further enhanced by prolonged use of steroids. 5. Miliary tuberculosis rather than pulmonary tuberculosis tended to develop in elderly patients, and required longer hospitalization.

Adrenal Cortex Hormones↗