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T Toyoshima

Publications and source records attributed to T Toyoshima.

At least 55 records · Page 3Linked to original sources
PubMed1995

Urachal adenocarcinoma accompanied by a large spherical calcified mass.

We report a case of urachal adenocarcinoma, accompanied by a large spherical calcified mass adherent to the bladder dome of a 63-year-old man. The patient underwent partial cystectomy including en bloc resection of the urachus, and remains free from the disease after a 32-month follow-up period.

Adenocarcinoma↗
PubMed1994

Plasmodium falciparum: the Pf332 antigen is secreted from the parasite by a brefeldin A-dependent pathway and is translocated to the erythrocyte membrane via the Maurer's clefts.

The transport of the megadalton protein Pf332 was studied during the asexual bloodstage development of Plasmodium falciparum. Four mouse monoclonal antibodies, produced against a recombinant polypeptide derived from the Pf332 protein, were used to analyze the kinetics of synthesis, the subcellular location, and transport of this giant molecule to the erythrocyte membrane. After parasite invasion of a red blood cell, the Pf332 antigen is first detected in young trophozoites at the parasitophorous vacuole membrane or in the cytoplasm of the erythrocyte as large vesicle-like structures. The number of vesicles increases during maturation of the parasite and thus forms a rim-like immunofluorescence pattern between the erythrocyte membrane and the parasitophorous vacuole at very late stages. The various anti-Pf332 antibodies react with the surface of erythrocytes infected with very mature parasites (segmenter stage 42-46 hr postinvasion). Immunoelectron microscopic analysis shows that the Pf332 antigen is transported in association with Maurer's clefts in the cytoplasm of the erythrocyte. This transport could be completely blocked by Brefeldin A, resulting in the accumulation of the antigen within the parasite. These data strongly suggest that the Pf332 antigen is exported to the erythrocyte cytoplasm via the classical Golgi secretory pathway.

Animals↗
PubMed1994

Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor.

Inhibitors of the human immunodeficiency virus type 1 protease represent a promising class of antiviral drugs for the treatment of AIDS, and several are now in clinical trials. Here, we report the in vitro selection of viral variants with decreased sensitivity to a C2-symmetric protease inhibitor (A-77003). We show that a single amino acid substitution (Arg to Gln or Lys) at position 8 of the protease results in a substantial decrease in the inhibitory activity of the drug on the enzyme and a comparable increase in viral resistance. These findings, when analyzed by using the three-dimensional structure of the protease-drug complex, provide a strategic guide for the future development of inhibitors of the human immunodeficiency virus type 1 protease.

Amino Acid Sequence↗
PubMed1994

[Circadian profiles of blood pressure with respect to age].

UNLABELLED: The effects of ageing on nocturnal blood pressure (BP) and the circadian rhythm of BP were studied. Ambulatory BP and heart rate (HR) were monitored at 30-minute intervals for 24 hours, in 326 normotensive volunteers aged 15-83. The following groups were monitored: young: < 40 yrs, n = 177; middle: 40 yrs < or = - < 60 years, n = 100; old: 60 yrs < or =, n = 49 Firstly, the ratio of nocturnal fall (RONF) of BP (or HR) was calculated as follows: [(average day time BP (or HR)-average night time BR (or HR)]/averaged whole day BP (or HR) x 100. Then we calculated 2 measurements: 1. The dipper (RONF of BP (or HR) > or = 10% 2. The non-dipper. (RONF of BP (or HR) < 10%. A cosine fitting technique using the least-squares method was employed to find the circadian rhythm of BP and HR. The results of the study showed that the incidence of the non-dipper on systolic BP (SBP) was higher for old subjects than for young subjects. In addition, the nocturnal BP and HR were higher for old subjects than for young subjects. The circadian amplitude of HR was lower in old subjects. The circadian midline estimating statistic of rhythm (MESOR) or SBP increased with age. The circadian acrophase of BP and HR increased with age. CONCLUSION: non-dippers of BP and HR were observed in any age groups. The frequency of BP and HR non-dipper was greater for old subjects than young subjects. This result may suggest the clinical significance of nocturnal BP and HR for the evaluation of hypertensive subjects.

Adolescent↗
PubMed1993

Transmission-blocking activity of a chitinase inhibitor and activation of malarial parasite chitinase by mosquito protease.

During development in the mosquito midgut, malarial parasites must traverse a chitin-containing peritrophic matrix (PM) that forms around the food bolus. Previously Huber et al. [Huber, M., Cabib, E. & Miller, L. H. (1991) Proc. Natl. Acad. Sci. USA 88, 2807-2810] reported that the parasite secretes a protein with chitinase activity, and they suggested that parasite chitinase (EC 3.2.1.14) plays an important role in the parasite's egress from the blood meal. We found that allosamidin, a specific inhibitor of chitinase, completely blocked oocyst development in vivo and thus blocked malaria parasite transmission. Addition of exogenous chitinase to the blood meal prevented the PM from forming and reversed the transmission-blocking activity of allosamidin. Using exogenous chitinase, we also found that the PM does not limit the number of parasites that develop into oocysts, suggesting that the parasite produces sufficient quantities of chitinase to penetrate this potential barrier. In addition, we found that treatment of parasite chitinase with a diisopropyl fluorophosphate-sensitive trypsinlike protease from the mosquito midgut or endoproteinase Lys-C increased its enzymatic activity. These results suggest that malaria parasite has evolved an intricate mechanism to adapt to the PM and the protease-rich environment of the mosquito midgut.

Acetylglucosamine↗
PubMed1993

Molecular cloning and localization of an abundant novel protein of Plasmodium berghei.

Screening of Plasmodium berghei genomic libraries using DNA insert corresponding to the 3' half of P. falciparum 70-kDa heat shock protein gene identified several abundant clones which represent a novel gene in the parasite. The complete sequence was obtained using an approach based on inverse polymerase chain reaction. Analysis of the deduced amino acid sequence revealed the presence of 19 imperfect repeats of the sequence Gly-Gly-Met-Pro toward the carboxy terminus. Except for the similar sequence repeated seven times in the malarial 70-kDa heat shock protein, the sequence of the cloned gene product is very different. Moreover, the sequence also revealed acidic and basic domains in the protein which are more than 60% similar in sequence to functional domains present in numerous DNA binding transcription factors. A 56-kDa protein was identified by immunoprecipitation from labeled P. berghei extract using antisera raised in mice against gene products expressed in Escherichia coli. The protein is present in all the different life cycle stages of the parasites as revealed by immunoelectron microscopy.

Amino Acid Sequence↗
PubMed1993

Morphologic effects of artemisinin in Plasmodium falciparum.

Ultrastructural changes induced in Plasmodium falciparum by artemisinin were studied in vitro. Electron microscopic autoradiography was performed on infected erythrocytes that were exposed in vitro to 3H-dihydroartemisinin and 14C-artemisinin. These drugs consistently were located in food vacuoles and mitochondria. Two hours after administration, changes were observed in parasite mitochondria, rough endoplasmic reticulum, and nuclear envelope. At four hours, in addition to the earlier changes, nuclear membranes and, to a lesser extent, some plasma membranes formed myelin figures. In addition, there was a disappearance of ribosomes, and a destruction of food vacuole membranes. These changes may lead to the total disorganization of the parasites. Approximately 30% of the parasites manifested these alterations.

Animals↗
PubMed1993

A nonhuman primate model for human cerebral malaria: effects of artesunate (qinghaosu derivative) on rhesus monkeys experimentally infected with Plasmodium coatneyi.

We studied the effects of artesunate on rhesus monkeys infected with Plasmodium coatneyi. Sixteen rhesus monkeys were divided in four groups. Group I consisted of three monkeys that were splenectomized and were treated with three doses (loading dose: 3.3 mg/kg, maintenance doses: 1.7 mg/kg) of artesunate, group II consisted of three monkeys that were treated with three doses of artesunate (same as group I), group III consisted of two monkeys that were treated with one dose (3.3 mg/kg) of artesunate, and group IV consisted of five untreated monkeys. Parasitemias of these groups ranged from 13.3% to 19.5% before treatment. Twenty-four hours after administration, the parasitemia was reduced to 2.2% in group I and to < 0.1% in group II; parasitemia was lowered to 10.6% in group III only 3 hr after drug administration. The rate of sequestration in the cerebral microvessels, which was 29.4% in untreated animals, was < 0.1% in groups I and II (24 hr after treatment), and 2.0% in group III (3 hr after treatment). These data clearly indicate that artesunate not only reduced parasitemia, but also reduced the rate of parasitized red blood cell (PRBC) sequestration in cerebral microvessels. In an immunohistologic study, endothelial-leukocyte adhesion molecule-1 (ELAM-1) was not detected in group I after treatment with artesunate, although the presence of CD36, thrombospondin, intercellular adhesion molecule-1, IgG, and C3 in the cerebral microvessels was not altered. This is the first in vivo study to show that artesunate interferes with continued PRBC sequestration in the cerebral microvessels in cerebral malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A randomized trial of reduced doses of azidothymidine in Japanese patients with human immunodeficiency virus type 1 infection.

Adverse reactions to the standard dose (1,200 mg/day-1,500 mg/day) of azidothymidine (AZT) are serious. An in vitro pharmacokinetic study of intracellular AZT-5'-triphosphate suggested the feasibility of a clinical trial with reduced doses of AZT. A randomized trial with reduced doses of AZT (group A; 400 mg/day, n = 15, group B; 800 mg/day, n = 13), was conducted enrolling 28 patients with human immunodeficiency virus infection. The effective rate of AZT on CD4+ lymphocyte counts was similar for both groups, but the duration of the effect of AZT was significantly longer in group A (p less than 0.05). In group B, adverse reactions were more frequently observed (p less than 0.01), and AZT was withdrawn or the dose was reduced more frequently (p less than 0.05). These results suggest that AZT at a dose of 400 mg/day is less toxic, and is more beneficial for long-term treatment.

Adolescent↗
PubMed1992

[Therapeutic evaluation of imipenem/cilastatin sodium for bacterial infections in patients with hematological diseases].

1. To evaluate the efficacy and tolerance of imipenem/cilastatin sodium (IPM/CS) in severe infections associated with hematopoietic disorders, IPM/CS was administered to a total of 105 patients. 2. Out of 96 patients evaluable for efficacy, clinical responses were excellent in 23 patients, good in 30, fair in 15, poor in 19 and unknown in 9, and the overall response rate was 60.9%. 3. The most common underlying hematopoietic disease was acute non-lymphocytic leukemia and the most common infections were sepsis and suspected sepsis. 4. Daily dose, severity of infection and neutrophil count had effects on the clinical response. 5. The overall eradication rate of bacteria was 83.7%. 6. Side effects were observed in 10 patients (9.5%) and abnormal laboratory test results in 12 (11.4%). From the above findings, we have concluded that IPM/CS is very useful for the treatment of severe infections in compromised patients with hematopoietic diseases.

Adult↗
PubMed1991

A sensitive nonisotopic method for the determination of intracellular azidothymidine 5'-mono-, 5'-di-, and 5'-triphosphate.

In order to analyze the efficacy of azidothymidine (AZT), it is important to know intracellular concentrations of AZT metabolites. However, it has been impossible to measure intracellular AZT 5'-monophosphate (AZT-MP), AZT 5'-diphosphate (AZT-DP), and AZT 5'-triphosphate (AZT-TP) without using isotopes. In the present study, we developed a new method to measure intracellular AZT metabolites without radiolabeled compounds. The method employed was a high-performance liquid chromatography (HPLC) system programmed for column switching technique, in which two columns were used: column 1 (TSK-G2000-SW, 300 x 7.5 mm) to preseparate AZT metabolites from major cell components, and column 2 (YMC-A-312-ODS, 150 x 6 mm) to determine the metabolites. The limit of detectability of this system was 3.3 pmol/injection. When MT-4 cells were incubated with various concentrations of AZT, intracellular concentrations of AZT-MP increased in parallel with extracellular AZT. Those of AZT-DP and AZT-TP, however, reached plateaus at 5 and 2 microM of AZT, respectively. In MT-4 and Molt-4 cells incubated with 5 microM AZT, concentrations of AZT-MP increased time dependently, while the AZT-DP/AZT-MP ratios decreased with time. These data suggest that high dose of AZT may not necessarily increase intracellular concentration of AZT-TP. The concentrations of AZT metabolites in peripheral blood mononuclear cells in a patient with AIDS and an asymptomatic carrier were measured; the concentrations were comparable to those in cultured cells. Quantitative analysis of intracellular AZT metabolites without the use of isotopes will increase safety and convenience of measurement, and take an effective step in studying pharmacokinetics of AZT in clinical materials.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[BEP (bleomycin, etoposide, cisplatinum) chemotherapy as an induction therapy of advanced extragonadal germ cell tumor].

Five patients with advanced extragonadal germ cell tumor (EGGCT) were treated with cisplatinum + vinblastine + bleomycin (BVP) or cisplatinum + etoposide + bleomycin (BEP) chemotherapy as an induction therapy. All patients had high levels of tumor markers and multiple distant metastasis in poor nutritious conditions. Two patients given BVP therapy died 6 and 9 months after the chemotherapy. By contrast, three patients given BEP therapy achieved complete remission and were surviving longer than one year without any evidences of disease. Granulocytopenic fever was seen soon after the first course of BEP therapy. Prophylactic granulocyte-colony stimulating factor (G-CSF) treatment, enabled two of them to receive full dose chemotherapy without any fever attacks. In conclusion, BEP chemotherapy is effective to EGGCT as well as far advanced testicular tumors and G-CSF treatment is useful for achievement of induction chemotherapy to advanced germ cell tumors.

Adult↗