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T Igarashi

Publications and source records attributed to T Igarashi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Absolute configuration at C14 and C85 in prymnesin-2, a potent hemolytic and ichthyotoxic glycoside isolated from the red tide alga Prymnesium parvum.

Prymnesin-2 is a potent red tide toxin characterized by a highly oxidized C(90) carbon chain and multiple functional groups. Succeeding the assignment of the relative stereochemistry in the polycyclic-ether segment, the absolute configurations of two chiral centers in linear chain parts were elucidated. The configuration at C14 bearing an amino group was determined to be S by using a chiral anisotropic reagent and that at chlorinated C85 to be S by fluorimetric chiral HPLC comparison between a degradation product and synthetic references.

Animals↗
PubMed2001

Regional vulnerability after traumatic brain injury: gender differences in mice that overexpress human copper, zinc superoxide dismutase.

Neuronal loss was quantified in both cortical and subcortical brain regions after traumatic brain injury in male and female nontransgenic (nTg) and transgenic (Tg) mice that overexpress human copper, zinc superoxide dismutase. Mice were euthanized at 7 days after a controlled cortical impact injury. Sections of brain were processed for immunolocalization of NeuN, a neuronal nuclear antigen, and the complement type 3 receptor, a marker of microglia/macrophages, and stained for iron. Cortical lesion volume and neuronal loss in the medial and/or lateral ventroposterior thalamic nuclei were significantly less in the nTg female compared to the nTg male (P = 0.0373 and P = 0.0023, respectively). In contrast, in CA3 of the hippocampus and laterodorsal thalamic nucleus (LD), there were no gender differences in neuronal loss between these nTg groups. Cortical lesion volume was significantly reduced in Tg males compared to nTg males (P = 0.0137) and was unchanged in the Tg females compared to the nTg females. Neuronal loss was attenuated in the CA3 and LD in the Tg females compared to the nTg females (P = 0.0252 and P = 0.0244, respectively). A similar protection was not observed in the Tg males. Microglial activation paralleled the pattern of neuronal loss and was most consistently aligned with iron deposition in the cortex and hippocampus. No overt differences were found in the pattern of microglial activation or iron staining between nTg and Tg mice nor between genders. Our findings demonstrate that neuroprotection, afforded by overexpression of copper, zinc superoxide dismutase, exhibits both regional and gender specificity.

Animals↗
PubMed2001

Differences in anti-LKM-1 autoantibody immunoreactivity to CYP2D6 antigenic sites between hepatitis C virus-negative and -positive patients.

Anti-liver kidney microsome type 1 autoantibodies (anti-LKM-1) are known to be present in sera of autoimmune hepatitis type II and a subset of chronic hepatitis C patients. The autoantigen to anti-LKM-1 has been identified to be cytochrome P450 IID6 (CYP2D6) and the most frequently cited CYP2D6 antigenic sites of anti-LKM-1 in sera from autoimmune hepatitis type II patients spans the region aa 256-269. Other antigenic sites on CYP2D6 exist and have been identified in the two patient groups. However, most of these sites are concentrated on the carboxyl-terminal side of the protein, and the amino-terminal region has not been thoroughly investigated. Here, we have studied the antigenicity of the CYP2D6 amino region and compared reactivities between hepatitis C virus (HCV)-negative and -positive Japanese patient groups. A total of 34 anti-LKM-1-positive sera (eight with autoimmune hepatitis type II and 26 with chronic hepatitis C) were included. The immunoreactivity of patients' sera was examined against four conformational and one linear CYP2D6 peptide fragments. A defined antigenic site spanning aa 181-245 was found to react with 88% (7/8) of autoimmune hepatitis type II patients, as opposed to only 38% (10/26) of chronic hepatitis C patients. This was a significant difference (P< 0.043). Among these positively reacting samples, five of the seven autoimmune hepatitis type II sera and four of the ten chronic hepatitis C sera also reacted with a synthetic peptide spanning aa 256-269. Anti-LKM-1 thus may be able to recognize simultaneously at least two antigenic sites on the CYP2D6 protein, and reactivities against individual epitopes may differ according to HCV infectivity status.

Adult↗
PubMed2001

Re-treatment of relapsed indolent B-cell lymphoma with rituximab.

The purpose of this study was to investigate the toxicity and the efficacy of re-treatment with rituximab, a chimeric mouse human anti-CD20 monoclonal antibody, in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (NHL) who responded to rituximab in the previous phase I or phase II study. Thirteen patients with relapsed B-cell NHL, each of whom was confirmed to have Revised European-American Lymphoma Classification type II, 1-6 histology (indolent B-NHL), enrolled in this re-treatment study. All were re-treated with rituximab at 375 mg/m2 weekly for 4 consecutive weeks. Rituximab re-treatment was well tolerated with no grade 3/4 nonhematological toxicities, similar to that of the initial treatment. No patients developed detectable human anti-chimeric antibody. Partial responses were observed in 5 of 13 patients (38%; 95% confidence interval [CI], 14% to 68%); 6 patients showed stable disease and 2 showed progressive disease. Overall survival rate was 93% at 19 months of median follow-up after rituximab re-treatment. Median progression-free survival (PFS) after the re-treatment was 5.1 months (95% CI, 4.1 to 5.6 months), and the median PFS after the initial treatment was 8.2 months (95%CI, 5.9 to 11.3 months). Although rituximab re-treatment induced prolonged depletion of normal peripheral blood B cells in all patients, no significant decrease in serum immunoglobulin or complement level was observed. In conclusion, rituximab re-treatment was well tolerated, and it may produce a prolonged PFS in some patients with indolent B-cell NHL who showed initial response to rituximab.

Adult↗
PubMed2001

HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta.

The vasorelaxant profile of a novel azulene-1-carboxamidine derivative, HNS-32 [N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethyl-azulene-1-carboxamidine, CAS 186086-10-2], was investigated in the isolated rabbit aorta precontracted with high KCl, noradrenaline (NA) or phorbol 12, 13-dibutyrate (PDBu) and compared with those of nifedipine and nitroglycerin. In preparations without endothelium, HNS-32 elicited concentration-dependent, full inhibition of contractions elicited by high KCI (80 mM), NA (3x10(-6) M) or PDBu (10(-6) M). In contrast, nifedipine inhibited only the contraction elicited by membrane depolarization with high KCl. Nitroglycerin also attenuated high-KCl-, NA- and PDBu-elicited contractions effectively, although full suppression was obtained only for NA-elicited contraction. Whilst the relaxant effect of HNS-32 was not affected by the presence of endothelium, the relaxant response to acetylcholine was endothelium dependent. Addition of excess Ca2+ restored both the HNS-32-reduced tension in muscle precontracted with high KCI and the nifedipine-mediated tension decrease. Relaxation elicited by HNS-32 was not affected by the adenylate cyclase inhibitor, 9-(tetrahydro-2'-furyl)adenine (SQ 22,536, 10(-4) M), the soluble guanylate cyclase inhibitor, 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one (ODQ, 10(-5) M) or a cocktail of K+ channel blockers (glybenclamide 10(-6) M, tetraethylammonium 2x10(-3) M, apamin 10(-7) M, 4-aminopyridine 10(-4) M and Ba2+ 10(-5) M). These findings indicate that HNS-32 inhibits both L-type Ca2+ channel-dependent and -independent vascular contraction. Blockade of Ca2+ entry through L-type Ca2+ channels may be involved in the inhibitory effect of HNS-32 on the contraction due to membrane depolarization with high KCl. On the other hand, HNS-32 seems to inhibit Ca2+ channel-independent contraction via mechanism(s) other than elevation of cyclic nucleotides (cAMP and cGMP) and opening of K+ channels.

Animals↗
PubMed2001

Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation.

OBJECTIVE: To characterize the pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation (LDLT). METHODS: Thirty-five patients were given tacrolimus as 18- to 60-h intravenous infusions after surgery, followed by a 4-week course of oral dose therapy (at 0900 hours and 2100 hours). Blood samples were collected daily in the morning (0800 hours) beginning the day after surgery. Whole blood concentration data were evaluated by nonlinear mixed-effect modeling using the program NONMEM and were characterized using a one-compartment model. RESULTS: The clearance (CL, l h(-1)) was related to the grafted hepatic weight, postoperative days (POD), and hepatic and renal dysfunction. Interindividual variabilities in CL, volume of distribution (V), and bioavailability (F) were 57.4%. 39.7%, and 63.0%, respectively, and the correlation between individual CL and F was 0.776. Residual intraindividual variability was 2.9 ng ml(-1). Based on the estimated final parameters, a typical recipient of LDLT with grafted hepatic weight of 600 g and normal hepatic and renal function would have a CL of 0.737 l h(-1) on POD 0 and 1.14 l h(-1) on POD 30, V of 1.52 l kg(-1) and F of 6.8%. CONCLUSIONS: Nonlinear mixed-effect modeling was useful for analysis of pharmacokinetic characteristics of tacrolimus in LDLT patients. Immediately after surgery, patients receiving LDLT showed a smaller CL value than other transplant patients, and CL value increased with POD within 30 days after surgery. The estimated population pharmacokinetic parameters can be applied for a priori dosage calculations in adult patients with LDLT.

Adolescent↗
PubMed2001

A new approach to mRNA in proximal tubule cells of patients with CLCN5 channelopathy.

ClC-5 is a chloride channel whose gene mutations have been reported to be associated with X-linked nephrolithiasis (XRN), X-linked recessive hypophosphatemic rickets (XLRH), Dent disease, and idiopathic low-molecular-weight proteinuria (ILMWP) in Japanese children. To establish more efficient screening for CLCN5 abnormalities, we developed a new diagnostic method using reverse transcription and polymerase chain reaction (RT-PCR) of cultured renal tubular cells from the urine of patients. Using this new method, we successfully detected microdeletion of ClC-5 mRNA in a patient and splicing abnormality of the CLCN5 Cl channel.

Cells, Cultured↗
PubMed2001

Identification of mutans streptococcal species by the PCR products of the dex genes.

A pair of polymerase chain reaction (PCR) primers was designed on the basis of the nucleotide sequence homology of dextranase genes (dex) of Streptococcus mutans, S. sobrinus and S. downei. The primer pair amplified a 530-bp DNA fragment on the dex genes of mutans streptococcal species: S. mutans, S. sobrinus, S. downei, S. rattus and S. cricetus. HaeIII digestion of the 530-bp fragments generated species-specific subfragments, which were easily distinguishable from each other by agarose gel electrophoresis. These results suggest that the PCR-amplification of the dex gene followed by the HaeIII digestion is useful for rapid identification of the five species of mutans streptococci.

Animals↗
PubMed2001

Identification of two novel mutations in the CLCN5 gene in Japanese patients with familial idiopathic low molecular weight proteinuria (Japanese Dent's disease).

Two Japanese patients, belonging to unrelated families, with idiopathic low-molecular-weight proteinuria (LMWP; Japanese Dent's disease) showed novel mutations of the gene encoding renal-specific chloride channel 5 (CLC-5). Proteinuria was first noticed at the ages of 2 and 3 years in patients 1 and 2, respectively. During follow-up, marked increases in urinary ss(2)-microglobulin levels, hypercalciuria, and high levels of urinary excretion of growth hormone were observed in both patients. Nephrocalcinosis was detected in patient 2. Renal biopsy specimens from both patients showed minimal alterations in glomeruli and tubulointerstitium, except for mild mesangial proliferation in patient 2. DNA sequence analysis of the entire 2,238-bp coding region and exon-intron boundaries of the CLCN5 gene showed the presence of two novel mutations in exon 10, consisting of one missense mutation (I524K) in patient 1 and one nonsense mutation (R637X) in patient 2. DNA analysis and measurement of urinary ss(2)-microglobulin levels in family members indicated an X-linked mode of inheritance in patient 1 and sporadic occurrence in patient 2. These results have expanded our understanding of the association between idiopathic LMWP (Japanese Dent's disease) and mutations of the CLCN5 gene.

Adolescent↗
PubMed2001

Factors affecting the pharmacokinetics of CPT-11: the body mass index, age and sex are independent predictors of pharmacokinetic parameters of CPT-11.

This study was conducted to describe the relationship between pharmacokinetics of CPT-11 and its active metabolite SN-38, and clinical values with special emphasis on the influence of relative weight referring to the appropriateness of a conventional dose adjustment method by body surface area (BSA). Thirty-six patients received 100 mg/m2 of CPT-11 intravenously over 90 min. Body Mass Index (BMI) was used as a measure of relative weight which is calculated from the equation: BMI=weight(kg)/[height(m)]2. The area under the concentration-time curve (AUC) of CPT-11 was significantly correlated with sex, age, poorer creatinine clearance and indocyanine green retention test (ICG). The peak plasma concentration (Cmax) of CPT-11 was significantly correlated with sex a larger BMI, BSA and age. The AUC of SN-38 was significantly correlated with ICG. The volume of distribution at steady state of CPT-11 inversely correlated with BMI. Multiple regression analysis revealed that the best fitting model with significant independent predictors for AUC of CPT-11 included age and sex (F=6.93, R2=0.29). That of Cmax of CPT-11 included sex and BMI (F=8.96, R2=0.35). The only independent predictor of AUC of SN-38 was ICG (F=7.75, R2=0.19). These results indicated that several factors affect pharmacological behaviors of CPT-11 even in patients with normal organ functions. The dose modification method based solely on BSA is not sufficient to reduce interpatient variability of cancer chemotherapy. The influence of relative weight, sex and age on pharmacokinetics/pharmacodynamics should be taken into consideration in every pharmacological approach to establish the ideal dose modification method.

Adult↗
PubMed2001

Prognostic significance of changes in prostate-specific antigen in patients with metastasis prostate cancer after endocrine treatment.

Patients with metastatic prostate cancer respond to androgen withdrawal therapy, but progression to androgen independence is frequently observed. To clarify the predictor of response to endocrine therapy, the role of PSA changes and the prognosis of the patients were evaluated in 115 Japanese cases of prostate cancer with distant metastases treated with androgen withdrawal therapy. When patients were divided according to the pretreatment PSA value (high, > or = 500, median; 500 > PSA > or = 100, low; 100 >), patients whose initial PSA levels were high had a worse cause-specific survival. PSA value at 3 or 6 months following endocrine treatment, PSA nadir, and percent decrease of PSA were associated with prolonged survival. Clinical relapse was observed in 68 patients. Patients with distant recurrence had shorter time to PSA elevation than those with local recurrence. In metastatic prostate cancer patients treated with androgen withdrawal, serial measurement of PSA could distinguish nonfavorable responders early in the course of treatment and assist in monitoring for disease progression.

Aged↗
PubMed2001

Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes.

AIMS: To study the influence of CYP2D6*10 on the formation of p-hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM) using microsomes from human liver of known genotypes. METHODS: Microsomes from human livers of genotype CYP2D6*1/*1 (n = 5), *1/*10 (n = 6) and *10/*10 (n = 6) were used in this study. The formation of PHM and HMM was determined by high-performance liquid chromatography. RESULTS: The formation rates of PHM and HMM were decreased by more than 50% and 85% in CYP2D6*1/*10 and *10/*10 microsomes, respectively, compared with *1/*1 microsomes. CONCLUSIONS: The metabolism of mexiletine to form PHM and HMM appears to be impaired to a significant extent in human liver microsomes from hetero- and homozygotes of CYP2D6*10.

Alleles↗
PubMed2001

Erythropoietin synthesis by tumour tissues in a patient with uterine myoma and erythrocytosis.

We report a patient with uterine myoma (leiomyoma) and erythrocytosis in whom erythropoietin (Epo) production in the leiomyoma tissue was identified by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). A 48-year-old Japanese woman with uterine myoma showed marked erythrocytosis (haemoglobin: 20.2 g/dl, haematocrit: 61.1%, red blood cells: 6.51 x 10(12)/1). After hysterectomy, erythrocytosis rapidly disappeared. In the leiomyoma tissue collected from the patient, Epo mRNA expression was confirmed using RT-PCR. Furthermore, ELISA showed that the Epo protein level was significantly increased compared with those in control tissues. It is suggested that the pathogenesis of erythrocytosis in patients with uterine myoma involves ectopic Epo production by leiomyoma tissues.

Enzyme-Linked Immunosorbent Assay↗
PubMed2001

Cloning and characterization of the Xenopus laevis p8 gene.

The p8 gene encodes a transcription factor with a basic helix-loop-helix motif and has been cloned in rat, mouse and human. It is upregulated in acute pancreatitis. In the present study, the Xenopus laevis homolog of p8 (Xp8) was isolated by PCR. The full-length Xp8 cDNA consists of 677 bp and encodes 82 amino acids. The basic helix-loop-helix region is well conserved between X. laevis and mammals. Overexpression of an Xp8-EGFP fusion protein indicated that Xp8 was localized to nucleus, as in mammals. Analysis by RT-PCR showed that expression of Xp8 was increased after gastrulation and maintained into later developmental stages. Expression was detected in the prospective neural region at the neurula stage by whole-mount in situ hybridization. At the larval stage, Xp8 was expressed in central nervous regions, such as ventrolateral brain, trigeminal nerve, vestibulocochlear nerve and dorsal neural tube. Expression was also detected in the basal cement gland, olfactory placode, ear vesicle, notochord and anus. This specific pattern of expression suggests that Xp8 may play a role in the development of the central nervous system in X. laevis.

Amino Acid Sequence↗
PubMed2001

Aberrant expression of Pax-2 mRNA in renal cell carcinoma tissue and parenchyma of the affected kidney.

BACKGROUND: Pax proteins are transcription factors that demonstrate oncogenic properties and appear to play a crucial role in ontogenesis. Pax-2 is expressed in early kidney organogenesis, Wilms' tumor and renal cell carcinoma. In order to determine whether the expression of Pax-2 mRNA is a frequent and specific event in renal cell carcinoma, its expression in nephrectomized specimens and cell lines was investigated. METHODS: The expression of Pax-2 mRNA was examined by reverse transcription polymerase chain reaction in 55 nephrectomized specimens, nine renal parenchyma specimens from patients without renal cell carcinoma and 16 cell lines from various malignant diseases. RESULTS: All tumor tissue specimens expressed Pax-2 mRNA. In addition, 38 of 55 specimens from the renal parenchyma of the affected kidney expressed Pax-2 mRNA. In contrast, only two of the nine kidney specimens from patients without renal cell carcinoma expressed Pax-2 mRNA, indicating that expression of this protein is significantly higher in renal cell carcinoma (P < 0.01). All three cell lines from renal cell carcinoma expressed Pax-2. In contrast, Pax-2 was only expressed in two of three cell lines from transitional cell carcinoma and in none of the other lines. CONCLUSION: The results indicate that Pax-2 expression is a frequent and highly specific event in renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2001

Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer.

BACKGROUND: Long-term results were analyzed to evaluate the role of endocrine therapy in the management of local and distant recurrence of prostate cancer following external radiation therapy. METHODS: Between 1976 and 1994, 92 patients with untreated prostate cancer underwent external beam radiation therapy alone. Endocrine therapy had been started when relapse was evident. RESULTS: Failure was seen in 35 of 92 patients: 10 local, 19 distant and six biochemical failures. Endocrine treatment was performed in 28 patients with nine local and 19 distant failures. The cancer-specific survival rate from the endocrine treatment was 54.5% at 5 years. Prostate-specific antigen level in 20 of 20 patients (100%) decreased to below the normal limit 3 months after the start of endocrine therapy. In univariate analysis, T classification was the most significant variable for cancer-specific survival from the initial treatment. CONCLUSIONS: A favorable outcome was achieved by endocrine therapy in patients who had relapsed after external beam radiation monotherapy. Even the recurrent tumor had a sensitivity to androgen. Patients with locally advanced disease (T2b and T3) had poorer prognosis than those with minimally extended disease (T1b and T2a).

Aged↗