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Biomedical subjects

T Tajima

Publications and source records attributed to T Tajima.

At least 37 records · Page 2Linked to original sources
PubMed2001

Clinical development of trastuzumab in breast cancer.

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) is now available for clinical use in the U.S.A. It is also expected to be available in Japan in the near future. In this paper, the details of this novel biologic agent are reviewed in conjunction with a phase I study performed in Japan.

Animals↗
PubMed2001

Compassionate use of humanized anti-HER2/neu protein, trastuzumab for metastatic breast cancer in Japan.

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) was approved for clinical use in the US in 1998. In Japan, it was approved and later became available in June, 2001. We have treated 41 patients with metastatic breast cancer with trastuzumab purchased from the US. In this paper, the details of the patients we experienced are reviewed.

Adult↗
PubMed2001

Quantitative analysis of infantile ureteropelvic junction obstruction by diuretic renography.

Infantile hydronephrosis detected by ultrasonography poses a clinical dilemma on how to treat the condition. This article reports a retrospective study to evaluate infantile hydronephrosis due to suspected ureteropelvic junction (UPJ) obstruction by means of standardized diuretic renography and to speculate its usefulness for quantitative assessment and management of this condition. Between November 1992 and July 1999, 43 patients who had the disease detected in their fetal or infantile period were submitted to this study. Standardized diuretic renograms were obtained with 99mTc-labeled diethylene-triaminepenta-acetate (Tc-99m-DTPA) or 99mTc-labeled mercaptoacetyl triglycine (Tc-99m-MAG3) as radiopharmaceuticals. Drainage half-time clearance (T 1/2) of the activity at each region of interest set to encompass the entire kidney and the dilated pelvis was used as an index of quantitative analysis of UPJ obstruction. Initial T 1/2s of 32 kidneys with suspected UPJ obstruction were significantly longer than those of 37 without obstruction. T 1/2s of kidneys which had undergone pyeloplasty decreased promptly after surgery whereas those of units followed up without surgery decreased more sluggishly. These findings demonstrate that a standardized diuretic renographic analysis with T 1/2 can reliably assess infantile hydronephrosis with UPJ obstruction and be helpful in making a decision on surgical intervention.

Child, Preschool↗
PubMed2001

Hepatic nodular hyperplasia in a boy with Alagille syndrome: CT and MR appearances.

A boy with Alagille syndrome complicated by hepatic nodular hyperplasia (HNH) is reported. During pre-transplantation evaluation, CT and MRI revealed a large hepatic lesion with multiple small nodular lesions. Angiography demonstrated a large hypervascular lesion and CT arterial portography (CTAP) showed a portal perfusion defect corresponding to the lesion. CTAP also revealed large portal vein branches running through the lesion. Although hepatocellular carcinoma is known to accompany Alagille syndrome, HNH should also be considered when large vessels running through the lesion are demonstrated.

Alagille Syndrome↗
PubMed2001

A pharmacological study of the weekday-on/weekend-off oral UFT schedule in colorectal cancer patients.

PURPOSE: The new weekday-on/weekend-off schedule for oral UFT administration consists of its administration for 5 consecutive days followed by 2 days off the drug. The intratumor 5-FU (5-fluorouracil) concentration has been reported to be correlated to the tumor response in patients treated with intravenous 5-FU. The aim of this study was to investigate the pharmacokinetics during the 2 days off the drug in cancer patients treated with the weekday-on/weekend-off schedule for oral UFT. METHODS: The subjects were 24 colorectal cancer patients. They were divided into three groups, and were all given UFT, 600 mg/day, for 5 days before surgery. Surgery was performed 2, 24, or 48 h after the final dose of UFT. The 5-FU concentrations in the serum, tumor, and in the normal mucosa were measured. RESULTS: The serum 5-FU concentrations after the final dose of UFT were: 23 +/- 12 ng/ml (mean +/- SD) at 2 h, 7 +/- 3 ng/ml at 24 h, and 6 +/- 3 ng/ml at 48 h. The intratumor 5-FU concentrations were: 113 +/- 45 ng/g at 2 h, 54 +/- 20 ng/ml at 24 h, and 54 +/- 35 ng/ml at 48 h, and the concentrations in the normal mucosa were: 36 +/- 15 ng/g (mean +/- SD) at 2 h, 17 +/- 6 ng/ml at 24 h, and 18 +/- 6 ng/ml at 48 h after the final dose. While the serum 5-FU concentration decreased to very low levels by 24 h after the final dose of UFT, the intratumor 5-FU concentrations were maintained at more than 50 ng/g at least until 48 h after the final dose. The 5-FU concentrations in the normal mucosa were maintained at about one third of the intratumor concentrations at all time points. CONCLUSION: Although the weekday-on/weekend-off schedule for UFT administration included intermittent 2-day drug-off periods, this pharmacokinetic study revealed that the 5-FU concentrations in the tumor were maintained at much higher levels than in the serum throughout these periods.

Administration, Oral↗
PubMed2001

Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia.

Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of Gsalpha protein, this mutation may impair Gs protein function. We report here one novel Gsalpha mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous.

Adult↗
PubMed2001

Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

Acetylcholine↗
PubMed2001

Capsid protein gene variation among feline calicivirus isolates.

We amplified the capsid protein gene fragments of 30 Japanese isolates of feline calicivirus (FCV), including the C, D, and E regions, by reverse transcription-polymerase chain reaction (RT-PCR), followed by direct sequencing. Alignment of the predicted amino acid sequences, together with other published sequences from the isolates obtained in other countries, demonstrated a marked heterogeneity among the isolates, confirming the current definition of hypervariable regions within the capsid protein: these regions give rise to the antigenic variations seen in FCV isolates. Phylogenetic analysis of the nucleotide sequences could not identify significant geographically or temporally separated clusters of FCV isolates, supporting the theory of a single genotype.

Amino Acid Sequence↗
PubMed2001

Comparative study of sequential expression of the organizer-related genes in normal Cynops pyrrhogaster embryos and mesodermalized ectoderm.

An artificially mesodermalized ectoderm (mE) of early Cynops pyrrhogaster gastrula acquires the organizer property; the mE is able to induce the secondary axis. The expression of organizer-related genes was investigated during the mesodermalizing process of the mE. The expression of C. pyrrhogaster organizer-related genes, such as bra, gsc, lim-1, chd and noggin, were analyzed. Cynops pyrrhogaster shh expression was also investigated. The organizer-related genes were activated by 12 h after the mesoderm-inducing stimulus. It was noted that there was a temporal gap in the expression of each gene. The expression of bra and gsc seemed to be more quickly activated during the mesodermalizing process. While expression of lim-1 and noggin was activated later than that of bra and gsc, lim-1 expression was earlier than chd and noggin expression. Shh expression was activated later than lim-1/noggin. The present study suggests the possibility that the bra/gsc, lim-1, chd, noggin and shh genes are expressed one by one in that order during the mesodermalizing of the presumptive ectoderm. It also indicates that the sequence is not always consistent with that of the whole embryo during normal embryogenesis. The meaning of the discrepancy will be discussed in connection with the cascade of certain genes expressed during the mesodermalizing process.

Actins↗
PubMed2001

A case with HER2-overexpressing breast cancer completely responded to humanized anti-HER2 monoclonal antibody.

This is a case report of a 57-year-old woman with a history of primary carcinoma of the right breast with metastases to the contralateral axillary lymph node. After a partial response (PR) was induced by high-dose chemotherapy with peripheral blood stem cell transplantation, she underwent mastectomy with biopsy of the bilateral axillary lymph nodes. Six months after surgery, the patient had multiple lung metastases. She was then treated with five cycles of fluorouracil, mitoxantrone and vindesine. Although a PR was achieved, further chemotherapy could not be given because of cardiac dysfunction. Since immunohistochemical staining for the HER2 gene product was strongly positive on the surface of primary tumor cells, humanized anti-HER2 monoclonal antibody (trastuzumab) was given intravenously. The metastatic lesion decreased in size and finally appeared to be only cicatricial. Twenty-one months after the initial administration of trastuzumab, the pulmonary lesion was excised. The pathological examination revealed no tumor cells in the resected specimen so further treatment was stopped. The relapse-free state has continued for 24 months after the pulmonary resection.

Antibodies, Monoclonal↗
PubMed2001

Prediction of osteonecrosis by magnetic resonance imaging after femoral neck fractures.

Thirty-one patients undergoing internal fixation for femoral neck fractures who were examined by magnetic resonance imaging at 2, 6, and 12 months after surgery and who could be followed up more than 2 years were enrolled in the current study. The items investigated were timing of the appearance of the band image on T1 weighted images, magnetic resonance imaging classification, and plain radiographs. Band images were observed 2 months after surgery in eight patients and 6 months in 12 patients (39% of all patients). According to the location and extent of the band image on magnetic resonance imaging, one patient was classified in the B1 Group (lateral type), four patients in the B2 Group (surface type), three patients in the B3 Group (intermediate type), and four patients in the B4 Group (extended type). Band images appeared in all patients in the B4 Group 6 months after surgery. Femoral heads of the patients in the B3 and B4 Groups by magnetic resonance imaging classification all were collapsed. On plain radiographs, osteonecrosis of the femoral head could be diagnosed in eight patients between 11 and 24 months after injury. The interval giving the greatest sensitivity, specificity, and accuracy of the diagnosis of osteonecrosis of the femoral head by magnetic resonance imaging was 6 months after surgery.

Adult↗
PubMed2001

Whole body PET for the evaluation of bony metastases in patients with breast cancer: comparison with 99Tcm-MDP bone scintigraphy.

The purpose of this study was to determine the potential role of positron emission tomography (PET) using 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) for the evaluation of bony metastasis compared with 99Tcm-methylene diphosphonate (99Tcm-MDP) bone scintigraphy in patients with breast cancer. Fifty-one female patients with breast cancer who had PET together with a bone scan within 1 month between September 1994 and March 1997 were included in this study. The median age was 49 years (range 29-79 years). The sensitivity, specificity and accuracy of the bone scan were 77.7%, 80.9% and 80.3%, respectively. On the other hand, for the detection of bone metastases PET had a sensitivity, specificity and accuracy of 77.7%, 97.6% and 94.1%, respectively. In the diagnosis of bony metastasis derived from breast cancer, FDG-PET was statistically superior to bone scintigraphy in its specificity. In conclusion, FDG-PET appears to be a powerful tool not only in the diagnosis of the primary lesion and soft tissue metastasis, but also in the diagnosis of bony metastasis among patients with breast cancer.

Adult↗
PubMed2001

Transcriptional analysis of p30 major outer membrane multigene family of Ehrlichia canis in dogs, ticks, and cell culture at different temperatures.

Ehrlichia canis, an obligatory intracellular bacterium of monocytes and macrophages, causes canine monocytic ehrlichiosis. E. canis immunodominant 30-kDa major outer membrane proteins are encoded by a polymorphic multigene family consisting of more than 20 paralogs. In the present study, we analyzed the mRNA expression of 14 paralogs in experimentally infected dogs and Rhipicephalus sanguineus ticks by reverse transcription-PCR using gene-specific primers followed by Southern blotting. Eleven out of 14 paralogs in E. canis were transcribed in increasing numbers and transcription levels, while the mRNA expression of the 3 remaining paralogs was not detected in blood monocytes of infected dogs during the 56-day postinoculation period. Three different groups of R. sanguineus ticks (adult males and females and nymphs) were separately infected with E. canis by feeding on the infected dogs. In these pools of acquisition-fed ticks as well as in the transmission-fed adult ticks, the transcript from only one paralog was detected, suggesting the predominant transcription of that paralog or the suppression of the remaining paralogs in ticks. Expression of the same paralog was higher whereas expression of the remaining paralogs was lower in E. canis cultivated in dog monocyte cell line DH82 at 25 degrees C than in E. canis cultivated at 37 degrees C. Analysis of differential expression of p30 multigenes in dogs, ticks, or monocyte cell cultures would help in understanding the role of these gene products in pathogenesis and E. canis transmission as well as in designing a rational vaccine candidate immunogenic against canine ehrlichiosis.

Animals↗
PubMed2001

Compound heterozygous mutations in the gamma subunit gene of ENaC (1627delG and 1570-1G-->A) in one sporadic Japanese patient with a systemic form of pseudohypoaldosteronism type 1.

The systemic form of pseudohypoaldosteronism type 1 (PHA1) is a rare autosomal recessive disorder with salt-wasting, hyperkalemia, metabolic acidosis, and multiorgan aldosterone unresponsiveness. Recently, this form of PHA1 was found to be caused by the loss-of-function mutations in the gene of each subunit (alpha, beta, and gamma) of the epithelial sodium channel (ENaC). To investigate the molecular basis of one sporadic Japanese patient with a systemic form of PHA1, we determined the nucleotide sequence of the genes of every subunit of ENaC of this patient. The patient was found to be a compound heterozygote for one base deletion in exon 12 (1627delG) in combination with 1570-1-->GA substitution at the 5' splice acceptor site of intron 11 in the gamma subunit gene of ENaC. The 1627delG mutation altered a reading frame, resulting in a premature stop codon in exon 12. Messenger RNA from the allele harboring the splice site mutation was not identified by RT-PCR. In conclusion, two novel mutations in the gamma subunit gene of ENaC caused systemic PHA1 in the sporadic Japanese patient. Identification of the molecular basis of PHA1 is helpful for early diagnosis and understanding the pathophysiology of the disease.

Asian People↗
PubMed2001

Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency.

Cytochrome P450scc, the mitochondrial cholesterol side chain cleavage enzyme, is the only enzyme that catalyzes the conversion of cholesterol to pregnenolone and, thus, is required for the biosynthesis of all steroid hormones. Congenital lipoid adrenal hyperplasia is a severe disorder of steroidogenesis in which cholesterol accumulates within steroidogenic cells and the synthesis of all adrenal and gonadal steroids is impaired, hormonally suggesting a disorder in P450scc. However, congenital lipoid adrenal hyperplasia is caused by mutations in the steroidogenic acute regulatory protein StAR; it has been thought that P450scc mutations are incompatible with human term gestation, because P450scc is needed for placental biosynthesis of progesterone, which is required to maintain pregnancy. In studying patients with congenital lipoid adrenal hyperplasia, we identified an individual with normal StAR and SF-1 genes and a heterozygous mutation in P450scc. The mutation was found in multiple cell types, but neither parent carried the mutation, suggesting it arose de novo during meiosis, before fertilization. The patient was atypical for congenital lipoid adrenal hyperplasia, having survived for 4 yr without hormonal replacement before experiencing life-threatening adrenal insufficiency. The P450scc mutation, an in-frame insertion of Gly and Asp between Asp271 and Val272, was inserted into a catalytically active fusion protein of the P450scc system (H2N-P450scc-Adrenodoxin Reductase-Adrenodoxin-COOH), completely inactivating enzymatic activity. Cotransfection of wild-type and mutant vectors showed that the mutation did not exert a dominant negative effect. Because P450scc is normally a slow and inefficient enzyme, we propose that P450scc haploinsufficiency results in subnormal responses to ACTH, so that recurrent ACTH stimulation leads to a slow accumulation of adrenal cholesterol, eventually causing cellular damage. Thus, although homozygous absence of P450scc should be incompatible with term gestation, haploinsufficiency of P450scc causes a late-onset form of congenital lipoid adrenal hyperplasia that can be explained by the same two-hit model that has been validated for congenital lipoid adrenal hyperplasia caused by StAR deficiency.

17-alpha-Hydroxyprogesterone↗