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N Katsumata

Publications and source records attributed to N Katsumata.

At least 73 records · Page 4Linked to original sources
PubMed1998

CD44 variant isoform expression and breast cancer prognosis.

We examined the expression of CD44 isoforms in samples of breast cancer tissues from 95 patients by reverse transcription-polymerase chain reaction and immunohistochemistry, and tried to correlate the results with survival period. At the RNA level, expression of exon v2 was observed in 33 (35%) and that of v6 in 69 (73%) of the 95 specimens. Patients with CD44v2 mRNA expression had significantly shorter survival times than those with v2-negative tumors (P = 0.05), but there was only a weak correlation, if any, between v6 mRNA expression and overall survival (P = 0.06). Tumor tissue from 22 (23%) and 72 (76%) patients showed positive immunoreactivity with monoclonal antibody (mAb) M23.6.1. (CD44v2) and mAb 2F10 (CD44v6), respectively. Immunohistochemical evidence of CD44v2 peptide expression correlated with overall survival (P = 0.02), but there was no such association with CD44v6 expression in these tumors (P = 0.67). There were significant correlations between v2 immunoreactivity and higher histological grade and lower levels of estrogen and progesterone receptor. There was no significant correlation between v6 immunoreactivity and such clinicopathological characteristics. Although the expression of v2 was significantly associated with reduced overall survival, it was not an independent prognostic factor because it also correlated with progesterone receptor status. These findings suggest that v2 isoform expression might have more value than v6 expression for clinical use.

Antibodies, Monoclonal↗
PubMed1998

Construction and validation of a practical prognostic index for patients with metastatic breast cancer.

PURPOSE: To identify the readily available prognostic factors most helpful in predicting survival and to construct and validate a prognostic index for metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Data from 233 MBC patients, accrued on a multiinstitutional randomized phase III trial (Japan Clinical Oncology Group [JCOG] study 8808), were analyzed to identify significant prognostic factors and a prognostic index was constructed by incorporating these prognostic factors. For validation of the prognostic index, another data set from 315 consecutive MBC patients, who had been treated with standard anthracycline-containing regimens, was analyzed. RESULTS: In multivariate regression analyses, history of adjuvant chemotherapy (ADJCT) (P = .0005), presence of distant lymph nodes (DLNs) (P = .0117) and liver (HEP) (P = .0099) metastases, elevation of serum lactate dehydrogenase (LDH) (P < .0001), and shorter disease-free interval (DFI) (P < .0001) significantly contributed to poorer survival. The prognostic index was constructed as follows: Prognostic Index = ADJCT (not received = 0, received = 1) + DLNs (absent = 0, present = 1) + HEP (absent = 0, present = 1) + LDH (< or = one times normal = 0, > one times normal = 1) + DFI (> or = 24 months = 0, < 24 months = 2). With this prognostic index, patients could be stratified into three risk groups. The median survival times (MSTs) of low-, intermediate- and high-risk groups were 45.5, 24.6, and 10.6 months, respectively (P < .0001). This prognostic index was applied to the validation patients. The respective MSTs for each risk group were 49.6,22.8, and 10.0 months (P < .0001). CONCLUSION: ADJCT, DLNs, HEP, LDH, and DFI were important prognostic factors for MBC patients. The prognostic index readily enables MBC patients to be stratified into three risk groups and is worth considering for future clinical trials.

Analysis of Variance↗
PubMed1998

Nutrition related hormonal changes in obese children.

Children with simple obesity (SO) show increased linear growth with normal or high serum insulin-like growth factor-I (IGF-I) levels during prepubertal period, despite low GH secretion. We measured IGF-I, IGFBP-1, GHBP and other factors to clarify the hormonal relation between the nutrition and the linear growth in SO and compared these factors with children with normal short stature (NS). Subjects were 23 SO and 19 NS children, and their height standard deviation (SD) scores were 0.7 +/- 0.2 SD and -3.4 +/- 0.3 SD (mean +/- SEM) (P < 0.01), respectively. Oral glucose tolerance test (OGTT) was performed in all the subjects and GH-releasing factor (GRF) test was also performed in 13 of SO and 17 of NS. The peak levels of GH in the GRF test were significantly lower in SO than in NS (12.8 +/- 1.7 vs. 39.8 +/- 6.9 ng/ml) and showed a significantly positive correlation with sigma IGFBP-1 (r = 0.63, P < 0.01). Serum GHBP level and IGF-I level were significantly higher in SO than in NS on pubertal stage matching. There was a positive correlation between GHBP and sigma insulin during OGTT (r = 0.75, P < 0.01). When the sum of the values during OGTT was expressed as sigma, sigma insulin, sigma C-peptide and sigma glucose were significantly higher in SO than in NS on pubertal stage matching. Basal and sigma IGFBP-1 were significantly lower in SO than in NS, but IGFBP-3 levels showed no significant difference between the two groups either in prepuberty or midpuberty. In conclusion, it can be hypothesized that the overnutrition causes hyperinsulinemia which increases GH receptor and IGF-I secretion despite low GH secretion. Hyperinsulinemia also may increase free IGF-I by lowering IGFBP-1. These two mechanism are supposed to be the nutrition related hormonal changes in SO and can explain the growth of SO. In addition, the increased free IGF-I may contribute the decreased GH secretion due to negative feedback in SO.

Adolescent↗
PubMed1998

Long term follow-up of a 46,XY phenotypic girl with 17alpha-hydroxylase deficiency treated with alternate-day dexamethasone.

We report an 18-year-old 46,XY phenotypic girl who has been on alternate-day dexamethasone therapy for 10 years. The patient was seen at our hospital for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue, and the karyotype of the peripheral lymphocytes was 46,XY. The diagnosis of 17alpha-hydroxylase deficiency was established by the evaluation of adrenal steroidogenesis at the age of 6.1 years when hypertension was clearly recognized, and was confirmed later by the gene analysis of CYP17 which disclosed a compound heterozygote. The growth rate was suppressed during the initial treatment with daily administration of 0.25-0.5 mg dexamethasone. Switching to alternate-day regimen of dexamethasone 0.5 mg/dose improved height velocity. Subsequent addition of low-dose estrogen therapy induced pubertal growth spurt. The blood pressure and adrenal hormone levels remained almost within the normal range throughout the course. Adrenal function was evaluated at the age of 15 years. Plasma ACTH and corticosterone levels were high only just before the next administration, when the plasma dexamethasone concentration should be at the nadir. Since corticosterone possesses glucocorticoid activity and can work as a glucocorticoid reserve, it is assumed that this mode of dexamethasone administration can be a safe treatment for this disorder. We conclude that the patient with childhood 17alpha-hydroxylase deficiency can be safely and effectively treated with alternate-day dexamethasone without interfering with linear growth.

Adolescent↗
PubMed1998

The regulatory effect of growth hormone on growth hormone-binding protein in human serum.

To study the acute and long-term effect of GH on its down-stream axis, we measured serum GH-binding protein (GHBP) by ligand-mediated immunofunctional assay. Diurnal changes in serum GHBP were determined by every 20-min sampling for 24 h in four normal short children. There were small or negligible fluctuations in serum GHBP levels, and no correlation with GH pulses was observed. The short-term effect of GH on GHBP levels was assessed in eight GH-deficient children by daily administration of GH (0.1 U/kg) for 10 days. Serum GHBP levels did not significantly change, but IGF-I levels increased significantly. We also studied the long-term effect of GH administration on GHBP levels in seventeen patients with GH deficiency over six months. In twelve out of 17 patients, serum GHBP levels showed an increase when compared to the levels before treatment. In these patients, BMI was not largely changed during treatment, while it tended to decrease in patients whose GHBP levels did not increase. In conclusion, endogenous pulsatile GH secretion and short-term exogenous GH administration had no effect on serum GHBP levels. On the other hand, long-term GH administration increased GHBP levels in 70% of patients with GH deficiency. Changes in BMI may partly be attributed to this change. The direct long-term regulatory effect of GH on GHBP should be further studied.

Adolescent↗
PubMed1998

G370C mutation in the FGFR3 gene in a Japanese patient with thanatophoric dysplasia.

Thanatophoric dysplasia (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, relative macrocephaly, platyspondyly and reduced thoracic cavity. It has recently been reported that TD is caused by mutations in the FGFR3 gene. In the present study, we report a missense mutation in the FGFR3 gene in a Japanese patient with TD. The patient was noticed to have typical features of TD type 1 (TD1) at birth. The genomic DNAs of the patient and his parents were isolated from whole blood. DNA fragments of the FGFR3 gene were amplified by polymerase chain reaction, and directly sequenced. The patient was revealed to be heterozygous for a missense mutation G370C, changing codon 370 (GGC) encoding Gly to TGC encoding Cys, but his parents did not have the G370C mutation. The G370C mutation introduces an unpaired cysteine residue in the extracellular domain of FGFR3, which may result in formation of an intermolecular disulfide bond between two mutant FGFR3 monomers and their constitutive activation. In conclusion, we have identified the G370C mutation in the FGFR3 gene in a Japanese TD1 patient.

Alleles↗
PubMed1998

[Neuromuscular inhibitory effects of propofol evaluated by cat's evoked EMG].

Neuromuscular inhibitory effects of propofol were investigated in 7 cats using muscular compound action potential (mCAP) elicited from the gastrocnemius muscle by sciatic nerve stimulation. A rectangular pulse of supramaximal strength and duration of 0.2 msec was applied serially to the sciatic nerve at 0.1 Hz during the experiments, and mCAPs obtained from the gastrocnemius muscle were recorded. After obtaining a constant mCAP amplitude, a series of 8 consecutive mCAPs (M 1-8) evoked by repetitive stimulation at 100 Hz was recorded, and M 8/M 1 amplitude ratio (M 8 amplitude/M 1 amplitude.100%) was calculated as the control value. After control variables had been obtained, initial dose of 2.5 mg.kg-1 of propofol was administered intravenously followed by continuous infusion with incremental dosages of 10, 20, 50 and 100 mg.kg-1.hr-1 of each 30 minute duration. The effects on mCAPs evoked by single and 8 consecutive repetitive stimulation were observed in each period. The depression of single mCAP amplitudes and fading responses in the M 8/M 1 amplitude ratios were not observed at any infusion rate. Our results suggest that propofol has no influence on neuromuscular transmission in cats when administered intravenously at 10 times of human clinical infusion doses.

Anesthetics, Intravenous↗
PubMed1997

Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1beta.

BACKGROUND: Although coronary artery spasm plays an important role in a wide variety of ischemic heart diseases, the intracellular mechanism for the spasm remains to be clarified. We examined the role of myosin light chain (MLC) phosphorylations, a key mechanism for contraction of vascular smooth muscle, in our swine model with interleukin-1beta (IL-1beta). METHODS AND RESULTS: IL-1beta was applied chronically to the porcine coronary arteries from the adventitia to induce an inflammatory/proliferative lesion. Two weeks after the operation, intracoronary serotonin repeatedly induced coronary hyperconstrictions at the IL-1beta-treated site both in vivo and in vitro, which were markedly inhibited by fasudil, an inhibitor of protein kinases, including protein kinase C and MLC kinase. Western blot analysis showed that during serotonin-induced contractions, MLC monophosphorylation was significantly increased and sustained in the spastic segment compared with the control segment, whereas MLC diphosphorylation was noted only in the spastic segment. A significant correlation was noted between the serotonin-induced contractions and MLC phosphorylations. Both types of MLC phosphorylation were markedly inhibited by fasudil. In addition, MLC diphosphorylation was never induced by a simple endothelium removal in the normal coronary artery, whereas enhanced MLC phosphorylations in the spastic segment were noted regardless of the presence or absence of the endothelium. CONCLUSIONS: These results indicate that enhanced MLC phosphorylations in the vascular smooth muscle play a central role in the pathogenesis of coronary spasm in our swine model.

Animals↗
PubMed1997

Serum protein determination by high-performance gel-permeation chromatography.

A general high-performance gel-permeation chromatography (HPGPC) method was developed to determine protein in human serum with improved sensitivity and speed. The optimum UV wavelength for protein detection was found to be 210 nm, by comparing the protein values obtained by varying the UV wavelength of the HPLC detection system with the protein values obtained from spectrophotometric protein assays, i.e., the bicinchoninic acid (BCA) method and the biuret method. The analysis time was less than 1 min. Since this HPGPC serum protein assay method is simple and rapid, it is expected to be particularly well adapted for use in clinical laboratories.

Adolescent↗
PubMed1997

Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo.

BACKGROUND: Although platelet activating factor (PAF) is an important vasoactive substance released from activated leukocytes, platelets and endothelial cells, little is known about its effect at the inflammatory coronary lesions in vivo. OBJECTIVE: To examine the coronary vasomotor responses to PAF at the inflammatory lesions in our swine model with interleukin-1 beta (IL-1 beta) in vivo. METHODS: Under aseptic conditions, the proximal segment of the porcine left coronary artery was dissected and wrapped with cotton mesh absorbing IL-1 beta. Two weeks after the operation, coronary vasomotion in response to intracoronary administration of 0.3 and 1 microgram/kg PAF, 1, 3, and 10 micrograms/kg serotonin, 1, 3 and 10 micrograms/kg histamine, and 5 and 50 micrograms/kg prostaglandin F2 alpha was examined by coronary arteriography. RESULTS: At the IL-1 beta-treated site, PAF, serotonin and histamine, but not prostaglandin F2 alpha, caused hyperconstriction (n = 8). A synergy of the vasoconstricting effects of PAF and serotonin was also noted (n = 6). Administration of TCV-309, a selective PAF receptor antagonist, abolished the hyperconstrictive responses to PAF but not those to other agonists (n = 6). The PAF-induced coronary hyperconstrictions were significantly inhibited by administrations of the protein kinase C inhibitors staurosporine and sphingosine, but not by administrations of ryanodine, thapsigargin, or indomethacin (n = 4 each). CONCLUSIONS: These results indicate that PAF causes hyperconstriction at the inflammatory coronary lesions in vivo by itself as well as in a synergistic manner with serotonin and that the PAF-induced hyperconstrictions are substantially mediated by a protein kinase C-dependent pathway in vivo.

Animals↗
PubMed1997

A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) characterized by early-onset hypertension and hypokalemia is due to congenital deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). Two isoforms of human 11 beta HSD are known, and the type 2 isoform (11 beta HSD2) has been recently shown to be responsible for AME. In this study we have analyzed the 11 beta HSD2 gene of a Japanese patient with AME. PCR amplification and subsequent nucleotide sequencing of the 11 beta HSD2 gene from the patient and his family members revealed that the patient has a compound heterozygous mutation of this gene. In 1 allele, an undescribed single nucleotide transition in codon 208 in exon 3 resulted in a substitution of arginine to histidine (CGC to CAC: R208H). In the other allele, a deletion of 3 nucleotides in codons 337-338 in exon 5 resulted in a substitution of arginine to histidine and a deletion of tyrosine residue (CGCTAT to CAT: R337H, delta Y338), which has been previously shown to abolish 11 beta HSD2 enzyme activity. A chloramphenicol acetyltransferase assay-based expression study involving the mineralocorticoid receptor indicated that the novel R208H mutation eliminates the enzymatic activity of 11 beta HSD2. From the genetic analysis of 50 healthy subjects, the novel R208H mutation was unlikely to be due to polymorphism. Together, these results indicate that this patient is a compound heterozygote for the mutation in the 11 beta HSD2 gene (R208H and R337H, delta Y338) and that these mutations inactivate the 11 beta HSD2 function and give rise to clinically manifest AME.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Magnetic resonance imaging in diagnosis of right coronary arteriovenous fistula--a case report.

We describe a patient with a right coronary arteriovenous fistula in whom magnetic resonance imaging (MRI) was useful in establishing the diagnosis. In a 36-year-old woman, T1 spin echo MRI demonstrated a massively dilated coronary arteriovenous fistula connecting the right coronary artery to the right atrium. The cine field echo technique showed a continuous shunt flow within the fistula as documented by the flow void throughout the cardiac cycle. These findings were confirmed by cardiac catheterization. We conclude that MRI is useful not only in detecting a coronary arteriovenous fistula but also in identifying its origin and the drainage site.

Adult↗
PubMed1997

Homozygous Q258X mutation in the steroidogenic acute regulatory gene in a Japanese patient with congenital lipoid adrenal hyperplasia.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. It has recently been reported that mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH. We analyzed the nucleotide sequences of exon 7 of the StAR gene in a Japanese CLAH patient with a karyotype of 47,XYY, and her parents. The patient was homozygous for a nonsense mutation Q258X, which changed codon 258 (CAG) encoding Gln to the stop codon TAG, and the her parents were heterozygous for the Q258X mutation. Since the Q258X mutation destroys a MvaI site normally present in the StAR gene sequence, we confirmed the Q258X mutation by means of the restriction endonuclease MvaI digestion of the PCR products. Endocrinological examinations of the parents revealed normal responses of adrenal steroid hormones to exogenous adrenocorticotropin administration, confirming the failure to detect the heterozygous carriers of CLAH by hormonal evaluation.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Urinary biotinidase and alanine excretion in patients with insulin-dependent diabetes mellitus.

Twenty-four-hour urine specimens from 21 juvenile insulin-dependent diabetics and 10 healthy controls were compared with respect to biotinidase activity and alanine content. Urinary biotinidase activity was analysed by a newly developed high-performance liquid chromatography (HPLC) method. It was found that the excretion of biotinidase in urine was elevated in diabetics (7.02 mU/d; p < 0.005) as compared with controls (not detectable). Alanine excretion was also found to increase (p < 0.01) in diabetics. Biotinidase excretion in diabetics was correlated with alanine excretion (rS = 0.667; p < 0.01), but not with protein, albumin or N-acetyl-beta-glucosaminidase excretion. The simultaneous elevation of urinary biotinidase and alanine excretion in juvenile diabetics suggests that changes in kidney metabolism arise in the early stages of diabetes.

Acetylglucosaminidase↗
PubMed1997

[Familial male-limited precocious puberty].

Familial male-limited precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. Affected males generally exhibit signs of puberty by the age of 4 years. Testosterone production and Leydig cell hyperplasia occur autonomously in context of prepubertal levels of luteinizing hormone (LH). The LH receptor is a member of the family of G-protein-coupled receptors. Thus far, eleven constitutively activating mutations of the LH receptor gene, which result in high basal cyclic AMP levels, have been identified in pedigree with FMPP and in sporadic cases. It has been suggested that some of the mutations have effects on the Gq coupling and phospholipase-C activation in addition to their effects on Gs coupling and activation of adenylate cyclase.

Child, Preschool↗
PubMed1996

High-performance liquid chromatographic determination of lipoamidase (lipoyl-X hydrolase) activity with a novel substrate, lipoyl-6-aminoquinoline.

An HPLC lipoamidase (lipoyl-X hydrolase) assay method has been developed, which uses a novel fluorescent substrate, lipoyl-6-aminoquinoline (LAQ). LAQ is synthesized from lipoic acid and 6-aminoquinoline (AQ) through lipoyl chloride as an intermediate and is conveniently purified by washing with chloroform-methanol. Mechanistic studies on the time-course, the dependence on enzyme and substrate concentrations were performed by using LAQ and a model enzyme (milk lipoamidase). Moreover, this method was successfully applied to the direct determination of the lipoamidase (LAQ hydrolase) activity in samples of human liver, milk, stools and porcine serum. Using this novel synthetic lipoyl substrate, we demonstrated that LAQ hydrolase was present in some specific tissues; LAQ hydrolase was solely present in the grey matter and not in the white matter in the human cerebrum. Furthermore, LAQ hydrolase activity was shown to increase in human liver cancer. Thus, this enzyme assay method is expected to be applicable to the tissue distribution study and also to the basic research on human diseases such as cancer.

4-Aminobenzoic Acid↗
PubMed1996

Prognostic factors and a predictive model of follicular lymphoma: a 25-year study at a single institution in Japan.

The incidence of follicular lymphoma in Japan is far lower than that in western countries, and no large-scale clinicopathologic studies on this neoplasm have been conducted in Japan. We reviewed histopathological specimens from 118 of 135 patients who had been diagnosed as having follicular lymphoma between 1968 and 1993. Prognostic factors influencing survival were analyzed using univariate and multivariate analyses. Factors that were independently significant upon multivariate analysis were incorporated into a predictive model. Ninety-three patients (78.8%) had a confirmed diagnosis of follicular lymphoma. Twenty-one of the remaining 25 patients were categorized as having other lymphoma subtypes, and four patients showed indefinite findings or those suggesting diseases other than lymphoma. Major characteristics of the 93 patients with follicular lymphoma were a median age of 53 years (20-85); 59 males (63%) and 34 females (37%); small cleaved cell type in 33 (35%), mixed cell type in 41 (44%) and large cell type in 19 (20%); stage I/II in 41 (44%) and stage III/IV in 50 (54%). Overall survival was 71% at 5 years, 58% at 10 years, and 43% at 15 years with a median survival of 13.3 years. Multivariate analysis revealed that two variables, age (>60) (P=0.001) and the serum LDH level (>1 x normal value) (P=0.026), were unfavorably significant prognostic factors influencing survival. The predictive model using these two variables identified three risk groups with estimated five-year survival rates of 88.5%, 56.8%, and 31.5%. Age and serum LDH were significant predictors of survival in Japanese patients with follicular lymphoma. Our predictive model may provide a basis for future therapeutic trials against follicular lymphoma in Japan.

Adult↗