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Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 199 records · Page 11Linked to original sources
PubMed2000

[A case of effective chemotherapy using CAF followed by docetaxel for advanced breast cancer].

A huge mass measuring 13 x 12 cm and wide cutaneous edema were detected in the right breast of a 51-year-old woman. Under a diagnosis of locally advanced breast cancer (T4bN2M1, stage IV) with liver metastases, we attempted sequential neoadjuvant chemotherapy. After three courses of CAF therapy (cyclophosphamide, doxorubicin (DXR), 5-FU), the primary tumor was decreased by 56% and the liver metastases had disappeared. A minor pathologic response was observed. Subsequently, three courses of docetaxel (TXT) administration were carried out. The primary tumor was then decreased by 75% and the axillary metastases had disappeared. Histopathological examination showed gross viable tumor cells in the residual tumor and positive axillary lymph nodes. The only toxic effect was nausea (grade 1) and no major adverse effects were observed. Neoadjuvant chemotherapy with sequential DXR followed by TXT is a useful treatment for locally advanced breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2000

[Two bedridden patients with bone metastases from breast cancer effectively treated with pamidronate therapy].

Case 1: A 43-year-old woman underwent mastectomy because of locally advanced breast cancer with multiple bone metastases. She was treated with CMF therapy but developed a compression fracture of a thoracic vertebra after 10 months and received pamidronate therapy. Pamidronate administration relived her back pain after 2 months and she was able to walk again after 3 months. However, she developed a resistance to the treatment, and then refused another treatment. She was found to have hypercalcemia 6 months later and received pamidronate again, but died 9 months after the treatment. Case 2: A 52-year-old woman underwent mastectomy because of breast cancer (T2) and was diagnosed as having multiple bone metastases 24 months after the operation. She could not turn over in bed due to progressing bone pain and received pamidronate therapy with CMF therapy at home 23 months after the diagnosis. After 2 months, pamidronate administration relieved her bone pain and she was free of pain after 4 months. After 5 months, X-rays revealed that lytic lesions showed sclerosis, and the pamidronate therapy was assessed as producing a PR. Pamidronate therapy improved her quality of life and activities of daily living, and she continues to receive it this time as an outpatient. Pamidronate therapy is promising as an effective treatment for bedridden patients with bone metastasis from breast cancer.

Adult↗
PubMed2000

[Diagnosis of breast cancer extent using dynamic multidetector-row CT: correlation between MPR imaging and pathological cross-sections].

PURPOSE: To evaluate the clinical usefulness of dynamic multidetector-row CT (dynamic MD-CT) for the detection of intraductal extension of breast cancer. MATERIALS AND METHODS: Dynamic MD-CT was performed in 31 patients with breast masses (26 invasive ductal carcinomas, 4 non-invasive ductal carcinomas and one benign lesion). We grouped the cases into four categories according to the degree of intraductal extension of the main tumor: IDS1: intraductal component less than 1 cm, IDS2: intraductal component 1 cm to 2 cm, IDS3: intraductal component 2 cm to 3 cm, IDS4: intraductal component more than 3 cm. To achieve complete CT-pathologic correlation, we retrospectively reconstructed MPR in the same plane as the histological cross-section. RESULTS: Thirty breast carcinomas (100%) showed strong enhancement in both the first and second phases of contrast enhanced dynamic MD-CT. The sensitivity and specificity of dynamic MD-CT for the detection of the intraductal component were 80.0% (12/15) and 100% (15/15). The accuracy of detection for the four tumor categories was 100% (15/15) for IDS1, 25% (1/4) for IDS2, 42.9% (3/7) for IDS3, and 100% (4/4) for IDS4. CONCLUSION: Dynamic MD-CT of the breast was found to be effective for the detection of intraductal extension of breast carcinoma and thought to be useful in the preoperative assessment of indications of breast-conserving surgery.

Adult↗
PubMed2000

[MRI of anterior cruciate ligament autografts].

The purpose of this study was to assess the usefulness of MRI in the evaluation of autografts after anterior cruciate ligament reconstruction. The subjects were 110 patients with anterior cruciate ligament reconstruction using patellar tendon autografts who underwent clinical examination, MRI, and arthroscopy of the knee. T1- and T2-weighted MR images were obtained in sagittal plane. Clinical findings were categorized into three groups: normal, borderline, and abnormal. The MRI appearances of the autografts were categorized into three types: straight continuous band (type I), interrupted band (type II) and generalized increased intensity band (type III). The clinical findings and MRI findings were compared with arthroscopic findings. Ninety-six percent of the type I showed no autograft tear on arthroscopy. In comparison with the clinical findings, MRI was found to be well correlated with arthroscopic findings. In conclusion, if the clinical findings are normal, patients are to be followed-up without MRI and arthroscopy. However, if clinical findings are either borderline or abnormal, MRI should be performed prior to arthroscopy.

Adolescent↗
PubMed2000

[Intra-arterial infusion therapy for unresectable liver metastasis of colorectal cancer].

Fifty-five colorectal carcinomas with metastatic liver tumor treated with intra-arterial 5-FU (> 5 g) infusion therapy at six hospitals were investigated retrospectively. The response rate reached 45%. The metastatic liver tumor from the rectum did not respond as well as that from the colon. Six patients could undergo liver resection and the infusion therapy was stopped in eleven patients due to a new extrahepatic lesion. The ratio of serum CEA levels of non-responders before infusion therapy and one month later was significantly higher and their survival period was shortened. This ratio indicated that this therapy could be continued.

Adenocarcinoma↗
PubMed2000

Optimal hematocrit for the maximum oxygen delivery to the brain with recombinant human erythropoietin in hemodialysis patients.

AIM: Although hematocrit (Ht) around 33 to 36% has been recommended, Ht of 30% is usually achieved as a target level during recombinant human erythropoietin (rHuEPO) therapy in the majority of hemodialysis (HD) patients. The present study aimed at estimating an optimal hematocrit (Ht) for the maximum oxygen delivery to the brain with rHuEPO. PATIENTS AND METHODS: Oxygen delivery was defined as a product of cerebral blood flow and arterial oxygen content (CaO2). The regional cerebral blood flow (rCBF) in each region of interest was measured by positron emission tomography and CaO2 was calculated from hemoglobin concentration, arterial oxygen saturation, and arterial oxygen tension before and after rHuEPO therapy (1,500 units, 3 times a week) in 5 HD patients (the mean age of 52 +/- 2 (SEM) years old and the mean HD duration of 98 +/- 21 months). RESULTS: Ht rose significantly from 21 +/- 1 to 31 +/- 1% (p < 0.001) after the 3-month rHuEPO treatment in association with a significant increase in CaO2 from 7.7 +/- 0.4 to 11.6 +/- 0.3 ml O2/100 ml (p < 0.01). Hemispheric rCBF decreased significantly from 40 +/- 3 to 32 +/- 1 ml/100 g/min (p < 0.02). In all data both before and after rHuEPO treatment, Ht inversely correlated with the hemispheric rCBF (y = 55.7 - 0.76x, where y is rCBF and x is Ht, r = 0.80, p < 0.01), and positively with CaO2 (y = 0.85 + 0.34x, where y is CaO2 and x is Ht, r = 0.95, p < 0.01). By using these correlations, the hemispheric oxygen delivery was expressed as a function of Ht, being y = 47.3 + 18.3x - 0.3 x2, where y is cerebral oxygen delivery and x is Ht. From this curve, Ht at the highest cerebral oxygen delivery in the hemisphere, i.e. an optimal Ht was found to be 35.2%. Above this level of Ht, the hemispheric cerebral oxygen delivery would rather decline. CONCLUSION: The present study indicated that Ht of about 35% is required for a better oxygen delivery to the brain metabolism during anemia correction with rHuEPO.

Anemia↗
PubMed2000

Validation of the Short Michigan Alcoholism Screening Test Thai version in northeastern Thailand.

This study aimed to validate the Short Michigan Alcoholism Screening Test-Thai version-12 items (SMAST-T) compared to the psychiatrist's diagnosis based on DSM-III-R criteria, as a gold standard, among psychiatric patients residing in the northeast of Thailand. Sixty-one pairs of male cases with alcohol use disorders (AUD) and controls were collected through routine examination of psychiatric outpatients, 18-65 years old, who visited the Khon Kaen Psychiatric Hospital or the Northeast Drug Dependence Treatment Center, located in Khon Kaen Province, northeast Thailand, between November, 1996 and February, 1997. Controls were matched for each case in terms of age (+/-5 years), province and urbanization of residence. They were interviewed using the SMAST-T and a structured questionnaire. Receiver operating characteristic analysis revealed that the optimum cutoff point of 4 or over on the SMAST-T yielded the best sensitivity and specificity (96.7% and 95.1%, respectively), along with the area under the curve of 0.994, indicating that it was sensitive and specific in discriminating AUD from the non-AUD patients. Validation of the SMAST-T suggests its applicability as a screening interview questionnaire to detect AUD among northeast Thai males, with a specific cutoff point.

Adolescent↗
PubMed1999

Hypertrophic stimuli augment expression of cMG1/ERF-1, a putative zinc-finger motif transcription factor, in rat cardiomyocytes.

We isolated the gene for cMG1/ERF-1, a known putative zinc-finger transcription factor, by differential display of mRNA extracted from cardiomyocytes with and without leukemia inhibitory factor (LIF) stimulation. LIF induced cMG1/ERF-1 mRNA at 15 min, and levels peaked at 10-fold initial levels at 30 min. cMG1/ERF-1 expression was inhibited by AG490 (JAK2 inhibitor) and genistein, but was unaffected by PD98059 or wortmannin. Phenylephrine, angiotensin II and endothelin-1 also induced cMG1/ERF-1 expression. Mechanical stretch in vitro and acute pressure overload in vivo increased cMG1/ERF-1 expression. To our knowledge, this is the first report showing that the cMG1/ERF-1 gene can be induced by various hypertrophic stimuli, and that Janus kinase 2 is involved in this process.

Angiotensin II↗
PubMed1999

The grading of lymphovascular space invasion in endometrial carcinoma.

BACKGROUND: This study was conducted to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI). METHODS: The prognostic significance of the grading of LVSI as compared with other pathologic variables was evaluated in a study of 303 Japanese women with endometrial carcinoma. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. The effects of different surgical methods and adjuvant therapies on survival were also examined. RESULTS: A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0. 0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. CONCLUSIONS: The grading of LVSI was found to be an important histologic prognostic variable. The severe degree of LVSI also was found to be a good indicator of lymph node metastasis. It is therefore important to evaluate the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.

Endometrial Neoplasms↗
PubMed1999

Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes.

This study was designed to investigate whether insulin-like growth factor-1 (IGF-1) transduces signaling through the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in cardiomyocytes and to assess the upstream signals of serine and tyrosine phosphorylation of STAT family proteins. Primary cultured neonatal rat cardiomyocytes were stimulated with IGF-1 (10(-8) mol/L). JAK1, but not JAK2 or Tyk2, was phosphorylated by IGF-1 as early as 2 minutes and peaked at 5 minutes. IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3. Tyrosine phosphorylation of STAT1 peaked at 15 minutes and correlated with that of JAK1, whereas that of STAT3 was sustained up to 120 minutes and was dissociated from the activation of JAK1. Tyrosine phosphorylation of STAT3 was unaffected by the preincubation with CV11974 (AT(1) blocker), TAK044 (endothelin-1 receptor blocker), RX435 (anti-gp130 blocking antibody), PD98058, wortmannin, EDTA, or KN62 but was significantly attenuated by BAPTA-AM and chelerythrine. The time course of a gel mobility shift of SIE (sis-inducing element) coincided with the phosphorylation of STAT3. Serine phosphorylation of STAT1 peaked at 30 minutes and that of STAT3 was observed from 5 to 60 minutes. These results indicated that (1) IGF-1 activated JAK1 but not JAK2 or Tyk2 in rat cardiomyocytes; (2) IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3; and (3) the tyrosine phosphorylation of STAT3 was not caused by JAK1 alone, and protein kinase C and intracellular Ca(2+) were required for phosphorylation.

Animals↗
PubMed1999

Effects of atypical antipsychotic drugs vs. haloperidol on expression of heat shock protein in the discrete brain regions of phencyclidine-treated rats.

Haloperidol augmented a trend of an increase in the heat shock protein (hsp70) mRNA levels induced by phencyclidine (PCP) in rat medial prefrontal cortex, nucleus accumbens and striatum, while the atypical antipsychotic drugs such as clozapine, olanzapine and risperidone decreased it. When administered alone, clozapine, but not haloperidol, decreased hsp70 mRNA levels. Haloperidol and the atypical antipsychotic drugs may thus have differential effects on hsp70 expression in some brain regions of PCP-treated rats.

Animals↗
PubMed1999

Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development.

During axial skeleton development, the notochord is essential for the induction of the sclerotome and for the subsequent differentiation of cartilage forming the vertebral bodies and intervertebral discs. These functions are mainly mediated by the diffusible signaling molecule Sonic hedgehog. The products of the paired-box-containing Pax1 and the mesenchyme forkhead-1 (Mfh1) genes are expressed in the developing sclerotome and are essential for the normal development of the vertebral column. Here, we demonstrate that Mfh1 like Pax1 expression is dependent on Sonic hedgehog signals from the notochord, and Mfh1 and Pax1 act synergistically to generate the vertebral column. In Mfh1/Pax1 double mutants, dorsomedial structures of the vertebrae are missing, resulting in extreme spina bifida accompanied by subcutaneous myelomeningocoele, and the vertebral bodies and intervertebral discs are missing. The morphological defects in Mfh1/Pax1 double mutants strongly correlate with the reduction of the mitotic rate of sclerotome cells. Thus, both the Mfh1 and the Pax1 gene products cooperate to mediate Sonic hedgehog-dependent proliferation of sclerotome cells.

Animals↗
PubMed1999

Significance of myocytes with positive DNA in situ nick end-labeling (TUNEL) in hearts with dilated cardiomyopathy: not apoptosis but DNA repair.

BACKGROUND: The presence of apoptotic myocytes has been reported in human hearts with dilated cardiomyopathy (DCM) on the basis of a positive finding of DNA in situ nick end-labeling (TUNEL). However, ultrastructural evidence of myocyte apoptosis has not been obtained. METHODS AND RESULTS: A total of 80 endomyocardial biopsies were obtained from right and left ventricles of 20 patients with DCM and 20 normal control subjects. TUNEL-positive myocytes were found by light microscope in 15% of DCM specimens (controls, 0%, P<0.05), and the percentage of TUNEL-positive myocytes per section in DCM was 1. 0+/-2.7% (mean+/-SD). According to TUNEL at the electron microscopic level (EM-TUNEL), immunogold particles, which label DNA breaks with 3'-OH terminals, were markedly accumulated in the bizarre-shaped nuclei, with widespread clumping of chromatin (so-called "hypertrophied nuclei") of the myocytes obtained from DCM. Their ultrastructure was neither apoptotic nor necrotic but rather that of living cells. Taq polymerase-based DNA in situ ligation assay, which detects double-stranded DNA fragments more specifically than TUNEL, did not detect a positive reaction in any case. In mirror sections, all of the TUNEL-positive myocytes in DCM simultaneously expressed proliferating cell nuclear antigen, which is required for both DNA replication and repair, but Ki-67, a replication-associated antigen, was completely negative in all cases, which appeared to rule out cell proliferation activity. CONCLUSIONS: Most of the TUNEL-positive myocytes in hearts with DCM are not apoptotic but rather living cells with increasing activity of DNA repair.

Apoptosis↗
PubMed1999

Mechanical stretch activates the JAK/STAT pathway in rat cardiomyocytes.

This study was designed to determine whether mechanical stretch activates the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in cardiomyocytes and, if so, by what mechanism. Neonatal rat/murine cardiomyocytes were cultured on malleable silicone dishes and were stretched by 20%. Mechanical stretch induced rapid phosphorylation of JAK1, JAK2, Tyk2, STAT1, STAT3, and glycoprotein 130 as early as 2 minutes and peaked at 5 to 15 minutes. It also caused gel mobility shift of sis-inducing element, which was supershifted by preincubation with anti-STAT3 antibody. Preincubation with CV11974 (AT1 blocker) partially inhibited the phosphorylation of STAT1, but not that of STAT3. Preincubation with TAK044 (endothelin-1-type A/B-receptor blocker) did not attenuate this pathway. RX435 (anti-glycoprotein 130 blocking antibody) inhibited the phosphorylation of STAT3 and partially inhibited that of STAT1. Phosphorylation of STAT1 and STAT3 was strongly inhibited by HOE642 (Na+/H+ exchanger inhibitor) and BAPTA-AM (intracellular calcium chelator), but not by gadolinium (stretch-activated ion channel inhibitor), EGTA (extracellular Ca2+ chelator), or KN62 (Ca2+/calmodulin kinase II inhibitor). Chelerythrine (protein kinase C inhibitor) partially inhibited the phosphorylation of STAT1 and STAT3. Mechanical stretch also augmented the mRNA expression of cardiotrophin-1, interleukin-6, and leukemia inhibitory factor at 60 to 120 minutes. These results indicated that the JAK/STAT pathway was activated by mechanical stretch, and that this activation was partially dependent on autocrine/paracrine-secreted angiotensin II and was mainly dependent on the interleukin-6 family of cytokines but was independent of endothelin-1. Moreover, certain levels of intracellular Ca2+ were necessary for stretch-induced activation of this pathway, and protein kinase C was also partially involved in this activation.

Angiotensin II↗
PubMed1999

Hepatitis C virus core protein regulates cell growth and signal transduction pathway transmitting growth stimuli.

To investigate the transforming potential of hepatitis C virus (HCV), HCV core protein was produced in BALB/3T3 A31-I-1 cells. The cells expressing HCV core gene cooperatively with the v-H-ras gene showed loss of contact inhibition, morphological alterations, and anchorage-independent and serum-independent growth. The cells producing HCV core protein showed enhanced growth against stimulus of growth factor. In addition, antisense oligodeoxynucleotides against mRNA encoding HCV core protein suppressed the growth of HCV core-producing cells. Furthermore, HCV core protein activated mitogen-activated protein kinase and serum response element, which respond to growth stimuli. From these results, we concluded that HCV core protein is involved in the acquisition of cell growth advantage.

3T3 Cells↗