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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 127 records · Page 7Linked to original sources

Rhabdomyolysis triggered by an asthmatic attack in a patient with McArdle disease.

We describe a patient with McArdle disease who developed rhabdomyolysis triggered by a bronchial asthmatic attack. A 64-year-old man had chronic pulmonary emphysema with asthma, and an asthmatic attack led to severe rhabdomyolysis that required continuous hemodiafiltration. After 2 years, a physical examination revealed atrophy of the extremities compared with previous examinations, especially of the intercostal muscles. During that time, he suffered two severe bronchial asthmatic attacks. His serum level of creatinine kinase remained between 4,000 and 7,000 IU/l when he did not suffer from asthmatic attacks and rhabdomyolysis had abated. Therefore, we suspected that his recent muscle atrophy was caused by asthmatic attacks, and discussed the possibility of his respiratory muscle weakness due to McArdle disease in relation to his severe bronchial asthmatic attacks as well as chronic obstructive pulmonary disease.

Asthma↗

Quantification of ground-glass opacity on high-resolution CT of small peripheral adenocarcinoma of the lung: pathologic and prognostic implications.

OBJECTIVE: The purpose of our study was to correlate the high-resolution CT findings of small peripheral adenocarcinoma of the lung with underlying histopathology and to evaluate the prognostic implications of the CT findings. MATERIALS AND METHODS: The high-resolution CT findings of small peripheral adenocarcinoma of the lung in 224 patients were analyzed by two independent observers for location, size, marginal characteristics, and extent of ground-glass opacity and necrosis. The pathologic specimens were reviewed by an experienced lung pathologist. RESULTS: One hundred and thirty-two patients had bronchioloalveolar carcinoma and 92 had adenocarcinoma. The extent of ground-glass opacity was greater in bronchioloalveolar carcinomas (mean +/- SD, 29% +/- 31.6%) than in other adenocarcinomas (8% +/- 13.3%) (p < 0.001). The extent of ground-glass opacity was significantly greater in patients without recurrence (p = 0.020) and those without nodal (p = 0.017) or distant (p = 0.007) metastases than in patients with nodal or distant metastases or in whom the carcinoma had recurred. CONCLUSION: The extent of ground-glass opacity in a nodule is greater in bronchioloalveolar carcinomas than in other adenocarcinomas. Greater extent of ground-glass opacity also correlates with improved prognosis.

Adenocarcinoma↗

Proinflammatory cytokines regulate the gene expression of hyaluronic acid synthetase in cultured rabbit synovial membrane cells.

To elucidate the mechanism of accumulation and fragmentation of hyaluronic acid (HA) under inflammatory conditions, we investigated the effect of proinflammatory cytokines on hyaluronic acid synthetase (HAS) mRNA expression using cultured rabbit synovial membrane cells. HASs mRNA levels were determined by real-time PCR. HAS2 mRNA expression was maximally enhanced 3.3- and 2.8-fold after 3-hour stimulation with IL-1beta (1 ng/ml) and after 1-hour stimulation with TNF-alpha (10 ng/ml). HAS3 mRNA expression was increased by a maximum of 4.3 times after 3-hour stimulation with IL-1beta (10 ng/ml), whereas 1-hour stimulation with TNF-alpha (10 ng/ml) and IFN-gamma (10 ng/ml) induced around a 2.5-fold increase in HAS3 mRNA. Although IFN-gamma (1-100 ng/ml) alone showed little effect on HAS2 mRNA expression, the effect was synergized by combined with both IL-1beta and TNF-alpha, substantially increasing HAS2 mRNA expression. These results suggest that proinflammatory cytokines regulate the HAS expression, and consequently may contribute to the accumulation and fragmentation of HA.

Animals↗

Treatment of post-transplanted, relapsed patients with hematological malignancies by infusion of HLA-matched, allogeneic-dendritic cells (DCs) pulsed with irradiated tumor cells and primed T cells.

Patients with hematological malignancies who relapse after bone marrow transplantation (BMT) are often treated with donor lymphocyte infusion. However, this procedure often results in graft-versus-host disease (GVHD). While, Dendritic cells (DCs), which present antigens to naive T cells, have been used in the immunotherapy of cancer, this approach has been logistically difficult due to limiting numbers of DCs. We have now developed a method for obtaining a large number of DCs by treating the granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) from healthy donors with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). The resulting cells possess the morphologic, phenotypic, and functional characteristics of mature DCs. In in vitro studies, culture of these HLA-matched donor derived-DCs with irradiated each patient's tumor cells as an antigen source, followed by incubation with T cells from the patient, induced the production of highly cytotoxic T lymphocytes (CTLs) specific for the respective tumor cells in the semi-allogeneic setting. A transient, but objective clinical response was obtained in the absence of GVHD when we injected the DCs which had been pulsed with irradiated tumor cells as well as primed T cells from the same original donor of related- allogeneic stem cell transplantation into the relapsed patients. Our findings suggest that treatment of relapsed patients with such donor-derived DCs, and primed T cells may be effective as an adjunctive immunotherapy.

Adult↗

[Two cases of renal cell carcinoma that underwent radical nephrectomy subsequent to complete tumor enucleation].

We have reported the favorable therapeutic results of non-ischemic complete enucleation using a microwave tissue coagulator as a method of nephron-sparing surgery for small renal cell carcinoma (RCC). We experienced two elective cases that underwent translumbar nephrectomy subsequent to the tumor enucleation. The first case showed another RCC in a cyst, concomitant with the enucleated RCC. The second case was a pT3a spindle cell carcinoma with high-grade malignancy. We decided to nephrectomize these enucleated kidney after obtaining well-informed consent. Here we report these controversial cases and discuss about the indication and outcomes of complete tumor enucleation for small RCC.

Adult↗

[Pitfall in the choice of the in situ arterial grafts in OPCAB].

Flow capacity with arterial grafts which have been used in off-pump CABG has been discussed. To analyze the hypoperfusion syndrome when in situ arterial grafts are selected, we made the simple mathematical model which consisted of two vessels with in parallel. We speculated the flow capacity of the various grafts, and flow distribution in the distal coronary artery, based on Poiseuille's law. This theoretical model clearly demonstrated that hypoperfusion syndrome occurred in reoperative coronary bypass grafting had a close relation with the diameters and lengths of bypass grafts.

Blood Viscosity↗

[A survey of 3,303 6th-year medical students from 36 universities concerning knowledge of resuscitation--more than 80% of medical students can not perform standard cardiopulmonary resuscitation?].

Questionnaires on knowledge of resuscitation were distributed to 3,303 6th-year medical school students from 36 universities. The questionnaire included 13 questions based on the 1992 guidelines for cardiopulmonary resuscitation. From the 13 questions, each student was instructed to select 6 questions concerning assessment of consciousness level, method for confirming respiration, method for securing the airway, method for confirming circulation, pressure points for cardiac massage, and the ratio of respiration and cardiac massage. If all of these six questions could not be answered correctly, it was considered that the student was not able to perform resuscitation according to the guidelines. At least one incorrect answer was given to the six questions by 84% of students, indicating that most medical students are not able to actually perform standard resuscitation. Possible reasons for these results may be the lack of desire on the part of students to master resuscitation, confusion over new findings concerning resuscitation and guideline, insufficient understanding of the difference between the guidelines and new findings by educators, and restricted teaching time for resuscitation. Possible ways to improve the situation include efforts to make students more responsible to master resuscitation, efforts to enhance students' desire to learn, adoption of more practical education, inclusion of such questions in graduation examinations and the national examination for a medical license, adherence by educators to the guidelines, and efforts by educators to make a clear distinction between the guidelines and new findings. With new guidelines for cardiopulmonary resuscitation due out in the year 2000, methods for teaching resuscitation should be reconsidered in order to ensure that all medical students can competently perform resuscitation.

Adult↗

[A case of polyarteritis nodosa presenting as a mass in scrotum].

A 16-year-old boy with a painful tumor in the left scrotum was referred to our department. CT scans showed a low density area in the left testis, so we diagnosed a left testicular tumor and performed left inguinal orchiectomy. Histological examination revealed polyarteritis nodosa (PN) of the testis and epididymis. Systemic examination revealed no other evidence of PN. Although induration developed in the right epididymis after the operation, it resolved with steroid therapy. The patient is currently asymptomatic and is being followed at our clinic. The pathogenesis and management of this rare condition are discussed.

Adolescent↗

[Screening methods in the detection of bladder cancer: comparison of nuclear matrix protein-22, bladder tumor antigen and cytological examinations].

We evaluated the utility of urinary parameters (Nuclear Matrix Protein-22: NMP-22, Bladder Tumor Antigen: BTA, and cytological examinations) for the diagnosis or post-therapeutic monitoring of bladder cancer. Thirty one tumor-bearing cases including 19 fresh cases and 40 tumor-free cases, were subjects of this study. Using identical voided urine samples, NMP-22, BTA and urinary cytology were examined. The mean values of NMP-22 (cut-off value is 12 U/ml) was 100.5 +/- 26.5 U/ml in the tumor-bearing group and 21.9 +/- 7.8 U/ml in the tumor-free group (p < 0.05): Sensitivity was 74.2%, and specificity was 67.5%. Sensitivity of BTA was 58.1%, and specificity was 97.5%. Only five cases were judged positive by urinary cytology: 16.1% in sensitivity and 100% in specificity. Thus, NMP-22 and BTA were more sensitive than urinary cytology. In conclusion, the new urinary parameters, NMP-22 and BTA, would be less invasive and useful as tumor markers of bladder cancer. NMP-22 seems suitable for screening before the diagnosis and BTA for the post-therapeutic follow-up study.

Adult↗

[Two cases of pulmonary disease with perinuclear anti-neutrophil cytoplasmic antibody].

We encountered two cases of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). The first was a case of idiopathic interstitial pneumonia diagnosed in a 73-year-old man since 1998. He was admitted to our hospital because of renal failure and anemia. The serum level of p-ANCA on admission was 264 EU, and specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis due to p-ANCA. He was treated with prednisolone pulse therapy and prednisolone (PSL), however interstitial pneumonia occurred during PSL tapering. We treated him for pulmonary fibrosis with plasmapheresis, methylprednisolone (mPSL) and cyclophosphamide (CPA), which suppressed the progress of the interstitial pneumonia. The second case was one of massive pulmonary hemorrhage in a 68-year-old man who was admitted to our hospital. Physical examination revealed anemia: the laboratory data, renal failure; and the serum level of p-ANCA was elevated to 611 EU. The specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis. The renal failure was not improved by PSL, but, together with the inflammation, responded to the combination of PSL and CPA. However, both patients died of serious infection. They were regarded as compromised patients because of the therapy mentioned above. No standard therapy has been established against p-ANCA positive pulmonary disease with renal failure. The treatment should control the progression of interstitial pneumonitis and pulmonary hemorrhage. It is important to consider the possibility of serious infection.

Aged↗

[A case of renal cell carcinoma producing alpha-fetoprotein].

Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare condition with only 11 cases reported in Japan to our knowledge. A 69-year-old man was admitted to our hospital for further examination of an incidental right renal tumor. Laboratory tests showed markedly increased serum level of AFP whereas both HBs antigen and anti-HCV antibody were negative. Computed tomography and magnetic resonance imaging imagings showed a right renal tumor but no tumor in liver, testis or lymph node. We performed right radical nephrectomy. Serum level of AFP declined within the normal range 7 weeks after nephrectomy according to its half-life curve. The tumor specimen was composed mainly of granular cells. Immunohistochemical examination of the tumor cells proved the presence of AFP in the cytoplasm. The possibility of AFP as a tumor marker of renal cell carcinoma in this case was presented.

Aged↗

[A case of prostate cancer with cyst formation].

A 73-year-old man with the complaint of dysuria of 2 years' standing was admitted to our hospital for further examination of an intrapelvic cystic mass, 8.6 cm in diameter, detected incidentally by abdominal ultrasonography. The serum concentration of prostate specific antigen (PSA) was elevated to 44.9 ng/ml. Pelvic computed tomography (CT) and magnetic resonance imaging (MRI) revealed a cystic mass with an irregular thick cyst wall posterior to the urinary bladder originating from the prostate. Transrectal needle biopsy presented a moderately differentiated adenocarcinoma of the prostate. The bloody fluid of the cyst obtained by transperineal aspiration contained a significantly increased level of PSA, but no cancer cells were detected by cytological examination. Total prostatectomy was performed under the diagnosis of clinical stage C (cT3N0M0) prostate cancer. Pathological diagnosis was that cancer cells were present in the prostate tissue and had partly infiltrated the cyst wall. These results suggest that the present cyst was associated with the development of prostate cancer as a pseudocyst without an epithelial lining. The patient has remained free from the disease for over ten months. We review 56 cases of this rare condition that have been reported in Japan.

Adenocarcinoma↗

[Current situation and problems inherent to long-term home medical care as compared with medical care provided in nursing homes].

We compared 18 patients under long-term home medical care and 11 patients who entered a nursing home after receiving home medical care, to analyze the factors thought to influence continuation of home care. There was no statistical difference between the mean age of both groups, but the mean age of main caretakers in the former (mean 59 years old) was lower compared with that of caretakers in the latter (mean 70 years old). There were various reasons for them to enter a nursing home after receiving home care. Five of the 11 patients entered the nursing home after long-term hospitalization in spite of no deterioration in their degree of handicap at discharge. We think the long-term hospitalization may reduce the motivation of caretakers. It is indicated that the age of caretakers and ability, especially motivation to provide care are important factors to continue home medical care.

Aged↗

[A case of renal cell carcinoma complicated with interstitial pneumonitis, complete A-V block and pleural effusion during interferon-alpha therapy].

A 76-year-old man with postoperative renal cell carcinoma accompanied by multiple lung metastasis was being treated with recombinant interferon-alpha. After administration of 3 MU/day on 3 days/week for 1 month, he complained of headache and tinnitus. During continuous treatment for 3 months, he complained of appetite loss, low-grade fever and dyspnea. He was then referred to our Department of Internal Medicine. Electrocardiography indicated a complete A-V block, and chest radiography (CXR) showed a reticular shadow in both lower lung fields and bilateral pleural effusion. Chest computed tomography (CT) indicated subpleural emphysematous changes, multiple nodules, consolidation shadow with ground glass opacity in both lower lobes, and bilateral pleural effusion. The findings in the bronchoalveolar lavage (BAL) fluid included increases in the numbers of lymphocytes and eosinophils. We reached a diagnosis of interferon-alpha-induced pneumonitis on the basis of the patient's clinical course, and the CXR, chest CT and BAL fluid findings. Treatment with methylprednisolone pulse therapy for 3 days and then administration of prednisolone for 1 month resulted in marked improvement in the complete A-V block and interstitial pneumonitis. At day 7 after discontinuation of prednisolone, the serum level of C-reactive protein increased, and CXR showed bilateral pleural effusion. We therefore believe that the pleural effusion was probably also induced by interferon-alpha. Interferon is an effective drug for chronic hepatitis C and malignant diseases. Many complications have been reported during interferon therapy. However, although these complications, such as interstitial pneumonitis, complete A-V block and pleural effusion, have rarely been reported, careful attention is required during interferon therapy in case any appear.

Aged↗

Effect of venlafaxine on imipramine metabolism.

The present study was designed to determine the effect of venlafaxine on imipramine metabolism in an attempt to elucidate the potential for cytochrome P450 drug-drug interactions with venlafaxine. We examined the metabolism of a single 100-mg dose of imipramine before and after treatment with venlafaxine, 50 mg three times a day. Eight male subjects were phenotyped for CYP2D6 activity. Two subjects were poor metabolizers of dextromethophan, and data from the remaining six subjects (mean age=45.3+/-15) were analyzed. Venlafaxine increased imipramine C(max) and elevated AUC by 40%. Desipramine clearance and volume of distribution were reduced by 20% and 25%, respectively. These findings are consistent with a statistically significant, but clinically modest impact of venlafaxine on CYP2D6-metabolized substrates.

Adult↗

Inhibition of pRb phosphorylation and cell cycle progression by an antennapedia-p16(INK4A) fusion peptide in pancreatic cancer cells.

In this study, we examined whether or not a small peptide derived from p16(INK4A) protein with the antennapedia carrier sequence could inhibit the growth of pancreatic cancer cells through the inhibition of cell cycle progression. Growth inhibition by the p16-derived peptide was observed in a time- and dose-dependent manner in AsPC-1 and BxPC-3 cells (p16-negative and pRb-positive), whereas Saos-2 cells (p16-positive and pRb-negative) showed no inhibitory effect. In AsPC-1 and BxPC-3 cells, the proportion of cells in the G(1) phase markedly increased 48 h after treatment with 20 microM p16-derived peptide. Cell-cycle analysis of Saos-2 cells showed little change during the entire period of treatment. Immunoblot analysis showed inhibition of pRb phosphorylation after treatment of BxPC-3 with 10 microM p16 peptide. Furthermore, the p16 peptide caused a decrease in cyclin A at later times of treatment. These results demonstrate that the p16-derived peptide can inhibit the growth of p16-negative and pRb-positive pancreatic cancer cells by means of G(1) phase cell cycle arrest resulting from the inhibition of pRb phosphorylation. Restoration of p16/pRb tumor-suppressive pathway by re-expression of p16(INK4A) may play a therapeutic role in the treatment of pancreatic cancer.

Amino Acid Sequence↗

Identification and characterization of negative regulatory elements of the human telomerase catalytic subunit (hTERT) gene promoter: possible role of MZF-2 in transcriptional repression of hTERT.

Human telomerase reverse transcriptase (hTERT) is a catalytic subunit of human telomerase and is a critical determinant of the enzymatic activity of telomerase. Expression of hTERT is known to be regulated mainly at the transcriptional level. In the present study, using transient expression assays, we identified a 400 bp silencer of the hTERT promoter between -776 and -378 upstream of the proximal core promoter. The inhibitory effects of this silencer were enhanced with cellular differentiation. A computer-assisted homology search identified multiple binding motifs for myeloid-specific zinc finger protein 2 (MZF-2) within this region. Mutation introduced in these sites resulted in significant activation of hTERT transcription. Gel shift assays demonstrated that MZF-2 proteins specifically bound to these sites. Overexpression of MZF-2 in cells led to down-regulation of hTERT transcription as well as telomerase activity. These findings suggest that the 400 bp region upstream of the hTERT core promoter that we identified functions as a negative regulatory region and that MZF-2 may be an effector of negative regulation of hTERT.

Base Sequence↗