Biomedical subjects

Toshihide Kumamoto

Publications and source records attributed to Toshihide Kumamoto.

At least 19 recordsLinked to original sources

PubMed2007

[Successful CPT-11 treatment in a patient with pancreatic cancer associated with multiple liver metastases and chronic renal failure].

A 56-year-old woman, who had been receiving treatment for chronic renal failure, was admitted to our Department because of a tumor of the pancreas head and multiple liver masses diagnosed by abdominal CT scans. Gastroduodenoscopy revealed a tumor which had invaded the Vater's papilla; the lesion was histopathologically pancreatic adenocarcinoma. Due to the presence of multiple metastases to the liver, we therefore performed general chemotherapy after obtaining the patient's informed consent (IC). CPT-11 was selected as the carcinostatic agent because the patient suffered from renal failure. The initial dose of CPT-11 was 80 mg, and we thereafter made minor adjustments in the dosage depending on the occurrence of side effects. After four courses of the treatment, a CT scan revealed both the tumor of the pancreas head and the multiple liver masses to have almost completely disappeared. Our clinical results indicate that CPT-11 may therefore be a strong candidate for first-line chemotherapy for the treatment of pancreatic cancer, especially in patients with renal failure.

Adenocarcinoma↗

PubMed2006

Elevated soluble ADAM8 in bronchoalveolar lavage fluid in patients with eosinophilic pneumonia.

BACKGROUND: ADAM (a disintegrin and metalloprotease) family members, characterized by a metalloprotease and a disintegrin domain, are membrane-anchored glycoproteins involved in proteolysis and cell adhesion. ADAM8 might have an important role in allergic inflammation. It can cleave a variety of substrates and is a sheddase for VCAM-1 and CD23, the low-affinity IgE receptors. METHODS: To evaluate the contribution of ADAM8 to the pathogenesis of eosinophilic pneumonia (EP), we measured the concentrations of soluble ADAM8 (sADAM8) and its substrates, soluble VCAM-1 (sVCAM-1) and soluble CD23 (sCD23), in bronchoalveolar lavage fluid from patients with smoking-induced acute eosinophilic pneumonia (AEP), chronic idiopathic eosinophilic pneumonia (CEP), and drug-induced eosinophilic pneumonia (drug-EP). RESULTS: The sADAM8 and sVCAM-1 concentrations were increased in AEP and CEP. The sCD23 concentration was elevated in AEP. In AEP, but not CEP, the sADAM8 concentration significantly correlated with those of both sVCAM and sCD23. CONCLUSION: The pathogenesis of AEP, CEP, and drug-EP was distinct with regard to ADAM8. Our results are the first to associate ADAM8 with eosinophilic responses and lung inflammation in humans.

ADAM Proteins↗

PubMed2006

Virus associated hemophagocytic syndrome accompanied by acute respiratory failure caused by influenza A (H3N2).

A 40-year-old Japanese woman was admitted to Oita University Hospital with progressive dyspnea, consciousness disturbance and severe cytopenias. Her chest roentgenogram showed diffuse bilateral infiltrates. She was therefore forced to receive mechanical ventilation. Bone marrow aspiration disclosed numerous hemophagocytic histiocytes, thus suggesting her condition to be hemophagocytic syndrome. In addition, she also developed myocarditis and renal failure. Pulsed methylprednisolone, gamma-globulin, granulocyte colony-stimulating factor and sivelestat sodium hydrate were administrated, and thereafter the patient recovered from cytopenia and organ failure. Afterwards, influenza A H3N2 was detected from bronchial extracts. We should recognize that an influenza A virus infection can induce hemophagocytic syndrome and acute respiratory failure as the initial manifestations of multiple organ failure.

Acute Kidney Injury↗

PubMed2006

Striated muscle fiber compositions of human male urethral rhabdosphincter and levator ani.

PURPOSE: We clarified the contractile properties of human male periurethral striated muscle fibers to better understand how the rhabdosphincter and the levator ani maintain urinary continence. MATERIALS AND METHODS: Muscle specimens were obtained from 52 male patients who underwent radical prostatectomy or radical cystectomy. The specimens were frozen in liquid nitrogen. Frozen sections (10 microm thick) were stained with myofibrillar ATPase at different pH values (pH 4.2, 4.6 and 10.6), and evaluated for quantitative parameters and fiber type distribution. Myosin heavy chain analysis was performed using SDS-PAGE. RESULTS: Of all 52 cases 37 provided specimens that could be divided into the 2 major fiber types, type 1 (slow twitch) and type 2 (fast twitch). Although type 1 muscle fibers were predominant in RS and LA muscle groups (RS 69.6 +/- 2.7%, LA 67.0 +/- 2.0%), mean muscle fiber size was significantly smaller in RS (mean area 906 +/- 86 microm(2)) than in LA (mean area 2,967 +/- 170 microm(2)) (p <0.0001). In 11 specimens type 2 muscle fibers could be subdivided into types 2A (fast fatigue resistant) and 2B (fast fatigable). Type 2A fibers were significantly more prevalent than type 2B fibers (p <0.05). Likewise, MHC analysis of these 11 specimens found a significantly higher percentage of fiber type 2A expression products (MHC 2A) than of fiber type 2B expression products (MHC 2X) (p <0.05). CONCLUSIONS: RS and LA contribute to urinary continence mechanism by slow contraction. Moreover, the smaller mean size of muscle fibers in RS suggests more fatigue resistance compared with muscle fibers in LA because small fibers have a shorter diffusion distance for metabolic substrates. These results should help contribute to a more detailed understanding of the function of periurethral striated muscles in the human male.

Aged↗

PubMed2006

Links between bronchial asthma and allergic rhinitis in the Oita Prefecture, Japan.

Recent studies have strengthened the concept that bronchial asthma and allergic rhinitis are manifestations of an inflammatory process within a continuous airway. This study was performed to compare clinical findings in asthma with or without rhinitis in Japan. Nasal symptoms were present in 99.6% of asthma patients. The prevalence of allergic rhinitis in patients with asthma was 52.4%. Bronchial asthma attacks in one third of patients with rhinitis were coincident with worsening of nasal symptoms. In adults (> 16 years of age), rhinitis frequently preceded asthma, whereas asthma preceded rhinitis in children (< 16 years of age). The frequency of rhinitis in asthma decreases with increasing age. This study demonstrated a clear link between upper and lower airway disorders in Japan.

Asthma↗

PubMed2006

[Successful bi-weekly paclitaxel treatment of an AFP-producing gastric cancer patient with peritoneal dissemination and multiple liver metastasis].

The patient was a 71-year-old man. Chemotherapy was conducted in two courses combining TS-1 (120 mg) and CDDP (80 mg) under the diagnosis of AFP-producing gastric cancer with multiple liver metastasis and peritoneal dissemination. Peritoneal dissemination disappeared, liver metastasis almost disappeared after completion of two courses, and the therapeutic efficacy was rated as PR. Then, the patient underwent distal gastrectomy and lymph node dissection. He received TS-1 monotherapy after surgery, but his condition gradually became worse. TS-1 and CDDP combination were given again, but an ileus resulted due to peritonitis carcinomatous. We therefore administered bi-weekly paclitaxel (80 mg/m(2)) intravenously. The ileus disappeared after one week, liver metastatic lesions and ascites were improved after completion of one course, and therapeutic efficacy was rated as PR. Grade 3 neutropenia and grade 1 alopecia occurred, but no other adverse reaction occurred. This therapy made it possible to eat foods, conduct chemotherapy safely while ambulatory. Paclitaxel can be expected to show good therapeutic efficacy and improve QOL of a peritonitis carcinomatosa patient with TS-1 resistant advanced gastric cancer.

Aged↗

PubMed2006

[A case of drug-induced pneumonitis due to bepridil].

A 66-year-old man had been given bepridil for the treatment of atrial fibrillation since April 28, 2002. The patient developed exertional dyspnea with hypoxemia in the middle of June 2002 and was admitted to our hospital. The chest X-ray and chest CT scans showed diffuse reticulonodular infiltrates in the lower lung fields. Pulmonary function tests revealed depletion of diffusion capacity for carbon monoxide. Bronchoalveolar lavage fluid contained increased percentages of lymphocytes, neutrophils and eosinophils, and a CD4/8 ratio was low. The transbronchial lung biopsy specimens demonstrated alveolar septal thickening with infiltration of mononuclear cells and intraalveolar organization. As drug-induced pneumonitis was suspected, bepridil was discontinued, resulting in improvement of dyspnea and hypoxemia. The patient was then treated with corticosteroid, which led to complete resolution of infiltration on chest X-ray. According to the clinical data consistent with drug-induced pneumonia, the prompt improvement after cessation of bepridil and the absence of other possible causes, we diagnosed this case as bepridil-induce pnemonitis.

Aged↗

PubMed2006

[Bilateral medial medullary infarction presenting as vertical gaze palsy].

A 79-year old man noticed paresthesia in all 4 limbs, quadriplegia and dysarthria, and then developed respiratory arrest requiring mechanical ventilation. After level of consciousness was improved, vertical gaze palsy, left hemifacial palsy (central type) and quadriplegia were noted. Brain magnetic resonance imaging (MRI) on day 9 revealed bilateral upper medial medullary infarction. In general, the vertical gaze center is thought to be present in the midbrain, including the rostral interstitial nucleus of the medial longitudinal fasciculus, posterior commissure and interstitial nucleus of Cajal. Few reports have described vertical gaze palsy due to medullary lesions. The upper medial medullary lesions, particularly the paramedian tract in the medulla, may have been responsible for vertical gaze palsy in this patient.

Aged↗

PubMed2006

[Diagnostic criteria of neurosarcoidosis].

We have collaborated with Japanese Sarcoidosis Society and Japanese Society of Respiratory Disease to provide a new diagnostic criteria of neurosarcoidosis. At least two of six examinations are important. These include bilateral hilar lymphadenopathy, abnormal uptake of 67Ga scintigraphy, broncho alveolar lavage fluid examination, elevated serum ACE, negative tuberculin reaction, and elevated serum or urinary calcium level. (definite) Having positive clinical findings which suggest a neurosarcoidosis. Pathology proven case. (probable) Having positive clinical findings which suggest a neurosarcoidosis. Pathology proven in other organ. At least two of six examinations are positive. (possible) Having positive clinical findings which suggest a neurosarcoidosis. At least two of six examinations are positive. CNS sarcoidosis, sarcoid neuroopathy and sarcoid myopathy are separately diagnosed. Kveim reaction which is time consuming, not so specific, and difficult to obtain its antigen is no more necessary.

Central Nervous System Diseases↗

PubMed2005

Early assessment of rapidly progressive interstitial pneumonia associated with amyopathic dermatomyositis.

Amyopathic dermatomyositis (ADM) is occasionally complicated by rapidly progressive interstitial pneumonia (RPIP), and in such cases, diffuse alveolar damage (DAD) is usually diagnosed at autopsy. Here, we present three patients with RPIP accompanied by ADM in whom lung disease was assessed at an early stage. High-resolution computed tomography (HRCT) carried out before the onset of dyspnoea revealed uniformly subpleural reticular opacity with faint ground-glass attenuation. At that stage, surgical lung biopsies from two patients showed histological patterns typical of cellular nonspecific interstitial pneumonia (NSIP). Despite pulse methylprednisolone and subsequent high-dose oral administration of prednisolone, lung disease progressed in all patients, with extensive areas of ground-glass opacity and consolidation observed in HRCT scans. DAD was confirmed histologically in one case. Additional administration of cyclosporine, pulse cyclophosphamide or high-dose intravenous administration of immunoglobulin rescued all patients. Our data suggest that ADM-associated interstitial pneumonia takes an aggressive course even when the radiological and histological features are consistent with NSIP. Aggressive combination therapy with high-dose steroids and immunosuppressive agents is required as early as possible for patients with this life-threatening disorder.

Adult↗

PubMed2005

Progressive multifocal leukoencephalopathy in an HTLV-I carrier.

This report describes a previously 28-year-old healthy woman, identified as an asymptomatic human T-lymphotropic virus type I (HTLV-I) carrier, who developed both progressive multifocal leukoencephalopathy (PML) and Pneumocystis jiroveci pneumonia. For diagnostic confirmation of PML, stereotactic brain biopsy demonstrated multiple demyelinating lesions with the presence of JC viral antigen. Intramuscular alpha-interferon therapy for 2 weeks brought considerable neurologic improvement. Three years later, the patient developed lymphoma-type of adult T-cell leukemia, suggesting that HTLV-I carrier might be one of the underlying diseases of PML.

Adult↗

PubMed2005

Role of ADAM8 in experimental asthma.

A disintegrin and metalloprotease (ADAM) family members, characterized by a metalloprotease and a disintegrin domain, are membrane-anchored glycoproteins involved in proteolysis and cell adhesion. ADAM8 is specifically induced in the experimental murine asthmatic lung. To evaluate novel pathways involved in asthma pathogenesis, using ADAM8 transgenic mice (ATMS2) in a murine model of asthma. Massive cellular infiltrates in peribronchovascular and interstitial lesions were observed in control mice, while in ATMS2 mice there were only occasional. Vascular cell adhesion molecule (VCAM-1) is involved in specific eosinophil adhesions via alpha4beta1 integrin. VCAM-1 shedding was mediated by the ADAM8 metalloprotease. Endothelial cell shedding of VCAM-1 was increased in ATMS2-stimulated human umbilical endothelial cells. ADAM8-mediated shedding of VCAM-1 might be important for the suppression of experimental asthma. Our data suggest that ADAM8 is a useful therapeutic target.

ADAM Proteins↗

PubMed2005

Skeletal muscle expression of clathrin and mannose 6-phosphate receptor in experimental chloroquine-induced myopathy.

Previous studies suggest that the muscle fiber lysosome system plays a central role in the increased formation of autophagosomes and autolysosomes that occurs in the context of chloroquine-induced myopathy. The goal of this study was to characterize the contribution of receptor-mediated intracellular transport, particularly the endosomal pathway, to the abnormal accumulation of vacuoles in experimental chloroquine myopathy. Expression of the mannose 6-phosphate receptor (M6PR) and clathrin were analyzed in innervated and denervated rat soleus muscles after treatment with either saline or chloroquine. Accumulation of vacuoles was observed only in chloroquine-treated denervated muscles. Further, clathrin immunostaining and M6PR messenger ribonucleic acid (mRNA) were significantly increased in denervated soleus muscle from saline- and chloroquine-treated rats compared to contralateral, innervated muscles. However, there was no difference in clathrin levels when comparing saline- and chloroquine-treated denervated muscles. These data suggest that chloroquine activates the transport of newly synthesized lysosomal enzymes from the secretory pathway via the trans-Golgi network of the Golgi apparatus (an endosomal pathway) as well as autophagosome formation (an autophagic process) in skeletal muscles. Vacuoles may subsequently accumulate secondary to abnormal formation or turnover of autolysosomes at or after fusion of autophagosomes with early endosomes.

Animals↗

PubMed2005

CC chemokine receptor 4 ligand production by bronchoalveolar lavage fluid cells in cigarette-smoke-associated acute eosinophilic pneumonia.

We examined the production of macrophage-derived chemokine (MDC/CCL22) and thymus- and activation-regulated chemokine (TARC/CCL17) by bronchoalveolar lavage fluid (BALF) cells in cigarette-smoke-associated acute eosinophilic pneumonia (CS-AEP). The CC Chemokine Receptor 4 (CCR4) ligand levels in BALF from patients with CS-AEP were considerably higher than those in healthy volunteers and correlated well with Th2 cytokine levels. Interleukin-4 enhanced CCR4 ligand production. MDC expression was observed in CD68-positive cells from patients with CS-AEP and in healthy control smokers. In contrast, TARC expression in CD68- or CD1a-positive cells was detected only in CS-AEP. An in vivo cigarette smoke challenge test induced increases in CCR4 ligands in the BALF and in the cultured supernatant of BALF adherent cells. These results suggest that alveolar macrophages and dendritic cells contribute to the pathogenesis of CS-AEP by generating CCR4 ligands, probably in response to cigarette smoke.

Adolescent↗

PubMed2005

Myosin loss in denervated rat soleus muscle after dexamethasone treatment.

OBJECTIVE: Critical illness myopathy (CIM) is an acute myopathy that appears in the setting of critical illness or during exposure to corticosteroids and neuromuscular blocking agents. Its pathological feature is selective loss of thick myosin filaments. Our aim is to gain further insight into the pathomechanism of myosin loss in this myopathy. METHODS: To clarify the expression of myosin heavy chain (MHC) and ubiquitin ligase atrogin-1 in this myopathy, histological, immunohistochemical, SDS-PAGE, and semiquantitative reverse transcriptase-polymerase chain reaction studies were performed on innervated and denervated rat soleus muscles after saline and dexamethasone treatments. RESULTS: Denervated muscles from dexamethasone-treated rats showed marked MHC loss. The mRNA expression of ubiquitin ligase atrogin-1 was significantly increased in denervated dexamethasone-treated muscles, suggesting that the ubiquitin-proteasome pathway plays an important role in muscular wasting in CIM. Furthermore, mRNA levels of MHC I, a myosin isoform, were decreased in the denervated dexamethasone-treated muscles. CONCLUSION: Our findings suggest that an altered transcription rate of myosin, as well as the upregulation of multiple ubiquitin ligases, may be responsible for selective myosin loss in this myopathy.

Animals↗

PubMed2005

[A case of pulmonary langerhans cell histiocytosis presenting disappearance of coalescing air wall cysts after smoking cessation].

A 17-year-old adolescent was admitted to Oita University Hospital with non-productive cough and exertional dyspnea. She had been smoking approximately 10 cigarettes per day for two years. When the patient was three years old, she underwent surgical removal of skull tumor of Langerhans cell histiocytosis. Initial chest CT scans showed coalescing thick-walled air cysts surrounded by micronodules in both lungs, most predominantly in the middle and upper lung fields. Bronchoalveolar lavage fluid contained 2.3% of CD1a-positive cells and video-assisted thoracoscopic lung biopsy disclosed granulomatous lesions consisting of histiocytic cells containing S-100 protein but without CD68 antigen allowing a diagnosis of pulmonary Langerhans cell histiocytosis. She stopped smoking, resulting in spontaneous resolution of the coalescing air cysts which were replaced by funicular scarring within two years. In case of extra-pulmonary Langerhans cell histiocytosis in children, the close relationship between cigarette smoking and pulmonary involvement should be informed to the parents to prevent the patient starting smoking in the future.

Adolescent↗

PubMed2005

[Diagnostic criteria of neurosarcoidosis].

We have collaborated with Japanese Sarcoidosis Society and Japanese Society of Respiratory diseases to make a new diagnostic criteria of neurosarcoidosis. (definite) Having positive clinical findings which suggest a neurosarcoidosis. Pathology proven case. (probable) Having positive clinical findings which suggest a neurosarcoidosis. Pathology proven in other organ. Elevated serum ACE or BHL demonstrated by chest XP or CT scan. (possible) Having positive clinical findings which suggest a neurosarcoidosis. Elevated serum ACE or BHL demonstrated by chest XP or CT scan. CNS sarcoidosis, sarcoid neuropathy and sarcoid myopathy are separately diagnosed. To evaluate our criteria, about 100 papers on neurosarcoidosis published worldwide in these 6 years were retrospectively examined. Our criteria showed a better results than 1988 criteria (former Japanese criteria) and Zajicek's criteria which was published in 1999 (QJ Med 92: 103). Point is there is no more need to depend upon Kveim reaction which is time consuming, not so specific and difficult to obtain its antigen. Our new criteria is calculated to be sensitivity of 78-98% (BHL or ACE), and specificity of 83-99% (ACE). Because of their low specificity, Gallium scintigraphy and broncho alveolar lavage fluid examination are excluded from our diagnostic criteria, however, their high sensitivity are still useful to begin with.

Central Nervous System Diseases↗

PubMed2005

[A case of sarcoidosis manifesting as acute febrile polyarthritis following bronchoalveolar lavage].

A 32-year-old man was incidentally found to have abnormal shadows on a chest X-ray film and was admitted on May 2004. His chest images showed mediastinal and bilateral hilar lymphadenopathy. The serum level of angiotensin-converting enzyme was elevated. We also found non-caseating epithelioid cell granulomas in transbronchial lung biopsy specimens, and confirmed the diagnosis of sarcoidosis. We carried out bronchoalveolar lavage (BAL) for evaluation of disease activity of sarcoidosis. After BAL, he suffered high fever and polyarthralgia. Both ankles were extremely inflamed. We suspected infectious arthropathy caused by atypical pathogens and thus administered antibiotics, but they had no effect at all. Also, no findings suggesting collagen-vascular disorders, including rheumatoid arthritis, were detected. His symptoms improved after three-weeks of treatment with non-steroidal anti-inflammatory drugs. Thus, this case was diagnosed as having acute sarcoid polyarthritis. BAL may have influenced the onset of febrile arthritis in this patient This case indicates that sarcoidosis should be considered as a possible cause of acute febrile polyarthritis.

Acute Disease↗