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Biomedical subjects

T Hayano

Publications and source records attributed to T Hayano.

At least 37 records · Page 2Linked to original sources

[Tumor lysis syndrome after treatment for mediastinal non-Hodgkin's lymphoma].

An 18-year man was admitted to the hospital because of acute dyspnea. Roentgenological examination revealed a large anterior mediastinal tumor. Histologic examination of a specimen from a cervical lymph node yielded a diagnosis of non-Hodgkin's lymphoma of, diffuse, large, T-cell type. Acute respiratory failure and a massive pleural effusion developed, and mechanical ventilation was begun. Chemotherapy with adriamycin, vincristine, cyclophosphamide, and prednisolone resulted in rapid shrinking of the mass. Acute renal failure developed because of hypoperfusion of the kidney caused by acute circulatory failure and the tumor lysis syndrome, and rapid increases in the concentrations of lactate dehydrogenase, creatine phosphokinase, and uric acid in serum after the tumor collapsed. Mediastinal malignant lymphoma often forms a bulky mass, and effective chemotherapy, while it can prolong survival, may also cause the tumor lysis syndrome.

Acute Disease↗

The substrate-binding site in Escherichia coli cyclophilin A preferably recognizes a cis-proline isomer or a highly distorted form of the trans isomer.

The three-dimensional structure of Escherichia coli cytosolic cyclophilin A (CyPA) complexed with a tripeptide (succinyl-Ala-Pro-Ala-p-nitroanilide) was refined at 1.8 A resolution by the multiple isomorphous replacement method to a crystallographic R-factor of 17.6%. As in human CyPA, the peptide binding site in E. coli enzyme is in a cleft created on the surface of the upper sheet of two orthogonal beta-sheets. In this cleft, the walls of the hydrophobic pocket are formed by the side-chains of five non-polar residues, Phe48, Met49, Phe107, Leu108, and Try120, with Phe99 at the bottom. When the cis isomer of the tripeptide binds to the enzyme, a cis-proline ring is inserted into the hydrophobic pocket. Since the binding pocket of CyPAs are largely hydrophobic, the cis isomer of a peptide can be bound more firmly than the trans isomer. Distortion of the trans isomer could lead to better binding, but at an energetic cost of the distortion energy. At the periphery of the upper beta-sheet in E. coli CyPA, conformations of loops L1, L3, and L4 and the segment connecting alpha1 and beta3 with deletions or insertions against human CyPA differ significantly from those in human CyPA. The refined model also shows that steric hindrance to attachment of cyclosporin A (CsA) prevents E. coli CyPA forming a complex with CsA. Thus, the extra amino acid residue of E. coli CyPA, polar Gln89, lies along the pathway to the hydrophobic pocket of CyPA and seems to prevent the access hydrophobic part of CsA to the cleft of CyPA.

Amino Acid Isomerases↗

Cytokines in bronchoalveolar lavage fluid in patients with high altitude pulmonary oedema at moderate altitude in Japan.

BACKGROUND: The precise mechanism of high altitude pulmonary oedema (HAPE) remains unclear. The purpose of this study was to evaluate the role of cytokines and P-selectin in the development of HAPE which occurred at moderate altitude in Japan. METHODS: The following cellular and biochemical markers and chemotactic cytokines were measured in the bronchoalveolar (BAL) fluid from four patients with HAPE at 2857-3180 m in the Japanese Alps: total proteins, albumin, lactate dehydrogenase (LDH), and interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist (ra), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, and the soluble form of P-selectin. RESULTS: At admission there were significant increases in the levels of total cells, especially macrophages and neutrophils, total protein, albumin and LDH when compared with 13 healthy individuals. Furthermore, the levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were also considerably increased but returned quickly to the normal ranges or were not detected after recovery. The levels of IL-1 alpha, IL-10, and P-selectin did not change. CONCLUSIONS: These results suggest that an inflammatory process almost identical with acute respiratory distress syndrome (ARDS) may occur in HAPE, but that these changes are transient and are not associated with any increase in P-selectin levels in the BAL fluid.

Adult↗

Endothelin-1 and interleukin-8 in high altitude pulmonary oedema.

We present a case of high altitude pulmonary oedema (HAPE) with pulmonary hypertension and polymorphonuclear leucocyte (PMN) accumulation in bronchoalveolar lavage fluid (BALF), which occurred in a 21 year old man. Plasma endothelin-1 (ET-1) and interleukin-8 (IL-8) concentration in BALF were elevated on admission, and returned to normal level at recovery, when the pulmonary artery pressure and the PMN counts in BALF were normal. In addition, E-selectin and intercellular adhesion molecule-1 (ICAM-1) in BALF were also slightly increased on admission. These findings suggest that endothelin-1 is a vasoconstrictor which contributes to the pulmonary hypertension in high altitude pulmonary oedema, and that some of the inflammatory mediators play an important role in chemotaxis and accumulation of polymorphonuclear leucocytes in the development of high altitude pulmonary oedema.

Adult↗

[Two cases of primary Sjögren's syndrome with pulmonary involvement histopathological study of open-lung biopsy specimens].

We report two cases of primary Sjögren's syndrome with pulmonary involvement, in which open lung biopsies were done. The patient in the first case was a 58-year-old woman and the patient in the second case was a 54-year-old woman. Both patients were admitted to our hospital because of dry coughing and exertional dyspnea. Chest X-ray films and CT scans showed interstitial shadows in both cases and multiple bullae in the first case. Pulmonary-function tests showed decreased diffusing capacity, and examination of bronchoalveolar lavage fluid revealed increased percentages of lymphocytes. Open-lung biopsy specimens showed thickening of the alveolar septa and interstitial mononuclear cell infiltration, composed predominantly of lymphocytes, with lymphoid follicles in both cases, and peribronchiolar mononuclear cell infiltration in the first case. Therefore, the histopathological diagnosis was cellular interstitial pneumonia with lymphoid follicles. Both patients were treated with oral corticosteroids. Symptoms were relieved and laboratory findings improved.

Biopsy↗

Fatal rhabdomyolysis during mountaineering.

We treated two rare cases of acute rhabdomyolysis induced by heat stroke encountered during mountaineering. The clinical findings were complicated by severe acute renal failure and disseminated intravascular coagulation (DIC), respectively. Though heat-related disorders occur frequently in mountain medicine in summer, severe and fatal rhabdomyolysis due to heat stroke is rare. It was also noteworthy that both patients had received treatment with antipsychotic drugs including phenothiazine. Even in a moderate exercise activity such as mountaineering, the possibility of rhabdomyolysis should be considered for all cases of heat stroke, especially those with a history of antipsychotic neuroleptics.

Fatal Outcome↗

Iodine-123-MIBG imaging in pheochromocytoma with cardiomyopathy and pulmonary edema.

We encountered a patient with pheochromocytoma associated with a catecholamine-induced cardiomyopathy that developed recurrently bilateral and unilateral pulmonary edema. The diagnosis of pheochromocytoma was made by elevated plasma catecholamine levels and the intense tumor [123I]MIBG uptake and was confirmed at the time of surgery. The patient showed reduced myocardial [123I]MIBG uptake with left ventricular dysfunction, and endomyocardial biopsy findings were consistent with the diagnosis of catecholamine-induced cardiomyopathy. After tumor resection, plasma levels of catecholamine were normalized, and pulmonary edema never recurred, although cardiac dysfunction did not show an improvement on echocardiography. Myocardial and lung [123I]MIBG uptake increased when compared to uptake levels on preoperative scans, but myocardial uptake was still below normal. These findings indicated that over-secreted catecholamines influenced both the heart and lungs. Pheochromocytoma can induce cardiac and lung injuries, and [123I]MIBG scanning may contribute not only to tumor characterization but also to assessing and monitoring the influence of catecholamines on the heart and lungs.

3-Iodobenzylguanidine↗

[Two patients with idiopathic pulmonary fibrosis and monoclonal gammopathy].

A 67-year-old man and a 70-year-old man were admitted to our hospital because of dyspnea and dry coughing. Chest X-ray films showed bilateral reticulonodular shadows in the middle and lower lung fields. Specimens were obtained by open lung biopsies and the findings were compatible with those of usual interstitial pneumonia. Immunoelectrophoresis revealed monoclonal gammopathy in both patients. The levels of interleukin 6 in bronchoalveolar lavage fluid were high. In these two patients, idiopathic pulmonary fibrosis was associated with multiple myeloma and monoclonal gammopathy, and the levels of interleukin-6 in bronchoalveolar lavage fluid were high. These findings may help to elucidate the pathogenesis and development of idiopathic pulmonary fibrosis.

Aged↗

Protein disulfide isomerase mutant lacking its isomerase activity accelerates protein folding in the cell.

We investigated the effect of protein disulfide isomerase (PDI) on in vivo protein folding of human lysozyme (h-LZM) in a specially constructed yeast coexpression system. Coexpression with PDI increased the amounts of intracellular h-LZM with the native conformation, leading to an increase in h-LZM secretion. The results indicated that PDI is a real catalyst of protein folding in the cell. The secretion of h-LZM increased even when both active sites of PDI were disrupted, suggesting that the effect of PDI resulted from a function other than the formation of disulfide bonds. This is the first finding that PDI without isomerase activity accelerates protein folding in vivo.

Base Sequence↗

Cloning and sequencing of the cDNA encoding human P5.

The cDNA encoding human P5 was cloned and sequenced. The predicted 440-amino-acid (aa) sequence of human P5 contains two thioredoxin-like domains, which are also found in members of the protein disulfide isomerase superfamily. The human and hamster P5 genes reveal 87 and 93% similarity in their nucleotide and deduced aa sequences, respectively.

Amino Acid Sequence↗

Molecular cloning of the cDNA encoding a novel protein disulfide isomerase-related protein (PDIR).

We isolated the cDNA of a novel protein disulfide isomerase (PDI)-related protein, designated PDIR, from a human placental cDNA library. Deduced from its nucleotide sequence, PDIR has the three CXXC-like motifs (Cys-Ser-Met-Cys, Cys-Gly-His-Cys and Cys-Pro-His-Cys), which are found in proteins within the PDI superfamily and are responsible for oxidoreductase activity. PDIR has a hydrophobic stretch at its amino terminus, which may serve as a signal sequence, and the putative endoplasmic reticulum (ER) retention signal 'Lys-Glu-Glu-Leu' at its carboxy terminus, indicating that PDIR is an ER resident protein. Northern blots showed that PDIR is preferentially expressed in cells actively secreting proteins and that the expression of PDIR is stress-inducible. These results suggested that PDIR has oxidoreductase activity of disulfide bonds against polypeptides and that it acts as a catalyst of protein folding in the lumen of the ER.

Amino Acid Sequence↗

[Acute lung injury and chemical mediators].

The essential abnormality in acute lung injury is an increase in pulmonary permeability. The mechanisms involved are complex, and may include direct effects on endothelial cells; the actions of neutrophils, macrophages, and lymphocytes; and chemical mediators generated by these cells. Neutrophils are known to be important in acute lung injury, and the mediators they produce, especially protease and oxidants, may be responsible for endothelial cell injury. We studied the roles of neutrophil elastase and oxygen radicals in acute lung injury by Escherichia coli endotoxin in sheep with lung lymph fistulae. The results of these and other studies indicate that these substances are related to the increase in pulmonary permeability during the late phase of injury.

Acute Disease↗

Effects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep.

The purpose of the present study was to assess the role of polymorphonuclear leukocyte (neutrophil) elastase in endotoxin-induced acute lung injury in sheep with lung lymph fistula. We studied the effects of ONO-5046, a specific inhibitor of neutrophil elastase, on the lung dysfunction induced by the intravenous infusion of 1 microgram/kg of Escherichia coli endotoxin. Endotoxin alone produced a biphasic response as previously reported. Early (0.5-1 h) after endotoxin, pulmonary arterial pressure increased from 19.5 +/- 0.9 cmH2O at baseline to a peak of 46.8 +/- 2.4 cmH2O (P < 0.05). Pulmonary vascular resistance increased from 3.03 +/- 0.17 cmH2O.l-1.min at baseline to a peak of 9.77 +/- 0.70 cmH2O.l-1.min (P < 0.05). Circulating neutrophils decreased from 7,355 +/- 434/mm3 at baseline to a nadir of 1,762 +/- 32/mm3 (P < 0.05). Thromboxane B2 and 6-ketoprostaglandin F1 alpha concentrations in plasma and lung lymph were significantly increased. Late (3-5 h) after endotoxin, pulmonary arterial pressure and pulmonary vascular resistance returned to baseline levels, but lung lymph flow remained increased from 4.2 +/- 0.3 ml/0.5 h at baseline to 7.3 +/- 0.7 ml/0.5 h (P < 0.05), with a slight increase in lung lymph-to-plasma protein concentration ratio, suggesting increased pulmonary vascular permeability. The histopathological features of the lungs during the early period in sheep treated with endotoxin alone revealed a large increase in neutrophils per 100 alveoli and changes of pulmonary edema such as thickening of the interstitium of the lung and alveolar flooding.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

[A case of lung metastasis from Meibomian gland carcinoma of eyelid with effective chemotherapy].

A 47-year-old man was admitted to Shinshu University Hospital in 1992 because of cough and chest abnormal shadow. In 1987, he had an operation for Meibomian gland carcinoma of his right lower eyelid, and also received radiotherapy. His chest X-ray film on admission showed tumor shadows in the bilateral upper lung fields. The chest CT scan showed tumors in the right S1 and the left S3. Bronchofiberscopic findings demonstrated stenosis of the right upper bronchus and an endobronchial mass occluding the left B3. A biopsy specimen of the endobronchial mass revealed sebaceous carcinoma, which was identical with that of the resected eyelid tumor. He received two courses of chemotherapy in a combination of CDDP 75 mg/m2 and ADM 50 mg/m2. The tumors on chest X-ray and CT scan became small by the chemotherapy. Bronchofiberscopy after the chemotherapy also revealed that the stenosis of the right upper bronchus improved and the endobronchial mass in the left B3 had disappeared. He died 8 months after initial chemotherapy with a response duration of 7 months.

Adenocarcinoma, Sebaceous↗

PDI and glutathione-mediated reduction of the glutathionylated variant of human lysozyme.

A mutant human lysozyme, designated as C77A-a, in which glutathione is bound to Cys95, has been shown to mimic an intermediate in the formation of a disulfide bond during folding of human (h)-lysozyme. Protein disulfide isomerase (PDI), which is believed to catalyze disulfide bond formation and associated protein folding in the endoplasmic reticulum, attacked the glutathionylated h-lysozyme C77A-a to dissociate the glutathione molecule. Structural analyses showed that the protein is folded and that the structure around the disulfide bond, buried in a hydrophobic core, between the protein and the bound glutathione is fairly rigid. Thioredoxin, which has higher reducing activity of protein disulfides than PDI, catalyzed the reduction with lower efficiency. These results strongly suggest that PDI can catalyze the disulfide formation in intermediates with compact structure like the native states in the later step of in vivo protein folding.

Animals↗

Allergen-induced histamine secretion associated with lactate production in mast cells detected by 1H NMR.

Allergen-induced histamine secretion in mast cells, obtained from rats infected with Nippostrongylus brasiliensis, was detected by a 1H NMR semi-selective excitation technique. Lactate production was also detected in association with histamine secretion as observed in mast cells stimulated with other nonimmunological agents, such as compound 48/80, polymyxin B, and melittin. The assignment of the lactate resonance was confirmed using lactate oxidase. Thus, 1H NMR spectroscopy is a useful method to study the activation of mast cells in allergic reaction.

Animals↗