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H Koga

Publications and source records attributed to H Koga.

At least 325 records · Page 18Linked to original sources

Rat cathepsin H-catalyzed transacylation: comparisons of the mechanism and the specificity with papain-superfamily proteases.

We found that rat cathepsin H showed strong transacylation activity under physiological conditions. It is a feature of cathepsin H to utilize amino acid amides not only as acyl-acceptors but also as acyl-donors in the reaction. The pH-dependence of the transacylation activity was distinct from those of other papain-superfamily proteases. The alkaline limb (pKapp = 7.5) could be regarded as the pKa of the alpha-amino group of the acyl-donor, which was also involved in the original amino-peptidase activity. The acidic limb (pKapp = 5.8) was suggested to be involved in the deacylation step, where amino acid amide attacked the acyl-intermediate as a nucleophile in place of water in the hydrolysis. Although the N alpha-deprotonated acyl-acceptor, which is supposed to govern the nucleophilic attack, has a small population in the acidic pH range (above pH5), the transacylation was detectable even at the acidic pH-range because of the high S1'-site binding ability and suitable nucleophilicity of the acyl-acceptor. In the transacylation between various amino acid amides, the S1 and S1' site appeared to prefer hydrophobic residues without and regardless of a branch at beta-carbon, respectively. From these results and the sequence homology in the papain superfamily, we concluded that the reaction was governed by the acyl-donor having a protonated amino group, the acyl-acceptor having a deprotonated amino group and the remarkable hydrophobic character (especially favoring tryptophan amide) of the S1' site, presumably reflecting the good conservation of Trp177 in papain-superfamily proteases.

Amino Acid Sequence↗

[Clinical evaluation of serological antigen detection tests for candidemia].

The new serological tests for candidemia were evaluated. In nine cases of candidemia, fungal index (Endotoxin D-Endospecy) was 146.8 +/- 116.8 pg/ml and D-arabinitol/creatinine 1.10 +/- 1.04 mumol/mg. Fungal index was significantly (p less than 0.01) higher in candidemia than suspected infections. All candidemia were positive for Cand-Tec latex agglutination, but twelve of the sixteen cases of suspected infections were also positive. Mannan latex agglutination was very specific for candidemia. Four cases of candidemia was positive for Mannan latex agglutination and only one case was positive in suspected infections. Fungal index and D-arabinitol/creatinine was decreased after treatment of antifungal agents. In poor clinical efficacy case, these titer remained high even after treatment. These data suggested the usefulness of these serological tests for candidemia.

Adolescent↗

[A mechanism of usefulness of treatment with erythromycin for diffuse panbronchiolitis].

The clinical usefulness of treatment with erythromycin for diffuse panbronchiolitis (DPB) patients have been well reported to date, although its mechanisms remain unknown. In a previous study, we demonstrated that DPB patients were found to have large percentages of neutrophils in their lower respiratory tracts and suggested that neutrophils play an important role in the pathogenesis of DPB (Chest 99: 917-923, 1990). While in vitro and in vivo studies have demonstrated that erythromycin decreases neutrophils directed migration. In the present study, we performed bronchoalveolar lavage (BAL) on eight patients with DPB to clarify the cell populations in the lower respiratory tract before and after treatment with erythromycin. Neutrophils percentages in BAL fluid were significantly reduced after treatment with erythromycin (54.3 +/- 22.4% to 13.1 +/- 13.5%, p less than 0.01). No significant variance of BAL lymphocyte percentages was demonstrated after treatment with erythromycin. These results suggest that a main mechanism of clinical usefulness of treatment with erythromycin for DPB may be inhibition of neutrophils migration into the lower respiratory tract instead of intrapulmonary bactericidal activity against organisms.

Adolescent↗

[Bacteriological studies on pharyngeal and tracheal colonization in patients of operations and patients in ICU].

Bacterial colonization of the pharynx before and one week after operation, and contamination of the trachea during intubation in 7 patients who underwent operations were investigated. And bacterial colonization of pharynx, tracheas, and mechanical-ventilators in 7 ICU patients was investigated. Flora of palms of 10 ICU personnel was also examined: 1) Oral bacteria began to be found in the trachea several hours after intubation. 2) In oropharyngeal flora, one week after operation, Neisseria and anaerobes which belong to normal flora decreased because of antibiotics, but no new resistant bacteria appeared. 3) Although isolates from pharynx of preoperative patients were normal flora, those of ICU patients were Staphylococcus epidermidis, Enterococcus spp., gram-negative rods such as Pseudomonas aeruginosa, and yeast liked organisms etc, which were resistant to antibiotics. 4) From the trachea of intubated patients in ICU, oral bacteria were isolated. 5) Pseudomonas pickettii was isolated from the expiratory side of ventilator circuits in one patient, but it was not isolated from the patient. 6) From hands of ICU personnel, gram-positive bacteria such as coagulase negative staphylococci, Coryne bacterium spp. and Bacillus spp. were isolated. 7) One patient in ICU, who developed pneumonia due to resistant Bacteroides fragilis following oropharyngeal colonization, was reported. These studies suggested the importance of environmental control, careful selection of antibiotics, and attention to change of flora.

Aged↗

[Elastase activity in bronchoalveolar lavage fluid from patients with diffuse panbronchiolitis].

The clinical and pathological features of diffuse panbronchiolitis (DPB) have been well reported to date though its pathogenesis remains unknown. This study was designed to evaluate the protease antiprotease imbalance in patients with DPB. For this purpose, we performed bronchoalveolar lavage (BAL) in sixteen patients with DPB, twelve patients with chronic bronchitis (CB) and control subjects (nine smokers and eleven non-smokers), and determined elastase activity and alpha 1 antitrypsin (alpha 1 AT) concentration in bronchoalveolar lavage fluid (BALF). Elastase activity was measured using a synthetic substrate, succinyl-tri-L-alanine-p-nitroanilide. BALF from eleven of sixteen patients with DPB showed elastase activity. However, only two of twelve patients with CB showed elastase activity, and control subjects did not show any elastase activity in BALF. Although alpha 1 AT concentration is elevated in BALF from patients with DPB, it is assumed that elastase burden exceeded the elastase inhibitory capacity of alpha 1 AT in BALF. The percentage of neutrophils in BALF correlated significantly with elastase activity which was inhibited by DFP, but not by EDTA. These data revealed that the elastase in BALF was a serine protease of neutrophil origin. In five DPB-patients treated with low-dose long-term erythromycin chemotherapy, elastase activity in BALF decreased significantly. The above mentioned findings suggest that the neutrophil elastase plays an important role in the pathogenesis of DPB, and the mode of action of erythromycin on DPB is to decrease the elastase burden.

Adolescent↗

[A case of Enterococcus faecalis brain abscess in a patient with suprapharyngeal cancer].

A 55-year-old male was admitted to our hospital for the treatment of suspected brain abscess on March 18, 1989. The brain CT scan showed low density area with ring enhancement. After admission, both cefminox 2 g/day and clindamycin 500 mg/day were administered intravenously. On March 29, 1989, the patient developed cerebral herniation suddenly. Therefore emergency burr hole operation was done. Many gram-positive cocci were observed on gram-staining of the aspirated pus. Moreover neutrophils with phagocytosed gram-positive cocci were also observed. Culture of aspirated pus revealed colonies of gram-positive cocci which were subsequently identified as E. faecalis. Same species of bacteria were also isolated from fistula of right mastoid. From both findings of brain CT scan and data of MICs of E. faecalis, it may be suggested that direct infection developed from right mastoiditis to intracranial space. We experienced a severe case who developed cerebral herniation because of brain abscess due to E. faecalis which is an infrequent pathogen of brain abscess.

Brain Abscess↗

[Laboratory and clinical investigation of lysis centrifugation blood culture method for fungemia].

We compared the lysis centrifugation blood culture system using Isolator (Du Pont) to the conventional blood culture bottle using BCB system (Roch), and the following results were obtained. In the investigation of experimental fungemia made by human blood and Candida albicans, the organism was detected 9/12 after 1 day and 11/12 after 3 days by Isolator, although the organism was detected 3/12 after 3 days and 11/12 after 6 days by the culture bottle system. In the experimental fungemia of Candida tropicalis, the organism was detected 12/12 after 2 days by Isolator, although it was detected 1/12 after 6 days and 4/12 after 10 days with the culture bottle system. Isolator showed faster and a more sensitive detection rate for fungemia. Clinical investigation of 94 cases (180 cultures) showed a 11.1% isolation rate with Isolator system and a 7.1% isolation rate with the culture bottle system. In 43 cases which were examined by the both systems, 7 cases were positive with Isolator, 3 positive with culture bottle. The culture bottle system isolated only Candida albicans and Candida parapsilosis, where as the Isolator isolated Candida albicans, Candida parapsilosis, Candida tropicalis, Candida krusei, and Candida spp. This investigation suggested that the Isolator system was an excellent method for the detection of fungemia.

Blood↗

Studies on uricosuric diuretics. II. Substituted 7,8-dihydrofuro[2,3-g]-1,2-benzisoxazole-7-carboxylic acids and 7,8-dihydrofuro[2,3-g]benzoxazole-7-carboxylic acids.

A series of substituted 7,8-dihydrofuro[2,3-g]-1,2-benzisoxazole-7-carboxylic acids 9 and 7,8-dihydrofuro[2,3-g]benzoxazole-7-carboxylic acids 12 were synthesized and evaluated for uricosuric and diuretic activities in rats. Many of the benzisoxazole derivatives 9 showed uricosuric and only weak diuretic activities, whereas the benzoxazoles 12 exhibited potent diuretic activities with little affecting urate excretion. Among these compounds, 5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carbo xylic acid (9b, AA-193) was found to be a potent uricosuric agent without diuretic activity and was selected for further development.

Animals↗

Dural arteriovenous malformation associated with occlusion of the superior sagittal sinus--case report.

The authors report a rare case of dural arteriovenous malformation (AVM) associated with occlusion of the superior sagittal sinus. A 78-year-old female developed transient aphasia, followed by generalized convulsion. Common carotid angiography showed a dural AVM fed by the bilateral middle meningeal arteries, draining to the superior sagittal sinus, and sinus occlusion. 123I-single photon emission computed tomography demonstrated decreased blood flow in the bifrontal-parasagittal regions. Transcatheter embolization via the feeding arteries improved the cerebral blood flow around the lesion, and the symptoms disappeared.

Aged↗

Treatment of metastatic brain tumor from esophageal carcinoma--report of four cases.

Metastasis to the brain from esophageal carcinoma is rare. Recently we had four cases, all treated by tumor removal. Three received postoperative whole or local brain irradiation. Anticancer pellets were implanted in two. The postoperative 1-year survival rate was 37.5%, which suggests the prognosis is not worse than for other metastatic brain tumors.

Aged↗

[Traumatic sinus pericranii. Case report].

The patient was involved in a traffic accident at the age of 1 and the left parieto-occipital scalp was contused without skull fracture. At the age of 5, an extracranial scalp mass was first noticed just beneath the multiple scalp scars. Angiography through the mass revealed that the extracranial mass cavity was connected to the superior sagittal sinus through the emissary veins. The mass located in the subgaleal, epiperiosteal space was totally resected and the connection with the intracranial sinus was closed with bone wax. Histologically, there were many capillaries and some large blood cavities with only one layered endothelium and connective tissue. Therefore, the mass was diagnosed as sinus pericranii and considered to be secondary to previous head trauma because: 1) The patient had a history of head trauma with considerably severe scalp injuries. 2) The extracranial blood sinus was located exactly beneath the traumatic scar. 3) There was no neoplastic tissue histologically. 4) No scalp mass was noticed before the traffic accident. 5) There was an elapsed time between the trauma and the growth of the mass. 6) No scalp nevus such as port-wine stain existed.

Child↗

[A case of chondrosarcoma in the cavernous sinus].

A 24-year-old female patient complained of headache and right abducens nerve paralysis. No abnormality was found in plain CT scan, but a ring-like enhanced mass was disclosed behind the right posterior clinoid process in enhanced CT scan. MRI revealed a low intensity mass in T1-weighted image and a ring-like enhanced mass in gadolinium-DTPA enhanced image. It was a circumferential high intensity mass in T2-weighted image and an isointensity mass in proton image. Cerebral angiography indicated that it was avascular. Preoperative diagnosis was trigeminal neurinoma or petroclival meningioma. The tumor was removed almost completely by orbitozygomatic infratemporal approach. Histologically, it was low grade chondrosarcoma. Postoperatively, neither radiation therapy nor chemotherapy was added. Differential diagnosis and treatment was discussed. It was suggested that MRI was the most useful diagnostic tool to distinguish chondrosarcoma from other skull base tumors.

Adult↗

[One-and-a-half syndrome due to a brain tumor--a case report and review of the literature].

A 69-year-old woman was admitted to our hospital on March 13, 1990, with a 1-month history of progressive gait disturbance. She had been operated on for colon cancer in May 1987. Examination in March 1989 revealed that she had metastatic liver tumor. On neurological examination, slight right abducens palsy, gaze-evoked horizontal nystagmus to the left, upbeat nystagmus and mild left hemiparesis were noted. Two weeks after admission, right lateral gaze palsy developed. Right MLF syndrome became apparent in the 3rd week. She was diagnosed as having one-and-a-half syndrome. Left hemi-hypesthesia and left limb ataxia were noted at that time. CT scan revealed ring-enhancing mass lesions in and around the right pontine tegmentum. Two weeks after development of the one-and-a-half syndrome, she became comatose with her eyes' conjugate deviation to the left and died on April 24, 1990. The metastatic lesions in both paramedian pontine reticular formation and medial longitudinal fasciculus were considered to be causative of her one-and-a-half syndrome. Clinical characteristics of 13 reported cases with one-and-a-half syndrome caused by brain tumor were reviewed. Half of them were caused by metastatic brain tumor.

Aged↗

[Observation of bleeding sites by fiberoptic bronchoscopy in a case of vasculo-Behçet's disease with pulmonary involvement].

A 45-year-old man complained of fever and bloody sputum. Chest X-ray films showed a round opacity in the left hilum. He developed massive hemoptysis (500 ml) and emergency embolization of the bronchial artery was performed. Pulmonary artery aneurysm and thrombosis were detected angiographically, and fiberoptic bronchoscopy revealed a reddish irregular eminence of the left main bronchus and lingulate++ ++ bronchus. These sites could have been the bleeding sites. Because of recurrent hemoptysis, left pneumonectomy was performed 26 days after the massive hemoptysis. Pathological findings showed panarteritis, luminal thromboembolism of the pulmonary artery and markedly dilated vessels of the bronchial wall. He developed genital ulceration after the operation and these findings suggested incomplete vasculo-Behçet's disease with rare pulmonary involvement. The disease is now well-controlled by corticosteroid therapy 27 months after the operation.

Aneurysm↗

[The comparison of drug susceptibility of antituberculous agents against colonizing M. intracellulare and infectious M. intracellulare].

The susceptibility of antituberculous agents against colonized M. intracellulare which were isolated from patients with pulmonary disease and infectious M. intracellulare (pathogens) isolated from atypical mycobacterial culture was investigated. Aminoglycosides were more potent against colonized organisms than against pathogens. Isoniazid, ethambutol and rifampicin showed less potent antimicrobial activity against both colonized organism and pathogens as compared to aminoglycosides. On the contrary susceptibility of cycloserine against colonized organisms was as potent as against pathogens.

Aged↗

[A case of immotile cilia syndrome accompanied by retinitis pigmentosa].

A case of immotile cilia syndrome accompanied by retinitis pigmentosa is reported. This syndrome involves congenital ciliary ultrastructural abnormality. A 27-year-old male complained of repeated pneumonia, sinusitis, and middle otitis. In addition, he had sperm motor insufficiency and electron microscopic finding of cilia led to the diagnosis of the present syndrome. Both fundi presented remarkable degeneration of retinal pigment epithelium and choroid and marked arterial narrowing. Constriction of the visual field and extinguished ERG were also noted. Abnormality of cilia of the retinal pigment epithelium was suggested. It was proposed that retinitis pigmentosa may be caused by abnormal cilia of the retinal pigment epithelium.

Adult↗

Uricosurics inhibit urate transporter in rat renal brush border membrane vesicles.

It has been proposed that a urate-anion exchanger system in brush border membrane vesicles (BBMV), which mediates hydroxyl ion (OH-) gradient-dependent urate uptake, is the most likely route for the mediation of urate transport in the first step of urate reabsorption in the proximal tubules. Luminal drugs which inhibit urate reabsorption would inhibit the transport of urate into the cell by blocking the urate-anion exchanger. To confirm this hypothesis, we investigated the inhibitory effects of well-known uricosuric drugs on the OH-/urate exchange in BBMV. The rank order of potency was benzbromarone greater than tienilic acid greater than sulfinpyrazone greater than probenecid, which is consistent with clinical doses in man. AA-193 (5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carb oxylic acid), an excellent candidate for a uricosuric, exerted the most potent inhibition on urate uptake (Ki = 0.12 microM). In contrast with that by stilbene disulfonates, the inhibition by AA-193 or benzbromarone was reversible.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗