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Biomedical subjects

S Ishihara

Publications and source records attributed to S Ishihara.

At least 163 records · Page 9Linked to original sources

Antimicrobial activity of a new fluoroquinolone, DU-6859a, against quinolone-resistant clinical isolates of Neisseria gonorrhoeae with genetic alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV.

The in-vitro antimicrobial activity of DU-6859a, a new fluoroquinolone, was tested against 55 clinical isolates of Neisseria gonorrhoeae. The MIC of DU-6859a inhibiting 90% (MIC90) of the isolates with genetic alterations of both the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV was 0.125 mg/L. The MIC90 for isolates with alterations of GyrA alone or without alterations of GyrA or ParC was 0.03 mg/L and 0.004 mg/L, respectively. The potency of DU-6859a against clinical isolates bearing genetic alterations associated with quinolone resistance was significantly greater than that of currently available fluoroquinolones.

Anti-Infective Agents↗

In-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, against clinical isolates of Neisseria gonorrhoeae with quinolone resistance-associated alterations in GyrA and ParC.

The in-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, was tested against 51 clinical Neisseria gonorrhoeae isolates in comparison with ciprofloxacin, levofloxacin and sparfloxacin. The MICs of HSR-903 for 11 isolates with alterations in both GyrA and ParC, for 19 isolates with alterations only in GyrA and for 21 isolates without alterations in either GyrA or ParC ranged from 0.03 mg/L to 1.0 mg/L (MIC90 = 0.25 mg/L), from 0.03 mg/L to 0.5 mg/L (MIC90 = 0.125 mg/L) and from < or = 0.001 mg/L to 0.008 mg/L (MIC90 = 0.004 mg/L), respectively. Levofloxacin and ciprofloxacin were the least active of the four quinolones tested, particularly against the mutant strains. Sparfloxacin was more active, but HSR-903 exhibited the most potent in-vitro activity against the clinical N. gonorrhoeae isolates, including those harbouring quinolone-resistance-associated alterations in GyrA and ParC.

Anti-Infective Agents↗

Detection of mutations in the gyrA and parC genes in quinolone-resistant clinical isolates of Enterobacter cloacae.

We have determined partial sequences of the gyrA and parC genes of Enterobacter cloacae type strain including the regions analogous to the quinolone resistance-determining region of the Escherichia coli gyrA gene. The deduced 65- and 49-amino acid sequences of the determined regions of the E. cloacae gyrA and parC genes were identical to the corresponding regions of the E. coli GyrA and ParC proteins, respectively. We examined 40 clinical strains of E. cloacae isolated from patients with urinary tract infection for susceptibilities to nalidixic acid and ciprofloxacin. Based on the nalidixic acid and ciprofloxacin MICs, these isolates were divided into 19 quinolone-susceptible strains (MICs of nalidixic acid, 3.13-25 mg/L; MICs of ciprofloxacin, < or = 0.025 mg/L) and 21 quinolone-resistant strains (MICs of nalidixic acid, 400 to > 800 mg/L; MICs of ciprofloxacin, 0.39-100 mg/L). We analysed five quinolone-susceptible and 21 quinolone-resistant strains for alterations in GyrA and ParC. The five quinolone-susceptible strains had amino acid sequences in GyrA and ParC identical to those of type strain. Of the 21 quinolone-resistant isolates, three (MICs of nalidixic acid, 400 to > 800 mg/L; MICs of ciprofloxacin, 0.39-3.13 mg/L) had a single amino acid change at the position equivalent to Ser-83 in the E. coli GyrA protein and no alterations in ParC; one (MIC of nalidixic acid, > 800 mg/L; MIC of ciprofloxacin, 3.13 mg/L) had a single amino acid change at Ser-83 in GyrA and a single amino acid change at the position equivalent to Glu-84 in the E. coli ParC protein; two (MIC of nalidixic acid, > 800 mg/L; MIC of ciprofloxacin, 25 mg/L) had double amino acid changes at Ser-83 and Asp-87 in GyrA and no alterations in ParC; and 15 (MICs of nalidixic acid, > 800 mg/L; MICs of ciprofloxacin, 25-100 mg/L) had double amino acid changes at Ser-83 and Asp-87 in GyrA and a single amino acid change at Ser-80 or Glu-84 in ParC. This study suggests, that in clinical isolates of E. cloacae, DNA gyrase is a primary target of quinolones, that only a single amino acid change at Ser-83 in GyrA is sufficient to generate high-level resistance to nalidixic acid and to decrease susceptibility to ciprofloxacin, and that the accumulation of amino acid changes in GyrA and the simultaneous presence of the ParC alterations play a central role in developing high-level resistance to ciprofloxacin.

Amino Acid Sequence↗

A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.

Adult↗

Effects of burns on inhalation injury.

BACKGROUND: There are few studies of smoke injury combined with thermal burn. METHODS: Seven sheep (G1) received smoke injury alone; eight (G2) received a 40% full-thickness scald burn immediately after smoke injury. All animals were resuscitated with lactated Ringer's solution and killed 48 hours after injury. Cardiopulmonary variables and blood gases were measured serially. Ventilation perfusion distribution was analyzed using the multiple inert gas elimination technique. Lung wet to dry weight ratio and malondialdehyde levels were determined. RESULTS: G2 resulted in early significant hemodynamic changes. Serum total protein concentration was significantly lower and malondialdehyde significantly higher in G2. However, PaO2, lung wet to dry weight ratio, and ventilation perfusion mismatching in G2 did not differ from those in G1. CONCLUSIONS: Although the addition of burn injury exaggerated the lung lipid peroxidation and hypoproteinemia in the presence of more pronounced hemodynamic changes, the pulmonary dysfunction was not accentuated.

Animals↗

Hypersensitivity to mosquito bites conceals clonal lymphoproliferation of Epstein-Barr viral DNA-positive natural killer cells.

In order to clarify the relationship between Epstein-Barr (EB) virus and hypersensitivity to mosquito bites (HMB), and to search for the mechanism which induces EB virus-associated lymphoproliferative diseases, we investigated patients with HMB, using hematological, immunological and virological techniques. Among 5 cases of HMB, CD56+ cells had proliferated and CD3+ cells were diminished in 4 cases. Although anti-EB virus antibody titers were not consistent with chronic active EB virus infection, EB viral DNA was detected in the peripheral blood mononuclear cells in all 5 cases. Moreover, EB viral DNA-positive cells had proliferated monoclonally in 4 cases, and biclonally in 1 case. It was proved that most of the EB viral DNA existed in natural killer (NK) cells through polymerase chain reaction analysis. These findings suggest that the basis of HMB may be clonal lymphoproliferation of EB viral DNA-positive NK cells and this hematological abnormality may induce the characteristic symptoms of HMB. In some cases, the proliferating NK cells can metamorphose into leukemic cells, and hemophagocytic syndrome, which has been assumed to be a complication of HMB, may then occur.

Adolescent↗

Clinicopathological characteristics of the focal and segmental form of idiopathic membranous nephropathy: comparison with the typical form of this disease.

Although idiopathic membranous nephropathy (IMN) is thought to represent a diffuse glomerulopathy, it was found that three of 31 children histologically diagnosed as IMN showed focal and segmental deposition of immunoglobulin G (IgG) and C3 on the glomerular capillary walls. The present study attempted to comparatively investigate clinical and pathological features of the diffuse group and the focal segmental group in 31 IMN children. Immunofluorescence study revealed that 28 of 31 IMN exhibited diffuse granular deposition of IgG along glomerular capillary walls. In contrast, focal and segmental deposition of IgG and C3 was noted in three children with IMN. In addition, focal and segmental electron-dense deposits were identified in these cases. In two children of the focal segmental group, immunofluorescent patterns of IgG deposition were unchanged even at the second biopsy. The focal segmental form of IMN tended to occur in younger children than diffuse IMN. However, other clinical parameters such as the range of proteinuria, hematuria, serum albumin and prognosis did not show any significant differences between both groups. Electrophoretic profiles of urinary proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis were not different between both groups. It is proposed that the focal segmental form of IMN may have a distinctive glomerulopathy from the typical form of IMN.

Child, Preschool↗

Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in quinolone-resistant clinical isolates of Klebsiella pneumoniae.

We determined a partial sequence of the Klebsiella pneumoniae parC gene, including the region analogous to the quinolone resistance-determining region of the Escherichia coli gyrA gene, and examined 26 clinical strains of K. pneumoniae for an association of alterations in GyrA and ParC with susceptibilities to quinolones. The study suggests that in K. pneumoniae DNA gyrase is a primary target of quinolones and that ParC alterations play a complementary role in the development of higher-level fluoroquinolone resistance.

Amino Acid Sequence↗

Synthesis and biological evaluation of a new reversely linked type of dual histamine H2 and gastrin receptor antagonist.

In an attempt to improve the low oral absorbability of previously reported dual histamine H2 and gastrin receptor antagonists, compounds of a different type were synthesized and evaluated for biological activity. These new compounds bear a histamine H2 receptor antagonist (H2A) pharmacophore moiety attached to a gastrin receptor antagonist (GA) pharmacophore moiety in a reversed manner, namely the head-to-head manner, different from the previously reported head-to-tail manner. These new hybrid compounds were classified into three types: type I, the regular amide type bearing a roxatidine moiety; type II, the reversed amide type bearing a roxatidine moiety; and type III, hybrid compounds bearing a famotidine moiety directly connected to a GA moiety without a spacer. Among them, only (R)-1-[3-(N'-(4-[2-(N-aminosulfonylamidino)ethylthiomethyl] thiazol-2-yl) guanidinomethyl)phenyl]-3- (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl) ure a (42), belonging to type III, showed a weak but distinct histamine H2 receptor-antagonistic activity as well as a modest gastrin receptor-antagonistic activity. Of most importance was the finding that this compound showed a weak but clearly improved in vivo oral antigastric acid secretory activity as a result of the structural changes, including the decreased molecular weight.

Animals↗

Helicobacter pylori infection accelerates gene expression of glicentin in the gastric mucosa. Its association with intestinal metaplasia of the stomach.

BACKGROUND: Glicentin is an intestinal polypeptide hormone which seems to promote intestinal metaplasia (IM) in the gastric mucosa. The aim of this study was to clarify whether Helicobacter pylori infection accelerates glicentin gene expression. METHOD: Glicentin mRNA was investigated by reverse-transcription polymerase chain reaction using gastric biopsies from 47 patients examined endoscopically and denying IM. RESULTS: IM was observed in 18 (38.3%) cases histologically, but not in the other 29 (62.7%). Glicentin mRNA was significantly correlated with histological IM (P < 0.01) and was positively correlated with H. pylori infection (P < 0.05). CONCLUSION: Our results indicate that H. pylori infection is associated with the induction of glicentin in the gastric mucosa, thus supporting the hypothesis that H. pylori infection accelerates IM of the stomach.

Adult↗

[A case of jugular foramen neurinoma originating from glossopharyngeal nerve].

A 39-year-old man was admitted with right hearing loss, tinnitus and vertigo. Neurological examination on admission revealed right facial palsy, right acoustic nerve disturbance and cerebellar ataxia. CT scan demonstrated a mass with intra-and extracranial extension in the pyramid bone concomitant with enlarged jugular foramen. MRI showed a ring-like enhanced, extra-axial mass in the right CP angle. Cerebral angiography showed no tumor stain. Venous phase of VAG revealed lateral displacement of the right sigmoidal sinus and obstruction of the internal jugular vein. Three dimensional CT was very useful to reveal enlarged jugular foramen. The tumor was resected totally and was approached through a right suboccipital craniectomy and mastoidectomy on July, 1994. Surgery confirmed that the tumor was a neurinoma originating from the glossopharyngeal nerve. After the operation, right facial palsy developed and transient fugitive CSF leakage was observed, but the patient is doing well. There was no amelioration of right hearing loss. JFN originating from the glossopharyngeal nerve is rare. Twenty-five cases of glossopharyngeal neurinoma are reviewed.

Adult↗

[Dural arteriovenous fistula presenting as acute-onset dementia: a case report].

We report here a unique case of acute-onset dementia caused by a posterior fossa dural arteriovenous fistula (AVF), which was successfully treated by surgical resection of the isolated transverse-sigmoid sinus combined with endovascular procedures. A 70-year-old female was admitted to our hospital with acute-onset dementia and pulsatile tinnitus on the left side. CT scan revealed a low-density area in the parieto-temporal region. Cerebral angiography revealed a dural AVF of the transverse-sigmoid sinus with retrograde drainage into cerebral cortical veins. After transarterial endovascular embolization of the dural AVF, a xenon-CT scan revealed increased cerebral blood flow. Four months postoperatively, however, she was admitted to our hospital again with seizure and aphasia due to recanalizaion of the dural AVF. After trans-arterial embolization, transvenous embolization was attempted, but was unsuccessful due to inaccessibility of the isolated sinus segment. Since this patient could not be cured by endovascular embolization, an open surgical resection of the isolated sinus segment was performed. Following this, CT scans revealed that the low density area present on the first admission had disappeared. The patient's dementia resolved postoperatively. We discuss the pathophysiological mechanism by which venous ischemia due to dural AVF can cause reversible dementia.

Acute Disease↗

[Removal of bronchial foreign bodies by suction with a bronchoscope].

We report two cases in which intrabronchial foreign bodies were removed with a fiberoptic bronchoscope. In both cases the foreign body was a seed of a small Japanese apricot. Atelectasis or obstructive pneumonia was seen on chest roentgenograms. The foreign bodies were associated with slight inflammation and polyps on the bronchial epithelium. The foreign bodies were removed by applying suction with a fiberoptic bronchoscope. This method may also be useful for removing other large, hard, uneven, and ball-like foreign bodies.

Aged↗

[Malignant hemangioendothelioma associated with chronic pyothorax].

A 67-year-old man was admitted to the hospital because of a fever. A chest CT scan showed multilobular heterogeneous shadows on the right side in the chest wall and the lung, but clinical examinations and examination of a biopsy specimen did not lead to a diagnosis. At autopsy, a hemorrhagic tumor was found on the right side in the chest wall. Microscopical examination showed that large atypical cells had proliferated and formed vascular structures, which were stained positively with anti-factor VIII antibody. The histological findings led to the diagnosis of malignant hemangioendothelioma. Chronic empyema-associated malignant hemangioendothelioma is rare.

Aged↗

[Clinical evaluation of nitrite test for the detection of bacteriuria].

A nitrite test for bacteriuria was compared with routine microscopic examination in 1,318 clinical urine specimens and with bacterial culture in 132. Sensitivity, specificity, positive predictive value and accuracy rate are as follows; for diagnosis of bacteriuria more than 10(4) CFU/ml, 53.4%, 88.6%, 90.4 and 65.2%, respectively; for more than 10(5) CFU/ml, 55.4%, 87.8%, 88.4% and 67.2%, respectively. The positive rate for the nitrite test was 21.4% for bacteriuria of > or = 10(4) CFU/ml in gram positive cocci and 56.9% in gram negative rods. False negative results were obtained from gram positive cocci without nitrate reductive activity or from patients with acute uncomplicated cystitis because of insufficient incubation time in urinary tract. However, this simple test is valuable in the detection of bacteriuria in clinical practice with high specificity.

Bacteria↗

Mechanistic investigation of photoreduction of 5-bromouracil-containing oligomers.

It was found that photoreduction of 5-bromouracil (BrU) occurs at 5'-ATBrU-3' sequence more efficiently than 5'-ABrU-3'. We introduced 5'-GG-3' sequence at the 5'-side of 5'-ATBrU-3' sequence and 5'-ABrU-3' sequence and investigated their photoreduction. As a result, dIz, an oxidation product originated from guanine cation radical, was detected.

Base Sequence↗

Molecular mechanism of the alternative expression of the Chlorella virus CVK2 chitosanase gene.

A novel viral strategy for expression of two mRNAs from a single gene yielding two products with seemingly different functions (alternative gene expression) has be found. The vChta-1 gene of Chlorella virus CVK2 produced two functional chitosanase proteins with apparently different roles in viral infection: The larger 65-kDa chitosanase assembled into virion and presumably function at the beginning of infection, while the smaller 37-kDa enzyme remains in the host cytoplasm where it most likely aids in the digestion of the host cell wall prior to viral release. These predicted activities are essential for a cycle of viral infection. The dual expression of the vChta-1 gene most likely occurred by read-through into a downstream gene, ORF245.

Chlorella↗