An outbreak of food poisoning due to Escherichia coli serotype O7:H4 carrying astA for enteroaggregative E. coli heat-stable enterotoxin1 (EAST1).

In June 2020, a large-scale food poisoning outbreak involving about 3000 elementary and junior high school students occurred in Yashio, Saitama, Japan. A school lunch was the only food stuff ingested by all of the patients. Escherichia coli serotype O7:H4 carrying the astA gene for enteroaggregative E. coli (EAggEC) heat-stable enterotoxin 1 (EAST1) was detected in faecal specimens from the patients, and sample inspection revealed its presence in a seaweed salad and red seaweed (Gigartina tenella) as one of the raw materials. Analysis of the antibiotic sensitivity of the isolates revealed resistance to ampicillin and cefotaxime. All isolates were confirmed to be of the same origin by pulsed-field gel electrophoresis after digestion with the restriction enzyme XbaI, and single nucleotide polymorphism analysis using whole genome sequencing. To our knowledge, this is the first report of a large-scale food poisoning caused by E. coli O7:H4, which lacks well-characterized virulence genes other than astA.

The effects of doxapram on medullary respiratory neurones in brainstem-spinal cord preparations from newborn rats.

Doxapram is the only dedicated respiratory stimulant used to aid recovery of breathing after major surgery. Doxapram acts on peripheral chemoreceptors and although the central action of doxapram has been suggested, its detailed neuronal mechanism is unknown. We assessed doxapram-induced changes in spontaneous cervical nerve (C4) inspiratory activity and the firing of action potentials in pre-inspiratory and inspiratory neurones in the medulla. Experiments were performed in neonatal rat brainstem-spinal cord preparations, which can produce respiratory rhythm for several hours under in vitro conditions. Doxapram application (for 15 min) increased the frequency and amplitude of C4 activity dose-dependently. Doxapram induced changes in the electrophysiological properties of pre-inspiratory and inspiratory neurones. Our results suggest that respiratory activity enhancement was likely to be induced via effects on the potassium channels of pre-inspiratory and inspiratory neurones and indicate the central actions of doxapram.

MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis.

BACKGROUND: MicroRNA (miRNA, miR)-18a is a member of the miR-17-92 cluster, an important locus that is markedly overexpressed in several cancers and associated with cancer development and progression. However, the mechanism of action of the miR-17-92 cluster and its individual miRNAs are largely unknown. METHODS AND RESULTS: In this study, we investigated the expression of the miR-17-92 cluster by in situ hybridisation (ISH) assay and copy-number analysis in gastric tissue microarray (TMA) specimens. We determined that miR-18a was present at higher levels than the other five miRNAs in the cluster. In addition, we identified Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3 (PIAS3) as a direct target of miR-18a in gastric cancer. miR-18a level was positively correlated with levels of Survivin, Bcl-xL, and c-Myc, which are downstream transcriptional targets of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3-induced transcription can be negatively regulated by PIAS3; consistent with this, PIAS3 level was negatively correlated with levels of Survivin, Bcl-xL, and c-Myc. CONCLUSION: Our findings indicate that miR-18a acts as an oncogene and plays a role in gastric adenocarcinogenesis, at least in part by negatively regulating PIAS3 and thereby modulating expression of STAT3 target genes.

[Rapidly growing progressive massive fibrosis that was difficult to differentiate from lung cancer: report of a case].

The subject was a 79-year-old male. When he was 50-years-old, he was diagnosed to have pneumoconiosis, and his clinical course was monitored periodically during his stay at our hospital. In October 2007, chest computed tomography (CT) revealed a new shadow of a tumor mass in the right lower lobe. Lung cancer could not be ruled out by either CT or fluorodeoxyglucose-positron emission tomography (FDG-PET), and a definite diagnosis could not be established. Therefore, to make a diagnosis, we performed a partial resection of the lung and a diagnosed of progressive massive fibrosis (PMF) was obtained pathologically. Patients with pneumoconiosis have a possibility of developing new manifestations of PMF as a rapidly growing mass like a case presented in this report

Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine.

BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. RESULTS: One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. CONCLUSION: Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

Myeloperoxidase in blood neutrophils during normal and abnormal menstrual cycles in women of reproductive age.

INTRODUCTION: We previously reported that granulocyte colony-stimulating factor (G-CSF) plays a critical role in ovulation, suggesting that neutrophils may maintain ovulation. We assessed myeloperoxidase (MPO), a major and specific enzyme of neutrophils, in women with abnormal and normal menstrual cycles to clarify the relationship between MPO and ovulation. METHODS: We analyzed MPO activity in blood neutrophils of women with abnormal menstrual cycles (indicative of anovulation, n = 12) and age- and body mass index-matched normal menstrual cycles (indicative of ovulation, n = 24) using two parameters as a marker of MPO, Neut X and mean peroxidase index (MPXI). RESULTS: MPO of women with abnormal menstrual cycles was significantly lower than that of women with normal menstrual cycles [Neut X: 62.6 ± 1.1 (mean ± standard error of the mean) vs. 66.2 ± 0.3, P = 0.009; MPXI: -0.54 ± 1.66 vs. 4.91 ± 0.53, P = 0.008]. Among women with normal menstrual cycles, MPO was highest in the follicular phase (Neut X: 67.0 ± 0.3; P = 0.033). CONCLUSION: The difference in MPO between women with abnormal and normal menstrual cycles and the upregulation of MPO before ovulation suggest that neutrophils and MPO are closely related to ovulation.

High linear energy transfer carbon radiation effectively kills cultured glioma cells with either mutant or wild-type p53.

PURPOSE: A mutation in the p53 gene is believed to play an important role in the radioresistance of many cancer cell lines. We studied cytotoxic effects of high linear energy transfer (LET) carbon beams on glioma cell lines with either mutant or wild-type p53. METHODS AND MATERIALS: Cell lines U-87 and U-138 expressing wild-type p53 and U-251 and U-373 expressing mutant p53 were used. These cells were irradiated with 290 MeV/u carbon beams generated by the Heavy Ion Medical Accelerator in the National Institute of Radiologic Science or X-rays. A standard colony-forming assay and flow cytometric detection of apoptosis were performed. Cell cycle progression and the expression of p53, p21, and bax proteins were examined. RESULTS: High LET carbon radiation was more cytotoxic than low LET X-ray treatment against glioma cells. The effects of the carbon beams were not dependent on the p53 gene status but were reduced by G(1) arrest, which was independent of p21 expression. The expression of bax remained unchanged in all four cell lines. CONCLUSION: These results indicate that high LET charged particle radiation can induce cell death in glioma cells more effectively than X-rays and that cell death other than p53-dependent apoptosis may participate in the cytotoxicity of heavy charged particles. Thus, it might prove to be an effective alternative radiotherapy for patients with gliomas harboring mutated p53 gene.

A horizontal CT system dedicated to heavy-ion beam treatment.

A horizontal helical CT system to be used for 3-D treatment planning and for positioning verification of patients in seated position was installed in the treatment room with a fixed horizontal heavy-ion beam line. The system achieved the expected mechanical consistency and reliability.

Detection of donor lymphocytes in the cerebrospinal fluid of a patient with metachromatic leukodystrophy following bone marrow transplantation.

An unrelated donor bone marrow transplant (UD-BMT) was carried out on a 10-year-old patient with metachromatic leukodystrophy (MLD). We collected cerebrospinal fluid (CSF) on day +168 and cultured it with recombinant IL-2 and PHA-P to examine the origin of cells in the CSF. Analysis on variable number of tandem repeat (VNTR) of lymphocytes in the CSF amplified by PCR revealed that lymphocytes in the CSF were of donor origin. These data support that BMT at an early stage may prevent deterioration in MLD. Although the patient developed grade III acute GVHD with rash and diarrhea, we successfully treated acute GVHD using rabbit anti-human thymocyte immunoglobulin (ATG). UD-BMT may be an alternative treatment for patients with MLD in the absence of an HLA matched family donor.

Long-term follow-up study of unruptured vertebral artery dissection: clinical outcomes and serial angiographic findings.

OBJECT: Although the spontaneous occurrence of an unruptured vertebral artery (VA) dissection has increasingly been recognized as a relatively common cause of stroke, and the clinical aspects of this lesion have gradually been determined, its natural course remains obscure. The main goal of this study was to clarify the management protocol for this condition by examining serial angiographic changes in patients with unruptured VA dissections. METHODS: Seventeen patients with unruptured VA dissections, including 13 men and four women, were clinically and angiographically examined between 1993 and 1998. All patients were observed using serial angiography studies. The initial angiography examinations most frequently revealed stenotic lesions (appearance of a pearl-and-string sign or string sign) in eight (47.1%) of 17 cases. In 15 cases (88.2%), changes in the lesions were evident on follow-up angiography studies. Stenotic lesions resulted in occlusion in four cases, normalization in three, and subsequent formation of an aneurysm in one case, which was treated successfully by proximal occlusion of the affected vessel performed using a detachable balloon. Occluded lesions, which were initially observed in three patients, recanalized in two patients and remained unchanged in one patient. Fusiform dilation alone was demonstrated in three patients during the initial angiography session; these lesions became normalized or were unchanged on follow-up studies. Saccular aneurysms were observed in two patients. In one of these cases, proximal ligation of the parent artery was successfully performed because of subsequent aneurysm enlargement. A double lumen, which appeared in one patient with an extradural VA dissection, became occluded. Magnetic resonance T2-weighted imaging studies revealed infarction corresponding to the posterior circulation in seven cases. During long-term observation in this series, good or excellent recovery was obtained in 14 (87.5%) of 16 patients, and moderate or severe disability in two (12.5%); one patient was lost to follow up after the second angiography study. CONCLUSIONS: A follow-up angiography study must be performed during the early stage (within approximately 3 weeks after onset of symptoms) to confirm the formation or enlargement of an aneurysm, because such conditions may be amenable to surgical treatment. Unruptured VA dissection could otherwise be treated and followed conservatively. Although the majority of dissected lesions seem likely to stabilize within a few months, as evidenced on angiography, in some cases a longer observation period is required.

Effect of an atypical adrenergic beta3-agonist, GS-332: sodium (2R)-[3-[3-[2-(3-chlorophenyl)-2-hydroxyethylamino]cyclohexyl]phenoxy] acetate, on urinary bladder function in rats.

We have developed an atypical adrenergic beta3-agonist, GS 332: Sodium (2R)-[3-[3-[2-(3 Chlorophenyl)-2-hydroxyethylamino]cyclohexyl]phenoxy]acetate, which has an unique structure compared to other beta3 agonists. In vitro study, we compared effects of GS 332 on rat urinary bladder muscle strip contractility with those of clenbuterol hydrochloride (clenbuterol), an adrenergic beta2 agonist. GS-332 relaxed isolated rat urinary bladder strips in a concentration dependent manner with 50% effective concentration (EC50) of 15.7 nM, and the relaxant activity of GS 332 was as potent as that of clenbuterol(EC50; 30.8 nM). The concentration response curve of GS 332 on isolated rat urinary bladder was competed by a specific beta3-antagonist, SR59230A in a concentration-dependent manner, in which Schild slope was 1.1 and pA2 value of SR59230A was 7.1. In vivo study, cystometory investigated in anesthetized rats demonstrated that GS 332 was more potent in increasing the urinary storage volume than clenbuterol and less potent in inhibiting the contractile force of urinary bladder at micturition reflex than clenbuterol. These data demonstrate that GS 332, a new adrenergic beta3-agonist, may be more useful to maintain continence than clenbuterol, an adrenergic beta3 adrenergic agonist.

Renal vein fibrin degradation products (FDP's) in glomerulonephritis.

In order to determine the role of intrarenal vascular coagulation (IVC) in chronic glomerulonephritis, coagulant parameters in renal blood (RVB), urine FDP's and renal histology were examined in 70 patients with chronic glomerulonephritis (CGN). RVB was obtained by Seldinger's technique. A correlation was obtained between an increase of fibrinogen, FDP and soluble fibrin monomer complexes (SFMC) in RVB and the degree of intraglomerular fibrin deposition shown on immunofluorescence. An increase of FDP's, SFMC and a slight decrease of fibrinolytic activity in RVB were observed in patients with CGN with decreased renal function or with the nephrotic syndrome. Daily excretion of FDP in the urine and the extent of intraglomerular fibrin deposition were greater in nephrotics than in non-nephrotics. We conclude that measurement of coagulation parameters in RVB is a reliable and sensitive method of assessing IVC, and that IVC plays an important role in aggravation of chronic glomerulonephritis, particularly when the nephrotic syndrome is present.

Caries inhibitory activity of cacao bean husk extract in in-vitro and animal experiments.

Cacao bean husk extract (CBH) was examined for inhibitory effects on the caries-inducing properties of mutans streptococci in vitro and on caries development in specific pathogen-free Sprague-Dawley rats infected with mutans streptococci. CBH reduced the growth rate of almost all oral streptococci examined, which resulted in the reduction of acid production. Furthermore, insoluble glucan synthesis by the glucosyltransferases from Streptococcus mutans MT8148R and Streptococcus sobrinus 6715 was significantly inhibited by CBH. Hence, the sucrose-dependent cell adherence of mutans streptococci was also depressed by CBH. The administration of CBH in drinking water resulted in significant reductions of caries development and dental plaque accumulation in rats infected with either Strep. sobrinus 6715 or Strep. mutans MT8148R, and the minimum cariostatic concentration was 1.0 mg/ml. These results indicate that CBH possesses powerful anticariogenic potential.

Cariostatic activity of cacao mass extract.

Chocolate is suspected to contain some caries-inhibitory substances. The cariostatic activity of cacao mass extract (CM), the main component of chocolate, was examined in vitro and in experimental animals. CM showed no detectable effects on the cellular growth and acid production of mutans streptococci. On the other hand, the cell-surface hydrophobicity of mutans streptococci was significantly reduced by the presence of CM. Furthermore, insoluble glucan synthesis by the glucosyltransferases from either Streptococcus mutans MT8148R or Strep. sobrinus 6715 was inhibited by CM, but not significantly. Hence, the sucrose-dependent cell adherence of mutans streptococci was also depressed by CM. Finally, CM in both a 40% sucrose diet and drinking water resulted in reductions of caries development and plaque accumulation in rats infected with Strep. sobrinus 6715, but not significantly. These results indicate that cacao mass extract possesses some anticariogenic potential, but its anticaries activity is not strong enough to suppress significantly the cariogenic activity of sucrose.

Comparison of plastic prostheses and self-expandable metallic stents in the treatment of malignant esophageal stenosis.

OBJECTIVE: We compared the efficacy of plastic prostheses and self-expandable metallic stents in the treatment of malignant esophageal stenosis and/or fistula. SUBJECTS AND METHODS: Subjects were 31 patients with esophageal cancer, 4 with esophagotracheal fistula, and 1 with esophageal stenosis. A plastic prosthesis was inserted in 15 patients (group A) and a self-expandable metallic stent in 21 patients (group B). We evaluated food ingestion improvement, effectiveness, complications, mean survival, food ingestion duration, the percentage of food ingestion capability in total survival time, and inhospital mortality. RESULTS: No differences were seen in food intake improvement or in the effectiveness between groups, whereas fatal complications were higher in Group A. No significant differences were seen in mean survival, food ingestion duration, percentage of food ingestion capability, or inhospital mortality between groups. CONCLUSION: We concluded that a self-expandable metallic stent was safer than a plastic prosthesis because of fewer serious complications such as bleeding, and recommended the use of metallic stents in the treatment of malignant esophageal stenosis and/or fistula.

[Three cases of pituitary abscess].

We report three cases of pituitary abscess. Three patients, all females, had suffered headache and complained of general fatigue. In each case magnetic resonance imaging (MRI) revealed a sellar mass with suprasellar extension. T1-weighted images revealed an isointense or slightly hypointense lesion with thin ring-enhancement following gadolinium injection. No inflammatory signs were found in two cases. In one case, a gradual change in clinical symptoms and MRI findings was noted: the hypophyseal hemorrhagic lesion detected on MRI changed into a cystic lesion with thin ring-enhancement. Transsphenoidal surgery was performed in all three cases. In each case, however, no organism was cultured and no tumor component was found. It is difficult to diagnose pituitary abscess prior to surgery if no inflammatory signs are present. Diagnosis of this condition requires careful radiological evaluation. Findings of a suprasellar round cystic mass with thin ring-enhancement on MRI associated with thickened stalk, hyperprolactinemia, and diabetes insipidus may be suggestive of a pituitary abscess.

["Disproportionately large, communicating fourth ventricle" due to membranous obstruction of Magendie's foramen].

A case of disproportionately large, communicating fourth ventricle (DLCFV) with the entire ventricular system dilated symmetrically due to membranous obstruction of Magendie's foramen is reported. A 20-year-old female complained of headache and nausea. Slight papilledema was found in both eyes. CT scan and MRI showed that the entire ventricular system was dilated symmetrically, but we could not locate the cause of this disease, for example, tumor, arachnoid cyst, cerebellar malformation and so on. Although cinemode-MRI showed CSF pulsation as if CSF flowed through Magendie's foramen, we were not convinced that CSF flowed through it. We speculated that something obstructed CSF flow at Magendie's or Luschka's foramen, so surgery was performed by suboccipital craniectomy. As expected, a membranous obstruction was found at Magendie's foramen. After excision of the membrane, all symptoms improved. Postoperative cinemode-MRI clearly demonstrated CSF flow through Magendie's foramen. Ventriculoperitoneal shunting is generally effective for DLCFV, but we do not consider it the optimal treatment. The cause of DLCFV must be confirmed by suboccipital craniectomy if evidence of NPH, mass lesion or cerebellar malformation cannot be found anywhere especially around Magendie's foramen.

[Surgical analysis for lung cancer with scalene node metastasis].

In this study, we evaluated 15 surgically treated cases of lung cancer with scalene node metastasis. Eleven males and 4 females with ages ranging from 41 years to 78 years (average 59.1 years) were examined. Seven cases was in the right upper lobe, 3 in the left upper lobe, 2 in the right lower lobe, 2 in the left lower lobe, 1 in the middle lobe. Adenocarcinomas were found in 9 cases squamous cell carcinomas were in 4 cases and large cell carcinomas were in 2 cases. Two cases was in T 1, 7 in T 2, 2 in T 3, 4 in T 4. In all cases, lobectomy was performed. Five year survival rate was 14.3% as determined by the Kaplan-Meier method. Average survival period was 26.6 months. Three cases survived over 3 years including one case survived over 10 years.

[A resected case of large cell neuroendocrine carcinoma].

Large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer and it has a poor prognosis. We describe our experience with a patient in whom LCNEC was diagnosed. 38-year-old woman who complained of a cough and low grade fever up was admitted to our hospital. Chest X-ray and CT shoued 6.5 x 5.0 mass in rt-S1 and S2. It was suspected as LCNEC of the right lung because of broncopscopic cytology. The upper lobectomy of the right lung and desection of mediastinal lymph nodes were performed. Pathological diagnosis was III B (T2N2M0) LCNEC. Four weeks after the operation, one cycle of chemotherapy (CDDP + VP - 16 + VDS) and one cycle of chemoradiotherapy (thoracic radiation of 40 Gy, CDDP + 5 - FU) were performed. There are no findings of tumor recurrence 7 months after operation.

[Clinical study on reoperation for recurrent pulmonary metastasis].

Ninety seven patients with metastatic lung tumors were treated surgically in our department. Second pulmonary resections were performed in 13 patients. They consists of 9 males and 4 females, their age ranged from 12 to 75 years old (average 54.4 years old). Tumors originate from sarcoma in 5 cases, laryngeal cancer, colorectal cancer, renal cell cancer in 2 cases respectively, oral cavity cancer and transitional cell cancer in 1 case respectively. No second pulmonary resection was performed in patients with metastatic lung tumors originating from lung cancer or breast cancer, because they metastatize not only lung but also general organs. No second pulmonary resection was required in patients with testicular tumor and choriocarcinoma, because chemotherapy take good effect on them.