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Surfer's myelopathy is non-traumatic spinal cord injury which develops in beginner surfers. The patient was a 17-year-old female who developed severe paraplegia with bilateral sensory dysfunction below the groin and bladder/rectal dysfunctions after her first surfing lesson. A spinal-cord MRI performed six hours after onset revealed an intramedullary hyperintensity area from T8 to the conus medullaris on the T2 weighted images. Expansion of this hyperintensity area was observed on Day 3 and showed a reduction on Day 8. After providing intravenous methylpredonisolone, intravenous glycerol and intravenous edaravone, motor function and bladder/rectal functions began to improve after approximately three weeks. In this study, the expansion of the lesion in the early stages of the disease course was observed by sequential spinal MRI. Furthermore, a time lag between improvement according to imaging and improvement in symptoms was also observed.

Multiple gastric cancers at the same time (synchronous) or recurrence after 1 year (metachronous) are frequently encountered. Since their genetic profiles were not well elucidated, we molecularly subtyped the genetic events of synchronous and metachronous early-stage gastric cancers. We studied mismatch repair (MMR) genes in 84 tumors from 31 patients (15 synchronous and 16 metachronous) by immunohistochemistry. We performed microsatellite instability analysis and targeted sequencing of 58 significantly mutated genes (SMGs) in 35 tumors from thirteen patients. Genomic data from TCGA were used for comparisons with advanced-stage cancers. Among the 31 patients, at least one deficient-MMR (dMMR) tumor was observed in eight (26%). Of eight patients, seven showed a mixture of proficient-MMR (pMMR) and dMMR tumors. The one case with only dMMR had six recurrent tumors within 2 years. To further subtype, we sequenced 58 SMGs in 35 samples (25 pMMR and 10 dMMR) from thirteen patients. In 35 samples, 163 mutations were identified, but none matched in almost cases, strongly indicating different clonal origins, whether synchronous or metachronous occurrences. Of the 25 pMMR cases, 1 belonged to Epstein–Barr virus (EBV), 24 belonged to chromosomal instability (CIN) subtypes. Of the thirteen cases, repetitive CIN, a mixture of CIN and MSI, a mixture of CIN and EBV, and repetitive MSI were observed in nine (70%), two (15%), one (8%) and one (8%), respectively. Despite multiple tumors occurring in the same patient simultaneously or several years apart, clonal origin was totally different. ‘Switching’ or ‘mixing’ of dMMR and pMMR, EBV or CIN occurred, which had clinical relevance with regard to immunotherapy.

Background: The Tokyo Guidelines (TG; 2013) indicated that emergency cholecystectomy is an important early treatment option for acute cholecystitis; however, surgical intervention is not necessarily indicated in patients with advanced age. We evaluated percutaneous transhepatic gallbladder aspiration (PTGBA), percutaneous transhepatic gallbladder drainage (PTGBD), and the administration of antibiotics alone as treatment options for acute ­cholecystitis. Methods: From January 2010 to December 2017, 159 patients with acute cholecystitis were treated at our institution. The data from these patients were retrospectively analyzed. Results: Of these 159 cases, 109 underwent PTGBA, 28 underwent PTGBD, and 22 were administered antibiotics alone. None of the 159 patients needed urgent (early) cholecystectomy, and all patients were discharged without mortality. PTGBA was unsuccessful in only 6 of 109 patients; PTGBD was performed in these 6 cases. Long-term follow-up was conducted in all cases. Of the 159 patients, 146 had gallbladder stones initially, while 13 had none at the time of presentation. Of these 146 patients with gallbladder stones, 84 underwent elective cholecystectomy, while 62 did not. Of the 84 patients who underwent elective cholecystectomy, 2 developed choledocholithiasis; of the 62 patients who did not undergo elective cholecystectomy, 5 developed choledocholithiasis and 2 developed acute cholecystitis. The incidences of choledocholithiasis and acute cholecystitis did not significantly differ between the 2 groups (p = 0.06). Conclusions: Despite the recommendations in the TG (2013), emergency cholecystectomy was not needed in any of the present patients with acute cholecystitis. Acute cholecystitis can be successfully treated with ­PTGBA or PTGBD, which are simple procedures with good short- and long-term safety. These procedures are highly recommended for patients with acute cholecystitis, especially in the elderly population.

Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.

BackgroundStudies indicate that gastric cancer (GC) incidence has decreased, whereas signet ring cell carcinoma (SRC) incidence has increased. However, recent trends in GC incidence are unclear. We used our hospital cancer registry to evaluate the changes in the incidence of GC, SRC, and non-SRC (NSRC) over time in comparison to changes in theH. pyloriinfection rates over time.MethodsWe identified 2532 patients with GC enrolled in our registry between January 2007 and December 2018 and statistically analyzed SRC and NSRC incidence. TheH. pyloriinfection rate in patients with SRC was determined by serum anti-H. pyloriantibody testing, urea breath test, biopsy specimen culture, and immunohistochemical analysis (IHC) of gastric tissue. Additionally, genomic detection ofH. pyloriwas performed in SRCs by extracting DNA from formalin-fixed paraffin-embedded gastric tissue and targeting 16S ribosomal RNA ofH. pylori.ResultsOverall, 211 patients had SRC (8.3%). Compared with patients with NSRC, those with SRC were younger (P P P H. pyloriinfection prevalence between the SRC and NSRC groups. IHC and genomic methods detectedH. pyloriin 30 of 37 (81.1%) SRCs.ConclusionsReduction inH. pyloriinfection prevalence may be associated with the decrease in the incidence of SRC, which was higher than that of NSRC.

Lenvatinib (an inhibitor of vascular endothelial growth factor (GF) receptors 1–3, fibroblast GF receptors 1–4, platelet-derived GF receptor α, rearranged during transfection, and stem cell factor receptor) was non-inferior to sorafenib in a phase 3 (REFLECT) trial of advanced hepatocellular carcinoma. This study examined the efficacy and safety of lenvatinib in a real-world setting. This was a retrospective, multicenter, observational study. Inclusion and exclusion criteria were based on the phase 3 trial, and participants were observed for at least 12 weeks. Therapeutic effect was determined using the modified Response Evaluation Criteria In Solid Tumors (m-RECIST) at the 8th week. Patients received oral lenvatinib 12 mg/day (body weight > 60 kg) or 8 mg/day (body weight

Previously, we reported that males with mental retardation (MR) (MR group) expended more energy than males without MR (control group) at a given work load. The precise physiological mechanisms for this difference remain unclear. Using the same set of subjects (23 age-, height-, and weight-matched male pairs, mean age: 36.3 y), we examined possible causes for the observed metabolic difference by monitoring physical movements and evaluating the metabolic capability of the skeletal muscles. In the supine position when no body movements were detected for any subjects, oxygen consumption (VO2) and heart rate (HR) were not markedly different between the MR and the control groups. By contrast, in the sitting and standing positions and during walking at 30 and 50 m/min, when significantly larger body movements were monitored in the MR group, VO2 and HR were significantly higher in this group than in the control group. Linear regression analyses, performed separately in the MR and control groups, revealed that the slope of the regression line of HR on relative exercise intensity (%VO2max) during walking, that of VO2 on walking speeds, and that of VO2 on the number of steps in the MR group were almost identical with those in the control group. These results suggest that the capability of skeletal muscles was not so different between the two groups. Thus, the high energy expenditure in the MR group was suggested to be a result of excessive body movements rather than an intrinsic incapability of skeletal muscles.

Zinc finger protein 521 (ZFP521) regulates a number of cellular processes in a wide range of tissues, such as osteoblast formation and adipose commitment and differentiation. In the field of neurobiology, it is reported to be an essential factor for transition of epiblast stem cells into neural progenitors in vitro. However, the role of ZFP521 in the brain in vivo still remains elusive. To elucidate the role of ZFP521 in the mouse brain, we generated mice lacking exon 4 of the ZFP521 gene. The birth ratio of our ZFP521 Δ/Δ mice was consistent with Mendel's laws. Although ZFP521 Δ/Δ pups had no apparent defect in the body and were indistinguishable from ZFP521+/+ and ZFP521 +/Δ littermates at the time of birth, ZFP521 Δ/Δ mice displayed significant weight reduction as they grew, and most of them died before 10 weeks of age. They displayed abnormal behavior, such as hyper-locomotion, lower anxiety and impaired learning, which correspond to the symptoms of schizophrenia. The border of the granular cell layer of the dentate gyrus in the hippocampus of the mice was indistinct and granular neurons were reduced in number. Furthermore, Sox1-positive neural progenitor cells in the dentate gyrus and cerebellum were significantly reduced in number. Taken together, these findings indicate that ZFP521 directly or indirectly affects the formation of the neuronal cell layers of the dentate gyrus in the hippocampus, and thus ZFP521 Δ/Δ mice displayed schizophrenia-relevant symptoms. ZFP521 Δ/Δ mice may be a useful research tool as an animal model of schizophrenia.

Rheological characteristics of red cells in two patients with refractory anemia (with single chromosomal abnormality of 20q- or 13q-, respectively) were investigated with the hematological and biochemical properties. (1) Whole blood viscosity was remarkably increased, and the red cell deformability was greatly impaired (the impairments were prominent in patient with 20q-). (2) The hematocrit of both patients was about half of the normal value. Remarkable anisocytosis with elliptocytes and poikilocytes was observed in the patient with 20q-, but the anisocytosis was not so prominent in the patient with 13q-. (3) 2,3-diphosphoglycerate content in red cells was markedly increased in both patients, but adenylate content was not. (4) The red cells were slightly resistant to osmotic hemolysis, but they were not heat-labile. (5) Structural abnormality of spectrin was suggested from the impaired dimer-dimer association in red cell membrane and from the different susceptibility of spectrin to tryptic digestion. In conclusion, the rheological impairments and the abnormal shape of red cells in refractory anemia probably originated from the structural abnormality of cytoskeletal proteins in membrane, and the functional and structural abnormality may be different among patients.

Nemaline myopathy is a representative form of congenital myopathy, and is characterized by nemaline bodies in muscle fibers. Here we report a 47-year-old man with congenital nemaline myopathy complicated with dilated cardiomyopathy-related heart failure, and restrictive respiratory failure. The complication of dilated cardiomyopathy in nemaline myopathy has rarely been reported. In this case, nemaline bodies were detected in the cardiac muscle fibers, demonstrating the presence of underlying disease-related myocardial degeneration. The patient responded to the combination of conventional therapy for heart failure including β-blocker and noninvasive continuous positive-pressure ventilation for respiratory failure. His general condition has been stable during a 10-month follow up period.

Hypertension is one of the risk factors of cardiovascular diseases, which are widely prevalent maladies that result in burdensome medical expenditures. Therefore, it is important to explore primary preventive measures for hypertension. Until recently, it was thought that exercise was a risk factor for hypertension, but recent reports have suggested that low-intensity physical training actually lowers blood pressure. However, habitual physical exercise has still not been clearly proven to prevent the development of hypertension. To clarify this point, one must first establish a method for predicting hypertension and second examine the possibility of preventing the development of hypertension by changing the subject's environment. In this study we have investigated a method for predicting hypertension by classifying blood pressure responses to increasing exercise intensity and the effect of habitual exercise on blood pressure response.This study was composed of three experiments. Experiment one involved female students (n=42) and experiment two, male students (n=38), in whom blood pressure response rates during exercise were recorded. In experiment three, the same group of female students (n=23) was subjected to training in order to chart its effects on blood pressure response, both while exercising and while at rest. The exercises were performed with a bicycle ergometer in an upright position. There were four different degrees of work intensity. Blood pressure was measured using the auscultation method, with Riva-Rocci mercury measured by the same investigator.High blood pressure responses at rest were noted among some normotensive female and male students. The systolic blood pressure responses during the peddling exercise showed significant individual differences at the lowest work load; the distribution of the increment of the systolic blood pressure ratio at the lowest work load against the increment while resting showed two peaks. This result suggests that this increment ratio is an important variable related to the prediction of hypertension. The increment ratio showed no significant change in female students after three months of aerobic exercise.The high-response group showed high readings of the TPR indicator (MBP/VO2). Aerobic training was shown to be effective in significantly lowering the TPR indicator both at rest and during exercise. This result suggests that habitual exercise may contribute to preventing the development of hypertension.

In pneumonia in the elderly, one occasionally encounters difficulties in evaluation with respect to both clinical observation and treatment. Thus a simple serum indicator is indicated. We measured secretory leukoprotease inhibitor (SLPI) concentrations in sera to see whether this can provide a useful indicator for pneumonia, especially in the elderly. Serum samples from patients over 65 yr of age, with (n = 54) or without (n = 87) pneumonia, and from healthy, young (n = 16) and aged (n = 188) control subjects were assayed using ELISA for human SLPI. Comparisons were made between groups with clinical diagnoses of either definite or probable pneumonia and among cases with various other respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease, and lung cancer. The mean SLPI concentration in patients with pneumonia was significantly higher than in patients without pneumonia or in healthy controls. The data suggest that the measurement of SLPI can provide a useful indicator for pneumonia to be used in clinical evaluation.

This study reports preliminary results of a controlled, multicenter trial on the quality of ulcer healing induced by lansoprazole (LPZ) or roxatidine (R) in gastric ulcer (GU) or duodenal ulcer (DU) patients. Group A received LPZ 30 mg q.d. and group B received R 75 mg b.i.d. All drugs were given for 8 weeks in GU and for 6 weeks in DU. Endoscopy and gastric biopsy were performed to detect Helicobacter pylori before and on completion of treatment. The healing rates ofgroups A and B were 100 and 69.2%, respectively, in GU and 100 and 70.0%, respectively, in DU. This difference (p < 0.01) was significant between the two groups in GU. There was no significant difference between the two groups in the S 2 stage shift rate in GU and DU. The H. pylori clearance rates of groups A and B were 33.3 and 20.0%, respectively, in GU and 62.5 and 33.3%, respectively, in DU. The differences in treatment response (healing rates and S 2 shift rates) between the LPZ group and the R group may be related to the differences in suppression of acid secretion and in bactericidal effects on H. pylori.

Objective Aceruloplasminemia is an iron metabolic disorder caused by mutations in the ceruloplasmin gene. It is characterized by progressive neurodegeneration in association with iron accumulation. Excess iron functions as a potent catalyst of biologic oxidation. Previously we showed that an increased iron concentration is associated with the products of lipid peroxidation in the serum, cerebrospinal fluid, and brain tissues. To clarify the free radical-mediated tissue injury caused by intracellular iron accumulation through mitochondrial dysfunction. Patients and Methods We have measure brain oxygen and glucose metabolisms using positron emission tomography (PET) and examined brains at autopsy for iron contents and activities of the mitochondrial respiratory chain in two affected patients who had different truncation mutations of the ceruloplasmin gene. Results PET showed a marked decrease in glucose and oxygen consumption in the entire brain of aceruloplasminemia patients, with a preponderance of metabolic reduction in basal ganglia. Enzyme activities in the mitochondrial respiratory chain of the basal ganglia were reduced to approximately 45% and 42% respectively for complexes I and IV. An inverse relationship was shown between the amounts of iron accumulated and the levels of mitochondrial enzyme activities in all the brain regions examined. Conclusion Iron-mediated free radicals may contribute to the impairment of mitochondrial energy metabolism in aceruloplasminemia.(Internal Medicine 41: 186-190, 2002)

Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in patients with insulin-dependent diabetes mellitus (IDDM) and stiff-person syndrome. We reviewed the case of a 46-year-old woman who had cerebellar ataxia before getting stiff-person syndrome and IDDM with high anti-GAD autoantibody titers. This was a rare case in which there were both the clinical symptoms of stiff-person syndrome and cerebellar ataxia. In western blot analysis her serum reacted with 65-kDa proteins from rat cerebellum, cerebral cortex, and spinal cord. Autoantibodies to GAD may cause functional impairment of gamma-aminobutyric acid (GABA) neurons in the spinal cord as well as in the cerebellum.

Activated microglial cells and peripheral macrophages are hardly distinguishable from the viewpoints of morphology and function. There are various immunological markers common to both microglial cells and peripheral macrophages. In the present study, however, we found that microglial cells have distinct characters in terms of adhesion and morphology. By using a "rheoscope," that is an apparatus to rheologically measure the strength of cell adhesion to substrates, rat microglial cells were found to attach to polystyrene dishes much more weakly than alveolar and peritoneal macrophages. Interferon-gamma (IFNgamma) strengthened the adhesion of alveolar and peritoneal macrophages, whereas it weakened that of microglial cells. Morphological changes of microglial cells induced by IFNgamma were also different from those of peripheral macrophages. Furthermore, alveolar and peritoneal macrophages produced NO in response to IFNgamma, while microglial cells did not. When cultured on astrocyte-derived extracellular matrix (AsECM) in serum-free medium, only microglial cells extended multiple ramified processes. Conversely, alveolar and peritoneal macrophages on AsECM shrunk their ruffling membrane and rounded up. These distinctions between microglial cells and macrophages may reflect differences in cell lineages as well as environments in which individual cells reside.

The purpose of this study is to evaluate the baroreflex function using lower body negative pressure (LBNP) and neck suction in young normotensive men with or without a family history of hypertension. Twenty-two young normotensive men with a family history of hypertension (FH+) and eight young normotensive men who had no family history of hypertension (FH-) were studied. FH(+) consisted of men who had a family history of hypertension within second degree relatives.We studied cardiopulmonary baroreflex function using LBNP and carotid sinus baroreflex function using neck suction and evaluated the reflex function under stimulated conditions using both LBNP and neck suction at the same time.Systolic arterial pressure (SAP) (F=5.42, p

Isometric exercise induces profound cardiovascular adaptations increasing mean arterial pressure and heart rate. We investigated effects of simulated +Gz and −Gz respectively on the central and peripheral cardiovascular system. Sustained handgrip exercise was performed at 40% of maximum for 2 minutes in five subjects. This maneuver increased mean arterial pressure by 40–45 mm Hg both during head out water immersion which simulates weightlessness, as well as bedrest during −25, 0, and +25 degrees tilt from the horizontal. Lower body negative pressure (−60 mm Hg for 10 min) attenuated the response to handgrip exercise to 30 mm Hg. It also increased the heart rate minimally by about 20 beats per minute while the water immersion, as well as head up, head down and horizontal bedrest showed increments of about 50 beats per min. It was concluded that the response to isometric contraction is mediated through the high pressure baroreceptors, because similar responses were seen during stresses producing a wide variation in central venous pressure. During lower body negative pressure the increased sympathetic nervous activity itself increased resting heart rate and mean arterial pressure. The responses to static exercise were, therefore, weaker.

Recombinant human erythropoietin [rhEPO (180 iu/micrograms); 1 or 10 micrograms polypeptide equivalent/kg] was intravenously administered daily to 6-week-old normal rats for 1 week. Rheologically, (1) blood viscosity at shear rate of 40-380 s-1 increased in a manner entirely dependent upon the haematocrit, (2) no change in erythrocyte deformability was detected by high shear rheoscopy, and (3) the velocity of rouleau formation in autologous plasma (at 7.5 s-1) decreased. Haematologically, rhEPO administration induced considerable polycythaemia with reticulocytosis in a dose-dependent manner, accompanying increased cell volume and decreased intracellular haemoglobin concentration, thus the density distribution of erythrocytes shifted towards low specific gravity. Plasma viscosity and plasma protein composition were unaffected by rhEPO-administration. In erythrocyte metabolism, no drastic alteration in the level of 2.3-DPG or ATP was detected.