A suspicious case of central neurosarcoidosis, manifesting as a progressive gait disturbance with a lesion in the central gray matter of the midbrain, accompanying an elevated level of angiotensin converting enzyme in the cerebrospinal fluid]

We present a suspicious case of central neurosarcoidosis that presented with progressive gait disturbance probably caused by central vestibular dysfunction. And this case showed elevated level of angiotensin converting enzyme (ACE) in the cerebrospinal fluid, compared with the average level of two cases with acute inflammatory demyelinating neuropathy syndrome and four cases of multiple sclerosis. A 33-year-old man was admitted to our hospital with chief complaint of a gait disturbance that had appeared 3 years prior to the admission. And the symptom had exacerbated in these 3 months. Except for the gait disturbance and positive Romberg's sign, no neurological abnormality was detected. The findings of the cerebrospinal fluid test supported the diagnosis of meningitis. An increased level of angiotensine converting enzyme was detected when compared with our previous samplings from two cases of Guillain Barré syndrome and four cases of multiple sclerosis. With T1 weighted imaging of brain MRI, a high intensity lesion with gadolinium enhancement was identified in the central gray matter of the midbrain. Scan of the chest confirmed bilateral hilar lymphadenopathy. Based on these findings and the patient's clinical course, central neurosarcoidosis was suspected. The patient's symptoms improved dramatically after the administration of corticosteroid. The enhancement of the central gray matter ameliorated, and the ACE level of the CSF was decreased to the level of the demyelinating disorders.     

Existence of phenol oxidase in the argasid tick Ornithodoros moubata

Phenol oxidase (PO, EC 1.10.3.1) activity was detected in the hemolymph of the fourth instar nymphs of the argasid tick, Ornithodoros moubata, with peak levels corresponding to the days before the majority of the nymphs had molted, suggestive of a protective role of PO during the ecdysial phase. Higher PO activity was detected in plasma relative to the hemolymph and was negligible in hemocytes. The concentration of the hemolymph and plasma assayed clearly influenced the level of PO activity, and was significantly reduced ( P<0.005) after treatment with 1-phenyl-2 thiourea, a specific PO inhibitor. This is the first report of the existence of PO in the hemolymph and plasma of a soft tick species. The regulation of PO activity and its precise role in soft tick immunity, particularly during the ecdysial phase, are interesting and need to be examined further.     

Spontaneous wheel running attenuates cardiovascular responses to stress in rats

We investigated the effect of chronic, 10-week spontaneous wheel running (SWR) exercise on stress-induced cardiovascular responses in free-moving male rats, using a biotelemetry system. During cage-switch stress or immobilization stress, blood pressure and heart rate were significantly increased in both the SWR (P<0.001 for each stress) and control groups (P<0.001 for each stress). However the blood pressure response was attenuated significantly in the SWR group (P<0.001) during cage-switch stress, and the blood pressure and heart rate responses were attenuated significantly in the SWR group (P<0.0001 and 0.01, respectively) during immobilization stress. The plasma norepinephrine (NE) response induced by immobilization stress tended to be attenuated in the SWR group, but the groups showed no significant differences in the plasma NE and epinephrine (E) responses to both stresses. These results suggest that daily SWR in rats has beneficial effects in suppressing excessive blood pressure and heart rate responses induced by two different types of stress. The mechanisms responsible for the greater resistance to these stresses in the SWR rats should be investigated further.     

Morphological characteristics of the life cycle of resting cartilage cells in mouse rib investigated in intrasplenic isografts

Summary Resting cartilages taken from 2-day-old mouse ribs were transplanted into spleens in order to carry out morphological investigations of the life cycles of their chondrocytes. The explants were isografted for periods of up to 60 days and examined at light and electron microscopic levels, using von Kossa's reaction or osmium-potassium ferrocyanide (OPF) fixation. By day 3 after transplantation, resting cartilage containing immature chondrocytes was well adapted to splenic tissue and by 7 days after transplantation these chondrocytes had changed into early hypertrophic chondrocytes containing large vacuoles, glycogen aggregates and abundant secretory organelles. It was also demonstrated by von Kossa's reaction that the initial calcification occurred in the territorial matrix during this period. In spite of the hypertrophic chondrocytes in the central zone being surrounded by an extensively calcified matrix during days 14–21 after transplantation, these cells had well-preserved organized organelles, except that Golgi-associated elements and endoplasmic reticulum revealed a tendency toward degenerative changes. With increased duration of the grafting period, from 30–60 days, the calcification zone progressed gradually, and the number of hypertrophic chondrocytes embedded in the calcified matrix decreased considerably. By day 60, degenerating hypertrophic chondrocytes of two types were distinguished: flattened cells containing large vacuoles, poorly developed Golgi apparatuses, and rough endoplasmic reticulum; and shrunken dark cells displaying terminal hypertrophy. During the present study, we observed no vascular invasion into the calcified matrix, or appearance of bone-related cells, and the morphological changes from the resting chondrocytes to cellular hypertrophy accompanied by the formation of a calcified matrix were observed at day 60. These findings indicate that resting cartilage cells of the mouse have the capacity for terminal differentiation when transplanted into the spleen.     

Effects of endurance training on myosin heavy-chain isoforms and enzyme activity in the rat diaphragm

We investigated the effects of endurance training (20 m/min, 60 min/day, 5 days/week) on myosin heavy-chain (MHC) isoforms and succinic dehydrogenase (SDH) activity in rat crural and costal diaphragms, and plantaris muscles. Although the 4-week endurance training produced significant (P<0.05) increases, both in SDH activity and the percentage of isoform HCIIa in the plantaris of the trained rat compared with the sedentary control rat, these alterations did not occur in either the crural or costal diaphragms. After 10 weeks of endurance training, trained animals had significantly (P<0.05) higher SDH activity in the costal diaphragm and the plantaris. Moreover, a significant (P<0.05) decrease occurred in the percentage of HCIIb in the costal diaphragm, and a significant (P<0.01) decrease in the percentage of HCIIb concomitant with a significant (P<0.05) increase of HCIIa resulted in the plantaris. However, the crural diaphragm did not show any significant changes after 10 weeks of endurance training. These results indicate that endurance training induces an alteration in the expression of an MHC phenotype, in addition to causing an increase in oxidative enzyme activity. However, the alterations in response to endurance training are apparently not uniform, varying between regions and/or kinds of muscles.     

Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

A novel videoendoscopy system by using autofluorescence and reflectance imaging for diagnosis of esophagogastric cancers

BACKGROUND: Image quality of the prior autofluorescence (AF) imaging systems, including the fiber-optic endoscope, was not feasible for general clinical use. The use of AF image alone resulted in low specificity. The objective of the study was to evaluate the resolution and the sensitivity of the novel videoendoscopy system by using AF and reflectance imaging (AFI) in the diagnosis of early esophagogastric cancers. METHODS: This was a case series study. The setting was a pretreatment examination at a cancer center. Five patients with superficial esophageal cancers (SEC) and 21 patients with 22 early gastric cancers (EGC) were included in the study. The extent of the tumors was diagnosed by white light (WL), AF and chromoendoscopic observations. The main outcome measurement was the diagnostic accuracy of each observation in relation to the histologic mapping as a criterion standard. RESULTS: Two of 5 SECs (40%) were correctly diagnosed in the WL image and all (100%) in the AF image as purple or magenta color in a green background. EGCs in atrophic mucosa were observed as purple or magenta areas in a green background, while diffuse-type EGCs in fundic mucosa were observed as green areas in a purple background. Of the 22 EGCs, diagnostic accuracy of WL, AF, and chromoendoscopic observations were 36%: 95% CI [16%, 56%], 68%: 95% CI [49%, 88%], and 91%: 95% CI [79%, 100%], respectively. AFI could reveal flat or isochromatic extensions that were not detected in the WL images. The limitations of the study were ulcerations or inflammation that caused overdiagnosis in the AF observation. CONCLUSIONS: The resolution of the AFI at present is limited, but the image quality was acceptable. The current system of AFI does not equal to chromoendoscopy in sensitivity but has an advantage over standard WL videoendoscopy.     

Rotavirus gastroenteritis‐associated urinary ammonium acid urate crystals

Although ammonium acid urate (AAU) calculi are extremely rare renal stone components, it was recently found that many urinary tract calculi that cause post‐renal renal failure in rotavirus (RV) gastroenteritis are AAU calculi. The mechanism of AAU calculi development in RV gastroenteritis has not been fully elucidated. We analyzed data from eight RV gastroenteritis patients who transiently had AAU crystals in their urinary sediment. In these patients, formation of AAU crystals occurred earlier than the formation of AAU calculi. No difference was observed in serum and urine uric acid levels between RV gastroenteritis patients with or without AAU crystals. Interestingly, fractional excretion of sodium was extremely low among patients with AAU crystals. These results suggest that the formation of AAU crystals might not be due to excretion of uric acid, but excretion of sodium.