Correlation of urine type I collagen-cross-linked N telopeptide levels with bone scintigraphic results in prostate cancer patients

The diagnostic potential of a new bone resorption marker, type I collagen-cross-linked N telopeptide (NTx), for bone metastasis of prostate cancer was evaluated. Ninty-one prostate cancer patients underwent bone scintigraphy, and urine NTx/creatinine (NTx/Cr) was measured. Urine NTx/Cr levels were compared with bone scintigraphic results. Urine NTx/Cr levels in the bone metastasis-positive group (n = 47) were 92.9 +/- 105.1 nmol/L of bone collagen, which is equivalent to per millimole of urinary creatinine (nmol/L BCE/mmol/L Cr), significantly higher than the level of the bone metastasis-negative group (n = 44) (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr). When patients were classified by the extent of disease grade (EOD grade) nomenclature, the urine NTx/Cr level of the EOD (4+) group was 209.5 +/- 186.5 nmol/L BCE/mmol/L Cr. This level was significantly higher than those of the EOD (-) group (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr), EOD (1+) group (59.0 +/- 47.8 nmol/L BCE/mmol/L Cr), and EOD (2+) group (81.1 +/- 41.3 nmol/L BCE/mmol/L Cr). However, no significant difference was observed between the EOD (-) and EOD (1+) groups. The mean change in urine NTx/Cr level 3 to 17 months after the first bone scintigraphy and urine NTx/Cr examination in the bone metastasis-progression group (n = 8) was 11.0 +/- 31.2 nmol/L BCE/mmol/L Cr, significantly higher than that in the bone metastasis-regression group (n = 15) (-26.8 +/- 40.7 nmol/L BCE/mmol/L Cr). In conclusion, urine NTx /Cr can be measured noninvasively and reflects the state of bone metastasis. However, the sensitivity of urine NTx/Cr is not as high as that of bone scintigraphy. Therefore, it may provide an auxiliary diagnostic index for bone scintigraphy.     

Requirement of gp130 signaling for the AGM hematopoiesis

OBJECTIVE: Definitive hematopoiesis starts in the aorta-gonad-mesonephros (AGM) region during mouse development and remarkably expands in the liver at a later stage of ontogeny. gp130 is a signal transducing receptor component shared by all the IL-6 family cytokines, whose gene ablation in mouse results in the significant reduction in the fetal liver hematopoiesis. The present study aims to evaluate the role of gp130 signaling in the fetal mouse AGM hematopoiesis. METHODS AND MATERIALS: Mouse AGM regions from the wild-type and gp130-deficient mice on embryonic day 11.5 were dissociated and cultured with a mixture of cytokines, including one which activates gp130. Wild-type human gp130 and its mutant constructs were introduced into cultured gp130-deficient AGM cells using retrovirus system. To further analyze gp130 downstream signaling, a dominant-negative mutant of STAT3 was also introduced. RESULTS: The gp130 deficiency in the culture of fetal mouse AGM cells resulted in the failure of the expansion of the c-kit(+), Sca-1(+), and lineage markers(-) population. Such failure was rescued by introduction of a wild-type gp130 expression construct but not its mutant constructs having no ability to activate STAT3. In the normal AGM cell culture, introduction of a dominant-negative form of STAT3 in which Y(705) was changed to phenylalanine suppressed the expansion of hematopoietic cell colonies. CONCLUSION: gp130 plays an indispensable role in the expansion of hematopoietic precursor cells in the fetal mouse AGM. In particular, the activation of STAT3 by gp130 is found to be important in this process.     

Hypertension in patients on chronic hemodialysis: the role of the renin-angiotensin system

The effects of volume-loading and removal on mean blood pressure were evaluated in patients with high blood pressure and on chronic hemodialysis. Simultaneous measurements of plasma renin activity, plasma angiotensin II and plasma norepinephrine were made. The patients were divided into two groups according to their levels of plasma renin activity. Group 1 (n = 10) had a basal plasma renin activity below 2.5 ng/ml/hr while the level in group 2 (n = 5) exceeded 2.5 ng/ml/hr. The mean blood pressure of the two groups was 105 +/- 5 mmHg and 107 +/- 4 mmHg, respectively. On the day of hemodialysis, saline loading (0.5 ml/kg/min for 20 min) was followed by routine hemodialysis. The mean blood pressure rose to 113 +/- 6 mmHg in group 1. However, the patients in group 2 did not respond to volume loading and hemodialysis. The plasma renin activity, plasma angiotensin II and plasma norepinephrine were not changed by volume loading in both group 1 and 2. Volume removal by hemodialysis caused a reduction in mean blood pressure in group 2 without alteration of vasoactive hormones. In group 1, the mean blood pressure was not reduced by hemodialysis, accompanied by increases in plasma renin activity, plasma angiotensin II, and plasma norepinephrine. In the high renin group, elevated circulating angiotensin II maintained a high blood pressure and in the low renin group, the renin-angiotensin system influenced the prevention of fall in blood pressure after hemodialysis. These results suggest that the renin-angiotensin system plays an important role in the regulation of blood pressure in relation to volume status regardless of whether the plasma renin activity is high or low.     

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.     

Nodular duodenitis involving CD8+ cell infiltration in patients with ulcerative colitis

BACKGROUND/AIMS: Limited efforts have been made to determine changes in the upper gastrointestinal tract in ulcerative colitis. The aim of this study was to analyze gastroduodenal lesions in patients with ulcerative colitis. METHODOLOGY: The endoscopical appearance of lesions in the duodenum and stomach was first examined. Biopsy specimens taken from 25 patients with ulcerative colitis, as well as 21 with Crohn's disease and 16 with nonspecific gastroduodenitis who had no Helicobacter pylori infection, were then evaluated by histology and immunohistochemistry for CD8, CD68 and HLA-DR. In ulcerative colitis patients, the HLA-phenotype was also analyzed by the standard NIH complement-dependent microlymphocyte toxicity assay. RESULTS: Endoscopically evident alteration of nodularity in the descending part of duodenum was prominent in ulcerative colitis and Crohn's disease, but not gastroduodenitis. Histological inflammatory change of the duodenal bulb in ulcerative colitis and Crohn's disease was mild as compared to gastroduodenitis cases. Endoscopic and histological change (redness and deformity of villi) in the duodenum were more prominent in ulcerative colitis patients with pancolitis than those with left-sided/proctitis. CD8+ cells infiltrating both the duodenum and stomach were increased in ulcerative colitis and Crohn's disease as compared to gastroduodenitis whereas focal perifoveolar accumulation of CD68+ cells and enhanced epithelial expression of HLA-DR were characteristic of Crohn's disease. Histopathological alteration in the duodenum was particularly prevalent in ulcerative colitis patients with HLA-DR4 and Cw1. CONCLUSIONS: Nodular, histologically mild duodenitis involving CD8+ cell infiltration, the severity of which positively correlates with the extent of colitis, is characteristic of ulcerative colitis.     

Early administration of fluvastatin, but not at the onset of ischemia or reperfusion, attenuates myocardial ischemia-reperfusion injury through the nitric oxide pathway rather than its antioxidant property.

BACKGROUND: Three-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are known to attenuate myocardial ischemia-reperfusion (IR) injury. Fluvastatin (FV) has a potent free radical scavenging action, but it is unclear whether the timing of FV administration could affect its cardioprotective effect or if the antioxidant property of FV might attenuate IR injury. METHODS AND RESULTS: IR was induced in rats by left coronary artery occlusion for 30 min followed by 24-h reperfusion. The rats were divided into 4 groups: oral FV group (10 mg/kg per day for 2 weeks before ischemia); iv, FV group (10 mg/kg) before ischemia; iv, FV group (10 mg/kg) before reperfusion; and control group. Oxidative stress was evaluated by myocardial 8-hydroxydeoxyguanosine (8-OHdG) content. The area at risk did not different among the 4 groups. Pretreatment with FV for 2 weeks significantly reduced the infarct size by 28% as compared with the control group, but FV administered just before ischemia or reperfusion did not. Myocardial 8-OHdG content was not affected by FV. The infarct-sparing effect of FV was completely abolished by N(omega)-nitro-l-arginine methyl ester or wortmannin. CONCLUSIONS: The present results indicate that pretreatment with FV, but not just before ischemia or reperfusion, attenuates IR injury primarily through the nitric oxide pathway, not through its antioxidant property.     

Innate control of adaptive immunity via remodeling of lymph node feed arteriole

The adaptive immune system relies on rare cognate lymphocytes to detect pathogen-derived antigens. Na?ve lymphocytes recirculate through secondary lymphoid organs in search of cognate antigen. Here, we show that the na?ve-lymphocyte recirculation pattern is controlled at the level of innate immune recognition, independent of antigen-specific stimulation. We demonstrate that inflammation-induced lymphocyte recruitment to the lymph node is mediated by the remodeling of the primary feed arteriole, and that its physiological role is to increase the efficiency of screening for rare antigen-specific lymphocytes. Our data reveal a mechanism of innate control of adaptive immunity: by increasing the pool of na?ve lymphocytes for detection of foreign antigens via regulation of vascular input to the local lymph node.     

Familial hemiplegic migraine

Familial hemiplegic migraine (FHM) is an autosomal dominant disorder characterized by transient hemiplegia followed by migraine headache, and recently approximately half of FHM families have been elucidated to be caused by mis-sense mutations in P/Q-type Ca channel alpha(1)-subunit gene (CACNA1A). This subunit forms channel pore and is implicated in the regulation of membrane excitability as voltage sensor, therefore FHM is thought to be channelopathy. The CACNA1A gene is causative of episodic ataxia type-2 and of spinocerebellar atrophy type 6. Moreover, FHM with cerebellar ataxia is only associated with the mutation in CACNA1A, dysfunction of the calcium channel may cause cerebellar degeneration. New genotype and phenotype have been reported, more reports and analyses are expected.