Adjuvant heparinization before manipulation of artery reduces early failure in primary arteriovenous fistula for end-stage renal disease patients

Clinical and Experimental Nephrology - Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable...     

Therapeutic effects of the combined androgen blockade therapy versus luteinizing hormone-releasing hormone analog monotherapy in patients with hormone naïve metastatic prostate cancer: a multi-institutional comparative analysis

BackgroundThe clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naïve metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC.MethodsWe retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients’ data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes.ResultsThe median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups.ConclusionsNo significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC.     

Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivit to TNF-{alpha}-mediated cell death

The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharideon the sensitivity to tumor necrosis factor (TNF)--medlatedcell death was studied In an In vitro system. Since secretionof TNF- Is a part of the early host response to viral and bacterialinfection, we examined whether mimicking the Infection withviral and bacterial products could affect the response of cellsto TNF-. Incubation of WEHI 164 fibrosarcoma cells with dsRNAor lipopolysaccharide (LPS) significantly increased their sensitivityto TNF--mediated lysis and to TNF-secreting inflammatory T cell-mediatedlysis. Thus, these products could induce Increased sensitivityto TNF- In cells In an inflammatory focus, possibly contributingto selective elimination of Infected but not healthy cells bythis non-specific cytokine. Additionally, our data show thatboth dsRNA and LPS, as well as TNF- Itself, rapidly Induce nuclearfactor-xB (NF-*B), a DNA-bindlng protein Implicated In regulationof gene expression. We suggest that NF-xB could regulate genescrucial for the induction of cell death by TNF-.     

Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic,immunohistochemical, and clinical analyses

Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.     

Does the pineal gland play a role in neuroendocrine fear responses?

The pineal gland secretes melatonin under an influence of suprachiasmatic nucleus neurones. Pinealectomy or melatonin administration affects behavioural responses to novel stimuli. Fear or novel stimuli inhibit vasopressin (VP) and facilitate oxytocin (OT) or prolactin (PRL) release from the pituitary. Thus the suprachiasmatic nucleus-pineal gland system may modulate VP, OT and PRL responses to conditioned fear stimuli. In the present experiments with male rats, pinealectomy or melatonin administration did not significantly change VP, OT or PRL responses to conditioned fear stimuli. Electrolytic lesions of the suprachiasmatic nuclei impaired VP but not OT or PRL responses. The results show that the pineal gland is not involved in neuroendocrine responses to conditioned fear stimuli and suggest that the suprachiasmatic nucleus is necessary for the VP response to fear stimuli.     

Efficacy of the axially loaded pivot shift test for the diagnosis of a meniscal tear

Although magnetic resonance imaging (MRI) has improved the diagnostic accuracy of meniscal pathology, the authors believe that physical examination remains essential to the evaluation of knee pathology. In this study, the diagnostic accuracy of five clinical tests for meniscal pathology was prospectively evaluated in 160 patients, who thereafter underwent arthroscopy. 69% (109 knees) of the knees tested had associated ACL deficiency. There were 144 meniscal lesions in 130 of the 160 knees which were examined. The sensitivity of the tests was lower than the specificity. Conventional tests such as McMurray and Apley tests showed a low accuracy rate of 45% and 28% respectively. The diagnostic value of the axially loaded pivot shift test was significantly higher, indicating that this remains a useful diagnostic aid.     

Effects of N-ethylmaleimide on the structure of skinned frog skeletal muscles

Summary The effects of N-ethylmaleimide (NEM) and other sulfhydryl modifiers on the structure of skinned frog skeletal muscles were studied using the X-ray diffraction technique. In sartorius muscle with full overlap between the thick and thin filaments, 0.1-1.0 mM NEM changed the intensity ratio of the (1,0) and (1,1) equatorial reflections from 4.35 to 0.72, and the (1,0) spacing of the hexagonal filament lattice from 40.4 to 41.4 nm. The axial X-ray diffraction pattern showed weak myosin layer-lines after the NEM treatment but enhancement of the actin layer-lines was not observed. In overstretched semitendinosus muscle, NEM did not affect the equatorial spacing but the myosin layer-lines were weakened. These results indicate that modification of myosin by NEM destroys the helical arrangement of myosin heads around the shaft of the thick filament and that when thin filaments are available, myosin heads move towards, and possibly bind to them. This binding is different from that in rigor since the ladder-like appearance of the higher actin layer-lines, which is typical of patterns from rigor muscles, was not observed. On removal of ATP after the NEM treatment, the diffraction pattern showed features characteristic of that from normal rigor muscles but no tension was produced. The pattern showed well-defined samplings on layer-lines in the small-angle region, indicating the presence of an extensive lattice order and exact axial alignment of the filaments. The first actin layer-line did not show samplings from the superlattice of the thick filaments, which are observed on the myosin layer-lines in patterns from resting muscles. This indicates that in NEM-treated rigor muscles the pattern of binding of myosin heads to the thin filaments is not influenced by the azimuthal orientation of the thick filament.