Studies on plasma immunoreactive human brain natriuretic peptide (hBNP) levels in patients with congestive heart failure and present forms of hBNP in human cardiac ventricle

By using a specific radioimmunoassay (RIA) for human brain natriuretic peptide (hBNP), we measured immunoreactive hBNP (ir-hBNP) in plasma from patients with congestive heart failure (CHF). There appeared to be relationship between the enhanced ir-hBNP secretory activity and the severity of the failing heart as well as that of immunoreactive human atrial natriuretic peptide (ir-hANP). However, the secretion of ir-hBNP was augmented much more than that of ir-hANP in sever CHF patients. Gel permeation chromatography coupled with the RIA revealed that ir-hBNP in human ventricle is composed with gamma-hBNP and hBNP (1-32) as well as that of human atrium. However, we found differences of the gamma-hBNP/hBNP (1-32) ratio in atrial and ventricular tissues. These findings suggest that the hBNP secretion mechanism differ in the two areas of human heart.     

Synthesis and side-chain crystallization of comb-like polymers obtained from isopropenyl-1,3,5-triazines carrying two,three, and four long alkyl groups

Monomers containing several octadecyl groups, e.g., 2-isopropenyl-4,6-bis(octadecylamino)-1,3,5-triazine ( 2 ), 2-dioctadecylamino-4-isopropenyl-6-octadecylamino-1,3,5-triazine ( 3 ) and 2,4-bis(dioctadecylamino)-6-isopropenly-1,3,5-triazine ( 4 ) were prepared by the alkylation reaction of 2,4-diamino-6-isopropenyl-1,3,5-triazine ( 1 ) with 1-bromooctadecane in the presence of sodium hydride. In the free-radical homopolymerization of these monomers, the polymer yield of 3 was lower than that of 2 due to a decrease in the ceiling temperature, and the polymerization of 4 did not proceed. Copolymerizations of these monomers with styrene or methyl methacrylate were carried out and the monomer reactivity ratios (r₁ and r₂) were determined. The monomer reactivity decreased with increasing the number of octadecyl groups in the monomers. Crystallinity of the octadecyl side chains in the resulting comb-like polymers was evaluated by differential scanning calorimetry.     

Diversity of Hepatitis G Virus within a Single Infected Individual

The extent of population diversity among GB virus C (GBV-C)/hepatitis G virus (HGV) within a persistently infected individual (Iw) was investigated by sequence analysis of multiple clones generated from polymerase chain reaction (PCR)-amplified products of cDNA analogous to fragments of 5 non-coding region (5NC), envelope region 1/2 (E1/E2) and non-structural region 3 (NS3) of viral genome. Although nucleotide substitutions were more common in coding regions than in the 5NC region, there was no region corresponding to the hypervariable region of hepatitis C virus in the E1/E2 region. Transition substitution exceeded transversion by 7 to 12-fold, and 79.4% of substitutions were synonymous. This bias against substitutions producing amino acid replacements and the use of Pfu DNA polymerase with an error rate 10 times lower than the observed frequency of substitution, suggests that most substitutions were not artefactual. This data suggests that individual genomes of HGV within an infected individual may differ from each other at 0.23–0.84% nucleotide position and at 0.42–0.61% amino acid position.     

A comparative study of portal vein embolization versus radiation lobectomy with Yttrium-90 micropheres in preparation for liver resection for initially unresectable hepatocellular carcinoma

BackgroundPortal vein embolization before liver resection is considered the therapy of choice for patients with inadequate future liver remnants. The concept of radioembolization with Yttrium-90 to achieve the same goal has limited data.MethodsWe retrospectively compared patients who underwent portal vein embolization and Yttrium-90 lobectomy before resection of hepatocellular carcinoma in patients with chronic liver disease.ResultsSeventy-three patients underwent portal vein embolization and 22 patients underwent Yttrium-90. Forty-seven percent of patients before portal vein embolization required additional procedures for tumor control, and 27% of patients after Yttrium-90 required additional procedure to mainly induce further hypertrophy. Both therapies achieved the goal of future liver remnants >40%, but the degree of hypertrophy was significantly higher in Yttrium-90 patients (63% for Yttrium-90, 36% for portal vein embolization, P < .01). Tumor response was significantly better with Yttrium-90, achieving complete response in 50% of patients. Resectability rate was higher after portal vein embolization (85% for portal vein embolization, 64% for Yttrium-90, P = .03). Tumor progression was the most common reason precluding surgery. Complete tumor control was the reason not to pursue surgery in 18% of patients after Yttrium-90.ConclusionBoth preoperative portal vein embolization and Yttrium-90, increases liver resectability rates by inducing hypertrophy of future liver remnants in patients with hepatocellular carcinoma and chronic liver disease. Yttrium-90 lobectomy achieved better tumor control and provided more time to assess therapy response, optimizing the indication for surgery.     

Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12⁺ stromal cells (“Adipo-CAR” cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12⁺ pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown. Here we highlight CXCL12-dependent physical coupling with hematopoietic cells as a potential mechanism regulating the adipogenic potential of CXCL12⁺ stromal cells. Single-cell computational analyses of RNA velocity and cell signaling reveal that Adipo-CAR cells exuberantly communicate with hematopoietic cells through CXCL12-CXCR4 ligand-receptor interactions but do not interconvert with Osteo-CAR cells. Consistent with this computational prediction, a substantial fraction of Cxcl12-creER⁺ pre-adipocyte-like cells intertwines with hematopoietic cells in vivo and in single-cell preparation in a protease-sensitive manner. Deletion of CXCL12 in these cells using Col2a1-cre leads to a reduction of stromal-hematopoietic coupling and extensive marrow adipogenesis in adult bone marrow, which appears to involve direct conversion of CXCL12⁺ cells to lipid-laden marrow adipocytes without altering mesenchymal progenitor cell fates. Therefore, these findings suggest that CXCL12⁺ pre-adipocyte-like marrow stromal cells prevent their premature differentiation by maintaining physical coupling with hematopoietic cells in a CXCL12-dependent manner, highlighting a possible cell-non-autonomous mechanism that regulates marrow adipogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study)

ObjectivesWe aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP).Materials and MethodsWe longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP.ResultsThe median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening.ConclusionsFrailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.     

VAMP2 is expressed in myogenic cells during rat development

Vesicle-associated membrane protein 2 (VAMP2) is a member of the SNARE family of proteins that regulate the intracellular vesicle fusion process. This study investigated the developmental expression of VAMP2 in the rat embryo. In the trunk, VAMP2 was primarily found in the heart on embryonic day (E) 10. On E12.5, VAMP2 expression was found in nerve fibers, somites, and heart. In somites, epithelial cells in the dorsomedial lip, and elongated myoblasts in myotome were positive for VAMP2. On E16.5, VAMP2 was expressed in the heart, nerve fibers, and skeletal muscles. In skeletal muscles, multinuclear myotubes were positive for VAMP2. In the head, where muscles are derived both from somitic and non-somitic origin, VAMP2 was found in myotubes of the extrinsic ocular muscles and masseter muscle on E16.5. These findings suggest the involvement of VAMP2 in the development of skeletal muscles of somitic and non-somitic origins.     

A double-blind trial on the effect of bunazosin hydrochloride for the symptoms of benign prostatic hypertrophy]

A multicenter clinical trial was carried out on 372 patients in double-blind conditions in order to determine the clinical effects of Ea-0643 (bunazosin hydrochloride) on voiding disorders in benign prostatic hypertrophy, compared with paraprost and placebo. Of the 372 patients, 129 were assigned to bunazosin hydrochloride, 118 to paraprost and 125 to placebo. The improvement rating for all five subjective symptoms improved with passage of time in all the bunazosin hydrochloride, paraprost and placebo groups. A higher improvement rating was obtained in the bunazosin hydrochloride group for retarded urination, urinary stream condition and abdominal pressure at voiding, while the improvement rating was higher for prolonged urination in the placebo group and for residual urine in the paraprost group, but there was no significant difference in improvement ratings between the groups. The daily frequency of voiding decreased to a significant extent in the bunazosin hydrochloride and placebo group at week 1, and there was a significant difference between the bunazosin hydrochloride and the paraprost groups and between the placebo and the paraprost groups. The improvement rating for conditions of voiding was higher with the bunazosin hydrochloride group, when "slightly or better improved" cases were taken into account, but there was no difference between the groups. As for objective symptoms, maximum and average flow rate, useful measures for clinical evaluation of drug effects on voiding disorders, were significantly increased, with a decrease to match in residual urine ratio in the bunazosin hydrochloride group. In terms of maximum and average flow rate bunazosin hydrochloride was significantly superior to paraprost at weeks 1 and 2 and superior to placebo at weeks 2 and 4 and at the final evaluation as well. In terms of residual urine ratio bunazosin hydrochloride was superior to both paraprost and placebo. The global improvement rating, as assessed by the U- and chi 2-tests, was significantly higher in the bunazosin hydrochloride group than in the paraprost group, and there was a significant difference in global improvement ratings, as assessed by the chi 2-test, between the placebo and the paraprost groups, when "moderately or better improved" cases were taken into account. The stratified analysis of the prostate glands, subjective symptoms, maximum flow rate and residual urine ratio revealed that in patients with more advanced conditions the bunazosin hydrochloride group showed significantly superior improvement rates than the paraprost and placebo groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

The 301 to 314 amino acid residue of beta-tubulin is not a target epitope for serum IgM antibodies in chronic inflammatory demyelinating polyneuropathy

Connolly et al. [Neurology 48 (1997) 243] reported that IgM M-proteins from three patients selectively binds to an epitope on beta-tubulin that consists of amino acids 301 to 314. We therefore investigated whether these 14 amino acid residues beta301-314 are the target epitope for serum IgMs in sera from 67 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 50 with Guillain-Barré syndrome, 50 with motor neuron diseases, and 50 normal controls. IgM anti-beta301-314 antibodies were not restricted to nor were selectively associated with CIDP. We conclude that beta301-314 is not a target epitope for serum IgMs in CIDP.