Strategies for construction of luteinizing hormone beta subunit analogs with carboxyl terminal extensions in non-primate,non-equid mammalian species

Chorionic gonadotropins (CG) are unique because they have a carboxyl terminal peptide (CTP) extension on their beta subunits that prolongs circulatory survival. CGβ genes from the human being and horse have evolved from ancestral luteinizing hormone (LH) beta genes by different pathways that involve deletions that change the reading frames and yield a CTP. Here we further review our previous analysis, aimed at determining whether LHβ genes in non-primate, non-equid species inherently possess DNA sequences that encode CTP-like domains. In multiple mammalian species, simple frame-shift mutations using either the human or equine CGβ gene as a model can be used to construct LHβ analogs with putative CTP domains. Furthermore, DNA sequences from mammalian LHβ genes can be aligned to maximize similarity with CGβ genes in order to devise more refined strategies for construction of CTP-bearing LHβ analogs as exemplified in the bovine case. Thus, mammalian LHβ genes have DNA sequences that can be potentially expressed in order to construct CTP-bearing glycoprotein hormone analogs.     

Delivering syringe exchange services through “satellite exchangers”: the Sacramento Area Needle Exchange, USA

An important operational aspect of Syringe Exchange Programmes (SEPs) is the venue of service delivery. This report describes the programmatic features of the Sacramento Area Needle Exchange (SANE), an illegal SEP operating in California, USA. SANE utilises “satellite exchangers” to distribute the bulk of its syringes and HIV risk reduction supplies. Advantages of relying primarily on Designated Exchangers (DE) for delivery of SEP services are that it: (1) allows for coverage of a large geographical area; (2) keeps operational cost low; (3) provides syringes to clients who may not want to or cannot use fixed site programmes; (4) limits the possibility of detection of programme personnel and clients by law enforcement. Limitations are that: (1) it is not as conducive as fixed sites to providing a wide range of ancillary services; (2) it may not be optimal for drug users who do not want to be reliant on other people for access to syringes; (3) those who receive services from a satellite exchanger may not derive as much counselling and referral services as direct exchangers. The lack of legal status, political support and adequate funding threatens the programme’s existence.     

Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO₂). The patterns of ischemia without congestion (IHB, ISO₂) during superior mesenteric artery occlusion, and ischemia with congestion (IHB, ISO₂) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO₂, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.Supported by the American Society for Gastrointestinal Endoscopy Career Development Award (H850208, H870212), Veterans Administration Medical Research Funds; and in part by research grants (0162-01, 0162-02; 0291-01) from the Smokeless Tobacco Research Council, Inc.; and by funds provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco Related Disease Research Program of the University of California.     

Patellofemoral joint cartilage restoration with particulated juvenile allograft in patients under 21 years old

BackgroundPatellofemoral joint cartilage defects are difficult to treat due to their unique thickness and topography.PurposeTo report the postoperative outcomes of patients age 21 and younger treated with particulated juvenile allograft cartilage (PJAC) for full-thickness cartilaginous defects of the patellofemoral joint. The primary aim was to report surgical outcomes and complication rates, as well as return to sport activity. A secondary aim was to provide objective scores of defect restoration by magnetic resonance imaging (MRI) assessment.MethodsA retrospective review of all PJAC cases conducted between 2012 and 2019 at a single tertiary care urban musculoskeletal institution was conducted. Patients 21 years old or younger with minimum clinical follow up of 1 year and postoperative MRI at a minimum of 6 months were included. Cartilage restoration by MRI was independently assessed using the International Cartilage Repair Society’s (ICRS) standardized system.ResultsThirty four patients, 36 knees, were included, with mean age 16.1 ± 3.1 years old. Return to sport rate among patients who participated in a sport preoperatively was 100%. On independent MRI assessment, two thirds of defects achieved an overall grade of normal or nearly normal, while 28 patients (78%) had majority defect fill. Primary graft failure occurred in two cases and one patient experienced a surgical complication.ConclusionRestoration of patellofemoral chondral defects in young patients with particulated juvenile allograft results in satisfactory short-term outcomes and postoperative MRI appearance, along with high rates of return to sport and low rate of complications and graft failure.What is known about the subject: Patellofemoral joint cartilage defects are difficult to treat due to their unique thickness and topography. Several cartilage restoration techniques are available, but these rarely achieve the same mechanical properties as native hyaline cartilage. PJAC is a cell-based technique that has demonstrated promise since its introduction in 2007.What this study adds to existing knowledge: This series of patients adds the largest single cohort of pediatric and adolescent patients who receive PJAC for defects of the patellofemoral joint. Surgeons treating patients in this age group should be aware of every technique, and their respective outcomes.     

STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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Na+/H+ exchange regulates intracellular pH of rat gastric surface cells in vivo

Intracellular pH (pH_i) and viability of gastric surface cells of the rat stomach in response to luminal acidification, and the role of Na⁺/H⁺ exchange in maintaining pH_i homeostasis were studied in vivo using a fluorescent microscopic technique. pH_i was measured during superfusion with buffers of pH 1.2–7.4. When the pH of the superfusate was 7.4, baseline pH_i was unchanged. Superfusion with pH 3 buffer rapidly decreased pH_i to 6.7, with subsequent recovery to baseline pH_i within 15 min despite continuing acid exposure. Superfusion with buffers of pH 1.7 and 1.2 decreased pH_i continuously to below 6.2 with no recovery observed. Despite the relentless decline in pH_i during superfusion with pH-1.2 and –1.7 solutions, over 75% of the surface cells were still viable, as measured by exclusion of the vital dye propidium iodide. We then examined the role of Na⁺/H⁺ exchange in the regulation of pH_i. Superfusion with amiloride did not affect recovery of pH_i from intracellular acidification induced by a NH₄Cl prepulse. Exposure to the potent, lipophilic Na⁺/H⁺ exchange inhibitor 5-(N,N-hexaniethylene)-amiloride (HMA), either in the superfusate or by close arterial perfusion, decreased baseline pH_i from 7.1 to 6.8. Close arterial perfusion of HMA additionally attenuated the recovery of pH_i to baseline during superfusion with pH 3 buffer. We conclude that luminal protons permeate into the cytoplasm of gastric surface cells, where they are eliminated by an Na⁺/H⁺ exchanger, most probably localized to the basolateral membrane.