Psammomabody content and DNA-flow cytometric results as prognostic factors in advanced ovarian carcinoma

138 advanced ovarian serous carcinoma--all FIGO stages III/IV--were investigated by prognostic morphological factors like tumour grading and rate of psammomabody content--subdivided in to serous carcinoma with a high, a moderate and a low rate of psammomabodies and a group of serous carcinoma without psammomabodies. Additionally 91 of these tumours were examined by DNA-flow-cytometry--respectively DNA-ploidy and s-phase-fraction. All prognostic factors were correlated to the overall survival time. The psammomabody content factor is only important if histologically a high or moderate rate of psammomabodies is found in the tumour tissue. Tumours with a low rate of psammomabodies do not differ from serous tumours without psammomabodies. DNA-flow-cytometry is a qualified method to demonstrate a slow tumour growth tendency. The majority of carcinomas with a high rate of psammomabodies is DNA-diploid and has a low -phase-fraction. The overall survival rate for these tumours is much better. Tumour grading--a more subjective method--is also of high value, but there is a certain difficulty in reproducing the results in individual cases. By the combination of the two morphological methods--semiquantitative assessment of psammomabodies and DNA-flow-cytometry--we were able to discover a small group of patients with advanced ovarian cancers who have a favourable prognosis.     

Structural and functional alterations of a colicin-resistant mutant of OmpF porin from Escherichia coli.

A strain of Escherichia coli, selected on the basis of its resistance to colicin N, reveals distinct structural and functional alterations in unspecific OmpF porin. A single mutation [Gly-119-->Asp (G119D)] was identified in the internal loop L3 that contributes critically to the formation of the construction inside the lumen of the pore. X-ray structure analysis to a resolution of 3.0 A reveals a locally altered peptide backbone, with the side chain of residue Asp-119 protruding into the channel, causing the area of the constriction (7 x 11 A in the wild type) to be subdivided into two intercommunicating subcompartments of 3-4 A in diameter. The functional consequences of this structural modification consist of a reduction of the channel conductance by about one-third, of altered ion selectivity and voltage gating, and of a decrease of permeation rates of various sugars by factors of 2-12. The structural modification of the mutant protein affects neither the beta-barrel structure nor those regions of the molecule that are exposed at the cell surface. Considering the colicin resistance of the mutant, it is inferred that in vivo, colicin N traverses the outer membrane through the porin channel or that the dynamics of the exposed loops are affected in the mutant such that these may impede the binding of the toxin.     

Cellular and paracellular magnesium transport across the terminal ileum of the rat and its interaction with the calcium transport.

Concentration and voltage dependence of unidirectional magnesium fluxes across the stripped mucosa of the rat terminal ileum were measured in an Ussing chamber. The mucosa-to-serosa magnesium flux exhibited a curvilinear concentration dependence, whereas serosa-to-mucosa flux of magnesium was linearly related to magnesium concentration between 0.25 and 5 mM. At low concentrations magnesium was absorbed, whereas at the magnesium concentration of 5 mM the serosa-to-mucosa magnesium flux was higher than the mucosa-to-serosa flux, resulting in magnesium secretion. Only the mucosa-to-serosa flux of magnesium had a voltage-independent (i.e., nondiffusive) cellular component. Due to the high capacity of this cellular mucosa-to-serosa transport of magnesium, which was about 7.5 times greater than that of calcium, absorption of magnesium was performed in the terminal ileum in contrast to calcium, which was secreted under the same conditions. However, magnesium serosa-to-mucosa flux was totally voltage dependent (i.e., diffusive) and probably restricted to the paracellular pathway. The diffusive serosa-to-mucosa flux of magnesium was about two times greater than the diffusive fraction of the mucosa-to-serosa transport of magnesium. The prevalence of the diffusive serosa-to-mucosa flux of magnesium over that from mucosa to serosa, responsible for magnesium secretion observed at the magnesium concentration of 5 mM, may be explained by an "anomalous solvent drag effect." Voltage clamp experiments showed that magnesium had no effect on the cellular mucosa-to-serosa transport of calcium. However, it decreased the diffusive calcium flux in this direction. 1 alpha,25-dihydroxyvitamin D3 did not influence the unidirectional or net magnesium transport but increased the calcium flux in both directions to the same degree. In conclusion, magnesium is absorbed in the terminal ileum at least partially by a cellular, vitamin D3-insensitive process that is different from the calcium transport mechanism.     

Nail changes in chronic renal failure patients under haemodialysis

Background Chronic renal failure is known to cause various nail pathologies. They may be directly related to the renal condition itself or its complications or to the therapy. Objective To compare nail changes in end‐stage renal failure patients under haemodialysis with healthy persons and to study the potential relationship with various parameters in the patients. Patients and Methods The study comprised 100 patients with chronic renal failure under regular haemodialysis as well as 100 healthy control subjects of matched age and sex. Both groups were subjected to full history taking and thorough general and nail examination. Complete blood picture, liver and kidney function tests and fasting blood glucose level were investigated. Results Nail disorders were more prevalent in patients (76%) than in control group (30%). The half and half nail was the most common finding (20%) followed by – in descending manner – absent lunula, onycholysis, brittle nail, Beau's lines, clubbing, longitudinal ridging, onychomycosis, subungual hyperkeratosis, koilonychias, total leukonychia, splinter hemorrhage, pitting and pincer nail deformity. There was non‐significant correlation between nail changes and age of the patients or duration of haemodialysis. In addition, no evidence of significant relation was found between nail changes and both haemoglobin and albumin levels. Conclusion Frequent nail changes are observed on systematic nail examination of uraemic patients undergoing haemodialysis; however, the cause of them remains obscure and could not be traced to a particular abnormality in the renal condition, medication or the procedure itself and it needs further investigations.     

Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces

Compared with our understanding of endochondral ossification, much less is known about the coordinated arrest of growth defined by the narrowing and fusion of the cartilaginous growth plate. Throughout the musculoskeletal system, appropriate cell and tissue responses to mechanical force delineate morphogenesis and ensure lifelong health. It remains unclear how mechanical cues are integrated into many biological programs, including those coordinating the ossification of the adolescent growth plate at the cessation of growth. Primary cilia are microtubule-based organelles tuning a range of cell activities, including signaling cascades activated or modulated by extracellular biophysical cues. Cilia have been proposed to directly facilitate cell mechanotransduction. To explore the influence of primary cilia in the mouse adolescent limb, we conditionally targeted the ciliary gene Intraflagellar transport protein 88 (Ift88^fl/fl) in the juvenile and adolescent skeleton using a cartilage-specific, inducible Cre (AggrecanCreER^T2 Ift88^fl/fl). Deletion of IFT88 in cartilage, which reduced ciliation in the growth plate, disrupted chondrocyte differentiation, cartilage resorption, and mineralization. These effects were largely restricted to peripheral tibial regions beneath the load-bearing compartments of the knee. These regions were typified by an enlarged population of hypertrophic chondrocytes. Although normal patterns of hedgehog signaling were maintained, targeting IFT88 inhibited hypertrophic chondrocyte VEGF expression and downstream vascular recruitment, osteoclastic activity, and the replacement of cartilage with bone. In control mice, increases to physiological loading also impair ossification in the peripheral growth plate, mimicking the effects of IFT88 deletion. Limb immobilization inhibited changes to VEGF expression and epiphyseal morphology in Ift88cKO mice, indicating the effects of depletion of IFT88 in the adolescent growth plate are mechano-dependent. We propose that during this pivotal phase in adolescent skeletal maturation, ciliary IFT88 protects uniform, coordinated ossification of the growth plate from an otherwise disruptive heterogeneity of physiological mechanical forces. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Efficacy of short‐course lansoprazole with clarithromycin and amoxicillin in the eradication of Helicobacter pylori in South‐East Asian patients: 5‐day t.d.s. versus 7‐day b.d. treatment regimens

OBJECTIVE : To determine and compare the efficacy of 5‐day t.d.s and 7‐day b.d. treatment regimens comprising lansoprazole, clarithromycin and amoxicillin in the eradication of Helicobacter pylori. METHODS : Patients with unequivocal evidence of H. pylori infection based on histology and rapid urease tests of both antrum and corpus biopsies were recruited for the study. The study was a randomized, investigator‐blind, comparative study. Patients received either 500 mg clarithromycin t.d.s. and 500 mg amoxicillin t.d.s. for 5 days (LAC5) or 500 mg clarithromycin b.d. and 500 mg amoxicillin b.d. for 7 days (LAC7) together with 30 mg lansoprazole (both groups) daily for either 5 or 7 days, depending on the treatment group. Patients were assessed for the successful eradication of H. pylori, defined as the absence of bacteria based on histology and urease tests on both antral and corporeal biopsies, carried out at least 4 weeks after completion of the therapy. RESULTS : One hundred and eight patients were recruited for the study. In the LAC5 treatment group, four patients failed to return for follow up and in the LAC7 group, two failed to return for follow up and two were not compliant with medications. Eradication rates based on an intention‐to‐treat analysis were: 46/54 for LAC5 (85.2%; 95% CI = 72.9–93.4) and 47/54 for LAC7 (87.0%; 95% CI = 75.1–94.6). Based on a per protocol analysis, the rates were: 46/50 for LAC5 (92.0%; 95% CI = 80.8–97.8) and 47/50 for LAC7 (94.0%; 95% CI = 83.5–98.7). Both treatment regimens were convenient for patients and except for two patients in the LAC7 group, all patients reported taking 100% of all prescribed medications. The side‐effects encountered were uniformly mild and no patient discontinued treatment because of intolerance to medications. The most common side‐effects were altered taste (LAC5 64.7%; LAC7 78.8%). Diarrhea, nausea and anorexia were reported in a minority of patients. CONCLUSIONS : Both the LAC5 t.d.s. and the LAC7 b.d. treatment regimens were well tolerated by patients and were highly effective in the eradication of H. pylori.