Macrophage-lymphocyte association in in vitro mouse spleen cultures; the formation of B-cell colonies.

Colonies of predominantly B lymphocytes have been grown in liquid culture, without agar or specific mitogen treatment. An essential component of the colonies is a macrophage-like cell. Colonies appear to result from continued growth of B lymphocytes following a primary macrophage-lymphocyte association which frequently occurs under a variety of culture conditions. Factors promoting colony growth are foetal calf serum and 2 mercapto-ethanol, the latter acting in part through reduction of a non-dialysable sulphur-containing component of serum.     

Post-awakening cortisol secretion during basic military training.

Salivary free cortisol concentrations in the first 30 min after awakening were assessed in 12 healthy army recruits at the beginning, middle and end of an 11-week intensive physical training course. To ensure strict adherence to protocol saliva collection was supervised and collected on each sampling day immediately on waking and again 15 and 30 min later. Self-rated psychological assessments of state levels of stress, arousal and fatigue were performed in the evening of each sampling day. A within-subjects repeated-measures analysis of participants who completed the course (12 of the original 20) showed a significant main effect of cortisol concentration across all three sampling points after awakening (F((2,22))=54.516, p<0.0001) and a significant main effect of weeks into the training course (F((3,33))=4.390, p=0.010). Further analysis of this effect of measurement-week revealed that at weeks 3 and 6 total cortisol secretion estimated by area under the curve was lower (F((3,33))=4.602, p=0.008) compared to the beginning and end of the course. Surprisingly self-reported stress, arousal and fatigue did not differ significantly across weeks, despite the large dropout rate (40%) and self-evident pressures of the course. We conclude that when controlling for many confounding variables, including participant adherence, post-awakening cortisol levels are sensitive to stressful challenge over a period of weeks.     

Effect of the AirStirrup in Controlling Ankle Inversion Stress

Subtalar ankle inversion with and without AirStirrup application was evaluated using high speed cinematographic techniques and a specially designed platform that inverts the ankle 35 O. Eighteen subjects aged 19 to 35 and with no history of ankle injury participated in the study. Two trials were filmed for each subject. Although the same ankle was tested in each trial, AirStirrups were applied to both ankles in one trial and to neither in the other trial so subjects could not anticipate the inversion stress. Points marked on the knee (posterior), the Achilles tendon, and the distal calcaneous were digitized. These data were smoothed employing cubic splines and used to calculate the maximum angular displacement (inversion) at the subtalar joint in each of the conditions tested. A t-test revealed a significantly (p c 0.001) larger inversion angle for the ankle not braced with fhe AirStirrup. J Orthop Sports Phys Ther 1987;9(5):190-193.     

Recent advances in pathology as applied to orbital biopsy. Practical considerations

Advances in pathology allow for more specific diagnoses of orbital disease. The authors discuss the value of awareness of advances in cytology, histochemistry, immunohistochemistry and electron microscopy as applied to orbital disease. Modern cytologic technique can aid in clearer visualization of cellular detail with improved diagnosis of thin needle aspiration biopsies. Histochemistry offers an increasing range of methods for identification of cellular and extracellular substances such as amyloid, fibrin, neuroglia, and collagen. Immunohistochemistry allows for identification of an ever-increasing number of component antigens including immunoglobulins, myoglobins, keratin, glial fibre protein, etc. Electronmicroscopic technique including plastic embedding allow for specific identification of lesions based on subcellular components and characteristic nuclear, cytoplasmic, membrane, basement membrane and stromal components. The value of these methods has been demonstrated with case presentations of "small round cell tumors" of the adult and child. In addition, the pathologic diagnosis of several rare lesions of the orbit including neuroendocrine carcinoma, histiocytosis X, simultaneously occurring poorly differentiated mucoepidermoid carcinoma of lacrimal gland and adenocarcinoma of the prostate are demonstrated to underline the advances in technology. Emphasis is placed on the management of biopsy material to maximize diagnostic potential.     

A phase 3, randomized,double-blind,parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation

BackgroundTezacaftor (TEZ)/ivacaftor (IVA) is an approved CFTR modulator shown to be efficacious and generally safe and well tolerated in people ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous for the F508del-CFTR mutation and a residual function mutation. Although previous studies with IVA alone showed clinical benefits in people with CFTR gating mutations, TEZ/IVA has not yet been evaluated in a Phase 3 study of participants heterozygous for F508del-CFTR and a gating mutation (F/gating genotypes). Here, we present results from a randomized, double-blind, IVA-controlled, parallel-group, Phase 3 study assessing the efficacy, safety, and pharmacokinetics (PK) of TEZ/IVA in participants ≥12 years of age with F/gating genotypes.MethodsEnrolled participants entered a 4-week IVA run-in period to create a stable IVA baseline. Participants were then randomized to receive IVA or TEZ/IVA for 8 weeks in an active comparator treatment period (ACTP). The primary endpoint was absolute change in percent predicted forced expiratory volume in 1 second (ppFEV₁). Key secondary endpoints were relative change in ppFEV₁ and absolute change in CF Questionnaire–Revised respiratory domain score. Secondary endpoints included absolute change in sweat chloride (SwCl) concentration, PK parameters, and safety. All endpoints except PK parameters and safety were assessed from baseline through Week 8.ResultsSixty-nine participants (92.0%) in the IVA group and 75 participants (98.7%) in the TEZ/IVA group completed treatment. No improvements were seen in efficacy endpoints from baseline at the end of the IVA run-in period through the end of the ACTP in the IVA group. No significant differences in ppFEV₁ or any key secondary endpoint were observed between the IVA and TEZ/IVA groups. SwCl concentrations decreased more in the TEZ/IVA versus IVA group during the ACTP. The safety profile and PK parameters of TEZ/IVA were consistent with those of previous studies in participants ≥12 years of age with CF.ConclusionsThis Phase 3 study showed that the dual-combination regimen of TEZ/IVA demonstrated clinical efficacy but did not have significantly greater clinical efficacy than IVA alone in participants ≥12 years of age with F/gating genotypes. However, as reported in other studies, TEZ/IVA was generally safe and well tolerated (NCT02412111).     

Photothermal effects of laser tissue soldering

Low-strength anastomoses and thermal damage of tissue are major concerns in laser tissue welding techniques where laser energy is used to induce thermal changes in the molecular structure of the tissues being joined, hence allowing them to bond together. Laser tissue soldering, on the other hand, is a bonding technique in which a protein solder is applied to the tissue surfaces to be joined, and laser energy is used to bond the solder to the tissue surfaces. The addition of protein solders to augment tissue repair procedures significantly reduces the problems of low strength and thermal damage associated with laser tissue welding techniques. Investigations were conducted to determine optimal solder and laser parameters for tissue repair in terms of tensile strength, temperature rise and damage and the microscopic nature of the bonds formed. An in vitro study was performed using an 808 nm diode laser in conjunction with indocyanine green (ICG)-doped albumin protein solders to repair bovine aorta specimens. Liquid and solid protein solders prepared from 25% and 60% bovine serum albumin (BSA), respectively, were compared. The efficacy of temperature feedback control in enhancing the soldering process was also investigated. Increasing the BSA concentration from 25% to 60% greatly increased the tensile strength of the repairs. A reduction in dye concentration from 2.5 mg ml(-1) to 0.25 mg ml(-1) was also found to result in an increase in tensile strength. Increasing the laser irradiance and thus surface temperature resulted in an increased severity of histological injury. Thermal denaturation of tissue collagen and necrosis of the intimal layer smooth muscle cells increased laterally and in depth with higher temperatures. The strongest repairs were produced with an irradiance of 6.4 W cm(-2) using a solid protein solder composed of 60% BSA and 0.25 mg ml(-1) ICG. Using this combination of laser and solder parameters, surface temperatures were observed to reach 85+/-5 degrees C with a maximum temperature difference through the 150 microm thick solder strips of about 15 degrees C. Histological examination of the repairs formed using these parameters showed negligible evidence of collateral thermal damage to the underlying tissue. Scanning electron microscopy suggested albumin intertwining within the tissue collagen matrix and subsequent fusion with the collagen as the mechanism for laser tissue soldering. The laser tissue soldering technique is shown to be an effective method for producing repairs with improved tensile strength and minimal collateral thermal damage over conventional laser tissue welding techniques.     

Family-based association studies of bipolar disorder with candidate genes involved in dopamine neurotransmission: DBH, DAT1, COMT, DRD2, DRD3 and DRD5

The dopaminergic system has been implicated in the aetiology of mood disorders. We conducted family-based association studies for polymorphisms at three genes involved in the metabolism of dopamine: dopamine transporter (DAT1), dopamine-beta-hydroxylase (DBH) and catechol-O-methyl transferase (COMT); and three dopamine receptors: DRD2, DRD3 and DRD5. We used a sample of 122 parent-offspring trios of British Caucasian origin where the proband had bipolar disorder I (BPI), and analysed the results with the transmission/disequilibrium test (TDT) which is robust to hidden population stratification. No statistically significant differences were found between transmitted and not transmitted alleles for any of the polymorphisms studied.