Modulation of the immune response by passive antibodies. I. Anti-hapten antibodies enhanced delayed hypersensitivity to the carrier and depressed antibody synthesis to the hapten.

The modulating effects of passive antibodies on both delayed hypersensitivity to the carrier and antibody synthesis to carrier and hapten determinants were studied in guinea pigs. Animals were injected with antibodies directed against either the carrier or the hapten prior to immunization with the hapten-carrier conjugate in Freund's complete adjuvant. Anti-hapten antibodies have been shown to have an enhancing effect on delayed hypersensitivity to the carrier and a suppressive effect on antibody synthesis to the hapten. In this experiment, anti-carrier anti-bodies seemed to have had no effect on delayed hypersensitivity to the carrier and on antibody synthesis to the hapten.     

Nuclear morphometry and molecular biomarkers of actinic keratosis, sun-damaged, and nonexposed skin.

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.     

Myosin detection in human myometrium with a monoclonal antibody

A monoclonal antibody was prepared from a mouse immunized with human gravid uterine myosin. This monoclonal antibody is specific for the myosin heavy chains of human smooth muscle as determined by radioimmunoassay and immunoblotting experiments. Frozen cryostat sections isolated from different uterine regions were studied by immunofluorescence in order to detect myosin distribution within cells of nongravid, gravid, and pathologic human uteri. Myosin was detectable in the cytoplasm of all uterine muscle cells. No fiber heterogeneity with regard to myosin distribution was detected among or within the different uterine regions, regardless of which physiologic or pathophysiologic situation was studied. A large increase in the cell size was observed during pregnancy. These preliminary observations suggest the value of further production of monoclonal antibodies specific for the different putative molecular variants of uterine myosin and their potential use in identifying individual cells containing different myosin variants.     

Ocular complications of paediatric patients with nephrotic syndrome

Purpose : To investigate ocular complications arising from nephrotic syndrome and/or its treatments in children. Methods : A cross‐sectional study was conducted in a teaching hospital. A total of 31 paediatric patients with nephrotic syndrome were studied. Comprehensive ophthalmic assessments on best‐corrected visual acuity, intraocular pressure, slit‐lamp and fundus examination were taken. Information regarding histological diagnosis of nephrotic syndrome and its treatment regimen in each patient was reviewed and analysed. Results : Bilateral posterior subcapsular cataracts were detected in three of 29 patients (10.3%) who received steroid therapy. Two had normal vision while one had visual acuity reduced to 6/15 in both eyes. The age of onset of the nephrotic syndrome in these three patients was 2 years, which was significantly younger than those without cataract (5.4 ± 3.2 years, P < 0.001). Three patients (9.7%) had isolated asymptomatic fundal findings of tortuous and dilated retinal vessels. Hypertensive retinopathy was found in one patient (3.2%). No steroid‐induced glaucoma, uveitis, ocular infection, or other eye complications related to the use of steroids or other immunosuppressive agents were noted. Conclusions : Children who have nephrotic syndrome often require prolonged, intermittent high dose of systemic corticosteroid therapy. Paediatricians should be aware of the potential risk of developing steroid‐related complications, especially posterior subcapsular cataract. It appears to have a higher risk when steroid therapy is used in very young patients. Early detection would help to prevent amblyopia development, particularly in the group of immature eyes.     

On the threshold conditions for electron beam damage of asbestos amosite fibers in the transmission electron microscope (TEM)

Asbestos amosite fibers were investigated to evaluate the damage caused by a transmission electron microscope (TEM) electron beam. Since elemental x-ray intensity ratios obtained by energy dispersive x-ray spectroscopy (EDS) are commonly used for asbestos identification, the impact of beam damage on these ratios was evaluated. It was determined that the magnesium/silicon ratio best represented the damage caused to the fiber. Various tests showed that most fibers have a current density threshold above which the chemical composition of the fiber is modified. The value of this threshold current density varied depending on the fiber, regardless of fiber diameter, and in some cases could not be determined. The existence of a threshold electron dose was also demonstrated. This value was dependent on the current density used and can be increased by providing a recovery period between exposures to the electron beam. This study also established that the electron beam current is directly related to the damage rate above a current density of 165 A/cm². The large number of different results obtained suggest, that in order to ensure that the amosite fibers are not damaged, analysis should be conducted below a current density of 100 A/cm².     

Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning

Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats were generated with human BChE cDNA under control of the goat beta-casein promoter. Milk from transgenic animals contained 0.1-5 g/liter of active rBChE. The plasma half-life of PEGylated, goat-derived, purified rBChE in guinea pigs was 7-fold longer than non-PEGylated dimers. The rBChE from transgenic mice was inhibited by nerve agents at a 1:1 molar ratio. Transgenic goats produced active rBChE in milk sufficient for prophylaxis of humans at risk for exposure to OP agents.     

Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year,real-world UCanADA study

BACKGROUNDA gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis (UC) patients treated in a real-world setting. The use of patient-reported outcomes (PROs) has been discussed as a primary endpoint in the context of the FDA PRO Guidance, for labelling purposes. Specifically, the efficacy and safety of adalimumab have been demonstrated in pivotal trials; however, data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients, such as symptoms, health-related quality of life (HRQoL), and disability.AIMTo assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC.METHODSUCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed—with psychologic distress/depression symptoms as the primary endpoint—by patients with moderate-to-severe UC. Assessments were performed during patients’ routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected.RESULTSFrom 23 Canadian centres, 100 patients were enrolled and 48 completed the study. Measured with the Patient Health Questionnaire–9 items at week 52, 61.5% (40/65) [95% confidence interval (CI): 49.7%-73.4%] of the patients improved in psychologic distress/depression symptoms, which was slightly higher in completers [65.9% (29/44); 95%CI: 51.9%-79.9%)]. At week 52, clinical response and clinical remission were achieved respectively by 65.7% (44/73) and 47.8% (32/73) of the patients. The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission (CI: 1.42, 44.41; P = 0.018). Significant changes from baseline to weeks 8 and 52 were observed in disability, HRQoL, and fatigue. Meaningful improvement was reported in work impairment.CONCLUSIONAt week 52, over 60% of the UCanADA patients had depressive symptoms significantly reduced, as well as HRQoL, fatigue symptoms, and work impairment improved. No new safety signals were detected.