Cryptosporidium parvum initiates inflammatory bowel disease in germfree T cell receptor-alpha-deficient mice

Flora-bearing mice with targeted disruption of T cell receptor (TCR)-alpha or -beta genes spontaneously develop intestinal inflammation with features similar to ulcerative colitis in humans. TCR-alpha-deficient mice maintained germfree or colonized with a limited number of intestinal bacteria failed to develop inflammatory bowel disease (IBD)-like lesions. Evidently, inflammation in these mice does not develop spontaneously or result from a generalized antigenic stimulation, but rather requires induction by a heretofore unidentified specific stimulus. We describe the development of IBD-like lesions in germfree TCR-alpha-deficient mice monoassociated with the protozoan Cryptosporidium parvum. Lesions were seen in distal ileum, cecum, and colon and were most severe in the cecum. A prominent leukocytic infiltrate within the lamina propria was a common characteristic of the lesions observed in the C. parvum-infected germfree TCR-alpha-deficient mice. The leukocytic infiltrate was composed of aggregates of B220+ cells, the majority of which expressed surface IgD (ie, conventional B lymphocytes). It has been proposed that antigenic stimulation by a microorganism(s) is needed to initiate intestinal inflammation in TCR-alpha-deficient mice. Our results indicate that a single microbial species, C. parvum, is capable of triggering the development of IBD-like lesions in germfree TCR-alpha-deficient mice.     

Gonadotrophin heterogeneity and biopotency: implications for assisted reproduction

The extensive heterogeneity of the gonadotrophin hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), is due primarily to the heterogeneous nature of their carbohydrate side-chains, in particular sialic acid residues. In this review, we discuss the role of carbohydrate chains in receptor binding and activation, biological activity, and metabolic half-life. The synthesis and secretion of the various glycoforms of both FSH and LH appear to be under endocrine control with gonadotrophin-releasing hormone (GnRH), oestradiol and testosterone playing important roles. Evidence for different glycoforms having variable biopotency or different encoded functions is increasing, and the production and secretion of more or less acidic gonadotrophin species in different physiological states may represent an important mechanism whereby the pituitary regulates gonadal cell and organ function. This has potential importance for the development of new pharmaceutical reagents and new therapeutic regimens in assisted reproduction. It is envisaged that the use of existing and new forms of FSH/LH will allow patients to be treated in a more controlled and physiological manner, with treatment regimens individualized to the needs of the patient.     

Molecular and geographic patterns of tuberculosis transmission after 15 years of directly observed therapy

Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used as a substitute for non-alcoholic sweetener. It has previously been shown to reduce blood pressure in studies in animals and human. The effect of intravenous stevioside on the blood pressure was studied in spontaneously hypertensive rats (SHR). The hypotensive effect on both systolic and diastolic blood pressure was dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious SHR. The maximum reductions in systolic and diastolic blood pressure were 31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg. Serum dopamine, norepinephrine and epinephrine levels were not changed significantly 60 min after intravenous injection of stevioside 100 mg/kg in anesthetized SHR. The present data show that stevioside given intravenously to conscious SHR was effective in blood pressure reduction and there was no change in serum catecholamines in anaesthetized animals with this natural compound.     

Oxidation of hafnium carbide and hafnium carbide with additions of tantalum and praseodymium

The oxidation behavior of HfC, HfC-25 wt. % TaC, and HfC-7 wt.% PrC₂ has been studied between 1200–2200° C. Parabolic growth of the oxide layer has been observed for both HfC and HfC-TaC over the entire temperature range. A break in the temperature dependence of the oxidation kinetics occurs around 1600°C. At lower temperatures, the kinetics are limited by gaseous diffusion via pores in the oxide. Above 1800°C, gaseous diffusion through pores becomes less important as scale-growth kinetics are dominated by bulk (ambipolar) diffusion of oxygen and electrons through the oxide.     

Amblyomma variegatum (Acari: Ixodidae): mechanism and control of arbovirus secretion in tick saliva

Saliva is considered to be the conduit by which pathogens are transmitted from blood-sucking arthropod vectors to their vertebrate hosts, but supporting evidence for this is fragmentary. To determine if Thogoto (THO) virus, a tick-borne member of the influenza virus family, is transmitted via tick saliva, and whether virus replication is a prerequisite for such transmission, two experimental conditions were compared: (1) "biological transmission" and (2) "mechanical transmission." In (1), THO virus was allowed to infect and replicate in a natural vector, Amblyomma variegatum: virus was detected in saliva collected from 3/22 (14%) ticks. In (2), virus was inoculated directly into the hemocoel with the drug used to induce salivation and saliva was collected immediately to preclude the possibility of virus replication: virus was detected in saliva collected from 31/170 (18%) ticks. The results demonstrate that THO virus is secreted in tick saliva and that virus can pass from the hemolymph to the salivary glands independently of viral replication within the tick. The comparatively low numbers of ticks that yielded virus-positive saliva samples together with the results from assays of serial saliva samples suggested that virus secretion may not be a continuous process during salivation. Ticks in which THO virus had established an infection showed an impaired secretory response compared with uninfected ticks and ticks used for mechanical transmission.     

A high-voltage cardiac stimulator for field shocks of a whole heart in a bath

Defibrillators are a critical tool for treating heart disease; however, the mechanisms by which they halt fibrillation are still not fully understood and are the subject of ongoing research. Clinical defibrillators do not provide the precise control of shock timing, duration, and voltage or other features needed for detailed scientific inquiry, and there are few, if any, commercially available units designed for research applications. For this reason, we have developed a high-voltage, programmable, capacitive-discharge stimulator optimized to deliver defibrillation shocks with precise timing and voltage control to an isolated animal heart, either in air or in a bath. This stimulator is capable of delivering voltages of up to 500 V and energies of nearly 100 J with timing accuracy of a few microseconds and with rise and fall times of 5 micros or less and is controlled only by two external timing pulses and a control computer that sets the stimulation parameters via a LABVIEW interface. Most importantly, the stimulator has circuits to protect the high-voltage circuitry and the operator from programming and input-output errors. This device has been tested and used successfully in field shock experiments on rabbit hearts as well as other protocols requiring high voltage.     

Application of a counter-current gaseous diffusion model to the oxidation of hafnium carbide at 1200 to 1530°C

A counter-current gaseous diffusion model is presented to describe the oxidation of hafnium carbide between 1200 and 1530°C. The model separates the porous hafnia scale into two gas diffusion regions separated by a flame front, where O ₂ and CO react to form CO ₂.In the outer region, O ₂ and CO ₂ counter-diffuse; in the inner region, CO ₂ and CO counter-diffuse. The concentration gradients of each gaseous specie in the pores of the hafnia are determined and the rate of oxidation is calculated. A porosity of 2% and a pore radius of 0.01 m are representative of the values observed in hafnia during the early stages of HfC oxidation. These values lead to predictions of parabolic rate constants that are close to those measured by thermogravimetric analysis. In addition, the predicted and measured parabolic rate constants are shown to have the same dependence upon temperature and oxygen partial pressure.     

Impedance cardiography used to assess patterns of cardiovascular response to behavioral stressors

This paper presents two examples of how impedance cardiography may be used to interpret the hemodynamic influences on blood pressures measured during behavioral stress. In Study 1, blood pressure changes which were similar during two tasks were shown to have important differences in their cardiac output and vascular resistance components. During work on a reaction time task having aversive incentives compared with a neutral task, the blood pressure changes were seen to be associated with lowered vascular resistance and raised cardiac activity, a "fight-flight" pattern. In Study 2, blood pressure response differences between two subject groups working on an identical task were found to have blood pressure changes differing in their underlying cardiac and vascular components as measured by impedance. Such uses impedance cardiography have widespread potential application in psychophysiological research with humans.     

Histopathologic spectrum of vaginal adenosis and related changes in stilbestrol-exposed females

A total of 98 colposcopically directed biopsies were obtained from the vagina, cervix, and cervicovaginal ridge (hood) of 80 young women believed to have had intrauterine exposure to stilbestrol (DES). Specific investigation of the patient's medical records corroborated the history of maternal stilbestrol administration in 36 patients (45%), while in the remainder the drug history was regarded as presumptive since medical records were unavailable for review. The findings did not differ significantly in those biopsies taken from patients with confirmed or presumptive drug histories. Histologic evidence of vaginal adenosis was detected in vaginal biopsies from 43 patients. In 30 cases (70%) benign Müllerian-type glandular epithelium was in the superficial vaginal wall, residing on the mucosal surface and/or in the lamina propria. The glandular epithelium predominantly was of endocervical type, but in six instances it resembled endometrial or fallopian tubal epithelium. The glands were accompanied by varying degrees of squamous metaplasia in 22 cases. When extensive the metaplasia produced transformation zones similar to those seen in the normal cervix. Vaginal biopsies of adenosis from the other 13 patients (30%) revealed squamous metaplasia without demonstrable glands due to complete transformation of all antecedent glandular epithelium by squamous metaplasia. Our studies indicate that squamous metaplasia is a component of major importance in the natural history of adenosis and that the concept of adenosis should be broadened to include those examples comprised exclusively of metaplastic epithelium. In such examples metaplasia is identified by the immaturity and poor glycogenation of the squamous cells and their accompanying squamous pegs which often contain residual gland openings or squamous "eddies." Similar findings were present in biopsies of seven cervicovaginal ridges and in cervical biopsies from 37 patients, except for the absence of endometrial or tubal type glands in the latter site. Although no adenocarcinomas were detected, six patients had squamous dysplasia of the vagina and/or cervix. In no case were premalignant or dysplastic changes of glandular cells found. Our findings support the thesis that stilbestrol-associated adenosis represents anomalous embryologic localization of the original squamocolumnar junction in the vagina rather than in the cervix. It is closely related to so-called cervical "erosions." The development of squamous metaplasia accounts for modifications in the clinical and histologic appearances by producing transformation zones which then may be subject to the same oncogenic stimuli for squamous neoplasia as are their counterparts in the cervix.     

Silicon phthalocyanine/methyl methacrylate copolymer slab directional couplers for all-optical switching

Slab waveguide directional couplers were fabricated from the third-order nonlinear optical polymer silicon phthalocyanine/methyl methacrylate 2/98 copolymer as the active material and poly(methyl methacrylate) as the cladding layer. The monomethacrylate copolymer was synthesized, device fabrication conditions determined, and five-layer slab directional couplers fabricated. Completed couplers demonstrated waveguide loss on the order of 5 dB/cm and coupling lengths of 0.5 mm at 1.29 μm. These vertically coupled devices may be useful for all-optical switching. © 1994 John Wiley & Sons, Inc.