Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in monkeys: a pathogenic mechanism of tubal damage

The role of delayed hypersensitivity in the pathogenesis of Chlamydia t trachomatis salpingitis was studied in the monkey "pocket" model. Pigtailed monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat-shock protein (rhsp60) was injected into pockets either previously sensitized with C. trachomatis or not sensitized in the same monkey. Delayed-type hypersensitivity reaction was observed, characterized by mononuclear cell infiltration with peak reaction at 48 h. Injection of rhsp60 into the pockets of a naive animal did not induce inflammation. This study showed that C. trachomatis infection in monkeys induced delayed hypersensitivity, which is mediated by hsp60. Histologic findings of the salpinx were consistent with delayed hypersensitivity reaction observed in ocular C. trachomatis infection, further suggesting a similar pathogenesis for both salpingitis and trachoma.     

The anti-inflammatory activity of boron derivatives in rodents

Acyclic amine-carboxyboranes were effective anti-inflammatory agents in mice at 8 mg/kg x 2. These amine-carboxyboranes were more effective than the standard indomethacin at 8 mg/kg x 2, pentoxifylline at 50 mg/kg x 2, and phenylbutazone at 50 mg/kg x 2. The heterocyclic amine derivatives as well as amine-carbamoylboranes, carboalkoxyboranes, and cyanoboranes were generally less active. However, selected aminomethyl-phosphonate-N-cyanoboranes demonstrated greater than 60% reduction of induced inflammation. The boron compounds were also active in the rat induced edema, chronic arthritis, and pleurisy screens, demonstrating activity similar to the standard indomethacin. The compounds were effecive in reducing local pain and decreased the tail flick reflex to pain. The derivatives which demonstrated good anti-inflammatory activity were effective inhibitors of hydrolytic lysosomal, and proteolytic enzyme activities with IC(50) 50 values equal to (-6)M in mouse macrophages, human leukocytes, and Be Sal osteofibrolytic cells. In these same cell lines, the agents blocked prostaglandin cyclooxygenase activity with IC(50) values of (-6)M. In mouse macrophage and human leukocytes, 5' lipoxygenase activity was also inhibited by the boron derivatives with IC(50) values of 10(-6)M. These IC(50) values for inhibition of these enzyme activities are consistent with published values of known anti-inflammatory agents which target these enzymes.     

Symptomatic subclavian steal syndrome four decades after operation for dysphagia lusoria

Congenital abnormalities of the aortic arch may lead to signs and symptoms of tracheal and esophageal obstruction secondary to a restrictive vascular ring. There are many case reports and monographs concerning the surgical management of dysphagia lusoria. This case provides the first example of long-term follow-up of surgical intervention for relief of dysphagia lusoria. A 45-year-old laborer presented with a several year history of episodic bilateral blindness and a more recent onset of "drop attacks." Notably this patient had presented at the age of 18 months with difficulty breathing and eating since birth. The patient also had frequent upper respiratory infections and episodes of pneumonia. Workup revealed a right-sided aortic arch with a left ligamentum arteriosum. When he was first seen in our clinic, history and physical examination revealed claudication and diminished pulses in the left upper extremity. Arteriography and duplex studies confirmed reversal of flow in the patient's left vertebral artery. The arteriogram demonstrated the presence of a right-sided aortic arch and descending aorta along with the proximal stump of the previously ligated left subclavian artery. He underwent left carotid to left axillary artery bypass for the treatment of symptomatic subclavian steal syndrome. His symptoms have resolved with return of antegrade vertebral flow and the presence of normal pulses in the left arm. Congenital aortic abnormalities that lead to tracheal and esophageal compromise are numerous and varied. Surgical management requires a thorough understanding of the person's anatomy and preoperative planning. The life expectancy of patients with dysphagia lusoria necessitates consideration of the long-term consequences of surgical intervention.     

Co-capping studies reveal CD8/TCR interactions after capping CD8 beta polypeptides and intracellular associations of CD8 with p56(lck)

A reaction-diffusion model was developed to predict the fate of nitric oxide (NO) released by cells of the immune system. The model was used to analyze data obtained previously using macrophages attached to microcarrier beads suspended in a stirred vessel. Activated macrophages synthesize NO, which is oxidized in the culture medium by molecular oxygen and superoxide (O2-, also released by the cells), yielding mainly nitrite (NO2-) and nitrate (NO3-) as the respective end products. In the analysis the reactor was divided into a "stagnant film" with position-dependent concentrations adjacent to a representative carrier bead and a well-mixed bulk solution. It was found that the concentration of NO was relatively uniform in the film. In contrast, essentially all of the O2- was calculated to be consumed within approximately 2 microm of the cell surfaces, due to its reaction with NO to yield peroxynitrite. The decomposition of peroxynitrite caused its concentration to fall to nearly zero over a distance of approximately 30 microm from the cells. Although the film regions (which had an effective thickness of 63 microm) comprised just 2% of the reactor volume and were predicted to account for only 6% of the NO2- formation under control conditions, they were calculated to be responsible for 99% of the NO3- formation. Superoxide dismutase in the medium (at 3.2 microM) was predicted to lower the ratio of NO3- to NO2- formation rates from near unity to <0.5, in reasonable agreement with the data. The NO3-/NO2- ratio was predicted to vary exponentially with the ratio of O2- to NO release rates from the cells. Recently reported reactions involving CO2 and bicarbonate were found to have important effects on the concentrations of peroxynitrite and nitrous anhydride, two of the compounds that have been implicated in NO cytotoxicity and mutagenesis.     

Long-term socioeconomic outcome following surgical intervention in the treatment of refractory epilepsy in childhood and adolescence

Surgical treatment of refractory epilepsy in childhood and adolescence has been shown to be effective in reducing the seizure frequency. This paper examines the question: "Does this result in a better socioeconomic outcome in later years?" Patients who underwent a surgical procedure for the treatment of their medically refractory epilepsy at our hospital, had more than 2-years' follow-up, and were less than 18 years old at time of survey were included. From a retrospective chart review, age at onset and at surgery, duration of seizures prior to surgery, years of follow-up, type of surgery, and neurological status were obtained. From a telephone survey, seizure frequency after surgery, marital, financial and driving status, level of education, and employment status were ascertained. Sixty-four patients in our epileptic surgical series meet entry criteria. Significantly higher levels of education, employment status and independence were found in patients with a class I Engel outcome compared to other Engel outcomes.     

Evaluating medication response in ADHD: cognitive, behavioral, and single-subject methodology

We introduce a novel application for linkage analysis: using bone marrow donor-recipient sib pairs to search for genes influential in graft-versus-host disease (GVHD), a major cause of morbidity and mortality following allogeneic bone marrow transplantation. In particular, we show that transplant sib pairs in which the recipient developed severe GVHD can be used to map genes in the same way as traditional discordant (affected/unaffected) sib pairs (DSPs). For a plausible GVHD model, we demonstrate that the transplant/discordant sib pair analog of the "possible triangle test" [Holmans (1993) Am J Hum Genet 52:362-374] has similar power to that of the simpler "restricted test" proposed by Risch [(1990b) Am J Hum Genet 46:229-241; (1992) Am J Hum Genet 51:673-675]. Moreover, we show that the restricted test has superior power in much of the DSP possible triangle and significantly inferior power in only a small region. Thus, we conclude that the restricted test is preferable for localizing genes with transplant/discordant sib pairs. Finally, we examine the effects of heterogeneity on the power to detect GVHD loci and demonstrate the gain in efficiency by dividing the sample into genetically more homogeneous subgroups.     

Developments in the treatment of alcoholism

The treatment of alcoholism has changed during the past 2 decades. Notable developments have occurred in pharmacotherapy, psychotherapy, and health-care delivery. A better understanding of the biologic basis for addiction has led to clinical trials of medications that target neuroreceptors. One such medication is the opiate antagonist naltrexone, which decreases the craving for alcohol. Psychosocial interventions continue to be the mainstay of alcohol treatment programs. The efficacy of three different therapies was demonstrated in a study called Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). This study, however, did not prove the patient-treatment "matching" hypothesis. In addition to therapies provided by addiction specialists, interest is growing in the use of brief motivational techniques in primary-care settings. As the field of addiction responds to an unfolding health-care delivery system, a broader range of treatment options in conjunction with a greater opportunity to individualize patient care is evolving.     

Protein topology of presenilin 1

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.     

Stability of linear discrete switched systems with delays based on average dwell time method

This paper deals with the problem of exponential stability for a class of linear discrete switched systems with constant delays.The switched systems consist of stable and unstable subsystems.Based on the average dwell time method, some switching signals will be found to guarantee exponential stability of these systems.The explicit state decay estimation is also given in the form of the solutions of linear matrix inequalities(LMIs).An example relating to networked control systems(NCSs) illustrates the effect...     

Diagnosis and treatment of aortic valve stenosis

The present review has attempted to summarize the classic symptoms and signs of aortic valve stenosis, especially in an adult. It is emphasized that all the classic signs rarely are present and their absence may mislead an unwary clinician. The diagnostic help provided by noninvasive tests, including echocardiography and phonocardiography, has been emphasized. A need for cardiac catheterization and angiography in most patients prior to corrective surgery is stressed. The natural history of the disease without operative intervention is dim and a significant risk of sudden death exists. The current surgical approach with immediate and long-term results is summarized. Finally, attention has been drawn to the special clinical circumstances when the aortic valve stenosis provides a strinkingly different clinical picture. We cannot find a better way to end this review than by quoting a warning note given by Thomas Lewis in 1920: "It is the faint cry of an anguished and fast failing muscle, which, when it comes, all should strain to hear, for it is not long repeated. A few months, a few years at most, and the end comes."