Hemostatic risk factors of coronary artery disease in the Chinese

Induction of the mitochondrial permeability transition in vitro is well-characterized and widely implicated in the mechanism of oxidant-induced cell death. Despite an abundance of in vitro evidence, implication of mitochondrial dysfunction in the mechanism of chemical toxicity in vivo awaits demonstration of the induction of the mitochondrial permeability transition in tissues from intoxicated animals. Menadione (2-methyl-1,4-naphthoquinone), an agent known to induce the permeability transition in isolated liver mitochondrial in vitro, was administered as a single bolus to adult male rats, and hepatic mitochondria were isolated 24 h later. Mitochondria from menadione-treated rats exhibited an increased sensitivity to calcium-induced inhibition of state 3 respiration and loss of respiratory control, as well as a greater sensitivity to calcium-induced calcium release that was inhibited by cyclosporine A. Associated with this was the depolarization of membrane potential and swelling of mitochondria from menadione-treated animals, but not control animals. Both the calcium-dependent depolarization and swelling of mitochondria from menadione-treated rats were inhibited by adding either cyclosporine A or ruthenium red. The results are consistent with the induction of the mitochondrial permeability transition and provide the first evidence for the manifestation of an increased sensitivity to this response as a result of chemical exposure in vivo.     

Vitrectomy for retained lens fragments after phacoemulsification

PURPOSE: Posterior lens fragments after phacoemulsification can be a serious complication of cataract surgery. This study is designed to evaluate the clinical features of eyes after pars plana vitrectomy has been performed to remove posteriorly dislocated lens fragments after phacoemulsification. METHODS: The authors performed a retrospective chart review of 126 consecutive eyes of 126 patients with dislocated lens fragments after phacoemulsification, managed with pars plana vitrectomy at Associated Retinal Consultants of Michigan. These eyes were operated on from January 1986 through January 1996. RESULTS: The relation of the intervals between cataract surgery and vitrectomy to various postoperative clinical parameters was studied. Clinical features at presentation included elevated intraocular pressure (IOP over 25 mmHg) in 52.4% of the eyes, uveitis in 69.6%, and corneal edema in 50.8%. Initial visual acuity was 20/400 or worse in 73.8% of the eyes. The mean preoperative visual acuity was 20/278 (median, 20/400), whereas the mean final visual acuity was 20/40 (median, 20/50) after a mean follow-up of 18.9 months. Retinal detachments were found in 20 eyes: 7 before vitrectomy and 13 during or after it. After surgery, 44% of eyes achieved a final visual acuity of 20/40 or better and 90% were 20/400 or better. The distribution of best-corrected final visual acuities among the eyes showed statistically significant differences based on the type of intraocular lens (IOL) used, with posterior chamber IOL greater than anterior chamber IOL, and anterior chamber IOL greater than aphakia. Reasons for a poor visual outcome included persistent corneal edema (four eyes), retinal detachment (two eyes), central retinal vein occlusion (two eyes), age-related macular degeneration (two eyes) glaucoma (one year), and endophthalmitis (one eye). CONCLUSIONS: There were no statistically significant differences between early (< 7 days) and delayed (8 days or more) vitrectomy when increased IOP, corneal edema, choroidal effusions, cystoid macular edema, and visual acuity were analyzed. The use of vitrectomy to remove posteriorly dislocated lens fragments has been shown to be an effective treatment method that significantly reduces the inflammatory response and hastens visual recovery.     

A novel mutant allele of Schizosaccharomyces pombe rad26 defective in monitoring S-phase progression to prevent premature mitosis

A semipermissive growth condition was defined for a Schizosaccharomyces pombe strain carrying a thermosensitive allele of DNA polymerase delta (pol delta ts03). Under this condition, DNA polymerase delta is semidisabled and causes a delay in S-phase progression. Using a genetic strategy, we have isolated a panel of mutants that enter premature mitosis when DNA replication is incomplete but which are not defective for arrest in G2/M following DNA damage. We characterized the aya14 mutant, which enters premature mitosis when S phase is arrested by genetic or chemical means. However, this mutant is sensitive to neither UV nor gamma irradiation. Two genomic clones, rad26+ and cds1+, were found to suppress the hydroxyurea sensitivity of the aya14 mutant. Genetic analysis indicates that aya14 is a novel allele of the cell cycle checkpoint gene rad26+, which we have named rad26.a14. cds1+ is a suppressor which suppresses the S-phase feedback control defect of rad26.a14 when S phase is inhibited by either hydroxyurea or cdc22, but it does not suppress the defect when S phase is arrested by a mutant DNA polymerase. Analyses of rad26.a14 in a variety of cdc mutant backgrounds indicate that strains containing rad26.a14 bypass S-phase arrest but not G1 or late S/G2 arrest. A model of how Rad26 monitors S-phase progression to maintain the dependency of cell cycle events and coordinates with other rad/hus checkpoint gene products in responding to radiation damage is proposed.     

Reduction in cerebral ischemic injury in the newborn rat by potentiation of endogenous adenosine

Because of ontogenic influences on the pathophysiologic mechanisms of brain injury in the perinatal brain, and in particular, the incomplete development of adenosine receptor systems, we investigated the potential for adenosine to provide cerebro-protection in a well established newborn rat model of hypoxia-ischemia. Fifteen litters of postnatal d 7 animals were subjected to unilateral carotid ligation and exposure to hypoxia (8% oxygen) for 3 h. Immediately after hypoxia-ischemia, animals received either the adenosine deaminase inhibitor deoxycoformycin (DCF; 2.5 mg/kg intraperitoneally) or the adenosine uptake inhibitor propentofylline (PPF; 10 mg/kg intraperitoneally); paired littermates received an equivalent volume of normal saline. On postnatal d 14, injury or protection was assessed by differences in hemispheric weights, morphometric determinations of infarct area, and histopathologic analyses. DCF resulted in a 34% (p = 0.02) and 31% (p = 0.03) reduction in hemispheric weight disparities and infarct area, respectively; for PPF, these reductions were 46% (p = 0.03) and 32% (p = 0.04), respectively. Light microscopic examinations of striatum, thalamus, hippocampus, and cortex revealed that both drugs significantly improved histologic scores as well. Measurements in six separate litters indicated that neither drug significantly reduced core body temperature for at least 6 h postadministration. These findings indicate that potentiation of endogenous adenosine levels in the perinatal brain can significantly ameliorate brain injury. Each of these treatment strategies was effective even when administered after the hypoxic-ischemic insult. Thus, further investigations of adenosinergic therapies are warranted in this and other perinatal models of cerebral ischemia to elucidate in detail their potential for clinical application.     

Reovirus growth in cell culture does not require the full complement of viral proteins: identification of a sigma1s-null mutant

The reovirus sigma1s protein is a 14-kDa nonstructural protein encoded by the S1 gene segment. The S1 gene has been linked to many properties of reovirus, including virulence and induction of apoptosis. Although the function of sigma1s is not known, the sigma1s open reading frame is conserved in all S1 gene sequences determined to date. In this study, we identified and characterized a variant of type 3 reovirus, T3C84-MA, which does not express sigma1s. To facilitate these experiments, we generated two monoclonal antibodies (MAbs) that bind different epitopes of the sigma1s protein. Using these MAbs in immunoblot and immunofluorescence assays, we found that L929 (L) cells infected with T3C84-MA do not contain sigma1s. To determine whether sigma1s is required for reovirus infection of cultured cells, we compared the growth of T3C84-MA and its parental strain, T3C84, in L cells and Madin-Darby canine kidney (MDCK) cells. After 48 h of growth, yields of T3C84-MA were equivalent to yields of T3C84 in L cells and were fivefold lower than yields of T3C84 in MDCK cells. After 7 days of growth following adsorption at a low multiplicity of infection, yields of T3C84-MA and T3C84 did not differ significantly in either L cells or MDCK cells. To determine whether sigma1s is required for apoptosis induced by reovirus infection, T3C84-MA and T3C84 were tested for their capacity to induce apoptosis, using an acridine orange staining assay. In these experiments, the percentages of apoptotic cells following infection with T3C84-MA and T3C84 were equivalent. These findings indicate that nonstructural protein sigma1s is not required for reovirus growth in cell culture and does not influence the capacity of reovirus to induce apoptosis. Therefore, reovirus replication does not require the full complement of virally encoded proteins.     

Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis

BACKGROUND: Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis. Changes in these parameters during disease progression merit further investigation. AIMS: To evaluate changes and the clinical relevance of superoxide radicals, endogenous antioxidants, and lipid peroxidation during the course of acute pancreatitis. PATIENTS AND METHODS: Superoxide radicals (measured as lucigenin amplified chemiluminescence), ascorbic acid, dehydroascorbic acid, alpha tocopherol, and lipid peroxidation (measured as thiobarbiturate reactive substances) were analysed in blood samples from 56 healthy subjects, 30 patients with mild acute pancreatitis, and 23 patients with severe acute pancreatitis. The association with grades of disease severity was analysed. Measurements were repeated one and two weeks after onset of pancreatitis. RESULTS: In the blood from patients with acute pancreatitis, there were increased levels of the superoxide radical as well as lipid peroxides. There was notable depletion of ascorbic acid and an increased fraction of dehydroascorbic acid. Changes in alpha tocopherol were not great except in one case with poor prognosis. Differences between severe and mild acute pancreatitis were significant (p < 0.01). Variable but significant correlations with disease severity scores were found for most of these markers. The normalisation of these indexes postdated clinical recovery one or two weeks after onset of disease. CONCLUSIONS: Heightened oxidative stress appears early in the course of acute pancreatitis and lasts longer than the clinical manifestations. The dependence of disease severity on the imbalance between oxidants and natural defences suggests that oxidative stress may have a pivotal role in the progression of pancreatitis and may provide a target for treatment.     

A comparison of the investment in hospital-based obstetrical ultrasound in Wales and Washington state

The purpose of this study was to examine differences in the way Britain and the United States invest in and deploy a new medical technology. We used structured interviews to obtain information on the technical sophistication and approximate replacement value of all hospital-based obstetrical ultrasound machines in every maternity hospital in Washington state and Wales. The supply of hospital-based ultrasound machines--approximately two machines per 1,000 births--was similar in both countries. Wales had fewer advanced ultrasound machines than Washington state, and they were based exclusively in high-volume district general hospitals; there were no obstetric ultrasound machines in the private sector. In Washington state, the majority of advanced machines were in small and medium-sized hospitals, and many private offices had ultrasound machines. The approximate replacement value of hospital-based machines was three times as high per birth in Washington state as in Wales. In the case of obstetrical ultrasound, centralization of facilities, a relatively small private sector, and global budgeting lead to lower expenditures per patient within the National Health Service without compromising access to care.     

Molecular genetics of familial hypercholesterolemia in Israel

Recreational SCUBA diving exposes individuals to environmental stresses not often encountered in other types of activity. These stresses include increased ambient pressure, raised partial pressure of O(2), increased resistance to movement, added weight and drag of diving equipment, cold stress, and a higher breathing resistance. One means to understand how such stresses affect a diver is to employ the stress-strain-adaptive response model. Physiologic adaptations, like an increase in VO(2) in response to cold stress, will minimize the strain placed on thermal balance. Nonphysiologic adaptive responses include those behavioral and equipment interventions that isolate the diver from a particular stress. Self-contained underwater breathing apparatus (SCUBA) isolates the diver from the inability to extract O(2) from the water; dive garments minimize the stress of cold water immersion. This review will focus on cardiorespiratory and thermal responses to SCUBA diving, using the stress-strain-adaptive response model to illustrate the interaction between diver and environment. Some responses like hyperventilation, cardiac arrhythmias, or cold injury due to vasoconstriction are not considered adaptive but are realistic possibilities in diving environments.