A nuclear mutant of Chlamydomonas that exhibits increased sensitivity to UV irradiation,reduced recombination of nuclear genes,and altered transmission of chloroplast genes

Summary Meiotic progeny of Chlamydomonas reinhardtii normally receive chloroplast genomes only from the mt ⁺ parent. However, exceptional zygotes, which transmit the chloroplast genomes of both parents or, more rarely, only those of the mt ^- parent, arise at a low frequency. Mutations at the mt ⁺-linked mat-3 locus were found previously to elevate the transmission of chloroplast genomes from the mt-parent, resulting in a much higher than normal frequency of exceptional zygotes. In this paper we demonstrate that an ultraviolet-sensitive nuclear mutation mapping at the uvsE1 locus, which is unlinked to mating type, also promotes chloroplast genome transmission from the mt ^- parent. This mutant, which was previously shown to reduce recombination of nuclear genes in meiosis, acts synergistically which the mat3-3 mutation to produce an extremely high frequency of exceptional zygotes. Through the use of restriction fragment length polymorphisms existing in the chloroplast genomes of C. reinhardtii and the interfertile strain C. smithii, we show that chloroplast DNA fragments from the mt ^- parent normally begin to disappear shortly after zygote formation. However, this process appears to be blocked totally in the absence of wild-type uvsE1 and mat-3 gene products. Our findings are consistent with the hypothesis that both gene products contribute to the mechanism responsible for uniparental inheritance of the chloroplast genome from the mt ⁺ parent.     

Ictal Single-Photon Emission Computed Tomography Imaging in Extra Temporal Lobe Epilepsy Using Statistical Parametric Mapping

PURPOSE: To examine the application of statistical parametric mapping (SPM) to analyze ictal single-photon emission computed tomography (SPECT) scans in surgical candidates with extratemporal lobe epilepsy. METHODS: The authors selected patients who underwent successful ictal SPECT acquisition in the process of surgical treatment of intractable partial epilepsy. Thirteen patients were identified who met inclusion criteria for confident seizure localization from either intracranial electroencephalogram recordings or epilepsy surgery outcome. In these cases, ictal scans were registered to an in-house-developed normal SPECT atlas composed of 14 spatially normalized brains of normal subjects. SPM96 was used to test on a voxel-by-voxel basis for statistically significant increases in blood flow associated with each patient's ictal scan. The results were then mapped back onto the patient's magnetic resonance image (MRI) for final interpretation. Statistical parametric mapping (SPM) analysis of ictal SPECT scans was compared to both conventional visual interpretation and the analysis of subtraction ictal SPECT co-registered to MRI (SISCOM). RESULTS: Ten of 13 patient scans showed localizing focal ictal increases in regional cerebral blood flow, all of which were concordant with ultimate epilepsy localization. Of the 3 cases not localized with SPM, 1 was localized by conventional visual interpretation and another, not localized by visual interpretation, was correctly localized with SISCOM. Two cases not localized by SISCOM were localized by both visual and SPM analysis. CONCLUSIONS: This work provides supportive evidence for proof of principle that SPM can be used to provide objective, accurate analysis of ictal SPECT scans in patients with extratemporal lobe epilepsy.     

Transplantation using hearts from primary pulmonary hypertensive donors for recipients with a high pulmonary vascular resistance

BACKGROUND: Transplantation for patients with a high pulmonary vascular resistance (PVR) carries an increased risk of mortality and right heart failure following heart transplantation and continues to be a major problem. We evaluated the use of hearts from patients who underwent heart and lung transplantation for primary pulmonary hypertension (PPH) as part of a domino procedure because these hearts have hypertrophied right ventricles used to increased pulmonary pressures, but could have a compromised left ventricle or irreversible damage of the right ventricle. METHODS: We reviewed 12 patients with PVR >4 Wood units who underwent orthotopic heart transplantation between 1989 and 1998 using hearts from donors with PPH as part of a domino procedure. RESULTS: We studied 10 men and 2 women, mean age 42.9 years. Mean PVR was 5.3 (range, 4-9) Wood units. Mean ischemia time was 85.3 minutes, and mean donor age was 32 years. Actuarial survival was 75% at 1 year and 75% at 5 years. In the early post-operative period, 3 patients had temporary arrhythmias, 2 required permanent pacemaker implantation, 1 had atrial fibrillation, and 1 had ventricular tachycardia that required defibrillator implantation. At a mean follow-up of 7.8 years, 2 patients had developed asymptomatic transplant coronary disease (both at 8.5 years after transplantation), 1 moderate and 1 very mild; the rest had none. Mean left ventricular ejection fraction at latest follow-up was 70.1% (range, 63%-78%). Right ventricular function assessed clinically and by echocardiography was adequate in the short and long term. CONCLUSIONS: Our results suggest that heart and lung recipients with PPH can provide useful donor hearts to patients with increased PVR and that these hearts function well in the intermediate and long term.     

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05–10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (−) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 μg) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methylpara-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, on an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.     

The relationship between subtalar and knee joint function as a possible mechanism for running injuries

The purposes of the study were: (1) to evaluate the effects of different surfaces on the relationship between subtalar and knee joint function, and (2) to examine/explore alternative approaches to the evaluation of these relationships. Five subjects ran under four different surface conditions of various hardness, while both rear and sagittal view kinematic data were collected (200 Hz). Critical parameters describing the knee angle and rearfoot motion were examined in conjunction with a curve analysis technique which incorporated slope differences and curve correlations. A repeated measure ANOVA design (surface × subject) was used along with single subject procedures. The results of the study support a strong inter-relationship between pronation and knee joint function via tibial rotation and underlined it as a possible mechanism for injury. Moreover, discrete point analysis might not be the most appropriate methodology for evaluating dynamic functions such as rearfoot motion and knee angle. Extreme methodological care must be exercised when evaluating these functions to avoid oversmoothing and/or masking correlations and differences due to differential subject responses and individual variability. The fact that increased impact force facilitated timing discrepancies between subtalar and knee joint function resulting in a transition of the pronation curve from a unimodal to bimodal configuration, is hypothesized as a possible explanation to better understand the inter-relationships among these lower extremity functions and their relationship to running injuries.     

Kynurenine aminotransferase activity in human liver: identity with human hepatic C-S lyase activity and a physiological role for this enzyme

The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate.     

Anaesthetists, the discourse on patient fitness and the organisation of surgery

The organization of daily procedures within the operating theatre is considered in terms of rival perspectives on their patient held by surgeon and anaesthetist. The privileging of the surgeon's authority is challenged in anaesthetists' efforts to fabricate a distinctive position on the patient. While surgeons focus on patient as the carrier of disease, for the anaesthetist, the focus is upon the patient's complement of fitness. A postmodern analysis of the organization of surgery reflects the continual struggle between the two specialisms to privilege its particular definition of the surgical patient. In some circumstances, the struggle can have damaging consequences for patient care.