Molecular identification and localization of Trp homologues,putative calcium channels,in pregnant human uterus

The mechanisms underlying the switch from uterine quiescence to contractile activity in labour are not clearly understood. Increasing evidence suggests that pathways of myometrial calcium homeostasis, including store-operated calcium entry (SOCE), may play an important role. The molecular basis of the membrane-associated calcium channels contributing to SOCE in pregnant human myometrium is not known, but they are likely to be hetero- or homo-oligomeric assemblies of transient receptor potential channel (TrpC) proteins, encoded by the mammalian homologues of Drosophila Trp genes. This study has therefore determined Trp gene expression and also TrpC protein expression and localization in term pregnant human myometrial tissue and primary cultured human myometrial smooth muscle (HMSM) cells. RT-PCR amplified fragments of Trp1, Trp3, Trp4, Trp6 and Trp7. PCR products were 100% homologous to published human sequences. Western blot analysis detected TrpC1, TrpC3, TrpC4 and TrpC6 proteins, which were of expected size. Immunolocalization revealed TrpC1, TrpC3, TrpC4 and TrpC6 protein expression in myometrial tissue and HMSM cells. TrpC protein immunostaining in HMSM cells was distributed in a distinct reticular fashion. TrpC proteins may be candidate proteins forming SOCE channels in term pregnant human myometrium.     

Pulmonary artery trunk sarcoma: a clinicopathologic, ultrastructural, and immunohistochemical study of four cases

Pulmonary artery sarcomas are rare tumors that arise in the region of the bulbus cordis, the embryologic structure that gives rise to the pulmonary trunk. Nearly 100 cases have been reported in the literature, yet considerable debate exists regarding the histogenesis and biologic properties of these neoplasms. We report four additional cases in which ultrastructural and immunohistochemical studies demonstrated that these tumors contain cellular constituents with features of myofibroblastic, cartilaginous, and osteogenic differentiation. Polyphenotypic expression of several mesenchymal lineages suggests that the progenitor cell has pluripotential properties. Our findings and a review of the literature appear to confirm that pulmonary artery sarcomas are histopathologically heterogeneous, possibly reflecting the indeterminate character of the mesenchymal cell(s) of origin. The poor prognosis is attributable to the critical anatomic location of the neoplasm rather than its metastatic potential, which is low.     

Slow excitatory amino acid receptor-mediated synaptic transmission in turtle cerebellar Purkinje cells

1. The excitatory synaptic responses of turtle Purkinje cells to climbing and parallel fiber (CF and PF) stimulation have been studied by the use of intrasomatic and intradendritic recordings in intact cerebellum and brain stem-cerebellum preparations in vitro. 2. Activation of CF inputs from the cerebellar peduncle or the region of the inferior olive evoked complex spikes followed by slow excitatory postsynaptic potentials (EPSPs), both of which were evoked in an all-or-none fashion. 3. Single stimuli applied to the cerebellar molecular layer activated fast PF-mediated EPSPs; brief trains of PF stimuli (2-5 stimuli, 50-100 Hz) evoked volleys of fast EPSPs followed by a slow, long-lasting EPSP. The amplitude of the fast and slow PF-mediated EPSPs were both graded with stimulus intensity. 4. Slow EPSPs evoked both by CF and PF stimulation were associated with an increase in membrane conductance and were increased in amplitude by hyperpolarization. 5. The CF-evoked slow EPSP was profoundly attenuated by repetitive activation at interstimulus intervals of less than 15-20 s, whereas the PF-evoked slow EPSP was not reduced by repetitive activation. 6. The PF-evoked slow EPSP readily triggered dendritic pacemaker discharges when activated at or near resting membrane potential. The activation of this potential by phasic PF volleys may, therefore, provide an appropriate synaptic drive to cerebellar Purkinje cells to entrain the intrinsic pacemaker properties of these cells to cycles of motor activity. 7. Both slow synaptic potentials were blocked by the excitatory amino acid antagonists kynurenate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not by DL-2-amino-5-phosphonovalerate (DL-AP5) or L-serine-O-phosphate (L-SOP). The PF-evoked slow EPSP was selectively antagonized by L-2-amino-4-phosphonobutyrate (L-AP4; 20-100 microM). 8. It is suggested that the CF- and PF-evoked slow EPSPs observed in this study represent a novel class of excitatory amino acid receptor-mediated slow synaptic potentials activated by Purkinje cell afferents, which may play a role in synaptic integration and motor pattern generation in the cerebellum.     

Multifactorial audit of invasive cervical cancer: key lessons for the National Screening Programme.

AIMS--To audit factors associated with the development of invasive cervical cancer. METHODS--Twenty cases of invasive cervical cancer in one health district for 1991-93 were audited by multifactorial analysis. RESULTS--The average age was 53 years with 20% (4/20) aged over 65 years. Of the patients, 45% (9/20) were identified by a cervical smear, with 40% (8/20) from the National Screening Programme (NSP) and 5% (1/20) opportunistically; 30% (6/20) had not received a smear, 10% (2/20) being aged under 65 and 20% 65 or over. Those with no smear had all been hospital patients during the previous five years. No response to a smear invitation occurred in 5%. In 20%, there had been a true negative smear two to five years previously. Inappropriate laboratory diagnosis or inappropriate clinical management occurred in 30% and 15% (3/20), respectively. In 20%, two or more factors were present in the same patient. CONCLUSIONS--Why cervical cancer occurs after a true negative smear requires research and women aged over 65 with no smear must be targeted. Failsafe systems should incorporate inadequate smears and smear adequacy should be given priority in quality assurance (QA) and training. False negative reports must be minimised but accepted as an inherent part of the NSP and not an automatic indicator of poor laboratory performance. Comprehensive national QA standards are required, to which providers must conform. Postcoital bleeding is an absolute indication for a smear and, when appropriate, opportunistic smears offered at all hospital attendance. Cervical cancer audit must be guaranteed access to all clinical and laboratory information and be seen as a means to improve the effectiveness and quality of the NSP.     

Detection of penicillin tolerance in streptococci.

"Tolerance" to penicillin in streptococci was investigated by two different techniques. Of 70 strains examined, 35 appeared tolerant in conventional titrations and 31 appeared tolerant when tested by a recently-described disc method. There was 88% agreement between the two methods, but the disc test failed to detect tolerance shown by titrations in six strains of streptococci, including three beta-haemolytic strains belonging to Lancefield's group D. A significant relationship was observed between tolerance and Eagle's optimum dosage effect: 71% of tolerant strains examined displayed the Eagle effect, whereas only 17% of non-tolerant strains exhibited the effect.     

Diet Quality of Elite Australian Athletes Evaluated Using the Athlete Diet Index

While athletes’ nutrient intakes have been widely reported, few studies have assessed the diet quality of athletes. This is the first study to evaluate the diet quality of athletes using the purpose-built Athlete Diet Index (ADI). A convenience sample of 165 elite athletes from Australian sporting institutions completed the ADI online, with subsequent automated results provided to their respective accredited sports dietitians (ASDs). At the completion of athlete participation, ASDs (n = 12) responded to a range of survey items using a Likert scale (i.e., 1 = strongly agree to 5 = strongly disagree) to determine the suitability of the ADI in practice. Differences in ADI scores for demographics and sport-specific variables were investigated using independent t-tests, analysis of variance (ANOVA) and Bonferroni multiple comparisons. Spearman’s rank correlation was used to assess the association between total scores and demographics. The mean total ADI score was 91.4 ± 12.2 (range 53–117, out of a possible 125). While there was no difference in total scores based on demographics or sport-specific variables; team sport athletes scored higher than individual sport athletes (92.7 vs. 88.5, p < 0.05). Athletes training fewer hours (i.e., 0–11 h/week) scored higher on Dietary Habits sub-scores compared with athletes training more hours (≥12 h/week; p < 0.05), suggesting that athletes who train longer may be at risk of a compromised dietary pattern or less than optimal nutrition practices that support training. Most (75%) ASDs surveyed strongly agreed with the perceived utility of the ADI for screening athletes and identifying areas for nutrition support, confirming its suitability for use in practice.     

Radioisotopic pulmonary lobectomy: feasibility study in dogs

In search for an alternate treatment for inoperable cancer of the lung in humans, we investigated the possibility that introduction of radioactive material into a selected lobe of the canine lung would effectively destroy that lobe without systemic effects or radiation injury to adjacent organs. Ten million ion exchange microspheres labeled with 740 MBq of phosphorus-32 (32P) were injected through a catheter placed in a selected lobar branch of a pulmonary artery in 12 anesthetized dogs. Six additional dogs served as controls and received 10 million microspheres not labeled with 32P. Organs were harvested from 1 wk to 12 mo after injection and examined grossly and histologically. There was progressive organization and contraction of each necrosed 32P treated lobe which was reduced to a scarred remnant by 12 mo, whereas only minimal inflammatory changes occurred in controls. Of the 32P injected dose, 94% remained in injected lobe, 4%-5% in nontargeted lobes and less than 0.08% in blood. Radioactivity in liver, kidneys, spleen, heart, and bone marrow was less than 0.1% for each organ. Thus, large doses of radiation in the order of 1,500 Gy can be effectively delivered to a selected lobe to produce a "radioisotopic pulmonary lobectomy."