Calcium-sensitive calcium influx in photoreceptor inner segments

The effect of external calcium concentration ([Ca2+]o) on membrane potential-dependent calcium signals in isolated tiger salamander rod and cone photoreceptor inner segments was investigated with patch-clamp and calcium imaging techniques. Mild depolarizations led to increases in intracellular Ca2+ levels ([Ca2+]i) that were smaller when [Ca2+]o was elevated to 10 mM than when it was 3 mM, even though maximum Ca2+ conductance increased 30% with the increase in [Ca2+]o. When external calcium was lowered to 1 mM [Ca2+]o, maximum Ca2+ conductance was reduced, as expected, but the mild depolarization-induced increase in [Ca2+]i was larger than in 3 mM [Ca2+]o. In contrast, when photoreceptors were strongly depolarized, the increase in [Ca2+]i was less when [Ca2+]o was reduced. An explanation for these observations comes from an assessment of Ca2+ channel gating in voltage-clamped photoreceptors under changing conditions of [Ca2+]o. Although Ca2+ conductance increased with increasing [Ca2+]o, surface charge effects dictated large shifts in the voltage dependence of Ca2+ channel gating. Relative to the control condition (3 mM [Ca2+]o), 10 mM [Ca2+]o shifted Ca2+ channel activation 8 mV positive, reducing channel open probability over a broad range of potentials. Reducing [Ca2+]o to 1 mM reduced Ca2+ conductance but shifted Ca2+ channel activation negative by 6 mV. Thus the intracellular calcium signals reflect a balance between competing changes in gating and permeation of Ca2+ channels mediated by [Ca2+]o. In mildly depolarized cells, the [Ca2+]o-induced changes in Ca2+ channel activation proved stronger than the [Ca2+]o-induced changes in conductance. In response to the larger depolarizations caused by 80 mM [K+]o, the opposite is true, with conductance changes dominating the effects on channel activation.     

Synthesis of (R,S)-10-methyloctadecanoic acid (tuberculostearic acid) and key chiral 2-methyl branched intermediates

Tuberculostearic acid, (R)-10-methyloctadecanoic acid, is a characteristic component of pathogenic mycobacteria and related organisms. Sensitive detection of this acid in infected material allows rapid detection of mycobacterial disease. A novel, convergent synthesis of tuberculostearic acid and key chiral intermediates is described in this communication, to provide a reference compound. Racemic and (R)- and (S)-1-iodo-2-methyldecanes were synthesised from 1-octanal and 1-carboethoxyethylidenetriphenylphosphorane as initial starting materials. 1-Hydroxyoct-7-yne was made from 1,6-hexanediol by two alternative methods and coupled with the above racemic iodide. Hydrogenation and oxidation of the resulting (R,S)-10-methyloctadec-7-yn-1-ol gave racemic tuberculostearic acid.     

On system design

The general, multiple attribute system design problem is formulated in total quality space which includes all of the microeconomic factors that influence the net value of a product to society. A hypothetical system design task—the development of improved system specifications and new subsystem requirements for the redesign of an automobile—is used to illustrate the approach. A new format is also given for describing design of experiment arrays which facilitates their use in spreadsheet calculations.     

Putative liver progenitor cells: conditions for long-term survival in culture

BACKGROUND AND OBJECTIVES: We operated on three patients with leiomyosarcoma of the inferior vena cava. METHODS: Complete excision was possible in all three patients. RESULTS: One patient developed widespread metastasis at 23 months, one patient is alive with no evidence of disease at 70 months, and one patient is alive at 15 months. The third patient had subcutaneous and pulmonary metastases at the time of presentation, which are radiologically nondetectable at present following postoperative chemotherapy. CONCLUSIONS: The clinicopathologic features, prognostic factors, and treatment of 130 cases found in a comprehensive literature search and our three cases are reported.     

The changing face of emphysematous cholecystitis

Emphysematous cholecystitis is a variant of acute cholecystitis characterized by the presence of gas in the gall bladder lumen, wall or pericholecystic tissues in the absence of an abnormal communication between the biliary system and the gastrointestinal tract. In the past, the diagnosis has relied on the plain abdominal radiograph (AXR), since there are no clinical features to separate this condition from simple acute cholecystitis. The apparently high mortality and morbidity associated with emphysematous cholecystitis has previously emphasized the importance of emergency cholecystectomy. We have reviewed eight cases of emphysematous cholecystitis presenting to this hospital over the last 5 years. The diagnosis was made on AXR in only one of these cases. Ultrasound (US) scans were performed in all eight cases, of which five were positive and three negative, due to non-visualization of the gall bladder. In the three negative cases, the diagnosis was made on subsequent CT scans. On initial clinical examination, only one of the eight patients appeared systemically unwell and conservative management was employed in five of the patients. The remaining three patients underwent cholecystectomy within 3-5 days because of continuing signs or symptoms. It is concluded that the AXR is relatively insensitive in the diagnosis of emphysematous cholecystitis. As a result of the regular use of US in suspected hepatobiliary disease, emphysematous cholecystitis is being diagnosed with increased frequency, uncovering a broad spectrum of disease ranging from mild to severe. Previously, failure to separate milder cases from simple acute cholecystitis may have been responsible for reports of unremitting severity and progression requiring emergency cholecystectomy. Based on clinical assessment, conservative surgical management is possible in a significant proportion of patients.     

Ultrastructural characteristics of Babesia odocoilei in vitro

Babesia odocoilei continuously cultured in white-tailed deer (Odocoileus virginianus) erythrocytes was examined by transmission and scanning electron microscopy. Merozoites, trophozoites, intermediate-stage forms, and dividing forms were observed. Merozoites possessed a single nucleus, inner membrane complex, rhoptries, free ribosomes, rough endoplasmic reticulum, and single membrane-bound vesicles. Trophozoites lacked an inner membrane complex and rhoptries. Intermediate stages were characterized by distinct segments of inner membrane complex. Dividing forms ranged from cells with an elongated nucleus to mature daughter cells joined by a ringlike structure. Babesia odocoilei was characterized by its close proximity to the erythrocyte membrane, membranous structures resembling feeding organelles, and reproduction via a method resembling budding sensu stricto.     

Benign breast changes and the risk for subsequent breast cancer: an update of the 1985 consensus statement. Cancer Committee of the College of American Pathologists

The Cancer Committee of the College of American Pathologists has prepared an update of the consensus statement on premalignant breast lesions and breast cancer risk that was originally published in the Archives of Pathology & Laboratory Medicine in 1986. The objective of this publication is to better define the relative breast cancer risk associated with specific histologic abnormalities by incorporating data derived from recent case-control studies. Explanatory notes are used to document and explain specific risk classifications. In addition to refining the degree of risk associated with individual lesions, such as fibroadenoma and atypical hyperplasia, this update includes a discussion of age-specific breast cancer risk and provides examples that can be used when counseling patients.