A histopathologic study of macular cysts and holes

Forty-four eyes from 39 patients with either lamellar macular holes (17 eyes), full-thickness macular holes (18 eyes), and/or macular cysts (9 eyes) were studied histopathologically. Lamellar and full-thickness holes were frequently found in eyes with a history of trauma or ocular surgery. Diabetes mellitus was the most common condition associated with macular cysts. Four lamellar holes and four full-thickness holes occurred in eyes with senile macular degeneration. Six lamellar holes, eight full-thickness holes, and one macular cyst developed on an idiopathic basis. Residual cystoid macular edema was the most prevalent accompanying pathologic feature. Cystoid macular edema was also noted in the opposite eye in seven cases of lamellar and full-thickness holes. A preretinal glial membrane, thought to be a secondary change, was found at or near the edges of the lamellar or full-thickness holes or over the macular cyst in the majority of cases. Wrinkling of the internal limiting membrane (ILM) was present in five cases. Vitreous traction, with or without an operculum, was infrequently associated with these entities.     

Cysteine and cystine transport at the blood-brain barrier

The nature of cysteine and cystine uptake from the cerebral capillary lumen was studied in the rat using the carotid injection technique, [35S]-Cysteine uptake was readily inhibited by the synthetic amino acid 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), the defining substrate for the leucine-preferring (L) system in the Ehrlich ascites cell. The addition of nonradioactive alanine or serine, representatives of the alanine, serine, and cysteine-preferring (ASC) system, produced no significant decrease in the uptake of cysteine after cysteine transport by the L system was blocked with BCH. This indicated that the major component of cysteine's transport from the brain capillary lumen was by the L system with no detectable uptake of cysteine by the ASC system. No carrier-mediated transport of cystine, the disulfide form of the amino acid, was detected, nor was there any inhibition by cystine of the transport of the neutral amino acid methionine or the basic amino acid arginine. These results suggest that the ASC system, if present, is not quantitatively important for the transport of neutral amino acids from the brain capillary lumen.     

The Employee Health Care Value Survey: round one

In a groundbreaking arrangement, a consortium of large employers--the Xerox, GTE, and Digital Equipment Corporations--launched the Employee Health Care Value Survey during fall 1993. Completed by 24,306 employees, this survey was used to develop comparable methods for assessing corporate health care benefit strategies. It also enabled fair comparisons of thirty-two health plans across the country on more than sixty criteria. Variation in performance among plans was substantial, with managed care plans--particularly prepaid group practices and individual practice associations (IPAs)--recording the most favorable rankings on disenrollment, overall satisfaction, and other measures of "bottom-line performance." Variation in enrollees' health among plans was more modest, with indemnity enrollees posing a somewhat greater illness burden to their plans than enrollees of other plan types. The employers and evaluated health plans are now using the results for multiple purposes, including quality improvement initiatives, employee-based plan performance reports, employee contribution strategies, and health promotion programs.     

Residues Val254, His256, and Phe259 of the angiotensin II AT1 receptor are not involved in ligand binding but participate in signal transduction

The role of the external third of helix VI of the angiotensin II (AII) AT1 receptor for the interaction with its ligand and for the subsequent signal transduction was investigated by individually replacing residues 252-256 by Ala, and residues 259 or 261 by Tyr, and permanently transfecting the resulting mutants to Chinese hamster ovary (CHO) cells. Binding experiments showed no great changes in affinity of any of the mutants for AII, [Sar1]-AII, or [Sar1, Leu8]-AII, but the affinity for the nonpeptide antagonist DuP753 was significantly decreased. The inositol phosphate response to AII was remarkably decreased in mutants V254A, H256A, and F259Y. These results indicate that AT1 residues Val254, His256, and Phe259 are not involved in ligand binding but participate in signal transduction. Based in these results and in others from the literature, it is suggested that, in addition to the His256 imidazole ring, the Phe259 aromatic ring interacts with the AII's Phe8, thus contributing to the signal-triggering mechanism.     

Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts

The effects of arginine vasopressin (AVP) and oxytocin (OT) upon thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) release were studied in euthyroid rats. Intracerebroventricular (i.c.v.) infusion of AVP in doses of 0.5 ng or 5 ng led to significant increases in plasma levels of TSH as well as FT4 and FT3. The effects of OT injected i.c.v. in similar doses were not consistent (there was no parallel between the changes of respective hormones plasma levels). It may be concluded that vasopressin modulate the pituitary-thyroid system function; AVP is probably a physiological stimulator of TSH and thyroid hormones secretion.     

Determinants of CPT-11 and SN-38 activities in human lung cancer cells

Irinotecan (CPT-11) is a semisynthetic camptothecin derivative with a broad spectrum of anti-tumour activity. Carboxylesterase (CE) catalyses the conversion of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin), the active form of CPT-11. The antiproliferative effects of CPT-11 and SN-38, CE-activity and topoisomerase I protein expression were investigated in five human small-cell lung cancer (SCLC) cell lines and four human non-small-cell lung cancer (NSCLC) cell lines. Antiproliferative activity, expressed as IC50 values, was determined using the MTT assay. CPT-11 was significantly more active in SCLC than in NSCLC cell lines (P = 0.0036), whereas no significant difference between histological types was observed with SN-38. A significant correlation (r2 = 0.52, P = 0.028) was observed between CE activity and chemosensitivity to CPT-11 but not to SN-38, and significantly higher CE activity was observed in SCLC compared with NSCLC cell lines (P = 0.025). Western blotting experiments showed topoisomerase I protein expressions within a factor of 2, and a granular nuclear staining was detectable in all cell lines by immunocytochemistry of cytospins. No correlation was observed between protein expression and sensitivity to CPT-11 or SN-38. Cellular and medium concentrations of CPT-11 and SN-38 were measured by high-performance liquid chromatography (HPLC) in one SCLC cell line with high CE activity and high sensitivity to CPT-11, and one NSCLC cell line with low sensitivity to CPT-11 and CE activity. Intracellular concentrations of CPT-11 and SN-38 were higher in the SCLC cell line, and this was associated with an increase in cellular uptake of CPT-11 compared with the medium, and an increased intracellular formation of SN-38. In conclusion, CE activity appears to be associated with higher sensitivity to CPT-11 in human lung cancer cell lines and may partly explain the difference in the in vitro sensitivity to CPT-11 between SCLC and NSCLC cells. The assessment of CE activity in clinical material of lung cancer patients undergoing treatment with CPT-11 may be warranted. However, other mechanisms may influence sensitivity to CPT-11, possibly including drug transport.     

An epidemic of roller-blade injuries in children

Roller blading is a new and increasingly popular leisure activity in many countries. We reviewed 110 consecutive patients with roller-blade injuries between 1 January and 30 June 1996. The patients ranged from 4 to 14 years in age (mean 6.5 years). Eighty-three (75.4%) sustained injuries to the upper limb and 27 (24.5%) injured the lower limb. Fifty-six patients, were girls and 54 were boys. Of the 110 patients, 79 (72.7%) sustained fractures, 28 (25.4%) soft tissue injuries and 3 (2.7%) dislocations. Eighty-three (75.4%) of the patients wore no protective equipment on the limbs. Four months following injury 103 (93.6%) patients were fully recovered. The mean duration of school absence was 3 days. Subsequently 101 children returned to using roller-blades following injury. Seventy-three (66.3%) of these now use protective equipment. We found that injuries were unrelated to age or duration of roller-blading experience or to the brand-name of roller blades used, and that most of our patients wore no protective equipment at the time of injury.