A re-investigation of questionable subclassifications of presynaptic alpha2-autoreceptors: rat vena cava, rat atria, human kidney and guinea-pig urethra

It has been suggested that at least the majority of mammalian presynaptic alpha2-autoreceptors belong to the genetic alpha2A/D-adrenoceptor subtype. The aim of the present study was to re-examine the alpha2-autoreceptors in tissues in which previous assignments conflicted with this alpha2A/D rule: in the rat vena cava and rat heart atria, where the autoreceptors were classified as alpha2B or similar to, but not identical with, alpha2D, and in the human kidney, where they were classified as alpha2C. Also re-examined were the autoreceptors in the guinea-pig urethra, where they were suggested to be alpha2A, in agreement with the rule, but in contrast to indications that the alpha2A/D-adrenoceptor of the guinea pig possesses alpha2D pharmacological properties. Tissue pieces were preincubated with 3H-noradrenaline and then superfused and stimulated electrically under autoinhibition-free or almost autoinhibition-free conditions. The Kd values of up to 14 antagonists (including the partial agonist oxymetazoline) against the release-inhibiting effect of the alpha2 agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) were determined. UK 14,304 reduced the evoked overflow of tritium with an EC50 between 6.3 and 13.2 nM. All antagonists (except prazosin in one case) shifted the concentration-inhibition curve of UK 14,304 to the right. Comparison of the Kd values thus obtained with Kd values at known alpha2 subtypes indicated that the autoreceptors in the rat vena cava, rat atria and the guinea-pig urethra were alpha2D and those in the human kidney alpha2A. For example, the pKd values of the antagonists in the rat vena cava, in rat atria and in the guinea-pig urethra were closely correlated with pKd values at the prototypic alpha2D radioligand binding sites in the bovine pineal gland (r = 0.96, P < 0.001; r = 0.92, P < 0.01; and r = 0.95; P < 0.001) and with the pKd values at the alpha2D-autoreceptors of guinea-pig atria (r = 0.99, P < 0.001; r = 0.95, P < 0.001; and r = 0.98, P < 0.001). The pKd values at the autoreceptors in rat vena cava, rat atria and guinea-pig urethra were not significantly or more loosely correlated with pKd values at alpha2A, alpha2B and alpha2C binding sites and alpha2A-autoreceptors. On the other hand, the pKd values of the antagonists in the human kidney were closely correlated with pKd values at the prototypic alpha2A radioligand binding sites in HT29 cells (r = 0.95; P < 0.001) and with pKd values at the alpha2A-autoreceptors of the pig brain cortex (r = 0.97; P < 0.001), but were not significantly or more loosely correlated with pKd values at alpha2B, alpha2C and alpha2D binding sites and alpha2D-autoreceptors. In contrast to previous suggestions, the autoreceptors in rat vena cava and atria are alpha2D, those in the human kidney alpha2A, and those in the guinea-pig urethra equally alpha2D. All, therefore, conform to the rule that alpha2-autoreceptors belong at least predominantly to the genetic alpha2A/D subtype of the alpha2-adrenoceptor. The apparent paradox of an alpha2A-autoreceptor in the urethra of the guinea pig, a species in which the genetic alpha2A/D-adrenoceptor otherwise has alpha2D pharmacological properties, is removed.     

Unindicated preoperative testing: ASA physical status and financial implications

Adenoid basal carcinoma of the uterine cervix is rare and its cell origin is still obscure. We report a case of adenoid basal carcinoma of the uterine cervix discovered incidentally in a 69-year-old woman who had been hysterectomized due to endometrial adenocarcinoma of the uterine corpus. Histologically, small round-to-oval cancer cell nests with peripheral cell palisading were seen budding from the basal cell layer of the uterine cervix showing carcinoma in situ. Immunohistochemically, the basaloid cells of the adenoid basal carcinoma were positive for keratins 14, 17 and 19 and resembled reserve cells of the cervical epithelium. The results of this study clearly demonstrated that adenoid basal carcinoma shows a phenotype similar to reserve cells of the uterine cervix. A review of the literature indicated that this tumor has a favorable prognosis and should be clearly separated from adenoid cystic carcinoma, which has a much poorer outcome.     

Overexpression of Rab3D enhances regulated amylase secretion from pancreatic acini of transgenic mice

Rab3D, a member of the ras-related GTP-binding protein Rab family, is localized to secretory granules of various exocrine tissues such as acinar cells of the pancreas, chief cells of the stomach, and parotid and lacrimal secretory cells. To elucidate the function of Rab3D in exocytosis, we have generated transgenic mice that over-express Rab3D specifically in pancreatic acinar cells. Hemagglutinin-tagged Rab3D was localized to zymogen granules by immunohistochemistry, and was shown to be present on zymogen granule membranes by Western blotting; both results are similar to previous studies of endogenous Rab3D. Secretion measurements in isolated acinar preparations showed that overexpression of Rab3D enhanced amylase release. Amylase secretion from intact acini of transgenic mice 5 min after 10 pM cholecystokinin octapeptide (CCK) stimulation was enhanced by 160% of control. In streptolysin-O-permeabilized acini of transgenic mice, amylase secretion induced by 100 microM GTP-gamma-S was enhanced by 150%, and 10 microM Ca2+-stimulated amylase secretion was augmented by 206% of that of the control. To further elucidate Rab3D involvement in stimulus-secretion coupling, we examined the effect of CCK on the rate of GTP binding to Rab3D. Stimulation of permeabilized acini with 10 pM CCK increased the incorporation of radiolabeled GTP into HA-tagged Rab3D. These results indicate that overexpression of Rab3D enhances secretagogue-stimulated amylase secretion through both calcium and GTP pathways. We conclude that Rab3D protein on zymogen granules plays a stimulatory role in regulated amylase secretion from pancreatic acini.     

Five-year survival rates of melanoma patients treated by diet therapy after the manner of Gerson: a retrospective review

OBJECTIVE: Compare 5-year melanoma survival rates to rates in medical literature. DESIGN: Retrospective. SETTING: Hospital in Tijuana, Mexico. PATIENTS: White adult patients (N = 153) with superficial spreading and nodular melanoma, aged 25-72 years. INTERVENTION: Gerson's diet therapy: lactovegetarian; low sodium, fat and (temporarily) protein; high potassium, fluid, and nutrients (hourly raw vegetable/fruit juices). Metabolism increased by thyroid; calorie supply limited to 2600-3200 calories per day. Coffee enemas as needed for pain and appetite. MAIN OUTCOME MEASURE: 5-year survival rates by stage at admission. RESULTS: Of 14 patients with stages I and II (localized) melanoma, 100% survived for 5 years, compared with 79% of 15,798 reported by Balch. Of 17 with stage IIIA (regionally metastasized) melanoma, 82% were alive at 5 years, in contrast to 39% of 103 from Fachklinik Hornheide. Of 33 with combined stages IIIA + IIIB (regionally metastasized) melanoma, 70% lived 5 years, compared with 41% of 134 from Fachklinik Hornheide. We propose a new stage division: IVA (distant lymph, skin, and subcutaneous tissue metastases), and IVB (visceral metastases). Of 18 with stage IVA melanoma, 39% were alive at 5 years, compared with only 6% of 194 from the Eastern Cooperative Oncology Group. Survival impact was not assessed for stage IVB. Male and female survival rates were identical for stages I-IIIB, but stage IVA women had a strong survival advantage. CONCLUSIONS: The 5-year survival rates reported here are considerably higher than those reported elsewhere. Stage IIIA/B males had exceptionally high survival rates compared with those reported by other centers.     

Comparing the effectiveness of different educational programs for patients with total knee arthroplasty

PURPOSE: To compare the effects of preadmission and postadmission educational programs for patients with total knee arthroplasty. DESIGN: Quasiexperimental study. SAMPLE: 60 total knee arthroplasty patients. METHODS: Subjects in the experimental group received preadmission preoperative teaching with an instruction booklet during a preoperative outpatient clinic visit. Upon admission to the hospital, they were presented with an educational video tape. The control group received only postadmission preoperative teaching with the same instruction booklet and no video. PREADMISSION AND POSTADMISSION: Preoperative anxiety level, knowledge about postoperative care, exercise performance and postoperative recovery were used as outcome measures. FINDINGS: The research results found: 1. there was no significant difference between the two groups in reduction of preoperative anxiety score: 2. the experimental group had a significantly higher knowledge level than the control group; 3. the experimental group performed exercise more regularly and correctly than those in the control group; 4. the experimental group had greater flexion of the operative knee joint than the control group. CONCLUSION: Preadmission teaching with a videotape program and a health manual for patients with total knee arthroplasty is recommended. IMPLICATIONS FOR NURSING RESEARCH: More indicators such as postoperative pain and patient satisfaction can be used to investigate the effectiveness of intervention. In addition, increasing the sample size is recommended for future studies.     

Reinforcement of weakened cusps by adhesive restorative materials: an in-vitro study

Pairs of extracted premolar teeth were prepared with MOD cavities reducing the lingual cusp at its base to one of five widths: 1.25-2.25 mm. One of each pair was then restored with one of five adhesive restorative techniques and the weakened cusp of both teeth fractured by a force applied to the cusp at an angle of 30 degrees to the long axis of the tooth. At all cusp widths a layered restorative technique in which the cavities were filled to the enamel-dentine junction with glass-ionomer cement and the enamel replaced by composite, reinforced the weakened cusp more than the other restorative materials tested. This combination of materials to reinforce weakened cusps is worth considering as a cost effective alternative to removing the cusp entirely and making a crown or protecting the cusp with a cuspal coverage gold inlay.     

Changes in carotenoid intake in the United States: the 1987 and 1992 National Health Interview Surveys

OBJECTIVES: To assess the changes in carotenoid intake between 1987 and 1992 among US adults by sociodemographic characteristics and high-risk groups for chronic disease; and to identify the dietary sources of specific carotenoid intake. DESIGN: A food frequency questionnaire (FFQ) was collected from a representative sample of respondents to the 1987 and 1992 National Health Interview Surveys throughout two calendar quarters. Black and white adults, 18 to 69 years old, participated in 1987 (n = 8,161) and 1992 (n = 8,341). METHOD: FFQ data were matched and linked to the US Department of Agriculture-National Cancer Institute carotenoid food composition database for analysis. STATISTICAL ANALYSIS: Mean differences in carotenoid intake over time were compared by sociodemographic characteristics and region of the country, after adjustment for sampling weights in a multiple linear regression model. RESULTS: Mean intake of the carotenoid lutein declined among white women (18%), among adults aged 40 to 69 years (16%), among persons with 9 to 12 years of education (11%), among nondrinkers (18%), among drinkers of 1 to 6 alcoholic drinks/ week (7%), among smokers (former smokers by 11%, current smokers by 7%, and never smokers by 9%), among income groups (< $20,000 by 7%, > or = $20,000 by 9%), and residents in the south and northeast (by 13% each, respectively). Mean intake of the carotenoid lycopene increased among white men (9%), among adults aged 18 to 39 years and aged 40 to 69 years (by 5% and 6%, respectively), among those with 13 years of education or more (12.5%), among alcohol drinkers (by 10% and 7% for 1 to 6 vs 7 or more drinks/week, respectively), among former and current smokers (by 6% each), among those with incomes > or = $20,000 (8%), and among residents in the west (16%) and midwest (5%). All differences described were statistically significant (P < .01). APPLICATION: The decline in lutein intake (from dark green leafy vegetables), particularly in white women, may have public health implications as a result of the recognized inverse association between carotenoid intake and disease risk.     

Synchronization of cell division in eight-cell bovine embryos produced in vitro: effects of 6-dimethylaminopurine

The effects of NS 1619, a newly developed activator of large-conductance Ca2+-activated K+ channels, were investigated on single smooth muscle fibers dissociated enzymatically from rat vas deferens and on contractions of the epididymal half of vas deferens. K+ currents were recorded using whole-cell patch-clamp methods in near-physiological K+ solutions (5.4 mM extracellular K+/145 mM intracellular K+). When cell membrane voltage was stepped to test potentials (-60 to +60 mV) from a holding potential of -10 mV, NS 1619 increased the outwardly rectifying K+ current in a concentration-dependent manner. The increased portion of the K+ current by NS 1619 was totally abolished by charybdotoxin (100 nM) but not by glibenclamide (3 microM). NS 1619 reduced electrically stimulated contractile responses of rat vas deferens in a concentration-dependent manner, and charybdotoxin but not glibenclamide partially inhibited the effect of NS 1619. NS 1619 (50 microM) inhibited the noradrenaline-induced contraction. Charybdotoxin (100 nM) partially reduced the NS 1619-induced inhibition while glibenclamide (3 microM) had no effect. NS 1619 (10-100 microM) reduced the high K+-induced contractions in a noncompetitive manner. The present results indicate that NS 1619 activates charybdotoxin-sensitive Ca2+-activated K+ channels and probably inhibits Ca2+ influx. These two effects might account largely for the observed mechanical inhibition induced by NS 1619 in the epididymal half of isolated rat vas deferens.