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Contrary to the position taken by Lewis (1989), several articles have demonstrated an association between season of birth and the risk of schizophrenia after controlling for the age-incidence effect. The method used by Pulver et al. (1983) was misinterpreted by Lewis. Clarification of this method is provided along with additional references related to the season-of-birth issue.
Fermentative capabilities of 140 strains of Actinobacillus actinomycetem-comitans were studied. Findings correspond closely with those reported previously by Heinrich and Pulverer (12 strains), and by King and Tatum (33 strains). All strains ferment glucose, levulose, and maltose and reduce nitrate to nitrite. Reactions with glycogen and starch are exceedingly diverse. Eight different biotypes have been identified on the basis of their reactions with galactose, mannitol, and xylose.
HYPOTHESIS: Because of its complicated clinicopathologic features, hepatolithiasis is difficult to treat, and there is no established method of treating patients with intrahepatic stones. DESIGN: Retrospective case-control study. SETTING: Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan (January 1, 1971-December 31, 2000). PATIENTS: Eighty-nine patients treated for hepatolithiasis (43 male; median age, 56.9 years). MAIN OUTCOME MEASURES: The rate of residual stones and complications after the treatments of hepatolithiasis. RESULTS: Between 1971 and 1985, 17 patients (41%) had stones located in the left or right intrahepatic duct, and 25 patients (60%) had stones located in the bilateral intrahepatic duct. From 1986 through 2000, 32 patients (68%) had stones located in the left or right intrahepatic duct, and 15 patients (32%) had stones located in the bilateral intrahepatic duct (P =.009). The rate of residual stones after surgical and nonsurgical treatment was 41% (17 of 42 patients) in 1971 through 1985, but decreased to 11% (5 of 47 patients) in 1986 through 2000 (P =.001). The rate of residual stones after cholangioenterostomy or T-tube insertion was 43.8% (21 of 48 patients), but the rate of residual stones after hepatectomy or percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) was 2.4% (1 of 41 patients, P<.001). In cases treated by PTCSL, we used a holmium (Ho):YAG laser in 3 cases since 1999. To our knowledge, there have been no reports describing the use of Ho:YAG lasers to treat hepatolithiasis. Also, board-shaped stones can be sufficiently pulverized without inducing hemorrhage from the bile duct wall. CONCLUSIONS: According to the current therapeutic strategy for hepatolithiasis, hepatectomy seems to be the most effective treatment for selected patients with isolated left hepatolithiasis if other surgical procedures cannot remove all the related lesions. In addition, PTCSL seems to be performed first in isolated right hepatolithiasis and bilateral lobe type hepatolithiasis. In PTCSL procedures, favorable results have been obtained using the Ho:YAG laser for fracturing intrahepatic stones.
Pulver et al. [1994a] reported modest linkage evidence for a dominantly (D) inherited "schizophrenia gene" in the vicinity of IL2RB on chromosome 22q12, and Coon et al. [1994] adduced moderate evidence under a recessive (R) model. We report here a replication study to test the hypothesis that one of these two models (or a third, intermediate (I) model) adequately describes the co-segregation of schizophrenia and chromosome 22q12 markers in an independent sample of 23 multiplex families. Altogether nine transmission models were evaluated. The models differed depending on whether the 15 family members with a diagnosis of schizophrenia spectrum disorders were considered unaffected (a "narrow" (N) definition), affected (a "wide" (W) definition), or declared "unknown" (U). The entire region between D22S268 and D22S307 is excluded (i.e., lod <-2) for models RN, RW, RU, and IW. Lod scores for the remaining models are uniformly negative; albeit, equivocal with respect to the dominant hypothesis over a small region between D22S268 and IL2RB. Nonparametric analysis under both diagnostic criteria also failed to yield any evidence for a susceptibility locus in this region of chromosome 22.
BACKGROUND: Apoptosis is a morphologically distinctive form of programmed cell death/cell suicide in which genomic DNA degradation/fragmentation and variegated dense chromatin aggregates are characteristic hallmarks that have never been demonstrated in mitotic cells. Perceptions of mutual exclusivity between apoptosis and mitosis imply that M-phase cells cannot be apoptotic. However, in the present study we show apoptotic morphologies in M-phase cells after an acute oxidative stress and endonuclease digestion. METHODS: Degradation of genomic DNA in human Chang liver cells (American Type Culture Collection, ATCC CCL13) was demonstrated by flow cytometric cell-by-cell evaluation of (a) propidium iodide intercalative binding to DNA and (b) terminal deoxynucleotidyl transferase (TdT)-mediated 3'OH nick end labeling (TUNEL) of fragmented DNA. Oxidative stress was imposed by a 30-min prepulse with 200 microM vanadyl(4), which produces hydroxyl free radicals (OH*), the most reactive of the free radical species. Oxidative stress in the cells was demonstrated by evaluating glutathione-S-transferase (GST)-mediated monochlorobimane-glutathione adduct fluorescence for glutathione content, the main reducing agent of a cell, and methylene blue redox metachromasia, which is a deep color when oxidized and colorless when reduced. Cells with DNA fragmentation were highlighted by TUNEL. Apoptotic morphologies were visualized by staining with Giemsa and neutral red dyes and by DNA-propidium iodide binding to chromatin. Direct endonuclease induction of apoptotic morphologies in permeabilized M-phase cells was produced by 1 hr incubation (37 degrees C) with 16 units/ml of micrococcal nuclease. RESULTS: The genomic DNA of proliferative cells, namely in G2/M phase of the cell cycle, was degraded by vanadyl(4) prepulsing and by micrococcal nuclease digestion, concomitantly with DNA fragmentation shown by TUNEL. Cytological profiles showed GSH depletion and M-phase cells with particularly high oxidative reactivity indicated by methylene blue redox metachromasia. DNA fragmentation in M-phase cells was highlighted by TUNEL. Characteristic apoptotic condensations, ranging from single-ball condensations to "pulverized" aggregates of a mitotic catastrophe, buddings, and "apoptotic bodies," were found in prophase, metaphase, anaphase, and telophase mitotic cells. The observed separation of condensed chromatin aggregates from the main chromosome mass in prophase and metaphase cells could explain micronuclei, linking it with apoptosis. Direct endonuclease digestion readily produced apoptotic morphologies in interphase and in M-phase cells. CONCLUSION: Apoptotic morphologies in M-phase cells can be induced indirectly via oxidative stress or directly via endonuclease activity, which has long been established as a pervading hallmark of apoptosis.
Most of the protocols for the recovery of ancient DNA from palaeontological specimens are time-consuming and tend to yield inconsistent polymerase chain reaction (PCR) results. "Voltage-induced release" is a novel and rapid approach for the extraction of ancient DNA. Nucleic acids are directly electrophoresed out of powder derived from hard and soft tissues. This technique is much faster than other methods in which pulverized tissue conventionally undergoes time-consuming crude lysis steps. The total preparation time is 5-6 h. The reliability of the voltage-induced release method was validated by (i) measuring the ratio of D-to L-enantiomers of the amino acids aspartic acid, alanine, and leucine, and (ii) by specific PCR amplification of four single-copy markers of human chromosome 17 and 18. We compare voltage-induced release to a frequently used silica-based protocol. DNA extracted employing voltage-induced release was more effective in PCR amplifications, which may be attributed to the effective removal of PCR inhibitors.
BACKGROUND: The recurrence or mortality rate of axillary lymph node-negative invasive breast cancer has been associated with the tumor S-phase fraction, which is measured by DNA flow cytometry. Because many of the studies that established this association were performed using frozen, pulverized tumor specimens, this association could not be tested for independence from the established prognostic factors of histologic and nuclear grading. METHODS: Histologic, nuclear, and mitotic grades, DNA ploidy, and S-phase fraction (SPF) were determined from paraffin-embedded tumors obtained from 280 women with node-negative invasive ductal carcinomas using standard grading schemes and flow cytometric techniques. These variables were compared with disease-free and cancer-specific survival (CSS) in univariate and multivariate analyses of these patients. RESULTS: Tumor diameter, SPF, histologic grade, and nuclear grade were significant predictors of disease-free survival (DFS); diameter and SPF had significant associations with CSS. Cox analysis showed histologic grade to be the only independent predictor of relapse, whereas diameter and SPF were independent predictors of mortality. The patients with low nuclear or histologic grade tumors had only a 5% risk of recurrence at 5 years. In contrast, 36% of patients in this series with medium-grade or high-grade high SPF tumors had a 30% risk of recurrence over the same interval. CONCLUSIONS: Histopathologic grading and flow cytometric determination of SPF appear to provide additive prognostic information for patients with early invasive ductal carcinomas of the breast.
Solid and gaseous emissions from a power plant fired with South African coal and maintained at full load (320 MWe) were characterized for their composition in polynuclear aromatic hydrocarbons (PAH) and n-alkanes (n-A). 25 n-A (from C12 to C36) and 34 PAH (from naphthalene to coronene) were determined by gas chromatography/mass spectrometry. Samples were collected in different points of the plant: the bottom hopper of the boiler, the electrostatic precipitator (ESP) hopper and the ductwork system before and after the ESP. The pulverized coal was also analysed by the same procedure in order to find any correlation with the composition of emissions. PAH concentration profiles of the coal and the combustion products, which will be useful for evaluation of environmental impact, were obtained.
A capillary gas chromatographic/mass spectrometric method for the determination of tebufelone, a new anti-inflammatory drug, in plasma and rat paw tissue is described. Trideuteriated tubufelone was employed as an internal standard and the drug quantified by selected ion monitoring using a mass-selective detector following positive electron ionization (70 eV). Tebufelone was recovered from plasma (greater than 93%) and pulverized paw tissue (greater than 88%) by ethereal extraction. Standard curves were linear between 5 ng ml-1 and 5 micrograms ml-1 with a detection limit (S/N = 2) of 2 ng ml-1. The coefficient of variation for successive injections of standards (200 ng ml-1) or samples (10-1500 ng ml-1) was 7.3% and 8.5%, respectively.
Our objectives were to determine procedural success, clinical complications, and follow-up restenosis rates after rotational burr and transluminal extraction atherectomy of coronary artery and saphenous vein graft ostial stenoses. Balloon angioplasty of ostial lesions has been associated with low rates of success and high rates of clinical complications and restenosis compared to nonostial lesions. Atherectomy, due to its ability to excise (extraction atherectomy) or pulverize (rotational atherectomy) atheroma and the internal elastic lamina, may result in improved procedural outcome. We retrospectively studied 101 patients with ostial stenoses treated by rotational burr and transluminal extraction atherectomy over a 3-yr period. Quantitative angiography and clinical follow-up were reviewed to determine success, complication, and restenosis rates. Rotational burr (n = 29) and transluminal extraction (n = 72) atherectomy were associated with high procedural success (93% and 90%, respectively) and a low incidence of complications (6.9% and 4.2%, respectively). Post-atherectomy angiographic success was low (52% and 69%, respectively) and required adjunctive balloon angioplasty in 85% of patients overall. This lower success rate likely reflects device undersizing as the overall post-atherectomy artery to device ratio was near unity (0.95). The rates of angiographic ostial restenosis remain high (39.1% and 65.9%, respectively, P < 0.05). The high rate of restenosis after transluminal extraction atherectomy was due to the higher rate of restenosis in saphenous vein grafts (80%) compared to TEC treated coronary arteries (59%). When only coronary artery lesions were compared, there was no significant difference between atherectomy device groups with respect to restenosis rates or late loss.(ABSTRACT TRUNCATED AT 250 WORDS)
It is known that nucleosides may have antimutagenic and anticlastogenic effects. Here, we have investigated the influence of nucleosides on the induction of shattered chromosomes (fragmentation and/or pulverization of chromosomes of a mitotic cell) and of micronuclei by ultraviolet (UV) light and caffeine. Asynchronous cell cultures of a V79 subline of the Chinese hamster were irradiated at wavelength 254 nm using fluences up to 5.2 joules/m2. Following irradiation, the cells were postincubated either with 1.0 mM or 2.0 mM caffeine alone or with caffeine plus the four deoxyribonucleosides (dXs) (concentration 0.1 mM each). After different incubation times (three to 24 hours), chromosome preparations were performed. In other experiments, synchronized cells were used. The percentage of metaphase spreads with shattered chromosomes and the percentage of cells with micronuclei were determined. Post-treatment with caffeine alone resulted in shattered chromosomes in a high percentage of cells at the first post-irradiation mitosis as described previously. Formation of cells with micronuclei was observed only afer the appearance of mitotic cells with shattered chromosomes, the maximum percentage of cells with micronuclei being smaller than the maximum percentage of cells with shattered chromosomes. The strong potentiating effect of UV-light plus caffeine was significantly reduced, however, if the post-treatment was performed with caffeine plus nucleosides. A significant reduction was also observed in the percentage of micronuclei. An evaluation of the mitotic indices and of cell-cycle parameters indicates that the effect of nucleosides was not due to enhanced interphase death.
Family studies with age at onset of the disease as the endpoint face two important problems: censoring and correlation of age at onset among relatives. We present a multivariate survival model for ages at onset of relatives which incorporates the problems cited above. The interpretations of regression coefficients and association parameter in the context of family studies are emphasized. The present paper describes a statistical method for estimating these parameters. In a companion paper [Pulver and Liang, Genet Epidemiol 8:339-350, 1991] this model is applied to a genetic epidemiologic study of schizophrenia.
We developed new composites consisting of comparatively high molecular weight poly(methyl methacrylate) (hPMMA) and delta-alumina powder or alpha-alumina powder (designated delta-APC and alpha-APC, respectively) that allowed direct bone formation on their surfaces in vivo. delta-Alumina powder was manufactured by the fusing and quenching of pulverized alumina powder. It was composed mainly of delta-crystal phases of alumina. The purpose of this study was to evaluate the static mechanical properties and biological properties of these composites. The hPMMA itself was used as a reference material. The bending strength and Young's modulus of both delta-APC and alpha-APC were significantly higher than those of hPMMA, and the alumina composites are believed to be strong enough for use under weight-bearing conditions. The three types of composites were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index. Rats were sacrificed 4 and 8 weeks after surgery. The affinity index, equal to the length of bone in direct contact with the composite surface and expressed as a percentage of the total length of the composite surface, was calculated for each composite at each interval. Histologically, new bone had formed along the surfaces of both delta-APC and alpha-APC within 4 weeks. The affinity indices for both delta-APC and alpha-APC increased significantly with time up to 8 weeks. At 8 weeks, the affinity index for delta-APC was significantly higher than the indices for alpha-APC and hPMMA. This study revealed that the excellent osteoconductivity of delta-APC was due to the delta-crystal phases of alumina and the high molecular weight of hPMMA. delta-APC shows promise as a base for developing a highly osteoconductive and mechanically strong biomaterial.
One of the most important concerns with the clinical use of plasma-sprayed hydroxyapatite (HA) coatings is the resorption of the coating, and dissolution at neutral pH is one of the two major resorption mechanisms. In this study, highly crystalline pure HA powders were atmospherically plasma sprayed using various parameters. Dissolution of both HA powders and coatings was measured using a calcium ion meter. Surface characteristics, including phase, morphology, and roughness, were compared for the coatings before and after dissolution. Pulverized HA coatings exhibited significantly higher dissolution compared with the same quantity of feedstock HA powders because of the decreased crystallinity and fine crystal size of the coating. Furthermore, the dissolution decreased with the crystallinity of the coating. Dissolution of HA coatings did not show much difference with respect to the coatings in the initial stage of immersion (4 h). However, dissolution of all coatings reached saturation in a fresh physiological solution. The saturation values were much lower compared with their counterparts in the form of powders, which may imply the stability of HA coatings in long-term use. In addition to crystallinity, the particle melting status in the coatings, i.e., the volume of nanocrystals, and porosity, was found to be another important factor for the dissolution of the HA coating. X-ray diffraction patterns of HA coatings indicated the complete dissolution of impurity phases and amorphous phase after the coatings were immersed in the solution for 4 days. Coatings sprayed at lower power (27.5 kW) exhibited a pattern of crystalline HA whereas coatings sprayed at higher power (42 kW) exhibited a pattern of bone apatite. Surface morphologies showed preferential dissolution of amorphous phase in all coatings accompanied with precipitation of bone apatite observable for coatings sprayed at higher power. Surface roughness measured after the dissolution studies increased for the two coatings sprayed at lower power level but decreased for coatings sprayed at higher power level. This decrease is attributed to the better match in solubility characteristics between the fine crystals and the amorphous calcium phosphate within the coating.
Poly[methacrylic acid-grafted-poly(ethylene glycol)] [P(MAA-g-EG)] is a complexation hydrogel molecularly designed for oral peptide delivery. In this work, the cytotoxicity and insulin-transport enhancing effect of P(MAA-g-EG) microparticles on intestinal epithelial cells were evaluated using Caco-2 cell monolayers. A series of P(MAA-g-EG) microparticles with different polymer compositions were prepared by a photo-initiated free radical solution polymerization and subsequent pulverization. The hydrogel microparticles were preswollen in either Ca2+-containing (CM+) or Ca2+-free medium (CM-; pH 7.4) and applied to the apical side of the Caco-2 monolayers. No significant cytotoxic effects, as determined by a calorimetric assay with P(MAA-g-EG) microparticles preswollen in the CM+, were observed at doses ranging from 3 to 31 mg/cm2 of cell monolayer. Transepithelial electrical resistance (TEER) measurements showed that the P(MAA-g-EG) microparticles induced a Ca2+ concentration-dependent lowering in TEER values. The reduction effect in CM- media was greater than that in CM+ media (17 +/- 2% reduction in CM+ and 45 +/- 3% reduction in CM-, respectively). Insulin transport in the presence of the preswollen P(MAA-g-EG) microparticles was also strongly depended on the Ca2+ concentration in the medium. The respective estimated permeability for insulin alone and the insulin with hydrogels in CM+ were 0.77 and 1.16 x 10(-8) cm/s, whereas those in CM- were 1.18 and 24.78 x 10(-8) cm/s. The results demonstrate that the P(MAA-g-EG) hydrogel microparticles could be used as a cytocompatible carrier possessing the transport-enhancing effect of insulin on the intestinal epithelial cells.
Two strains, Penicillium corylophilum and Aspergillus giganteus, of the most frequent species found in a survey of triatomines, were used for bioassays in the second and fourth nymphs stage of Triatoma infestans and Panstrongylus megistus. Two procedures, bite and pulverization, were used and compared. A. giganteus was most effective, causing mortality in at least 50% of the nymphs of the two species tested with exception of the nymphs of the fourth stage of P. megistus. Variation in entomopathogenic capacity of the fungal species were observed in the experiments. The two procedures used proved effective.
The respective alcoholic terpenes carvacrol, linalool, and alpha-terpineol were used at 5% w/v in propylene glycol (PG) to increase the in vitro permeation of haloperidol (HP) through human skin. The possible enhancement mechanism was then elucidated with HP-stratum corneum (SC) binding studies, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The greatest increase in the permeation of HP was achieved with linalool followed by carvacrol and terpineol. HP permeation with linalool was predicted to reach a therapeutic plasma concentration and therapeutic daily-permeated amounts. Carvacrol increased lag time, which was attributed to slow redistribution of the enhancer within SC. Carvacrol increased the partition of the drug to the pulverized SC. Pure PG extracted lipids from SC but less than that achieved by the terpenes in PG. Terpenes extracted lipids to a similar extent. An increase in bilayer cohesion in the remaining lipids present in the SC could be attributed to the alignment of terpenes within the lipid bilayer. The higher permeation with linalool was attributed to its molecular orientation within the lipid bilayer. Terpenes showed different rates of SC dehydration but did not change the percentages of secondary structures of keratin.
In this study the single-crystal X-ray structure of the solvated species (nifedipine)2. 1,4-dioxane is reported for the first time. Included solvent molecules are located in isolated cavities in the crystal, yielding a very stable solvate. Desolvation of this species involves complete disruption of the crystal structure at the relatively high temperature of 150-153 degrees C, i.e., 50 degrees above the boiling point of 1,4-dioxane, and yields a monoclinic polymorph (Modification I) with a melting point of 174 degrees C. When exposed to an aqueous medium for 48 h, the solvate transformed into a dihydrate. The aqueous solubilities of the above species were in the order: 1,4-dioxane solvate >or= Modification I > dihydrate. The solubility of nifedipine was increased sixfold when transformed into an amorphous form by quenched fusion. This amorphous form was relatively stable at room temperature but converted to Modification I when suspended in water at pH 1. The fused materials also converted to Modification I through an intermediate, Modification III, within 6 days when kept at 40 degrees C for 6 days. XRPD analysis showed that grinding increased the crystallinity of the amorphous form due to partial transformation to Modification I. The pulverized amorphous powder was more stable at 40 degrees C and was approximately three times as soluble as Modification I.