bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transitional Zone and Anterior Peripheral Zone of the Prostate
Authors: Mai Kien T. , Moazin Maher , Morash Christopher , Collins John P. 
Published: April 2003

<i>Introduction</i>: Prognostically significant prostatic adenocarcinomas (PAC) may pose diagnostic problems if they were localized in the anterior peripheral zone (APZ) or transitional zone (TZ). <i>Materials and Methods: </i>108 cases of PAC were reviewed along with serum PSA and TRUS biopsies. The PACs were divided into 22 TZ, 17 APZ and 69 posterior peripheral zone (PPZ) PACs according to the location of the main tumor mass in the TZ and anterior or posterior half of the peripheral zone in the radical prostatectomy (RP) specimens. <i>Results: </i>In comparison with PPZ PAC, TZ PAC had a higher cancer volume in RP specimens (4 ± 2.1 vs. 2.5 ± 1.7 cm<sup>3</sup>, p < 0.01), a higher serum PSA (16.5 ± 9.8 vs. 8.4 ± 4.5 µg/l, p < 0.001), a biopsy with a small cancer volume (3.8 ± 2.1 vs. 11.8 ± 9.4 mm, p < 0.005), and a lower Gleason’s score (4.8 ± 2.1 vs. 6.5 ± 1.7). APZ PAC was characterized by the cancer volume in RP and biopsy and PSA intermediate between those of TZ and PPZ PAC. Among 24 PACs with a total cancer core length of <3 mm, 19 cases were from the TZ and APZ groups and also had a higher cancer volume and PSA than those from the PPZ group (2.9 ± 1.8 vs. 1.5 ± 1.3 and 13.7 ± 8.3 vs. 9.6 ± 4 µg/l, respectively). Furthermore, there was a better correlation coefficient (r<sup>2</sup>) of tumor volume in the biopsy and RP for PPZ than for all zones PAC (r<sup>2</sup> = 0.75 vs. 0.29). TZ and APZ carcinomas were associated with extension or satellite nodules of PAC in the PPZ that may be diagnosed with biopsies. These PACs were associated with positive anterior resection margin due to extracapsular extension of the carcinoma or intracapsular dissection in 6 and 5 cases respectively. <i>Conclusions: </i>TZ and APZ PACs accounted for the poor correlation between the tumor volume in the biopsy and the RP, and were associated with positive anterior resection margins. One core biopsy with a total cancer core length of <3 mm and PSA >10 µg/l are suspicious for TZ and APZ PCA in patients with undetectable tumors with DRE or TRUS. Clinically insignificant PACs tend to be associated with cancer core <3 mm and PSA <10 µg/l.
Expansion of repetitive DNA into cytogenetically visible elements
Authors: Serakıncı N. , Pedersen B. , Koch J. 
Published: April 2003

Two cases of amplified repetitive elements accidentally identified in cancer samples are reported. In both cases, repeated DNA that is normally not visible by traditional chromosome banding had increased in amount to become cytogenetically visible. In one case, an addition to the short arm of chromosome 1 was originally diagnosed. However, upon molecular analysis the diagnosis could be corrected to an amplification of the D1Z2 repeat. In the second case, a strongly DAPI-positive band was visible at the top of the short arm of chromosome 22, and the original diagnosis was add(22). Staining for telomeric repeats revealed their presence inside the DAPI-positive element, thus confirming that the element in question was truly added to the end of the chromosome. Curiously, no telomeric repeats could be detected distal to the DAPI-positive element. The identity of the DAPI-positive element could not be established, as it was not stained by any of the specific probes applied, nor in a scanning hybridization with labeled Cot-1 DNA. It thus seems to represent an expansion from some lowly repetitive AT-rich DNA translocated to the tip of chromosome 22.
Progesterone Induces Dephosphorylation and Inactivation of Tyrosine Hydroxylase in Rat Hypothalamic Dopaminergic Neurons
Authors: Arbogast Lydia A. , Voogt James L. 
Published: April 2003

After in vivo treatment, progesterone initially decreases tyrosine hydroxylase (TH) activity in the TIDA neurons, but subsequently increases TH activity with prolonged treatment. In order to explore the cellular mechanism for progesterone’s effect, this study examined the acute inhibitory action of progesterone on TH activity in rat fetal hypothalamic dopaminergic neurons in vitro. Progesterone caused a rapid decrease in TH activity within 1 h, which was sustained for at least 6 h. However, the dopaminergic cells became refractory to progesterone with continuous treatment for 12 h to 10 days. Progesterone (10–100 n<i>M</i>) treatment suppressed TH activity in a concentration-dependent manner. The inhibitory effect of progesterone was dependent on prior exposure to estradiol. Whereas progesterone decreased TH activity, A ring-reduced metabolites of progesterone did not alter TH activity, suggesting that the response was specific to progesterone. Progesterone decreased radiolabeled phosphate incorporation into TH protein. Okadaic acid, a phosphoprotein phosphatase inhibitor, prevented the progesterone-induced suppression of TH activity and phosphate incorporation into TH, implicating dephosphorylation of TH as the cellular mechanism. In contrast, neither TH mRNA levels nor TH protein content was altered after 1 or 12 h of progesterone treatment. Progesterone decreased TH activity after pretreatment of the hypothalamic cells for 2 or 24 h with actinomycin D, an RNA synthesis inhibitor, suggesting that increased transcription does not mediate the effect. These data indicate that the acute progesterone-induced decline in TH activity is caused by dephosphorylation of TH.
Vaginocervical Stimulation Releases Oxytocin within the Spinal Cord in Rats
Authors: Sansone Giorgio R. , Gerdes Carolyn A. , Steinman Judith L. , Winslow James T. , Ottenweller John E. , Komisaruk Barry R. , Insel Thomas R. 
Published: April 2003

Vaginocervical stimulation (VS) significantly elevated the concentration of oxytocin (OT) in spinal cord superfusates of 8 intact urethane-anesthetized rats measured 10–15 min after VS (median [interquartile range]: 1.7 [1.00–3.37] pg/ml) compared to that measured 10–15 min before VS (1.1 [1.01–1.40] pg/ml). When VS was administered once (n = 8), it produced a 55% increase over baseline values; when administered a second time 45 min later (n = 6), it produced only a 22% increase over pre-VS values. The effects of estrogen on the VS-induced release of OT were then investigated using ovariectomized rats that were treated either with estradiol benzoate (EB; 10 µg/100 g bw) (n = 6) or with an oil vehicle (n = 6) subcutaneously for 3 days. The EB treatment significantly elevated the basal levels of OT released into spinal cord superfusates above vehicle control levels. Within 5–10 min after the onset of VS, OT concentrations in the superfusates were significantly higher in EB-treated than in vehicle-treated rats. The vehicle-treated rats did not show a significant elevation in OT concentration following VS. To rule out the possibility that the posterior pituitary gland was the source of this OT, the effect of hypophysectomy (HYPOX) was assessed on the VS-induced release of OT into spinal cord superfusates and plasma. The concentration of OT in spinal cord superfusates of both the HYPOX (n = 5) and intact rats (n = 6) increased significantly from 5.8 [4.4–6.5] pg/ml pre-VS to 7.9 [6.7–10.3] pg/ml immediately after VS, and from 4.4 [3.8–5] pg/ml pre-VS to 5.1 [4.6–5.7] pg/ml immediately after VS, respectively. There was no significant difference in baseline levels of OT in cerebrospinal fluid between the two groups. By contrast, plasma OT levels, while significantly elevated in response to VS from 3.42 [2.9–5.34] pg/ml baseline to 7.25 [5.33–15.77] pg/ml in the intact group, failed to respond significantly to VS in the HYPOX group (n = 5). The present findings provide evidence of a direct estrogen-dependent release of OT within the spinal cord in response to VS, presumably via descending oxytocinergic neurons.
High-Glucose Media Enhance the Responsiveness of Tubular Cells to Growth Promoters: Effect on Lysosomal Cathepsins and Protein Degradation
Authors: Schenk Oliver , Ling Hong , Šebeková Katarina , Vamvakas Spiros , Heidland August 
Published: April 2003

Nephromegaly is a prominent feature of diabetic nephropathy and predominantly reflects increased renal tubule mass, mostly due to hypertrophy. To elucidate pathogenetic factors involved, we studied the effects of high glucose (HG) alone, and in combination with hormones/growth promoters: angiotensin II (10<sup>–7</sup> <i>M</i>); parathyroid hormone (10<sup>–7</sup> <i>M</i>); insulin-like growth factor-1 (10<sup>–7</sup> <i>M</i>), or transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>, 10 ng/ml) in a renal cell line (LLC-PK1) with many characteristics of the proximal tubule. Activities of lysosomal cathepsins (B, L+B and H) and the protein turnover were investigated. Exposure to HG (25 m<i>M</i>) for up to 48 h increased cellular protein content, due to enhanced protein synthesis, while protein degradation rate and cathepsin activities tended to lower values. Hyperosmotic mechanisms of glucose action were excluded, since these effects were not induced by mannitol. In normoglycemic conditions only TGF-β<sub>1</sub> decreased cathepsin activities and protein degradation rate significantly. However, in HG media all applied hormones/growth factors significantly lowered the protein degradation rate, as well as lysosomal cathepsin activities. The enhanced responsiveness could contribute to the impaired protein turnover, with consequent hypertrophy of the tubulointerstitium in diabetic nephropathy.
Inhibition of Protein Synthesis by Acid in L6 Skeletal Muscle Cells: Analogies with the Acute Starvation Response
Authors: Bevington Alan , Poulter Chris , Brown Jeremy , Walls John 
Published: April 2003

Impaired protein synthesis (PS) occurs in skeletal muscle during acute starvation. Even though it is well established that uraemic metabolic acidosis (MA) stimulates protein degradation (PD) and is a major contributor to skeletal muscle wasting in chronic renal failure, the accompanying effects of MA on PS are much less clear. Previous work has shown that, in cultured L6 skeletal muscle cells, PD and leucine oxidation are stimulated by acid. The aim of the present study was to determine whether acid (like acute starvation) can also inhibit PS. PS (<sup>14</sup>C-phenylalanine incorporation) was measured in L6 cells in MEM + 2% serum at acid pH (7.1) or control pH (7.5). After 24 h, acid inhibited PS (7.7 ± 0.2 vs. 8.9 ± 0.1 nmol Phe/4 h/35-mm culture well in controls, p = 0.01) and this was maintained at 72 h. In vitro this could arise because acid only inhibits the rapid PS occurring in dividing cells. However, when division was abolished with 10<sup>–5</sup> mol/l cytosine arabinoside, PS inhibition by acid still occurred (6.9 ± 0.1 vs. 8.3 ± 0.2 at control pH, p < 0.05). Acid also had no effect on the specific radioactivity of cellular phenylalanine, suggesting that the impaired PS was not a consequence of inadequate labelling of this pool. Elevated PD and impaired PS together led to loss of 7% of the total protein in only 28 h (–21 ± 3 µg/well, p = 0.004). This combination of impaired PS with increased PD and increased leucine oxidation in response to acid resembles the response of skeletal muscle to acute starvation. These superficial similarities between the starvation state and MA suggest that fundamental metabolic signals may occur which are common to both states.
Normal Vitamin D Receptor Concentration and Responsiveness to 1,25-Dihydroxyvitamin D<sub>3</sub> in Skin Fibroblasts from Patients with Absorptive Hypercalciuria
Authors: Zerwekh Joseph E. , Reed Bernice Y. , Heller Howard J. , González Gilberto B. , Haussler Mark R. , Pak Charles Y.C. 
Published: April 2003

To evaluate whether there is an increase in vitamin D receptor (VDR) concentration which could raise intestinal calcium absorption in absorptive hypercalciuric (AH) patients and promote hypercalciuria, we measured VDR concentration and VDR mRNA levels in skin fibroblasts from 16 patients with AH and 17 age-matched normal subjects before and following a 16-hour incubation in the presence of 10<sup>–8</sup> <i>M</i> 1,25-dihydroxyvitamin D<sub>3</sub> [1,25(OH)<sub>2</sub>D<sub>3</sub>]. There were no significant differences in VDR concentration between normal subjects and AH patients in the basal state (30 ± 11 vs. 30 ± 15 ng/mg protein, respectively) or following 1,25(OH)<sub>2</sub>D<sub>3</sub>-mediated upregulation (43 ± 18 vs. 42 ± 16 ng/mg protein) as measured by immunoblot methodology. Analysis of VDR mRNA/β-actin mRNA ratios demonstrated no significant differences between normal subjects and AH patients prior to (2.1 ± 1.7 vs. 1.8 ± 2.4) or following (2.7 ± 2.8 vs. 1.9 ± 1.8) 1,25(OH)<sub>2</sub>D<sub>3</sub> exposure. As a measure of VDR bioactivity, we quantitated 1,25(OH)<sub>2</sub>D<sub>3</sub>-mediated induction of 25-hydroxyvitamin D<sub>3</sub>-24-hydroxylase. Again, no significant differences were observed between normal subjects and all patients (2.1 ± 1.6 vs. 1.9 ± 1.6 pmol/mg/30 min, respectively). These findings indicate that there is neither an increase in VDR concentration in skin fibroblasts, a recognized vitamin D responsive cell, nor increased sensitivity to upregulation of VDR numbers by 1,25(OH)<sub>2</sub>D<sub>3</sub> in patients with AH. This suggests an alternative cause of intestinal hyperabsorption of calcium in AH other than alteration of the VDR number.
Quantitative Analysis of the Retinal Ganglion Cell Layer in the Ostrich, <i>Struthio camelus</i>
Authors: Boire Denis , Dufour Jean-Sébastien , Théoret Hugo , Ptito Maurice 
Published: April 2003

The total number, distribution and peak density of ganglion cells were evaluated in the Nissl-stained retina of the ostrich <i>(Struthio camelus)</i>. The mean (n = 4) total number of retinal ganglion cells (RGC) was estimated at 2,274,128 (s.d. = 273, 152). The ostrich retina exhibited a prominent horizontal visual streak along which a central area located nasal to the pecten had a peak density of 9,500 cells/mm<sup>2</sup>. A high concentration of cells with a peak density of 2,646 cells/mm<sup>2</sup> was also observed in the temporal retina, slightly dorsal to the visual streak. The results further showed that the ostrich eye has a 15-mm pupil entrance diameter, its mean axial length is 39.81 mm, the estimated retinal magnification factor is 0.4075 mm/deg and the maximum visual acuity along the well-defined visual streak was estimated to be 19.32 cycles/deg. The latter component of the retina might subserve vision along the horizon while the temporal region mediates binocular processing. The data also showed that the degree of retinal illumination in this bird could be comparable to that noted in some nocturnal species. The findings in this study suggest that the ostrich might not be restricted to diurnal activity.
Serum Cystatin C Reliably Detects Renal Dysfunction in Patients with Various Renal Diseases
Authors: Kazama Junichiro James , Kutsuwada Keiko , Ataka Ken , Maruyama Hiroki , Gejyo Fumitake 
Published: April 2003

A clinical investigation was conducted to clarify the reliability and efficacy of serum cystatin C measurement for estimation of the glomerular filtration rate (GFR). Two hundred twelve patients with various renal diseases enrolled in the study. All patients were evaluated for 24-hour creatinine clearance (24 h C<sub>Cr</sub>) and the standard sodium thiosulfate clearance test (C<sub>Thio</sub>) within a week of blood sample collection. Serum cystatin C concentration was determined by a particle-enhanced immunonephelometry method. C<sub>Thio</sub> and 1/cystatin C, 24 h C<sub>Cr</sub>, 1/β<sub>2</sub>-microglobulin and 1/creatinine were well correlated. The correlation coefficients for C<sub>Thio</sub> obtained by 24 h C<sub>Cr</sub> and 1/cystatin C were comparable to each other (0.701 vs. 0.679). Receiver-operated characteristic (ROC) analysis revealed that 24 h C<sub>Cr</sub> showed the highest area under the curve when C<sub>Thio</sub> = 60 ml/min or C<sub>Thio</sub> = 100 ml/min were applied as the discrimination point. However, the ROC value obtained by cystatin C was slightly greater than 24 h C<sub>Cr</sub> when C<sub>Thio</sub> = 80 ml/min was used as the discrimination point. Patient age, gender, glucose tolerance, presence of proteinuria, systemic inflammation, lupus, or systemic use of steroids did not interfere in the relationship between C<sub>Thio</sub> and 1/cystatin C. In conclusion, serum cystatin C measurement is an excellent diagnostic test for detecting patients with subclinical renal dysfunction.
Comparative Pharmacokinetic and Pharmacodynamic Profile of Piperacillin/Tazobactam 3.375G Q4H and 4.5G Q6H
Authors: Mattoes Holly M. , Capitano Blair , Kim Myo-Kyoung , Xuan Dawei , Quintiliani Richard , Nightingale Charles H. , Nicolau David P. 
Published: April 2003

When piperacillin/tazobactam has been used to treat hospitalized patients with serious infections, including nosocomial pneumonia caused by <i>Pseudomonas aeruginosa</i>, it has usually been dosed at 3.375 g q4h to provide serum concentrations above commonly encountered organisms’ MICs (T > MIC) for at least 40–50% of the dosing interval. Pharmacodynamic principles suggest that a similar efficacy can be realized with extended dosing intervals when a larger dose (e.g. 4.5 g q6h) is administered, which was the objective of this study. Twelve healthy volunteers, 29.4 ± 8.9 years of age, were enrolled in this multiple-dose, open-labeled, randomized, two-period crossover study. Blood samples were collected after the third dose and concentrations of piperacillin/tazobactam were determined with a validated HPLC method. Pharmacokinetic profiles were determined by noncompartment analysis. T > MIC of piperacillin was calculated for a range of MIC values. Piperacillin/tazobactam was well tolerated in 11 subjects who completed both regimens. The C<sub>max</sub>, T<sub>1/2</sub>, K, and AUC of P were significantly different according to a paired t test (p < 0.05) between two study regimens. Significant differences (p < 0.05) in tazobactam regimens were noted for C<sub>max</sub>, and AUC. The piperacillin/tazobactam regimen of 4.5 g q6h achieved a 44% T > MIC for MIC values of ≤16 µg/ml, while the 3.375-gram q4h regimen achieved 42% T > MIC, for MIC values of ≤32 µg/ml. Dosage regimens for treating serious infections can be extended safely and effectively to 4.5 g q6h and obtain at least 40–50% T > MIC in the coverage of pathogens implicated with serious infections, including <i>P. aeruginosa</i>.
Bactericidal Activities of Commonly Used Antiseptics against Multidrug-Resistant <i>Mycobacterium tuberculosis</i>
Authors: Rikimaru T. , Kondo M. , Kajimura K. , Hashimoto K. , Oyamada K. , Sagawa K. , Tanoue S. , Oizumi K. 
Published: April 2003

Seventeen clinical isolates of <i>Mycobacterium tuberculosis</i> were selected in order to study the bactericidal activities against drug-resistant <i>M. tuberculosis</i>. The effects of different antiseptics against multidrug-resistant <i>M. tuberculosis</i> (MDR-TB) were examined. Each of the test strains was cultured on the surface of an agar slant containing Löwenstein-Jensen medium. 0.05 ml of the bacillary suspension was poured into a test tube, and 0.45 ml of various antiseptics was added. After the bacilli had been exposed to the antiseptic solution with 2% human serum for various periods of incubation time, the antiseptic was inactivated by addition of 0.45 ml neutralizer, a mixture containing 10% Tween 80, 3% soybean lecithin and 0.5% sodium thiosulfate. As the results, povidone-iodine (PVP-I) at a concentration of 0.2% killed 99.9% or more of all strains tested within 30 s. All of the strains tested with PVP-I were killed almost completely within 60 s. There was no difference in bactericidal activities of PVP-I between standard strain H37Rv and MDR-TB. 99.9% or more of all strains tested were killed after exposure to 1.0% cresol for 60 s. In the case of cresol however, the exposure time of 30 s was not enough to get satisfactory effects. 2.0% glutaraldehyde needed 5 min to kill 99.99% or more of the bacilli tested, and 0.2% alkyldiaminoethylglycine hydrochloride required 60 min to do so. The results of bactericidal activities of common antiseptics against MDR-TB were similar to those against H37Rv. We conclude that the commercially available PVP-I product is a useful antiseptic against MDR-TB similar to other <i>M. tuberculosis</i>.
Longitudinal Assessment of Pituitary-Thyroid Axis and Adrenal Function in Preterm Infants Raised by ‘Kangaroo Mother Care’
Authors: Weller Aron , Rozin Aviram , Goldstein Abraham , Charpak Nathalie , Ruiz-Pelaez Juan G. , Figueroa de Calume Zita , Charpak Yves , Sack Joseph 
Published: April 2003

<i>Objective:</i> To assess whether complete kangaroo mother care (KMC), a skin-to-skin contact intervention, would affect longitudinal/developmental patterns of hormonal change. <i>Method:</i> An open randomized controlled trial was conducted in a large tertiary care hospital, comparing KMC and traditional care for newborn infants weighing less than 2,001 g. Eighty-seven healthy preterm (<37 weeks gestational age) infants from this study provided three blood-spot samples on filter paper: at randomization (postnatal age 1–5 days), 2 weeks later, and at calculated term (41 weeks gestational age). They met a number of additional inclusion criteria including discharge from the hospital within the first postnatal week. The levels of 17α-hydroxy-progesterone (17-OHP), thyroxine-stimulating hormone (TSH) and thyroxine (T<sub>4</sub>) were assessed by radioimmunoassay. Birth weight (<1,800 or ≧1,800 g) and prenatal maternal corticosteroid treatment were taken into account in the analysis. <i>Interventions:</i> Complete KMC includes early discharge, positioning the infant on the parent’s chest in an upright position, 24 h/day in skin-to-skin contact, and breast-feeding. In the traditional care group, infants were discharged according to routine hospital practice. <i>Results:</i> Levels of 17-OHP and TSH decreased significantly from eligibility to calculated term while T<sub>4</sub> levels did not change significantly over time. Most importantly, overall, treatment (KMC) did not interact with the pattern of physiological change. <i>Conclusions:</i> Maturation of the pituitary-thyroid axis and adrenal function is apparently not compromised by KMC, at least in healthy preterm infants.
Different Kinetics in Anti-Cytomegalovirus Immunity Reconstitution Evaluated by Lymphocyte Proliferation and IFN-γ Production in Allogeneic and Autologous Bone Marrow Transplantation
Authors: Mendes A.V.A. , Benard G. , Pereira C.B. , Kallas E.G. , Duarte A.J.S. , Pannuti C.S. , Dulley F.L. , Machado C.M. 
Published: April 2003

Allogeneic bone marrow transplantation (ALLOBMT) is associated with an increased risk of cytomegalovirus (CMV) morbidity compared to autologous BMT (AUTOBMT). To investigate this, we evaluated AUTOBMT and ALLOBMT patients regarding anti-CMV immune reconstitution at 1 and 4 months after BMT and on the day after first CMV antigenemia detection. Intermittent ganciclovir preemptive therapy was prompted by antigenemia of ≧2 cells. One month after transplant, AUTOBMT recipients already displayed larger CD8+ T cell numbers than ALLOBMT recipients, but comparably small CD4+ T cell numbers. Most AUTOBMT patients had positive CMV antigen (CMV-Ag)-induced lymphoproliferation (86%) and IFN-γ secretion (86%), whereas this was infrequently seen in ALLOBMT patients (20 and 10%, respectively). This early AUTOBMT immune reconstitution was associated with a lower frequency of CMV reactivation up to +4 months in AUTOBMT (21%) than ALLOBMT patients (91%). At +4 months, most ALLOBMT recipients had also recovered CMV-Ag immune responses. At first antigenemia detection, all 3 AUTOBMT recipients already displayed anti-CMV immune functions and 2 cleared the infection without therapy, whereas of the 10 ALLOBMT recipients only 1 had positive lymphoproliferation. In the latter group, none had IFN-γ secretion or cleared the infection without therapy. Thus, differences in anti-CMV immune reconstitution may help to explain the contrasting rates of CMV morbidity between ALLOBMT and AUTOBMT patients.