bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the human NBC3 Na+/HCO3− cotransporter by carbonic anhydrase II and PKA
Authors: Loiselle Frederick B. , Morgan Patricio E. , Alvarez Bernardo V. , Casey Joseph R.
Published: May 2004

Human NBC3 is an electroneutral Na+/HCO3− cotransporter expressed in heart, skeletal muscle, and kidney in which it plays an important role in HCO3− metabolism. Cytosolic enzyme carbonic anhydrase II (CAII) catalyzes the reaction CO2 + H2O ⇆ HCO3− + H+ in many tissues. We investigated whether NBC3, like some Cl−/HCO3− exchange proteins, could bind CAII and whether PKA could regulate NBC3 activity through modulation of CAII binding. CAII bound the COOH-terminal domain of NBC3 (NBC3Ct) with Kd = 101 nM; the interaction was stronger at acid pH. Cotransfection of HEK-293 cells with NBC3 and CAII recruited CAII to the plasma membrane. Mutagenesis of consensus CAII binding sites revealed that the D1135-D1136 region of NBC3 is essential for CAII/NBC3 interaction and for optimal function, because the NBC3 D1135N/D1136N retained only 29 ± 22% of wild-type activity. Coexpression of the functionally dominant-negative CAII mutant V143Y with NBC3 or addition of 100 μM 8-bromoadenosine to NBC3 transfected cells reduced intracellular pH (pHi) recovery rate by 31 ± 3, or 38 ± 7%, respectively, relative to untreated NBC3 transfected cells. The effects were additive, together decreasing the pHi recovery rate by 69 ± 12%, suggesting that PKA reduces transport activity by a mechanism independently of CAII. Measurements of PKA-dependent phosphorylation by mass spectroscopy and labeling with [γ-32P]ATP showed that NBC3Ct was not a PKA substrate. These results demonstrate that NBC3 and CAII interact to maximize the HCO3− transport rate. Although PKA decreased NBC3 transport activity, it did so independently of the NBC3/CAII interaction and did not involve phosphorylation of NBC3Ct.
Selective activation of STAT3 in human monocytes stimulated by G-CSF: implication in inhibition of LPS-induced TNF-α production
Authors: Nishiki Saori , Hato Fumihiko , Kamata Noriko , Sakamoto Erina , Hasegawa Taro , Kimura-Eto Akiko , Hino Masayuki , Kitagawa Seiichi
Published: May 2004

Lipopolysaccharide (LPS) induced tumor necrosis factor (TNF)-α production in human monocytes, which was dependent on activation of extracellular signal-regulated kinase (ERK), p38, c-Jun NH2-terminal kinase (JNK), and nuclear factor (NF)-κB. LPS-induced TNF-α production was inhibited by granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-10. G-CSF, like IL-10, exerted the inhibitory effect even when simultaneously added with LPS. Among the signaling pathways, signal transducer and activator of transcription 3 (STAT3) was selectively activated in monocytes stimulated by G-CSF or IL-10. G-CSF-mediated inhibition of LPS-induced TNF-α production as well as G-CSF-induced STAT3 phosphorylation and suppressor of cytokine signaling 3 mRNA expression were prevented by pretreatment of monocytes with AG-490, an inhibitor of Janus kinase 2. G-CSF did not affect LPS-induced activation of ERK, p38, JNK, and NF-κB, indicating that G-CSF affects the pathway downstream or independently of these signaling molecules. G-CSF-induced, but not IL-10-induced, STAT3 phosphorylation was attenuated in the presence of LPS. These findings suggest that G-CSF, like IL-10, inhibits LPS-induced TNF-α production in human monocytes through selective activation of STAT3, and the immunomodulation observed in vivo by G-CSF administration may be partly ascribed to the direct effect of G-CSF on monocyte functions.
Channel-forming peptide modulates transepithelial electrical conductance and solute permeability
Authors: Broughman James R. , Brandt Robert M. , Hastings Christy , Iwamoto Takeo , Tomich John M. , Schultz Bruce D.
Published: May 2004

NC-1059, a synthetic channel-forming peptide, transiently increases transepithelial electrical conductance ( gTE) and ion transport (as indicated by short-circuit current) across Madin-Darby canine kidney (MDCK) cell monolayers in a time- and concentration-dependent manner when apically exposed. gTE increases from <2 to >40 mS/cm2 over the low to middle micromolar range. Dextran polymer (9.5 but not 77 kDa) permeates the monolayer following apical NC-1059 exposure, suggesting that modulation of the paracellular pathway accounts for changes in gTE. However, concomitant alterations in junctional protein localization (zonula occludens-1, occludin) and cellular morphology are not observed. Effects of NC-1059 on MDCK gTE occur in nominally Cl−- and Na+-free apical media, indicating that permeation by these ions is not required for effects on gTE, although two-electrode voltage-clamp assays with Xenopus oocytes suggest that both Cl− and Na+ permeate NC-1059 channels with a modest Cl− permselectivity ( PCl: PNa = 1.3). MDCK monolayers can be exposed to multiple NC-1059 treatments over days to weeks without diminution of response, alteration in the time course, or loss of responsiveness to physiological and pharmacological secretagogues. Together, these results suggest that NC-1059 represents a valuable tool to investigate tight junction regulation and may be a lead compound for therapeutic interventions.
Tropomyosin interacts with phosphorylated HSP27 in agonist-induced contraction of smooth muscle
Authors: Somara Sita , Bitar Khalil N.
Published: May 2004

Displacement of the contractile protein tropomyosin from actin filament exposes the myosin-binding sites on actin, resulting in actin-myosin interaction and muscle contraction. The objective of the present study was to better understand the interaction of tropomyosin with heat shock protein (HSP)27 in contraction of smooth muscle cells of the colon. We investigated the possibility of a direct protein-protein interaction of tropomyosin with HSP27 and the role of phosphorylated HSP27 in this interaction. Immunoprecipitation studies on rabbit smooth muscle cells indicate that upon acetylcholine-induced contraction tropomyosin shows increased association with HSP27 phosphorylated at Ser82 and Ser78. Transfection of smooth muscle cells with HSP27 phosphorylation mutants indicated that the association of tropomyosin with HSP27 could be affected by HSP27 phosphorylation. In vitro binding studies with glutathione S-transferase (GST)-tagged HSP27 mutant proteins show that tropomyosin has greater direct interaction to phosphomimic HSP27 mutant compared with wild-type and nonphosphomimic HSP27. Our data suggest that, in response to a contractile agonist, HSP27 undergoes a rapid phosphorylation that may strengthen its interaction with tropomyosin.
The tight junction: a multifunctional complex
Authors: Schneeberger Eveline E. , Lynch Robert D.
Published: May 2004

Multicellular organisms are separated from the external environment by a layer of epithelial cells whose integrity is maintained by intercellular junctional complexes composed of tight junctions, adherens junctions, and desmosomes, whereas gap junctions provide for intercellular communication. The aim of this review is to present an updated overview of recent developments in the area of tight junction biology. In a relatively short time, our knowledge of the tight junction has evolved from a relatively simple view of it being a permeability barrier in the paracellular space and a fence in the plane of the plasma membrane to one of it acting as a multicomponent, multifunctional complex that is involved in regulating numerous and diverse cell functions. A group of integral membrane proteins—occludin, claudins, and junction adhesion molecules—interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity.
Steroid sulfatase gene variation and DHEA responsiveness to resistance exercise in MERET
Authors: Riechman Steven E. , Fabian Tanya J. , Kroboth Patricia D. , Ferrell Robert E.
Published: May 2004

Genetic influences and endurance exercise have been shown to alter circulating concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate, DHEAS. We hypothesized that acute resistance exercise (RE) and training (RET) would increase DHEA steroids, and the magnitude of the increase would be influenced by a steroid sulfatase (STS) gene variation. Fasting blood samples were collected before and after the first ( S1) and last ( S30) session of a 10-wk RET program in 62 men and 58 women [age: 21.0 yr (2.4)]. Acute RE increased both DHEA [+2.8 (0.4), S1; +1.6 ng/ml (0.4), S30; P < 0.001] and DHEAS [+154 ( 24 ), S1; +166 ng/ml ( 15 ), S30; P < 0.001] and decreased DHEAS:DHEA [−27 ( 8 ), S1; −15 ( 7 ), S30; P < 0.01]. RET reduced resting DHEAS (−122 ng/ml, P < 0.01) and decreased DHEA response to RE (−50%, P < 0.05). Subjects with an STS “G” allele ( n = 36) had greater acute changes in DHEA [+4.4 (0.7) vs. +2.0 ng/ml (0.5), S1; +3.2 (0.6) vs. +1.0 ng/ml (0.4), S30; P < 0.01] and DHEAS:DHEA [−37 ( 11 ) vs. 5 ( 7 ), S30, P < 0.05] than those subjects with only an “A” allele ( n = 84). The observed increase in DHEA and DHEAS and decrease in DHEAS:DHEA suggest RE-induced STS activation which is influenced by the STS polymorphism.
Treatment of Resistant/Relapsing Chronic Lymphocytic Leukemia with a Combination Regimen Containing Deoxycoformycin and Rituximab
Authors: Tsiara S.N. , Kapsali H.D. , Chaidos A. , Christou L. , Bourantas K.L.
Published: May 2004

Background: Patients with chronic lymphocytic leukemia (CLL) are sometimes resistant to treatment or relapse soon after the administration of the currently available frontline therapy including chlorambucil-prednisolone CHOP and fludarabine. We report the beneficial effect of an alternative chemotherapeutic regimen containing 2’-deoxycoformycin (pentostatin) and the monoclonal antibody anti-CD20 (rituximab) in 5 patients with resistant/relapsing CLL. Patients: Five patients (4 men and 1 woman) with CLL at stage C, according to Binet’s classification, were included in the therapeutic protocol. The median age of the patients was 76 years (range 57–84 years). Previous treatment consisted of chlorambucil-prednisolone, fludarabine, and CHOP. The current regimen comprised six 2-week cycles of pentostatin, 4 mg/m2 i.v., combined with four cycles of rituximab, in a dose of 375 mg/m2, every other week. Results: Three patients responded to therapy, 2 achieved complete remission and 1 a partial response. Two patients did not respond to treatment. Toxicity was mild and well tolerated. The median survival duration of the responders was 19 months. These promising results suggest that salvage therapy with a combination regimen including pentostatin and rituximab may have a beneficial effect in patients with resistant/relapsing CLL.
Treatment of a Patient with Chronic Immune Thrombocytopenic Purpura with Rituximab and Monitoring by Flow Cytometric Analysis
Authors: Thude Hansjörg , Gruhn Bernd , Werner Uta , Schorner Uta , Häfer Ralf , Zintl Felix , Barz Dagmar
Published: May 2004

Treatment modalities of patients with chronic immune thrombocytopenic purpura (ITP) include the administration of intravenous immunoglobulins (IVIG), corticosteroids, anti-D(Rh) immunoglobulin (anti-D), and splenectomy. Approximately 25–30% of patients with chronic ITP do not respond to established therapeutic regimens. We describe a 19-year-old patient with chronic ITP refractory to standard therapies treated with rituximab (anti-CD20 antibody). Initially, the therapy with rituximab appeared to be successful; however, the patient relapsed after a surveillance of 57 weeks documenting that the rituximab therapy has failed. Flow cytometric analyses during and after the administration of rituximab revealed new aspects of monitoring rituximab therapy.
Present Status of Renal Cell Carcinoma in Dialysis Patients in Japan: Questionnaire Study in 2002
Authors: Ishikawa Isao
Published: May 2004

Aims: To determine the incidence and recent trends of renal cell carcinoma (RCC) in dialysis patients, a nationwide investigation was performed in Japan. Methods: In February 2002, 3,155 questionnaires were sent to dialysis units in Japan. The variables studied for RCC diagnosed between March 2000 and February 2002 included patient age, duration of dialysis, diagnostic aids, cancer size, histology of cancer, and the presence of metastasis and acquired cysts. Results: 489 RCCs (381 males, 104 females, and 4 unknown) were studied. The mean age of the RCC patients was 57.5 ± 11.4 (mean ± SD) years, and the mean duration of dialysis was 136.9 ± 95.2 months. RCC was detected by symptoms alone in 5.3% of the cases, by sonographic screening in 46.1%, and computed tomographic screening in 44.2%. The metastasis rate was 15.2%. The standardized incidence ratio was 9.7 (95% confidence interval, CI: 8.3–11.2) for the male dialysis patients and 11.0 (95% CI: 8.2–14.4) for the female patients. Eighty-four of the RCC patients with more than 20 years of hemodialysis were younger, were more frequently male, and demonstrated a larger cancer size, a higher incidence of papillary RCC, a higher metastasis rate, and a higher incidence of fatal RCC than 215 patients with less than 10 years of dialysis. Conclusion: 54.6% of the patients with RCC received dialysis for more than 10 years. For RCC patients with more than 20 years of dialysis, the mean age was younger, and the metastasis rate was higher than for RCC patients with less than 10 years of dialysis.
Safety and Efficacy of Sevelamer in the Treatment of Uncontrolled Hyperphosphataemia of Haemodialysis Patients
Authors: Almirall Jaume , Lopez Thaïs , Vallve Montserrat , Ruiz Ana , Llibre Joan , Betriu Angels
Published: May 2004

Background/Aim: The treatment of hyperphosphataemia is of major importance in the management of patients on dialysis. Traditional phosphate binders can be associated with undesirable effects. Recently, a new non-absorbable phosphate-binding polymer, sevelamer hydrochloride, has been available. Clinical information is scarce, and its cost could be a limiting factor for its wider use. No studies have evaluated its usefulness in uncontrolled hyperphosphataemic patients. Methods: We identified 34 patients with a maintained serum phosphorus concentration >6.5 mg/dl and/or toxicity related to standard phosphorus-binding treatment (aluminium or calcium based). Sevelamer was added and titrated up fortnightly to achieve phosphorus control. Previous phosphate binders were decreased, whenever possible. The period of the study was 6 months. Results: Thirteen patients (38%) dropped out because of side effects, mainly related to the gastro-intestinal tract. The efficacy analysis disclosed that the phosphorus concentration decreased from 2.39 ± 0.48 to 1.84 ± 0.48 mmol/l (p < 0.001). The mean dose of sevelamer was stabilised at 3.4 ± 1.8 g/day. The amount of calcium- and aluminium-based phosphate binders could be decreased from 5.1 ± 3.5 to 3.1 ± 2.7 g/day (38% decrease) and from 2.4 ± 1.5 to 1.5 ± 1.7 g/day (36% decrease), respectively. The Ca × P product was significantly decreased from 5.83 ± 1.19 to 4.36 ± 1.12 mmol/l2 (p < 0.001). The total cholesterol concentration decreased from 4.34 ± 0.9 to 3.98 ± 0.9 mmol/l (p < 0.01) and the low-density lipoprotein cholesterol level from 2.61 ± 0.98 to 2.20 ± 0.77 mmol/l (p < 0.03). Conclusions: Sevelamer is an effective phosphate binder that allows a better serum phosphorus control, while allowing a decrease in the dose of calcium- and aluminium-based phosphate binders in these difficult patients. The drawbacks are the high intolerance rate and the price of the product.
Changes of Rat Kidney AQP2 and Na,K-ATPase mRNA Expression in Lithium-Induced Nephrogenic Diabetes insipidus
Authors: Laursen Ulla Helt , Pihakaski-Maunsbach Kaarina , Kwon Tae-Hwan , Østergaard Jensen Erik , Nielsen Søren , Maunsbach Arvid B.
Published: May 2004

Background/Aim: In a rat model, lithium treatment is associated with polyuria and severe downregulation of aquaporin-2 (AQP2) protein in the inner medulla (IM) or in the whole kidney. However, it is not known (1) to what extent this downregulation occurs at the mRNA level; (2) whether the main sodium transporter of the nephron, Na,K-ATPase, is regulated in parallel at the mRNA level, and (3) whether lithium treatment induces zonal or segmental differences in AQP2 and Na,K-ATPase mRNA levels. Method: We examined the changes in mRNA expression levels for AQP2 and Na,K-ATPase in kidney cortex, inner stripe of the outer medulla (ISOM), and IM of rats treated with lithium orally using semiquantitative Northern blot analyses and in situ hybridization at the light and electron microscopic levels. Results: The AQP2 mRNA levels decreased significantly (p < 0.01) in lithium-treated rats to 37 ± 4% in the cortex, to 17 ± 4% in the ISOM, and to 23 ± 5% in the IM, while the Na,K-ATPase mRNA levels were not altered in the cortex, but were significantly (p < 0.05) altered in the ISOM (144 ± 15% after 10 days, but 68 ± 4% after 4 weeks) and in the IM (63 ± 8% after 10 days, but normalized after 4 weeks). In situ hybridization showed reduced levels of AQP2 mRNA in all zones of the kidney, but the Na,K-ATPase mRNA expressions were slightly decreased only in IM collecting ducts. At the ultrastructural level, principal cells in the IM collecting ducts showed slight hypertrophy, but no cell damage after 4 weeks of lithium treatment. The results demonstrate substantial downregulation of AQP2 at the mRNA level throughout the collecting duct in experimental lithium-induced nephrogenic dabetes insipidus and moderately decreased Na,K-ATPase mRNA levels in the ISOM and in the IM. Conclusion: The results suggest that decreased mRNA expressions of AQP2 and Na,K-ATPase contribute to the development of lithium-induced nephrogenic diabetes insipidus.
Fractalkine and Its Receptor, CX3CR1, Upregulation in Streptozotocin-Induced Diabetic Kidneys
Authors: Kikuchi Yuichi , Ikee Ryota , Hemmi Noriaki , Hyodo Naomi , Saigusa Takamitsu , Namikoshi Tamehachi , Yamada Muneharu , Suzuki Shigenobu , Miura Soichiro
Published: May 2004

Background: Fractalkine is induced on activated endothelial cells and promotes strong adhesion of T cells and monocytes via its receptor CX3CR1. In kidney, fractalkine expression might be induced by high shear stress and play an important role in prolonged glomerular diseases. We examined whether fractalkine and CX3CR1 upregulation are found in streptozotocin-induced diabetic kidneys. Methods: Diabetic rats were randomized to receive an angiotensin-converting enzyme inhibitor (temocapril), aminoguanidine or no treatment. Reverse transcription-competitive polymerase chain reaction, Western blot analysis and immunohistochemistry were used. Results: At 4 weeks, fractalkine and CX3CR1 mRNA expression in diabetic kidneys increased compared with that in controls. Fractalkine staining in diabetic kidneys was clearly detected, along with glomerular capillary lumen and peritubular capillaries. A few CX3CR1 positive cell infiltration in diabetic glomeruli were found. Treatment with temocapril or aminoguanidine did not affect these changes. At 8 weeks, fractalkine and CX3CR1 mRNA expression in untreated diabetic kidneys markedly increased compared with that in controls. Membrane-anchored fractalkine protein expression in untreated diabetic rats also increased. The increased expression was suppressed by the treatment with temocapril and aminoguanidine. Increased CX3CR1-positive cell infiltration in diabetic glomeruli was also inhibited by both treatments. Some CX3CR1-positive cells were ED3 positive. Conclusions: Fractalkine and CX3CR1 upregulation were demonstrated in an early stage of diabetic kidney. These upregulation, as well as urinary albumin excretion, were suppressed by treatments with temocapril and aminoguanidine for 8 weeks. These findings suggest that fractalkine expression and CX3CR1-positive cell infiltration in diabetic kidneys might play an important role for progression of diabetic nephropathy.
Chronic Administration of Bumetanide Upregulates Calbindin D28k mRNA and Protein Abundance in Rat Distal Convoluted Tubules
Authors: Rizzo Maria , Metafora Salvatore , Morelli Francesco , Russo Ferdinando , Ciani Francesca , Capasso Giovambattista
Published: May 2004

Background/Aims: Calbindin D28k has been reported to be involved in transcellular calcium transport along the rat distal convoluted tubule (DCT). It has also been shown that administration of bumetanide is associated with hypercalciuria. The experiments reported here were designed to verify whether chronic infusion of this diuretic affects the gene expression and protein abundance of calbindin D28k along rat kidney DCT. Methods: Bumetanide was subcutaneously infused by an osmotic minipump for 7 days at a rate of 1.5 mg·h–1·kg–1. cDNA was synthesized from total RNA extracted from DCT microdissected from collagenase-treated kidneys. Results: Calbindin D28k mRNA abundance, quantified by competitive PCR, was found to be 13.7 ± 1.9 amol·ng–1 total RNA in DCT of control rats (n = 4) as compared to 24.2 ± 2.4 amol·ng–1 total RNA in DCT of bumetanide- treated rats (n = 5) (p < 0.01). This effect was associated with a 52% increase (p < 0.005) in calbindin D28k protein abundance, as detected by Western blot performed on tissue slices from renal cortex (n = 4). Conclusion: These data not only demonstrate that bumetanide upregulates the mRNA and protein abundance of calbindin D28k in rat DCT, but also suggest that DCT calcium reabsorption is increased following the administration of this loop diuretic.
Pubovaginal Cutaneous Fascial Sling Procedure for Stress Urinary Incontinence: 10 Years’ Experience
Authors: Reichelt Olaf , Weirich Torsten , Wunderlich Heiko , Schubert Jörg
Published: May 2004

Objectives: There is a considerable lack of consensus regarding indications and long-term efficacy of the many techniques for treating urinary stress incontinence. We report the long-term results of a modified pubovaginal sling procedure. Methods: From 1989 to 1998, 129 consecutive patients underwent a pubovaginal sling by two urologists. 86 of the subjects (67%) replied to a questionnaire designed to assess the outcome of the procedure and the subjective satisfaction with the operative result. During surgery we performed a modified sling procedure using a cutaneous strip strengthened by rectus fascia and placed with almost no tension. Special care was taken not to lacerate or damage but support the urethral musculature. We routinely did an anterior vaginoplasty, and posterior vaginoplasty if necessary. Results: Mean patient age was 56.8 years, mean follow-up 39 months, mean parity 2.1, previous surgery 0.4. Improvement rates were determined as follows (‘Are you satisfied with the operation?’): Significantly reduced incontinence (i.e. 50–100% improvement) was found in 65.2%, slight reduction (10–40% improvement) in 15.2%, no change in 17.4% and worsening in 2.2% of all 103 cases. The majority of all complications were wound infections. Conclusion: Despite the considerable failure rate, the substantial improvement in the quality of life of almost two thirds of the patients during a 3-year follow-up recommends a pubovaginal sling as a treatment option for urinary incontinence.
Silver Nitrate Sclerotherapy for ‘Clinically Significant’ Chyluria: A Prospective Evaluation of Duration of Therapy
Authors: Dalela D. , Rastogi M. , Goel Apul , Gupta Vipul P. , Shankhwar S.N.
Published: May 2004

Objectives: To evaluate and compare the results of regimen A (3 instillations at 8-hourly intervals in 1 day) with the control regimen B (9 instillations at 8-hourly intervals in 3 days) of using 1% silver nitrate solution for renal pelvic instillation sclerotherapy in ‘clinically significant’ filarial chyluria. Materials and Methods: Forty-seven patients with clinically significant chyluria attending on 2 different days our urology clinic were prospectively randomized between two groups; the study group received regimen A (n = 21) while the control group received regimen B (n = 26). The variables evaluated included visualization of pyelolymphatic fistulae on retrograde pyelography, hospital stay, outcome and morbidity of the two regimens. Results: Patients in both groups were comparable for age and sex. The morbidity (fever, symptomatic UTI, hematuria) following regimen A was less than that of regimen B although not statistically significant. The average hospital stay was 3 days for regimen A and 5.5 days for regimen B (p = 0.001). The initial success rate was 80.95% in group A and 92.30% in group B (p = 0.47). The mean duration of follow-up was 15 months (range 9–18). There was no significant difference in recurrence between the two groups during follow-up (group A: 21.05% and group B: 22.72%; p = 0.98). Conclusions: Regimen A was as effective as regimen B. Regimen A had the advantages of having less morbidity and shorter duration of hospital stay. We recommend only a 3-instillation regimen in patients with clinically significant chyluria, particularly those who demonstrate pyelolymphatic fistulae on retrograde pyelography.
Simultaneous Heterogenotypic Renal Cell Carcinoma: Immunohistochemical and Karyoptic Analysis by Comparative Genomic Hybridization
Authors: Cho Nam Hoon , Kim Sungeun , Ha Man Jun , Kim Hyun Joo
Published: May 2004

We report a rare collision tumor of a nodule-in-nodule pattern between a clear cell-type carcinoma and a collecting duct carcinoma in a 24-year-old man. Whereas the outer nodule is quite different from the ‘conventional renal cell carcinoma (RCC)’ with respect to vascularity, the inner nodule is quite distinctive as regards immunophenotype and karyotype results. Karyotyping the latter by means of comparative genomic hybridization (CGH) disclosed gains of chromosome regions in 1q21.2-qter, 5q21-qter, 6q16.3-qter and 17q21.2-qter along with a loss in 1p21-p31.14, 9q31-pter, 11, 13q12-qter, 15q12-qter and 18q21.1-qter. The clear cell carcinoma surrounding the daughter nodule revealed no 3p loss by means of CGH, unlike most cases of conventional RCC that are seemingly associated with poor vasculature. In summary, to our knowledge, this is the first reported case of an unclassified RCC featuring a unique growth pattern composed of a mixed clear cell type without a 3p loss and a variant of CDC with a unique karyotypic alteration.
Hydronephrosis due to Malrotationin a Pelvic Ectopic Kidney withVascular Anomalies
Authors: Collura G. , De Dominicis M. , Patricolo M. , Caione P.
Published: May 2004

A particular case of hydronephrosis in ectopic kidney due to a malrotation and vascular anomalies in a young girl is described. The patient was previously operated for ureteropelvic junction obstruction at the age of two. Clinic and radiographic and pathologic findings are discussed and the literature is reviewed.
Mucinous Metaplasia of the Renal Pelvic Epithelium in a Case of Recurrent Urolithiasis and Pyelonephritis
Authors: Mathur Sandeep , Singh Manoj K. , Rao Satish I. , Seth Amlesh
Published: May 2004

The occurrence of mucinous metaplasia of the renal pelvis in the absence of an associated malignancy is quite uncommon. We report a case of mucinous metaplasia of the renal pelvic epithelium without an associated squamous metaplasia in a 40-year-old male with history of recurrent left renal calculi and urinary tract infections since the age of 10 years.
Changes in Dental Caries 1953–2003
Authors: Marthaler T.M.
Published: May 2004

In the first half of the 20th century, indices and methods of conducting surveys of the level of dental diseases were developed. Modern epidemiological studies began in the fifties and many reliable studies have been conducted after 1960. In the following decades, a substantial decline of caries prevalence was documented in the majority of the highly industrialized countries, with reductions of lifetime caries experience exceeding 75%. The decline comes to an end when low or very low levels of prevalence are reached. Children of low socioeconomic status and immigrants from outside Western Europe, however, generally have higher disease levels and may cause increases in caries prevalence. For this and other reasons, caries epidemiology will remain an indispensable part of dental public health.
Application of the Zürich Biofilm Model to Problems of Cariology
Authors: Guggenheim Bernhard , Guggenheim Merlin , Gmür Rudolf , Giertsen Elin , Thurnheer Thomas
Published: May 2004

The term biofilm is increasingly replacing ‘plaque’ in the literature, but concepts and existing paradigms are changing much more slowly. There is little doubt that biofilm research will lead to more realistic perception and interpretation of the physiology and pathogenicity of microorganisms colonizing plaques in the oral cavity. There is clear evidence that the genotypic and phenotypic expression profiles of biofilm and planktonic bacteria are different. Several techniques are available today to study multispecies biofilms of oral bacteria, each having its particular advantages and weaknesses. We describe a biofilm model developed in Zürich and demonstrate a number of applications with direct or indirect impact on prophylactic dentistry: spatial arrangement and associative behavior of various species in biofilms; multiplex fluorescent in situ hybridization analysis of oral bacteria in biofilms; use of the biofilm model to predict in vivo efficacy of antimicrobials reliably; mass transport in biofilms; de- and remineralization of enamel exposed to biofilms in vitro. The potential of biofilm experimentation in oral biology has certainly not yet been fully exploited and dozens of possible interesting applications could be investigated. The overall physiological parameters of multispecies biofilms can be measured quite accurately, but it is still impossible to assess in toto the multitude of interactions taking place in such complex systems. What can and should be done is to test hypotheses stemming from experiments with planktonic cells in monospecies cultures. In particular, it will be interesting to investigate the relevance to biofilm composition and metabolism of specific gene products by using appropriate bacterial mutants.
Antimicrobials in Future Caries Control?
Authors: Twetman Svante
Published: May 2004

The aim of this paper was to examine recent evidence for the effect of the antibacterial approach to prevent and control caries with special reference to the use of chlorhexidine (CHX). Existing information from the mid 1990s provided limited evidence for the effectiveness of CHX gels, rinses and toothpaste in preventing caries in permanent teeth of children and adolescents. An updated literature search on CHX intervention in controlled clinical trials from 1995 to May 2003 unveiled 22 studies covering over 4,500 patients with clinical caries as end point. The vast majority (n = 21) were dealing with CHX-containing varnishes. Since the studies exhibited disparities in design, diagnosis and intervention, the findings were subgrouped with respect to caries type and localization. According to the ranking system of the Swedish Council on Technology Assessment in Health Care, the evidence for an anticaries effect of CHX varnishes was rated as inconclusive for caries-active schoolchildren and adolescents with regular fluoride exposure. Regarding fissure caries, a preventive effect of CHX varnishes was demonstrated in 4 studies out of 5 when compared to no treatment in children with low fluoride exposure. The evidence for arresting root caries in dry-mouth patients and frail elderly subjects was inconclusive. In conclusion, the evidence from the recent literature was inconclusive for the use of CHX varnishes for caries prevention in risk groups.
Salivary Enhancement Therapies
Authors: Fox Philip C.
Published: May 2004

When salivary output is reduced chronically to a significant extent, there is a marked increase in dental caries. As the role of saliva in protection of the oral hard tissue is well recognized, there have long been efforts to enhance salivary function in conditions with associated secretory hypofunction. The rationale is that by stimulating salivary output, caries and other oral complications will be reduced or eliminated. The most widely used method for increasing salivary function is a combination of masticatory and gustatory stimulation. A large number of systemic agents have also been proposed as secretagogues, but only a few have shown consistent salivary enhancing properties in well-designed, controlled trials. Pilocarpine has been shown to improve symptoms of oral dryness and to increase salivary output in patients with Sjögren’s syndrome and postradiation xerostomia. Recently, cevimeline has shown significant salivary enhancement in Sjögren’s syndrome. Pilocarpine and cevimeline have a similar mechanism of action, side effect profile and duration of activity. No secretagogues have been linked directly in clinical trials to either caries prevention or a reduction in the existing caries rate of salivary dysfunction patients. Improved secretagogues are needed, with fewer side effects, increased duration of activity and greater potency. Future research directions include gene therapeutic approaches to direct salivary growth and differentiation or modify remaining tissues to promote secretion, creation of a biocompatible artificial salivary gland and salivary transplantation. With improved secretagogues, the effects of conditions that result in reduced salivary function and increased caries will be ameliorated.
Fluorides in Caries Prevention and Control: Empiricism or Science
Authors: ten Cate J.M.
Published: May 2004

The caries-preventive effects of fluoride are beyond any reasonable doubt! Inclusion of fluoride use in caries prevention protocols has resulted in significant reduction in caries prevalence in the majority of the population. Nevertheless, even in low-caries prevalence populations up to 20% of individuals may suffer to an unacceptable degree from caries. In the history of caries research various phases can be discerned. Starting with the initial – laboratory – studies to reveal the mode of action of fluoride, attention later shifted to intra-oral studies and in situ product testing. Currently much emphasis is given to evidence-based dentistry and guidelines for clinical practice, which trend has also focussed the research on fluoride and caries. While on some topics, such as the efficacy of fluoride toothpastes, evidence is convincing, additional research is indicated to resolve remaining questions. One such question is that of high-prevalence individuals for which a comprehensive research programme focussing both on caries aetiological and behavioural aspects should be further developed. Efforts should continue to be directed at improving our understanding of fluoride, in particular on topics where success so far has failed.
Sugar Alcohols: What Is the Evidence for Caries-Preventive and Caries-Therapeutic Effects?
Authors: van Loveren C.
Published: May 2004

The most widely used sugar alcohols are: xylitol, sorbitol, mannitol, maltitol, lactitol and the products Lycasin® and Palatinit®. It is often claimed that xylitol is superior to the other sugar alcohols for caries control. This paper examines clinical studies on the caries-preventive and therapeutic effects of sugar alcohols with emphasis on sorbitol and xylitol. It is concluded that chewing sugar-free gum 3 or more times daily for prolonged periods of time may reduce caries incidence irrespective of the type of sugar alcohol used. It may be sufficient to do this only on school days. Sucking xylitol-containing candies or tablets may have a similar effect as chewing xylitol chewing gum. Clinical trials suggest greater caries reductions from chewing gums sweetened with xylitol than from gums sweetened with sorbitol. However, the superiority of xylitol was not confirmed in 2 out of 4 clinical trials comparing the caries-preventive effect of xylitol- with sorbitol-sweetened gums. The caries-preventive effects of polyol-containing gums and candies seem to be based on stimulation of the salivary flow, although an antimicrobial effect cannot be excluded. There is no evidence for a caries-therapeutic effect of xylitol. These conclusions are in line with those of recent reviews and with the conclusions of the Scientific Committee on Medicinal Products and Medical Devices of the EU Commission.
How ‘Clean’ Must a Cavity Be before Restoration?
Authors: Kidd E.A.M.
Published: May 2004

The metabolic activity in dental plaque, the biofilm at the tooth surface, is the driving force behind any loss of mineral from the tooth or cavity surface. The symptoms of the process (the lesion) reflect this activity and can be modified by altering the biofilm, most conveniently by disturbing it by brushing with a fluoride-containing toothpaste. The role of operative dentistry in caries management is to restore the integrity of the tooth surface so that the patient can clean. Thus, the question, ‘how clean must a cavity be before restoration?’ may be irrelevant. There is little evidence that infected dentine must be removed prior to sealing the tooth. Leaving infected dentine does not seem to result in caries progression, pulpitis or pulp death. However, some of the bacteria survive. What is their fate and if they are not damaging, why is this?
Getting Research into Clinical Practice – Barriers and Solutions
Authors: Clarkson J.E.
Published: May 2004

The success of current efforts towards evidence-based health services in many countries depends on efficient transfer of research findings to health practitioners. However, there is a lag in research being adopted. In part this is due to difficulties in interpreting or generalising research findings, in part to inertia, organisational structures and information. Clinical guidelines are usually cited as being the most effective product of evidence assessment and means of getting research into practice. The processes by which they are prepared and disseminated are discussed. Current clinical practice requires that health professionals adapt to changing systems and adopt new techniques. Therefore, in future, practice research to evaluate (a) clinical interventions and (b) dissemination and implementation strategies will become increasingly important. Recognised barriers to such research include lack of interest, lack of involvement, lack of time and lack of remuneration. High-quality research in dental primary care requires academics and dental service providers working in partnership on topics that are relevant both to clinicians and policy makers. Good project management, education and training are essential.
Sensory Nerve Conduction in Demyelinating and Axonal Guillain-Barré Syndromes
Authors: Kuwabara Satoshi , Ogawara Kazue , Misawa Sonoko , Mizobuchi Keiko , Sung Jia-Ying , Kitano Yukiko , Mori Masahiro , Hattori Takamichi
Published: May 2004

Guillain-Barré syndrome is divided into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) based on motor nerve conduction studies. We investigated whether sensory nerve conduction studies contribute to the electrodiagnosis of AIDP and AMAN. In consecutive 59 patients with AIDP (n = 26) or AMAN (n = 33), results of sensory nerve conduction studies in the median, ulnar and sural nerves were reviewed. Sensory nerve conduction abnormalities were found for 85% of AIDP patients and for only 6% of AMAN patients. In AIDP patients, the abnormalities were present in 85% of patients in the median nerves, 85% in the ulnar nerves and 38% in the sural nerves. AMAN is very rarely associated with sensory nerve involvement. Abnormal sensory nerve conduction is supportive of AIDP and is more frequently found for the median and ulnar nerves than sural nerves.
Vaginal Müllerian Papilloma in a 2-Year-Old Child
Authors: Arbo Elisangela , dos Reis Ricardo , Uchoa Diego , Acetta Solange Garcia , Rivoire Waldemar Augusto , Capp Edison
Published: May 2004

Papillomas of the lower genital tract are rare benign lesions, which cause vaginal bleeding in girls. We report a case in a 2-year-old girl. Few cases have been described in children and adolescents. However, it should be considered as a possible diagnosis in girls with sanguineous vaginal discharge.
Continuous Renal Replacement Therapy after Cardiac Surgery
Authors: Lugones Facundo , Chiotti Gilberto , Carrier Michel , Parent Daniel , Thibodeau Jacinthe , Ducharme Brigitte , Cardinal Jean , Leblanc Martine
Published: May 2004

Background/Aims: To evaluate the outcome of patients who require continuous renal replacement therapy (CRRT) following cardiac surgery. Methods: All patients who received CRRT after cardiac surgery over more than 4 years at the Surgical Intensive Care Unit of the Montreal Heart Institute were reviewed. Among 5,564 consecutive patients, 85 underwent CRRT postoperatively. Results: The mean delay between surgery and CRRT initiation was 5 days, and the duration of CRRT was 9 days, without a difference between survivors and non-survivors. Delivered clearances with CRRT were estimated at 25–28 ml/min (≈40 liters/day), 29–32 ml/min (≈46 liters/day) and 17 ml/min (≈ 25 liters/day) for continuous veno-venous hemofiltration, continuous veno-venous hemodiafiltration and continuous veno-venous hemodialysis, respectively. In-hospital mortality was 43.5%. No difference in mortality was observed between patients with normal renal function at baseline and those with pre-operative renal dysfunction. Mortality was 33.3% after a coronary artery bypass graft (CABG), 57.1% after CABG and valve surgery, 60% after valve surgery, and 72.7% for redo-CABG or redo-valve surgery. 79% of survivors and 86% of non-survivors had received a cardiopulmonary bypass (p = NS). The Simplified Acute Physiology Score II upon intensive care unit (ICU) admission and the requirement of an intra-aortic balloon pump were higher in non-survivors (p < 0.05). The mean length of ICU and hospital stay was 27.4 and 34.2 days for survivors and 17.9 and 22.3 days for non-survivors, respectively (p < 0.05). Conclusions: Renal impairment is relatively common after cardiac surgery. The mortality of patients who required CRRT after cardiac surgery was 43.5% and was particularly influenced by the type of surgery.
Effect of Polymyxin B-Immobilized Fiber on Blood Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Levels in Acute Respiratory Distress Syndrome Patients
Authors: Nakamura Tsukasa , Kawagoe Yasuhiro , Matsuda Takaharu , Shoji Hisataka , Ueda Yoshihiko , Tamura Naoaki , Ebihara Isao , Koide Hikaru
Published: May 2004

Background/Aims: Metalloproteinase (MMP)-9 plays a role in the pathogenesis of acute respiratory distress syndrome (ARDS). Polymyxin B-immobilized fiber (PMX-F) treatment improves circulatory disturbance and oxygenation in ARDS patients. We aimed to assess whether PMX-F treatment alters the blood MMP-9 and tissue inhibitor of MMP (TIMP)-1 levels in ARDS patients. Methods: Twelve ARDS patients who received PMX-F treatment and 20 healthy control volunteers were included in this study. PMX-F was carried out twice at a rate of 100 ml/min for 2 h with a time interval of 24 h. Blood MMP-9 and TIMP-1 levels were measured before and after PMX-F treatment. We monitored blood pressure and the PaO2/FiO2 (PF) ratio before and after PMX-F treatment. Results: The mortality of ARDS patients after PMX-F treatment was 16.7%. Chest X-ray abnormalities were ameliorated in surviving patients after PMX-F treatment. Systolic and diastolic blood pressure increased significantly after PMX-F treatment (p < 0.01). The PF ratio also increased significantly after PMX-F treatment (p < 0.01). Blood MMP-9 and TIMP-1 levels in ARDS patients (126.4 ± 36.4 and 326.5 ± 52.5 ng/ml) were significantly higher than in controls (34.5 ± 12.5 and 160.5 ± 24.5 ng/ml; p < 0.01). PMX-F treatment reduced these levels significantly (the first treatment: MMP-9 85.4 ± 28.6 ng/ml, p < 0.05, TIMP-1 265.8 ± 36.6 ng/ml, p < 0.05; the second treatment: MMP-9 56.5 ± 18.8 ng/ml, p < 0.01, TIMP-1 220.6 ± 30.5 ng/ml, p < 0.01). Conclusion: These data suggest that MMP-9 and TIMP-1 may play a role in the pathogenesis of ARDS and that PMX-F treatment ameliorated increased MMP-9 and TIMP-1 levels in ARDS patients.
Classification of Functional Psychoses and Its Implication for Prognosis: Comparison between ICD-10 and DSM-IV
Authors: Jäger Markus , Bottlender Ronald , Strauss Anton , Möller Hans-Jürgen
Published: May 2004

Background: The aim was to examine the agreement and differences between ICD-10 and DSM-IV in the classification of functional psychoses. Sampling and Methods: In a sample of 218 first-hospitalised patients, ICD-10 diagnoses were compared with DSM-IV diagnoses. Functional psychoses of both diagnostic systems were classified into the four diagnostic groups schizophrenia, transient/episodic psychoses, delusional disorders and affective disorders. Based on information from a 15-year follow-up, it was examined which course is associated with each diagnostic group. Results: Although in ICD-10 there was a higher frequency of schizophrenia and a lower one of affective disorders, a high agreement between ICD-10 and DSM-IV (kappa value of 0.82) was found. In both diagnostic systems, transient/episodic psychoses and affective disorders were mainly associated with a non-chronic course and schizophrenia was mainly associated with a chronic one. Nevertheless, several patients with transient/episodic psychoses showed a chronic course (ICD-10: 10%, DSM-IV: 15%) and more than one third of patients with schizophrenia a non-chronic one (ICD-10: 40%, DSM-IV: 33%). Conclusions: In the cross-sectional assessment, there is a high diagnostic agreement between ICD-10 and DSM-IV. With respect to the long-term course, the delimitation of transient/episodic psychoses from schizophrenia was neither completely achieved by ICD-10 nor by DSM-IV.
Shepherds, Merchants, and Credit: Some Observations on Lending Practices in Ur III Mesopotamia
Authors: Garfinkle Steven
Published: May 2004

The numerous surviving loan documents from the Ur III period illustrate the vital role that credit played in the early Mesopotamian economy. The availability of credit was critical at every level of society. In this article, the form and function of credit in the Ur III period are described, along with lending practices and the activities of individual creditors. Despite the overwhelming scale of the institutional economies, there was significant room for non-institutional households to pursue economic gains through money-lending. This entrepreneurial activity took place in an economy that was familiar with a sophisticated range of possible credit transactions. Les nombreux documents de prêt qui survivent de l'époque de la Troisième Dynastie d'Ur illustrent le rôle essentiel que le crédit joue dans l'économie mésopotamienne archaïque. À chaque niveau de la société disposer de crédit était d'une importance essentielle. Cette contribution décrit les forme et fonction du crédit à la période d'Ur III, les pratiques de prêt et les activités des créanciers. En dépit de la grande taille des économies institutionnelles, il existait un secteur important où des maisons non-institutionelles pouvaient faire des gains en prêtant à intérêt. Cette activité d'entrepreneur s'exerçait dans une économie qui possédait une gamme sophistiquée de transactions de crédit.
Ultrasound Investigation of Suspected Renal Artery Stenosis
Authors: Freeman Simon J
Published: May 2004

Renal artery stenosis (RAS) is an important and potentially reversible cause of both hypertension and renal failure. Ultrasound offers an attractive, non-invasive, method to examine the renal arteries and confirm or exclude the presence of RAS. This article will describe the techniques and diagnostic criteria employed in the ultrasound diagnosis of this condition and will also evaluate the usefulness of ultrasound in comparison with other non-invasive imaging techniques.