Truncal Adiposity Influences High-Density Lipoprotein Cholesterol Levels and Cardiovascular Events in Hemodialysis Patients.

OBJECTIVE: Adiposity influences lipid metabolism and atherosclerotic cardiovascular disease (CVD) in the general population. The aim of the present study was to assess the association between fat mass (FM) and lipid metabolism and CVD events among patients on hemodialysis (HD). METHODS: This prospective observational study examined 240 patients on prevalent HD. Blood samples were obtained before dialysis at baseline to measure lipids, high-sensitivity C-reactive protein (hs-CRP), interleukin-6, and adiponectin. Lipids and hs-CRP were measured every 3 months for 12 months. FM was estimated by dual energy x-ray absorptiometric scan at baseline and 12 months later. Patients were then prospectively followed up for 36 months after the 1-year measurement period, and composite CVD events were estimated. RESULTS: Truncal FM was positively correlated with body mass index, hs-CRP, interleukin-6, total cholesterol, low-density lipoprotein-C, triglyceride, and negatively correlated with high-density lipoprotein (HDL)-C and adiponectin at baseline. HDL-C levels were repeatedly decreased, and triglyceride and non-HDL-C were serially increased in the patient group with truncal FM > 7,000 g at both baseline and 12 months (large truncal FM group) compared with the other groups. Cox proportional hazards models adjusted for confounders showed composite CVD events occurred significantly in patients with large truncal FM and continuous low HDL-C levels. CONCLUSIONS: Truncal adiposity influences lipid metabolism in patients on HD, and the prevalence of CVD events may be increased in those patients with high fat and lipid abnormalities, especially continuously low HDL-C levels.

[Complete response in a case of advanced oropharyngeal cancer (T4aN2bM0) treated with concomitant cetuximab and radiotherapy].

We report favorable results achieved using a combination of cetuximab and radiotherapy to treat an elderly patient with advanced oropharyngeal cancer complicated by cardiovascular disease and renal dysfunction.The case was a 78-year-old man who was referred to our hospital with the chief complaint of pharyngeal pain and swelling of the right side of the neck. The patient was diagnosed with oropharyngeal cancer (T4aN2bM0) based on a cytological diagnosis of Class V squamous cell carcinoma and CT findings.Because the patient had a history of hypertension, chronic renal failure, diabetes mellitus, cerebral infarction, angina pectoris, and prostate cancer, we determined that surgical excision and chemoradiotherapy using platinum-based drugs would be difficult.We therefore treated the patient with a combination of cetuximab and radiotherapy. Grade 3 mucous membrane disorder and Grade 2 dermatitis were observed during the course of treatment, but the treatment was completed without any other adverse events.A contrasted CT image taken after the completion of treatment showed that the primary tumor and cervical lymph node metastases had disappeared and the patient thus achieved a complete response.As of 6 months after treatment, there has been no recurrence or metastasis.As shown in this case, combination therapy with cetuximab and radiotherapy can be curative even in elderly patients with advanced oropharyngeal cancer and numerous complicating conditions.

Infective Endocarditis Caused by Streptococcus sanguinis Resulting in Stroke, Ruptured Infected Pseudoaneurysm of Superior Mesenteric Artery, and Rapidly Progressive Glomerulonephritis.

A 71-year-old-man was admitted to our hospital with a cerebral embolism and diagnosed with infective endocarditis (IE) caused by Streptococcus sanguinis. Mitral valve replacement was performed. About one month later, he experienced sudden abdominal pain and shock due to a ruptured infected mesenteric artery pseudoaneurysm. Forty-four days after abdominal surgery, he presented with rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibodies. He was treated with plasma exchange and prednisolone, and his renal function gradually improved. Since postoperative complications often occur within a few years after surgery for IE, careful follow-up is important, even after antimicrobial therapy and valve surgery.

Control of stem cell behavior by CLE-JINGASA signaling in the shoot apical meristem in Marchantia polymorpha.

Land plants undergo indeterminate growth by the activity of meristems in both gametophyte (haploid) and sporophyte (diploid) generations. In the sporophyte of the flowering plant Arabidopsis thaliana, the apical meristems are located at the shoot and root tips in which a number of regulatory gene homologs are shared for their development, implying deep evolutionary origins. However, little is known about their functional conservation with gametophytic meristems in distantly related land plants such as bryophytes, even though genomic studies have revealed that the subfamily-level diversity of regulatory genes is mostly conserved throughout land plants. Here, we show that a NAM/ATAF/CUC (NAC) domain transcription factor, JINGASA (MpJIN), acts downstream of CLAVATA3 (CLV3)/ESR-related (CLE) peptide signaling and controls stem cell behavior in the gametophytic shoot apical meristem of the liverwort Marchantia polymorpha. In the meristem, strong MpJIN expression was associated with the periclinal cell division at the periphery of the stem cell zone (SCZ), whereas faint MpJIN expression was found at the center of the SCZ. Time course observation indicates that the MpJIN-negative cells are lost from the SCZ and respecified de novo at two separate positions during the dichotomous branching event. Consistently, the induction of MpJIN results in ectopic periclinal cell division in the SCZ and meristem termination. Based on the comparative expression data, we speculate that the function of JIN/FEZ subfamily genes was shared among the shoot apical meristems in the gametophyte and sporophyte generations in early land plants but was lost in certain lineages, including the flowering plant A. thaliana.

The potential role of prostaglandin D2 in nasal congestion observed in a guinea pig model of allergic rhinitis.

BACKGROUND: Allergic rhinitis is the most common allergic disease, displaying the typical nasal symptom of congestion. Prostaglandin D(2) (PGD(2)), a chemical mediator released in large amounts by mast cells upon allergic stimulation in humans, is known to be involved in nasal congestion. However, the mechanism by which this congestion occurs remains unclear. METHODS: The effect of PGD(2) on the nasal airflow in guinea pigs was measured using a noninvasive approach that avoided any anesthetic effect. Isometric tension of isolated nasal mucosa and the nasal vascular corrosion resin cast technique were used to clarify the area of nasal mucosal vessels affected by PGD(2), and to examine the mechanism of PGD(2)-induced nasal congestion. Moreover, the involvement of second messengers in PGD(2)-induced mucosal relaxation was investigated. RESULTS: PGD(2) induced an increase in intranasal pressure in a guinea pig model of rhinitis. Additionally, sinusoidal microvessel dilatation appeared around the septum using the vascular corrosion resin cast technique in the nasal mucosa. Moreover, relaxation of the nasal mucosa following stimulation of the prostanoid DP-1 receptor was associated with cAMP levels in the tissue. CONCLUSIONS: PGD(2)-induced nasal congestion is caused by direct dilatation of the sinusoid vessels through the increase of cAMP levels in the nasal mucosa, demonstrating that the mechanism of PGD(2)-induced nasal congestion is different from other chemical mediators. Consequently, antagonists for the prostanoid DP-1 receptor would be an alternative approach for the relief of nasal congestion. Alternatively, the combined administration with antagonists for other mediators involved in nasal congestion may also be a valuable therapy for allergic rhinitis.

Interactions between zebrafish pigment cells responsible for the generation of Turing patterns.

The reaction-diffusion system is one of the most studied nonlinear mechanisms that generate spatially periodic structures autonomous. On the basis of many mathematical studies using computer simulations, it is assumed that animal skin patterns are the most typical examples of the Turing pattern (stationary periodic pattern produced by the reaction-diffusion system). However, the mechanism underlying pattern formation remains unknown because the molecular or cellular basis of the phenomenon has yet to be identified. In this study, we identified the interaction network between the pigment cells of zebrafish, and showed that this interaction network possesses the properties necessary to form the Turing pattern. When the pigment cells in a restricted region were killed with laser treatment, new pigment cells developed to regenerate the striped pattern. We also found that the development and survival of the cells were influenced by the positioning of the surrounding cells. When melanophores and xanthophores were located at adjacent positions, these cells excluded one another. However, melanophores required a mass of xanthophores distributed in a more distant region for both differentiation and survival. Interestingly, the local effect of these cells is opposite to that of their effects long range. This relationship satisfies the necessary conditions required for stable pattern formation in the reaction-diffusion model. Simulation calculations for the deduced network generated wild-type pigment patterns as well as other mutant patterns. Our findings here allow further investigation of Turing pattern formation within the context of cell biology.

An Evolutionarily Conserved Coreceptor Gene Is Essential for CLAVATA Signaling in Marchantia polymorpha.

Growth and development of land plants are controlled by CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) family of peptide hormones. In contrast to the genetic diversity of CLE family in flowering plants, the liverwort Marchantia polymorpha possesses a minimal set of CLE, MpCLE1(TDIF homolog), and MpCLE2 (CLV3 homolog). MpCLE1 and MpCLE2 peptides exert distinct function at the apical meristem of M. polymorpha gametophyte via specific receptors, MpTDIF RECEPTOR (MpTDR) and MpCLAVATA1 (MpCLV1), respectively, both belonging to the subclass XI of leucine-rich repeat receptor-like kinases (LRR-RLKs). Biochemical and genetic studies in Arabidopsis have shown that TDR/PXY family and CLV1/BAM family recognize the CLE peptide ligand in a heterodimeric complex with a member of subclass-II coreceptors. Here we show that three LRR-RLK genes of M. polymorpha are classified into subclass II, representing three distinct subgroups evolutionarily conserved in land plants. To address the involvement of subclass-II coreceptors in M. polymorpha CLE signaling, we performed molecular genetic analysis on one of them, MpCLAVATA3 INSENSITIVE RECEPTOR KINASE (MpCIK). Two knockout alleles for MpCIK formed narrow apical meristems marked by prom MpYUC2:GUS marker, which were not expanded by MpCLE2 peptide treatment, phenocopying Mpclv1. Loss of sensitivity to MpCLE2 peptide was also observed in gemma cup formation in both Mpclv1 and Mpcik. Biochemical analysis using a Nicotiana benthamiana transient expression system revealed weak association between MpCIK and MpCLV1, as well as MpCIK and MpTDR. While MpCIK may also participate in MpCLE1 signaling, our data show that the conserved CLV3-CLV1-CIK module functions in M. polymorpha, controlling meristem activity for development and organ formation for asexual reproduction.

Effect of diesel exhaust particles on house dust mite-induced airway eosinophilic inflammation and remodeling in mice.

Recent research has focused on the effects of ambient particulate pollution and much evidence has indicated that particulate pollution is associated with the onset of asthma and allergy; however, the effect of diesel exhaust particles (DEP) on the development of allergen-induced airway remodeling has not been fully investigated in vivo. In the present study, we examined the effects of DEP on Dermatophagoides farinae allergens (Der f)-induced asthma-like phenotypes in mice. Mice were administered i.t. 8 times with Der f. DEP were injected i.t. with Der f 4 times throughout the experiment or twice at the sensitization period. In both cases, DEP aggravated Der f-induced increases in airway responsiveness to acetylcholine, the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), serum Der f-specific IgG1 levels, Th2 cytokines and transforming growth factor-beta1 levels in BALF, and amount of hydroxyproline in the right lungs. Furthermore, goblet cell hyperplasia and subepithelial fibrosis were also markedly aggravated. These findings indicate that DEP can potentiate airway remodeling induced by repeated allergen challenge as well as Th2-drived airway hyperresponsiveness, eosinophilic inflammation, and IgG1 production and that DEP can exhibit adjuvant activity for airway remodeling, probably due to the enhancement of allergen sensitization and/or of Th2 polarizing pathways.

Basal cell carcinoma of the prostate: A case report and review of the literature.

Basal cell carcinoma (BCC) of the prostate is a rare tumor exhibiting various morphological characteristics, and its progression varies from an indolent to an aggressive type, with local recurrence or distant metastasis. We herein report the case of a patient who was diagnosed with early-stage BCC of the prostate and treated by surgery. A 68 year-old-man visited our hospital for a follow-up for bladder cancer. In August 2017, his serum prostate-specific-antigen (PSA) level was measured to be 5.61 ng/ml and prostate biopsy was performed. Histological examination revealed BCC of the prostate, with immunostaining examination of tumor cells showing positive results for p63 but negative results for PSA. Imaging examination showed no metastasis. Retropubic radical prostatectomy with extended lymph node dissection was performed. Pathological examination of the surgical specimen revealed coexistence of a predominant basaloid component and an adenoid cystic-like tumor with cribriform appearance. There was no extracapsular infiltration or lymph node metastasis. The patient remained alive and recurrence-free after 1 year of follow-up.

Immunomodulatory effects of CpG oligodeoxynucleotides on house dust mite-induced airway inflammation in mice.

BACKGROUND: CpG oligodeoxynucleotides (CpG ODNs) are reported to protect against airway eosinophilia and hyperresponsiveness in animal models of asthma. However, little is known about the effects of CpG ODNs on house dust mites, one of the most common environmental allergens, causing allergic asthma. In the present study, we evaluated the immunomodulatory effects of CpG ODNs on the development of house dust mite-induced airway inflammation and remodeling in mice. METHODS: Mice were instilled with Dermatophagoides farinae (Der f) into the trachea 8 times without any additional adjuvants. 48 h after the final allergen instillation, the airway responsiveness to acetylcholine (Ach) was measured, and bronchoalveolar lavage (BAL) and histopathological examination were carried out. CpG ODNs were instilled into the trachea mixed with Der f at the first allergen instillation. RESULTS: Repeated instillation of Der f induced increases in airway responsiveness to Ach, the numbers of inflammatory cells, the levels of T-helper type 2 cytokines and transforming growth factor-beta(1) in the BAL fluid. Furthermore, goblet cell hyperplasia, the thickness of the epithelium and subepithelial fibrosis were observed. The simultaneous instillation of CpG ODNs with Der f at the first allergen instillation showed significant inhibition of these parameters dose dependently. CONCLUSIONS: Our results demonstrate that CpG ODNs have inhibitory effects on Der f-induced airway hyperresponsiveness and eosinophilia, as well as airway remodeling, and that CpG ODNs can be a therapeutic approach for the treatment of house dust mite-induced asthma.

Repeated instillations of Dermatophagoides farinae into the airways can induce Th2-dependent airway hyperresponsiveness, eosinophilia and remodeling in mice: effect of intratracheal treatment of fluticasone propionate.

Dermatophagoides farinae are known to be a common environmental allergen causing allergic asthma; however, little is known about their pathophysiological effect via the allergenicities in vivo. Therefore, we first established a mouse model of asthma induced by repeated instillations of D. farinae. Second, to investigate whether the asthmatic responses are Th2-dependent, we examined the effect of the deficiency of interleukin-4 (IL-4) receptor alpha chain gene. Finally, we examined the effect of fluticasone propionate on this model. Mice were instilled with D. farinae without additional adjuvants into the trachea 8 times. After the final allergen instillation, the airway responsiveness to acetylcholine was measured, and bronchoalveolar lavage and histological examination were carried out. The instillation of the allergen-induced airway hyperresponsiveness, the accumulation of inflammatory cells and increases in the levels of Th2 cytokines and transforming growth factor-beta(1) production in the bronchoalveolar lavage fluid dose dependently. The number of goblet cells in the epithelium and the extent of the fibrotic area beneath the basement membrane were also increased in the morphometric study. In contrast, the defect of IL-4/IL-13 signaling through IL-4 receptor alpha chain completely abrogated all these responses. Furthermore, the simultaneous instillation of fluticasone propionate with the allergen showed significant inhibition or an inhibitory tendency of these changes. These findings demonstrate that the repetitive intratracheal instillations of D. farinae can induce airway remodeling through Th2-type inflammation, and that fluticasone propionate inhibits D. farinae-induced airway remodeling in mice, and this model would be useful for studying mechanisms involved in the development of allergic asthma.

High fibroblast growth factor 23 levels are associated with decreased ferritin levels and increased intravenous iron doses in hemodialysis patients.

A recent study demonstrated the association between inflammation, iron metabolism and fibroblast growth factor (FGF) 23. The present clinical study aimed to assess associations between anemia, iron metabolism and FGF23 in hemodialysis (HD) patients. This prospective observational study examined a cohort of prevalent HD patients (n = 282). Blood samples were obtained before dialysis sessions to measure baseline levels of hemoglobin (Hb), transferrin saturation (TSAT), ferritin, albumin-adjusted calcium (Ca), phosphate (P), intact (i)-PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact (i)-FGF23, high sensitive (hs)-CRP, and interleukin-6. After the baseline measurement, study patients were followed-up for 6 months. Biochemical measurements were subsequently performed at 1 (Hb), 2 (TSAT and ferritin) or 3 (Ca, P and hs-CRP) month intervals. Doses of ESAs and intravenous iron supplementation during the study period were recorded. i-FGF23 was positively correlated with Ca, P, i-PTH and inversely correlated with TSAT and ferritin. However, levels of Hb and hs-CRP and doses of ESAs during the study period did not differ among the i-FGF23 tertiles, with levels of ferritin and TSAT in the higher i-FGF23 tertile being consistently lower than in the middle to lower i-FGF23 tertiles. Multivariate repeated measures analysis indicated that the higher i-FGF23 tertile was independently associated with repeated measurements of ferritin, but not of TSAT. Doses of intravenous iron supplementation were significantly increased in the higher i-FGF23 tertile in multivariate models. In conclusion, high i-FGF23 levels may be associated with prolongation of low levels of ferritin, resulting in increased usages of iron supplementation in HD patients.

Squeezing at 946nm with periodically poled KTiOPO(4).

We report generation of squeezed vacuum in sideband modes of continuous-wave light at 946nm using a periodically poled KTiOPO (4) crystal in an optical parametric oscillator. At the pump power of 250mW, we observe the squeezing level of -5.6+/- 0.1dB and the anti-squeezing level of +12.7+/- 0.1dB. The pump power dependence of the observed squeezing/anti-squeezing levels agrees with theoretically calculated values when phase fluctuation of locking is taken into account.

Alkynes as activators in the nickel-catalysed addition of organoboronates to aldehydes.

Alkynes act not as substrates but as co-catalysts in the presence of a nickel catalyst, an organoboronate and an aldehyde to promote the addition reaction between the substrates in combination with H2O.

Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma.

Prostaglandin (PG) D2 elicits responses through either the DP1 and/or DP2 receptor. Experimental evidence suggests that stimulation of the DP1 receptor contributes to allergic responses, such that antagonists are considered to be directed therapies for allergic diseases. In this study, we demonstrate the activity of a novel synthetic DP1 receptor antagonist termed asapiprant (S-555739) for the DP1 receptor and other receptors in vitro, and assess the efficacy of asapiprant in several animal models of allergic diseases. We determined the affinity and selectivity of asapiprant for the DP1 receptor in binding assays. In the animal models of allergic rhinitis, changes in nasal resistance, nasal secretion, and cell infiltration in nasal mucosa were assessed after antigen challenge with and without asapiprant. Similarly, in the animal models of asthma, the effect of antigen challenge with and without asapiprant on antigen-induced bronchoconstriction, airway hyper-responsiveness, mucin production, and cell infiltration in lung were assessed. In binding studies, asapiprant exhibited high affinity and selectivity for the DP1 receptor. Significant suppression of antigen-induced nasal resistance, nasal secretion, and cell infiltration in nasal mucosa was observed with asapiprant treatment. In addition, treatment with asapiprant suppressed antigen-induced asthmatic responses, airway hyper-responsiveness, and cell infiltration and mucin production in lung. These results show that asapiprant is a potent and selective DP1 receptor antagonist, and exerts suppressive effects in the animal models of allergic diseases. Thus, asapiprant has potential as a novel therapy for allergic airway diseases.

Nickel-catalysed addition of organoboronates to 1,3-dienes.

Aryl- and alkenylboronates were found to add to 1,3-dienes in the presence of a catalytic amount of bis(1,5-cyclooctadiene)nickel, where a proton source in combination with a solvent considerably controls the regioselectivity.

Melanophores in the stripes of adult zebrafish do not have the nature to gather, but disperse when they have the space to move.

Animal skin pattern is one of the good model systems used to study the mechanism of pattern formation. Molecular genetic studies with zebrafish have shown that pigment cells play a major role in the mechanism of stripe formation. Among the variety of cellular events that may be involved in the mechanism, aggregation of melanophores has been suggested as an important factor for pattern formation. However, only a few experimental studies detected the migration ability of melanophores in vivo. Here, we tried to determine whether melanophores really have the ability to aggregate in the skin of zebrafish. Melanophores in the adult stripes are packed densely and they rarely move. However, when the neighboring pigment cells are killed, they move and regenerate the stripe pattern, suggesting that melanophores retain the migration ability. To analyze the migration, we ablated a part of the melanophores by laser to give free space to the remaining cells; we then traced the migration. Contrary to our expectation, we found that melanophores repulsed one another and dispersed from the aggregated condition in the absence of xanthophores. Apparent aggregation may be forced by the stronger repulsive effect against the xanthophores, which excludes melanophores from the yellow stripe region.

Snodgrass procedure for primary hypospadias repair.

BACKGROUND: In this study, the authors' experience in adaptation of the Snodgrass technique for primary hypospadias repair, with an alternative way to create a barrier layer of dartos flap for neourethral covering, is presented. METHODS: Between March 2000 and January 2001, Snodgrass urethroplasty was consecutively done on 24 boys aged between 14 months and 9 years (median: 3 years). The position of the meatus was coronal in one boy, at the distal shaft in two, at mid-shaft in eight, at the proximal shaft in five, penoscrotal in four, scrotal in three and perineal in one. Dorsal plication was carried out in nine patients (37.5%) to correct residual ventral curvature after penile degloving. Postoperatively the neourethra was stented for 10-12 days and suprapubic diversion was used for 12-14 days. RESULTS: Postoperative follow up ranged from 4 to 14 months (median: 8 months). All patients undergoing Snodgrass repair obtained a neourethra with a slit-like meatus at the tip of the glans. A small urethrocutaneous fistula occurred in one patient with mid-shaft and two with proximal-shaft hypospadias (an overall fistula rate of 12.5%). Urethral stricture had not been encountered at the time of this report. One patient developed mild meatal stenosis and was successfully managed by simple dilatation. CONCLUSIONS: The results indicate that Snodgrass urethroplasty provides satisfactory cosmetic and functional results and is versatile in repairing almost all types of hypospadias.

Down-regulation of inducible nitric oxide synthase (iNOS) in rat with congenital hydronephrosis.

BACKGROUND: Most of our knowledge concerning obstructive uropathy has been derived mainly from surgically manipulated animal models, and the pathogenesis of congenital obstructive hydronephrosis is not fully elucidated. Nitric oxide (NO) acts as an important biological modulator with diverse physiological functions, which can be either toxic or protective depending on the situation. NO is synthesized from l-arginine by nitric oxide synthase, and in the kidney iNOS is expressed spontaneously. The aim of our study is to investigate the expression of iNOS protein and its relationship with tubulointerstitial fibrosis and tubular cell apoptosis in congenital hydronephrosis. METHODS: We conducted histological studies on 18 kidneys of six-week-old-rats from an inbred colony of congenital hydronephrosis with reference to the histological grading of the affected kidney, tubulointerstitial fibrosis, renal tubular atrophy, and tubular cell apoptosis. Renal transforming growth factor-beta1 (TGF-beta1) level was determined by a sandwich ELISA assay and the expression of iNOS was analyzed by western blotting. RESULTS: Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. Renal TGF-beta1 level was higher in hydronephrotic kidneys than normal control kidneys (364.81 +/- 52.60 vs. 221.19 +/- 22.53 pg/mg protein, P < 0.05). Tubular apoptotic score in hydronephrotic kidneys was also significantly higher than in the normal control kidneys (1.97 +/- 0.42 vs. 0.14 +/- 0.02/HPF, P < 0.01). The expression of iNOS protein was lower in the affected kidneys compared with the normal control kidneys (8.79 +/- 0.78 vs. 14.00 +/- 0.83 arbitrary unit, P < 0.01). There was a negative correlation between iNOS expression and histological grading in congenital hydronephrosis. The iNOS expression also correlated negatively with renal interstitial fibrosis, TGF-beta1 level and tubular cell apoptosis. CONCLUSION: Our study confirmed the down-regulation of iNOS expression in affected kidneys from rats with congenital hydronephrosis, in which the cytoprotective effect of NO may be lost or weakened.

Increased transforming growth factor-beta1 and tubulointerstitial fibrosis in rats with congenital hydronephrosis.

OBJECTIVES: Most of our knowledge concerning renal obstruction has been derived from experimental animal models, and it is not yet well defined in spontaneous hydronephrosis. The aim of our study is to evaluate the roles of transforming growth factor-beta1 (TGF-beta1) and apoptosis in congenital hydronephrotic kidneys in comparison with experimental models. METHODS: We made histological studies on kidneys from 6-week-old Wistar-Imamichi rats with congenital unilateral hydronephrosis as well as surgical models of complete or partial unilateral ureteral obstruction. The severity of hydronephrotic kidneys was evaluated on routine hematoxylin and eosin (H&E) stained sections, and the tubulointerstitial fibrosis analyzed morphometrically on Masson's trichrome stained sections. Renal tubular atrophy was assessed on periodic acid Schiff (PAS) stained sections, and tubular cell apoptosis assessed with TUNEL technique. The renal TGF-beta1 level was determined by a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a significant loss of kidney weight with profound compensatory growth of the contralateral kidney in rats with congenital hydronephrosis. Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, renal parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. The renal TGF-beta1 level was markedly elevated in hydronephrotic kidneys as compared with normal controls (326.01 +/- 30.64 pg/mg protein vs 227.81 +/- 11.07 pg/mg protein, P < 0.01). The tubular apoptotic score in hydronephrotic kidneys was also significantly higher than normal controls (2.17 +/- 0.50/HPF [high power field]vs 0.14 +/- 0.04/HPF, P < 0.01). The increased TGF-beta1 and apoptotic status paralleled the histological changes of tubulointerstitial fibrosis and tubular atrophy. Similar findings were also obtained in experimental obstructive models. CONCLUSION: In comparison with surgical models of partial and complete ureteral obstruction, our data provide solid morphological and molecular evidences of renal obstruction in rats with congenital hydronephrosis.