Densitometric kneecap changes after unilateral knee arthroplasty.

PURPOSE: To assess bone density of kneecaps in subjects with femoro-tibial prosthesis before and after surgery by means of DEXA examination. SUBJECTS AND METHODS: We examined 34 patients with unilateral femoro-tibial prosthesis, 20 healthy subjects of the same age and non-carriers of knee replacement and 14 healthy young adult subjects. All the data sets were analysed by two radiologists (AS and AM). The coincidence of the results between the two specialists was evaluated by means of Cohen's Kappa index and the results were considered statistically significative if p value is < of 0.05. RESULTS: The values of patellar BMD in the group of 34 patients, were: a minimum of 0.386 g/cm(2) (K = 0.879, p = 0.0012), a maximum 1.707 g/cm(2) (K = 0.886, p = 0.0016). The comparison between the left and right knee showed the following data: minimum difference 0.034 g/cm2 (K = 0.901, p = 0.0015), maximum difference of 0.622 g/cm(2) (K = 0.908, p = 0.0017), the average was found to be of 0.277 g/cm(2) (K = 0.894, p = 0.0018). But this difference tends to decrease 6 months after surgery. In the group of healthy young adults, we obtained the following values: a minimum of 0.782 g/cm(2) (K = 0.907, p = 0.0025), maximum 1.503 g/cm(2) (K = 0.932, p = 0.0012). Between both knees, the difference was minimal 0.006 g/cm(2) (K = 0.951, p = 0.0035) and maximum 0.096 g/cm(2) (K = 0.926, p = 0.0007) with an average difference of 0.058 g/cm(2) (K = 0.954, p = 0.0026). In the group of healthy subjects of the same age and non-carriers of knee replacement the values were average higher. A maximum value of 1.134 g/cm(2) (K = 0.894, p = 0.0028) and a minimum value of 0.944 g/cm(2) (K = 0.892, p = 0.0023) were found; between both knees a minimum difference of 0.010 g/cm(2) (K = 0.918, p = 0.0047) and a maximum of 0.090 g/cm(2) (K = 0.937, p = 0.0017) were found, with an average difference of 0.052 g/cm(2) (K = 0.956, p = 0.0024). CONCLUSIONS: DEXA examination of the patellar is recommended as a supplementary study to the clinical and radiological standard exams because it is able to provide additional information to determine when to intervene surgically, on the basis of patellar bone density values.

Human prostatic urethra expresses vitamin D receptor and responds to vitamin D receptor ligation.

BACKGROUND: Chronic inflammation is now considered a determinant of benign prostatic hyperplasia (BPH), promoting, together with the hormonal milieu, prostate overgrowth and lower urinary tract symptoms (LUTS). Prostatic urethra actively participates in determining progression of LUTS associated with BPH. AIM: To investigate the expression of the vitamin D receptor (VDR) and the ability of the VDR agonist elocalcitol to reduce inflammatory responses in human prostatic urethra (hPU) cells. MATERIALS AND METHODS: Human prostatic urethra, prostate and bladder neck were obtained from patients affected by BPH. Immunohistochemical studies for VDR expression were performed in tissue samples, from which primary cell cultures were also derived. In hPU cells, proliferation and chemiotaxis were studied, along with Rho kinase (ROCK) activity (MYPT-1 phosphorylation) by western blot. Quantitative RT-PCR was performed for VDR, cyclooxygenase (COX-2), and interleukin (IL)-8 expression. RESULTS: Urethra displays higher VDR expression compared to prostate and bladder neck tissues. The VDR agonist elocalcitol partially reverts COX-2 and IL-8 mRNA upregulation induced by a pro-inflammatory cytokine mixture (IL-17, interferon-γ, tumor necrosis factor-α) and inhibits cell migration in urethral cells. Elocalcitol prevents activation of ROCK, as previously demonstrated in bladder and prostate cell cultures. CONCLUSIONS: Our results suggest that prostatic urethra is, within the lower urinary tract, a novel target for VDR agonists, as shown by the capacity of elocalcitol to inhibit ROCK activity and to limit inflammatory responses in human primary urethra cells.

Regulation of the human HBA genes by KLF4 in erythroid cell lines.

KLF1/EKLF and related Krueppel-like factors (KLFs) are variably implicated in the regulation of the HBB-like globin genes. Prompted by the observation that four KLF sites are distributed in the human alpha-globin gene (HBA) promoter, we investigated if KLFs could also act to modulate the expression of the HBA genes. Among the KLFs tested, only KLF4/GKLF bound specifically to three out of four alpha-globin KLF sites. The occupancy of the same sites by KLF4 in vivo was confirmed by chromatin immunoprecipitation assays with KLF4-specific antibodies. In luciferase reporter assays in MEL cells, high levels of the wild type HBA promoter, but not mutated promoters bearing point mutations that disrupted KLF4-DNA binding, were transactivated by over-expression of KLF4. In K562 cells, induced KLF4 expression with a Tet-off regulated cassette stimulated the expression of the endogenous HBA genes. In a complementary assay in the same cell line, knocking down KLF4 with lentiviral delivered sh-RNAs caused a parallel decrease in the transcription of the HBA genes. All experiments combined support a regulatory role of KLF4 in the control of HBA gene expression.

[Collateral effects of intraoperative hyperthermic chemotherapy in peritoneal carcinomatosis]. / Effetti collaterali della ipertermochemioterapia intraoperatoria nel trattamento della carcinosi peritoneale.

The association between chemotherapy and hypertermia produces a synergic effect. In this study the Authors present their experience, by the analysis of the results. From 1993 to 2000, 17 patients have been treated with surgery associated with hypertermic chemotherapy for peritoneal carcinomatosis. For the management of these patients a constant cooperation among surgeon, cardiologist and anaesthetist is very important.

Purification of the aldehyde oxidase homolog 1 (AOH1) protein and cloning of the AOH1 and aldehyde oxidase homolog 2 (AOH2) genes. Identification of a novel molybdo-flavoprotein gene cluster on mouse chromosome 1.

We report the cloning of the AOH1 and AOH2 genes, which encode two novel mammalian molybdo-flavoproteins. We have purified the AOH1 protein to homogeneity in its catalytically active form from mouse liver. Twenty tryptic peptides, identified or directly sequenced by mass spectrometry, confirm the primary structure of the polypeptide deduced from the AOH1 gene. The enzyme contains one molecule of FAD, one atom of molybdenum, and four atoms of iron per subunit and shows spectroscopic features similar to those of the prototypic molybdo-flavoprotein xanthine oxidoreductase. The AOH1 and AOH2 genes are 98 and 60 kilobases long, respectively, and consist of 35 coding exons. The AOH1 gene has the potential to transcribe an extra leader non-coding exon, which is located downstream of exon 26, and is transcribed in the opposite orientation relative to all the other exons. AOH1 and AOH2 map to chromosome 1 in close proximity to each other and to the aldehyde oxidase gene, forming a molybdo-flavoenzyme gene cluster. Conservation in the position of exon/intron junctions among the mouse AOH1, AOH2, aldehyde oxidase, and xanthine oxidoreductase loci indicates that these genes are derived from the duplication of an ancestral precursor.

Perianal Crohn's disease.

A 13-year-old girl with a history of 4 months of perianal skin lesions is described. Physical examination revealed three 0.5 I 1-cm red, swollen, fleshy, skin tags extending from the perianal area to the perineum (Fig. 1). The patient reported intermittent fever, diarrhea, and abdominal pain, and her body weight was below the third percentile for her age. Laboratory studies showed an erythrocyte sedimentation rate of 101 mm/h; hematocrit of 26%; white blood cell count of 9800/mm3; serum iron of 15 mg/L (normal value (NV), 60-160 mg/L); ferritin of 43.4 microg/L (NV, 12-150 microg/L); transferrin of 203 mg/100 mL (NV, 200-400 mg/100 mL); transferrin saturation of 6% (NV, 20-50%); hypoalbuminemia; negative purified protein derivative (PPD), cytomegalovirus (CMV), human immunodeficiency virus (HIV), venereal disease research laboratory (VDRL), and antinuclear antibody tests; and Toxoplasma titers of 1/16, Van de Kamer 1.67 g/day. A barium examination revealed marked irregularity of the descending colon, and a colonoscopy showed uneven areas of mucosal edema and pseudopolyps in the transverse and descending colon, associated with irregular thickening and stenosis. Histopathologically, large intestine and skin lesions consisted of noncaseating epithelioid and giant cell granulomas (Fig. 2). Cultures for acid-fast bacilli and fungi were negative, and under polarized light no foreign bodies were seen. Treatment with metronidazole (250 mg three times a day), prednisone (0.5 mg/kg/day), and acetylsalicylic acid (75 mg/kg/day) was moderately effective. Vitamin, folic acid, and iron supplements were also added.

Cloning of the cDNAs coding for two novel molybdo-flavoproteins showing high similarity with aldehyde oxidase and xanthine oxidoreductase.

The cDNAs coding for two novel mouse molybdo-flavoproteins, AOH1 and AOH2 (aldehyde oxidase homolog 1 and 2), were isolated. The AOH1 and AOH2 cDNAs code for polypeptides of 1336 amino acids. The two proteins have similar primary structure and show striking amino acid identity with aldehyde oxidase and xanthine oxidoreductase, two other molybdo-flavoenzymes. AOH1 and AOH2 contain consensus sequences for a molybdopterin-binding site and two distinct 2Fe-2S redox centers. In its native conformation, AOH1 has a molecular weight consistent with a homotetrameric structure. Transfection of the AOH1 and AOH2 cDNAs results in the production of proteins with phenanthridine but not hypoxanthine oxidizing activity. Furthermore, the AOH1 protein has benzaldehyde oxidizing activity with electrophoretic characteristics identical to those of a previously identified aldehyde oxidase isoenzyme (Holmes, R. S. (1979) Biochem. Genet. 17, 517-528). The AOH1 transcript is expressed in the hepatocytes of the adult and fetal liver and in spermatogonia. In liver, the AOH1 protein is synthesized in a gender-specific fashion. The expression of AOH2 is limited to keratinized epithelia and the basal layer of the epidermis and hair folliculi. The selective cell and tissue distribution of AOH1 and AOH2 mRNAs is consistent with the localization of the respective protein products.

Computed tomography of bowel wall in patients with Crohn's disease: relationship of inflammatory activity to biological indices.

Bowel wall thickening in Crohn's disease can be demonstrated by Computed Tomography. The aim of this investigation was to correlate different patterns of bowel wall thickening, detected with Computed Tomography, with serological parameters of activity of Crohn's disease. Thirty-eight patients (24 males, 14 females, aged 21 to 62 years) were studied. Patients were divided into 3 groups according to Computed Tomography appearance of bowel wall: 1) homogeneous symmetrical thickening of wall; 2) bowel showing a layer of submucosal low attenuation; 3) scarred narrowing of wall producing stenosis. A patient was considered to have biochemically active disease if at least 2 of the following parameters were abnormal: ESR, C-reactive protein, seromucoids, serum albumin, serum alpha-2 globulin. The first group comprised 20 patients (16 active disease, 4 inactive) and the second group 13 (all inactive); the 2 groups showed a significant difference (Fisher exact test: p < 0.0005) in biological activity. Since only 5 patients belonged to the third group (3 active, 2 inactive disease), no definite conclusion can be drawn on the possible correlation between this Computed Tomography pattern and activity of disease. Results shows a correlation between Computed Tomography patterns of bowel wall disease and biochemical activity of Crohn's disease.