Clinical and immunohistochemical evidence for an X linked retinitis pigmentosa syndrome with recurrent infections and hearing loss in association with an RPGR mutation.
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Biomedical subjects
Publications and source records attributed to F Baldi.
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Neoplastic transformation of heterotopic cervical salivary gland tissue is extremely rare. The Authors describe a case of pleomorphic adenoma arising in this tissue, on the right side of the neck in a 40-year old man. The characteristics of salivary heterotipias of the neck, and their diagnostic difficulties and histogenetic problems are reviewed.
Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone, and it is a fundamental element in the diagnosis of spondyloarthropathies. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and the late alterations (erosions and enthesophytes); it is also an inexpensive, biologically harmless and easily repeatable technique. The aim of this study was to compare the prevalence of quadricipital enthesitis in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document any clinical and echostructural differences in this lesion between the two diseases. The results show that enthesitis is more frequent in PsA patients, more than half of whom are asymptomatic. Knee inflammation was found in the PsA patients with enthesitis regardless of the concomitant presence of joint effusion; none of the RA patients suffered from enthesitis alone. Quadricipital enthesitis is more frequent in male patients. There was no significant correlation between the presence of peripatellar psoriatic lesions and enthesitis. Sonographic examinations of patients with enthesitis revealed that those with RA had dominantly inflammatory lesions, whereas PsA patients also showed major new bone deposition.
Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone, and it is a fundamental element in the diagnosis of spondyloarthropathies. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and late alterations (erosions and enthesophytes); it is also an inexpensive, biologically harmless and easily repeatable technique. The aim of this study was to compare the prevalence of quadricipital enthesitis in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document any clinical and echostructural differences in this lesion between the two diseases. The results show that enthesitis is more frequent in PsA patients, more than half of whom are asymptomatic. Knee inflammation was found in the PsA patients with enthesitis regardless of the concomitant presence of joint effusion; none of the RA patients suffered from enthesitis alone. Quadricipital enthesitis is more frequent in male patients. There was no significant correlation between the presence of peripatellar psoriatic lesions and enthesitis. Sonographic examinations of patients with enthesitis revealed that those with RA had predominantly inflammatory lesions, whereas PsA patients also showed major new bone deposition.
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OBJECTIVE: For the long term maintenance treatment of reflux esophagitis several strategies have been proposed with the aim of reducing the daily dosage or the frequency of drug administration. However, the available clinical studies are scarce and are often not controlled or conducted on a reduced number of cases. We aimed to compare the efficacy of two doses of lansoprazole (15 mg once daily and 30 mg on alternate days) in maintaining endoscopic healing and symptom relief over a 6-month period. METHODS: One hundred thirty-seven patients with Savary-Miller grades I-III reflux esophagitis healed after an 8-wk treatment with lansoprazole (30 mg daily) were divided into two main groups for a 6-month maintenance therapy period: lansoprazole, 15 mg once daily (group 15qd) and lansoprazole, 30 mg on alternate days (group 30qod). These two main groups were further subdivided according to the time of drug administration; morning (15qdm and 30qodm) and evening (15qde and 30qode). Each patient underwent esophagogastroduodenoscopy before entry into the study, after 8 wk of acute therapy, and after 6 months of maintenance therapy; 24-h esophageal-gastric pH monitoring was performed at baseline and during the last week of maintenance therapy. RESULTS: At the end of the maintenance period the recurrence of esophagitis was observed in 12.1% of group 15qd patients and in 19.0% of group 30qod patients, without significant differences between the two groups. The frequency of patients without reflux symptoms after the 6-month period was the same for both groups; however, a significant increase of heartburn was observed in group 30qod patients (from 12.1% to 28.6%, p = 0.007). The time of drug administration (morning and evening) had no influence on the outcome of treatment. Both regimens significantly reduced esophageal acid exposure time and increased the median 24-h gastric pH. CONCLUSIONS: Both long term lansoprazole regimens are equally effective in preventing the recurrence of esophagitis, independent of the modality of drug administration. The daily administration seems to have a better effect on the prevention of symptom recurrence.
BACKGROUND: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma. METHODS: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences. RESULTS: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001). CONCLUSIONS: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.
BACKGROUND/AIMS: Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. METHODS: We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). RESULTS: Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. CONCLUSIONS: Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.
The enterobacterium Klebsiella oxytoca strain BAS-10 was isolated from sediments under an iron mat formed in a stream receiving leached waters from pyrite mine tailings. Under anaerobic laboratory conditions, BAS-10 fermented Fe(III)-citrate and Na-citrate giving CH(3)COOH and CO(2). In the presence of ferric citrate, BAS-10 secreted quantities of a thick gel containing glucose and/or mannose, if not other sugars. Sugar residues were observed in microbial aggregates using the sugar-specific concanavalin A lectin conjugated with fluorescein and imaged by a scanning confocal laser microscope. The gel bound Fe(III) which quickly precipitated. During fermentation, however, half the initial Fe(III) concentration was reduced to Fe(II) which did not bind to the gel and remained in solution. BAS-10 showed a high tolerance to heavy metals. Its growth was not inhibited by 1 mM Zn-, Pb- or Cd-acetate. These cations also co-precipitated with the iron gel, suggesting a possible application of this strain for abatement of toxic metals under anaerobic conditions.
OBJECTIVE: To evaluate the efficacy of extracorporeal shock wave treatment (ESWT) in calcaneal enthesophytosis. METHODS: 60 patients (43 women, 17 men) were examined who had talalgia associated with heel spur. A single blind randomised study was performed in which 30 patients underwent a regular treatment (group 1) and 30 a simulated one (shocks of 0 mJ/mm(2) energy were applied) (group 2). Variations in symptoms were evaluated by visual analogue scale (VAS). Variations in the dimension of enthesophytosis were evaluated by x ray examination. Variations in the grade of enthesitis were evaluated by sonography. RESULTS: A significant decrease of VAS was seen in group 1. Examination by x ray showed morphological modifications (reduction of the larger diameter >1 mm) of the enthesophytosis in nine (30%) patients. Sonography did not show significant changes in the grade of enthesitis just after the end of the treatment, but a significant reduction was seen after one month. In the control group no significant decrease of VAS was seen. No modification was observed by x ray examination or sonography. CONCLUSION: ESWT is safe and improves the symptoms of most patients with a painful heel, it can also structurally modify enthesophytosis, and reduce inflammatory oedema.
Cyclin T1 was recently identified, together with cdk9 (previously named PITALRE), as part of the TAK multiprotein complex, a co-factor targeted by the human immunodeficiency virus Type 1 (HIV-1) protein named Tat, suggesting a role for this complex in transcription elongation. Although studies on mRNA and protein expression have shown that cyclin T1 is ubiquitous in adult human tissues, no data have yet been reported regarding the expression of this protein in different cell lineages. Using a polyclonal antiserum raised against cyclin T1, we investigated the pattern of expression of this protein in adult human tissues by immunohistochemistry. Cyclin T1 was expressed ubiquitously, although different levels of expression were found in various organs. Some specialized tissues, such as blood, lymphoid tissues, and cells of connective tissue origin, showed high cyclin T1 expression. These specific expression patterns are only partially justified by some well-known specialized functions of cyclin T1 in certain cell types, such as its involvement in peripheral blood lymphocytes and monocyte differentiation. The high expression level found in other tissues suggests new possible roles for cyclin T1 in cell types other than those of lymphoid tissue.
Cyclin T2a was recently identified as one of the regulatory subunits of the cdk-cyclin complex P-TEFb, the most studied positive factor in the regulation of transcription elongation. By fluorescent in situ hybridization (FISH), the gene codifying for cyclin T2a has been mapped on human chromosome 2q21. This locus also has been linked to different forms of myopathy. By use of a new specific antiserum raised against cyclin T2a, the immunohistochemical pattern of expression of cyclin T2a in human tissues has been examined and compared to that of cyclin T1, described in the previous report. The observation that immunohistochemical expression of cyclin T2a was high in skeletal muscle cells, whereas it was undetectable in two cases of centronuclear myopathy, together with its chromosomal location, suggests an involvement of the cdk9-cyclin T2a complex in this disease.
OBJECTIVE: Little information is available concerning bone mass in patients with psoriatic arthritis (PsA): the existence of less severe periarticular osteoporosis is considered possible, but there are no data concerning the existence of systemic osteoporosis. We investigated bone mineral density (BMD) in patients with PsA. METHODS: We studied 186 patients with non-axial PsA and 100 healthy subjects, equally divided into 3 groups: women of child-bearing age, women in menopause, and men. No patient had previously received steroid treatment. In all patients, evaluation was made of disease duration, inflammation indices (erythrocyte sedimentation rate, C-reactive protein), functional indices (Steinbrocker scale), and the Health Assessment Questionnaire (HAQ). BMD was measured by fan-beam x-ray densitometry of the lumbar spine, femur, and total body (evaluating the whole skeleton, as well as the spine, trunk, and upper and lower limbs). Ultrasound densitometry of the heel was also performed. RESULTS: BMD was significantly lower in the arthritic than in the healthy subjects regardless of sex, menopausal status, or age, as expressed in g/cm2 (lumbar spine 1.112 vs 1.326; femoral neck 0.870 vs 1.006; total body 1.125 vs 1.203) or by T and Z scores (lumbar T = -1.36, Z = -0.98; femoral neck T = -1.12, Z = -0.83; total body T = -1.09, Z = -0.65). Ultrasound densitometry of the heel was similarly altered (stiffness 96 vs 77; T -1.78; Z -1.29). Among the PsA patients, demineralization in at least one skeletal region was observed in 67% of premenopausal women (marked in 11%), 100% of postmenopausal women (marked in 47%), and 80% of the men (marked in 29%). In premenopausal women, demineralization did not correlate with the disease variables; in postmenopausal women and the men, it correlated with a decline in the functional indices and the HAQ score. This was confirmed by analysis of the relative risk of osteoporosis expressed in odds ratios (HAQ: 1.6; age: 1.4; years since menopause: 1.7). CONCLUSION: Demineralization was observed in more than 2/3 of our PsA patients without axial involvement. This demineralization was not related to the indices of inflammation or disease duration, but there is a delayed correlation with HAQ score, as well as age and the number of years since menopause.
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An iron-poor stream of nearly neutral pH polluted by mine tailings has been investigated for a natural phenomenon responsible for the polishing of heavy metals in mine wastewaters. A white mineralized mat, which was determined to be hydrozincite [Zn(5)(CO(3))(2)(OH)(6)] by X-ray diffraction analysis, was observed in the stream sediments mainly in spring. The precipitate shows a total organic matter residue of 10% dry weight and contains high concentrations of Pb, Cd, Ni, Cu, and other metals. Scanning electron microscopy analysis suggests that hydrozincite is mainly of biological origin. Dormant photosynthetic microorganisms have been retrieved from 1-year-old dry hydrozincite. The autofluorescent microorganisms were imaged by a scanning confocal laser microscope. A photosynthetic filamentous bacterium, classified as Scytonema sp. strain ING-1, was found associated with microalga Chlorella sp. strain SA1. This microbial community is responsible for the natural polishing of heavy metals in the water stream by coprecipitation with hydrozincite.
OBJECTIVES: The cyclin-dependent kinase p16 (also known as Ink4A, Mts1, Cdkn2, and Cdkn4i) has been proposed as a tumor suppressor gene mapped on chromosome segment 9p21. This study evaluated p16 protein expression in 135 lung cancer specimens and investigated potential genetic alterations occurring in this gene. RESULTS: We found altered p16 immunohistochemical expression to be a frequent event in lung cancer and to be independent of either the histologic type or any other clinical-pathologic feature. Western blot analyses performed on about one third of the specimens correlated highly with these results. In addition, we found p16 immunohistochemical expression to be a favorable prognostic factor in lung cancer in that its reduction or loss correlated with a worse outcome for the patients. Polymerase chain reaction amplification and direct sequencing of p16 exons 1 and 2 revealed no mutations, indicating that p16-altered expression in lung cancer is not necessarily linked to mutational events of these genes. CONCLUSIONS: We conclude that p16-altered expression is both an independent and frequent event in lung cancer and may have an important role in tumorigenesis and in malignant progression of a significant proportion of these cancers. However, the actual incidence and relevance of p16 mutations in this neoplasm continues to be debated, and its analysis seems inconclusive. Our results suggest a prognostic role for the immunodetection of this protein on formalin-fixed and paraffin-embedded specimens. They further suggest its routine use in the evaluation of the frequently unpredictable behavior of lung cancer.
The adhesion of a recently described species, Acinetobacter venetianus VE-C3 (F. Di Cello, M. Pepi, F. Baldi, and R. Fani, Res. Microbiol. 148:237-249, 1997), to diesel fuel (a mixture of C12 to C28 n-alkanes) and n-hexadecane was studied and compared to that of Acinetobacter sp. strain RAG-1, which is known to excrete the emulsifying lipopolysaccharide, emulsan. Oxygen consumption rates, biomass, cell hydrophobicity, electrophoretic mobility, and zeta potential were measured for the two strains. The dropping-mercury electrode (DME) was used as an in situ adhesion sensor. In seawater, RAG-1 was hydrophobic, with an electrophoretic mobility (&mgr;) of -0.38 x 10(-8) m2 V-1 s-1 and zeta potential (zeta) of -4.9 mV, while VE-C3 was hydrophilic, with &mgr; of -0.81 x 10(-8) m2 V-1 s-1 and zeta of -10.5 mV. The microbial adhesion to hydrocarbon (MATH) test showed that RAG-1 was always hydrophobic whereas the hydrophilic VE-C3 strain became hydrophobic only after exposure to n-alkanes. Adhesion of VE-C3 cells to diesel fuel was partly due to the production of capsular polysaccharides (CPS), which were stained with the lectin concanavalin A (ConA) conjugated to fluorescein isothiocyanate and observed in situ by confocal microscopy. The emulsan from RAG-1, which was negative to ConA, was stained with Nile Red fluorochrome instead. Confocal microscope observations at different times showed that VE-C3 underwent two types of adhesion: (i) cell-to-cell interactions, preceding the cell adhesion to the n-alkane, and (ii) incorporation of nanodroplets of n-alkane into the hydrophilic CPS to form a more hydrophobic polysaccharide-n-alkane matrix surrounding the cell wall. The incorporation of n-alkanes as nanodroplets into the CPS of VE-C3 cells might ensure the partitioning of the bulk apolar phase between the aqueous medium and the outer cell membrane and thus sustain a continuous growth rate over a prolonged period.
We developed an immunohistochemical assay specific for cyclin D1 and suitable for formalin-fixed and paraffin-embedded sections, to evaluate cyclin D1 expression in a group of 135 surgically resected lung-cancer patients for the purpose of investigating the prognostic role of this protein in lung cancer. In addition, we compared cyclin D1 expression with the expression of proliferating cell nuclear antigen (PCNA), considered to be a reliable index of the proliferation rate. We found cyclin D1 expressed in more than 60% of the neoplastic cells in 26.5% of our specimens. A total of 24.5% of the specimens showed cyclin D1 expression in a percentage of cells ranging from 30 to 60%; 36.7% of the specimens expressed cyclin D1 in less than 30% of the cells; and 12.2% of the specimens expressed cyclin D1 in less than 1% of the evaluated cells. Western blot analyses confirmed the specificity of this assay by correlating statistically in a highly significant fashion with the immunohistochemical results (P = 0.0003). Furthermore, we found a direct relationship between cyclin D1 and PCNA immunodetection (P = 0.0004), which correlated cyclin D1 overexpression with a higher tumor proliferation rate. When we analyzed our data statistically, cyclin D1 expression was found to be a negative prognostic marker (P < 0.00005) whose expression correlates with a shorter patient survival time.