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Biomedical subjects

M Rosati

Publications and source records attributed to M Rosati.

At least 19 recordsLinked to original sources

CCAAT-enhancer-binding protein beta (C/EBP beta) activates CCR5 promoter: increased C/EBP beta and CCR5 in T lymphocytes from HIV-1-infected individuals.

C/EBPbeta is a member of a family of leucine zipper transcription factors that are involved in regulating the expression of several cytokines, including IL-1, IL-6, IL-8, TNF, and macrophage-inflammatory protein-1alpha. We identified multiple C/EBPbeta binding sites within the gene for CCR5, suggesting that C/EBPbeta may be involved in its regulation. Transient transfection experiments in both myeloid and lymphoid cells showed an increase in CCR5 promoter-driven green fluorescent protein production in the presence of C/EBPbeta. Deletion analysis identified two C/EBPbeta-responsive regions in the CCR5 gene, one in the promoter region and one at the 3' part of the intron. We provide evidence that, in myeloid cells (U937), C/EBPbeta independently activates CCR5 expression through sites located either in the promoter region or in the intron of the CCR5 gene. In contrast, in lymphoid cells (Jurkat) the presence of the intronic cis-regulatory regions is required for C/EBPbeta-mediated activation. In agreement with the functional data, EMSA demonstrated that in both myeloid and lymphoid cells C/EBPbeta binds specifically to sites present in the intron, whereas interaction with the sites located in the promoter was cell type specific and was detected only in myeloid cells. Analysis of C/EBPbeta in primary PBMCs obtained from HIV-1-infected individuals revealed a significant increase in C/EBPbeta expression. The enhanced C/EBPbeta activity correlated with a higher frequency of circulating CCR5(+) lymphocytes in AIDS patients and with a decline in CD4 lymphocyte numbers. Taken together, these results suggest that C/EBPbeta is an important regulator of CCR5 expression and may play a relevant role in the pathogenesis of HIV disease.

Binding Sites↗

Assignment to chromosome 12q24.33, gene organization and splicing of the human KRAB/FPB containing zinc finger gene ZNF84.

FISH analysis was used to assign the human ZNF84 gene to chromosome 12q24.33, a region associated with recurrent breakpoints and allelic loss in several human cancers. In this report we show that the ZNF84 coding region is organized in four exons; two are dedicated to encoding the KRAB/FPB-A and KRAB/FPB-B modules, the remaining exons encode the N-terminal amino acids and C-terminal array of zinc finger units, respectively.

Amino Acid Sequence↗

Semi-inclusive lambda and K(S) production in p-Au collisions at 17.5 GeV/c

The first detailed measurements of the centrality dependence of strangeness production in p-A collisions are presented. Lambda and K(S) dn/dy distributions from 17.5 GeV/ c p-Au collisions are shown as a function of "grey" track multiplicity and the estimated number of collisions, nu, made by the proton. The nu dependence of the Lambda yield deviates from a scaling of p-p data by the number of participants, increasing faster than this scaling for nu</=5 and saturating for larger nu. A slower growth in K(S) multiplicity with nu is observed, consistent with a weaker nu dependence of K&Kmacr; production than YK production.

Journal Article↗

A variety of RNA polymerases II and III-dependent promoter classes is repressed by factors containing the Krüppel-associated/finger preceding box of zinc finger proteins.

KRAB/FPB (Krüppel-associated/finger preceding box) domains are small, portable transcriptional repression motifs, encoded by hundreds of vertebrates C2-H2-type zinc finger genes. We report that KRAB/FPB domains feature an unprecedented, highly promiscuous DNA-binding dependent transcriptional repressing activity. Indeed, template bound chimeric factors containing KRAB/FPB modules actively repress in vivo the transcription of distinct promoter classes that depend on different core elements, recruit distinct basal transcriptional apparatuses and are transcribed either by RNA polymerase II or III. The promoter types repressed in transient assays in a dose- and DNA-binding dependent, but position- and orientation-independent manner, by GAL4-KRAB/FPB fusions include an RNA polymerase II-dependent small nuclear RNA promoter (U1) as well as RNA polymerase III-dependent class 2 (adenovirus VA1), class 3 (human U6) and atypical (human 7SL) promoters. Down-modulation of all of these templates depended on factors containing the A module of the KRAB/FPB domain. Data provide further insights into the properties and mode of action of this widespread repression motif, and support the notion that genes belonging to distinct classes may be repressed in vivo by KRAB/FPB containing zinc finger proteins. The exquisitely DNA-binding dependent transcriptional promiscuity exhibited by KRAB/FPB domains may provide a unique model system for studying the mechanism by which a promoter recruited repression motif can down-modulate a large variety of promoter types.

Animals↗

Coding region intron/exon organization, alternative splicing, and X-chromosome inactivation of the KRAB/FPB-domain-containing human zinc finger gene ZNF41.

ZNF41 belongs to a cluster of human zinc finger genes residing within a gene-rich region at Xp11.23. ZNF41 encodes a KRAB/FPB (Krüppel-associated/finger preceding box) domain, a potent transcription repression motif present in hundreds of vertebrate zinc finger protein genes, composed of two protein modules, A and B. Three introns, placed at identical positions in paralogous genes, interrupt four exons encoding the ZNF41 N-terminal amino acids, the KRAB/FPB-A and KRAB/FPB-B modules, and the remaining coding region adjoined to the C-terminal zinc finger domain. Since the KRAB/FPB-A and KRAB/FPB-B modules are encoded by dedicated exons in ZNF41 and paralogous genes, exon skipping may lead to differential usage of these modules in alternative gene products. RT-PCR analysis of ZNF41 mRNAs showed that, while skipping of the KRAB/FPB-A and/or KRAB/FPB-B exons was not detected, the use of alternative donor/acceptor sites upstream of the KRAB/FPB-A exon generates multiple ZNF41 transcripts potentially encoding polypeptides differing in the N-terminal region and expressed in different tissues. The expression pattern in cell hybrids containing either active or inactive X chromosomes indicates that ZNF41, which resides within a region of the X chromosome that includes genes that are both subject to and escape X-inactivation, is susceptible to X-chromosome inactivation.

Alternative Splicing↗

Dual effect of interleukin 4 on HIV-1 expression: implications for viral phenotypic switch and disease progression.

We report that interleukin 4 (IL-4) inhibits the propagation of non-syncytia-inducing and increases the propagation of syncytia-inducing HIV-1 isolates by two mechanisms. It differentially regulates the two major HIV-1 coreceptors, CCR5 and CXCR4, in human peripheral blood mononuclear cells, increasing CXCR4 and decreasing CCR5 expression in primary CD4(+) T-lymphocytes. In addition, IL-4 stimulates the expression of all HIV-1 isolates via a transcriptional activation mechanism. The combination of these effects results in increased propagation of CXCR4-using and inhibition of CCR5-using HIV-1 strains. IL-4 also activates HIV-1 expression in primary monocytes/macrophages but does not affect CCR5 expression. These results identify IL-4 as an important regulator of HIV-1 and suggest a critical role for this cytokine in the control of viral evolution and in the phenotypic switch from non-syncytia-inducing to syncytia-inducing, which leads to accelerated disease progression.

CD4-Positive T-Lymphocytes↗

Nitrite and nitrate levels in cerebrospinal fluid of normal subjects.

In order to evaluate the involvement of nitric oxide in neurologic disorders it is important to generate controlled values of its metabolites nitrite and nitrate in human cerebrospinal fluid (CSF). Samples of CSF obtained from 14 patients without neurologic diseases were analysed for nitrite and nitrate concentration by reverse phase chromatography with ultraviolet (UV) detection. For comparison, the levels of nitrite in the same samples were also measured by reverse phase chromatography coupled with electrochemical detection and those of nitrate by ion chromatography coupled with UV detection. A good correlation was found for the concentration values of both ions obtained with the two procedures. Then, 10.41 +/- 0.47 ng/ml of nitrite and 2.92 +/- 0.37 ng/ml of nitrate could be regarded as reliable values in control subjects. No correlation between age and levels of nitrite and nitrate was observed.

Aged↗

Clinical validity of the elbow flexion test for the diagnosis of ulnar nerve compression at the cubital tunnel.

We evaluated the elbow flexion test in 216 elbows without compression of the ulnar nerve at the cubital tunnel and without other neuropathies. We used Rayan's four positions as our test. The percentage of positive tests was only 3.6% at one minute, whereas evaluating the responses at three minutes we saw positive results in 16.2%. Therefore we find that if the test is performed for one minute it may be useful to help in diagnosing ulnar nerve compression at the cubital tunnel.

Adult↗

Trapeziometacarpal joint arthrodesis for osteoarthritis. Results of power staple fixation.

Fifty-two cases of trapeziometacarpal joint osteoarthritis were treated with arthrodesis using small staple fixation. Eighty-five per cent of the patients were free of pain, with normal thumb. Opposition to the fourth finger tip was always possible and opposition to the little finger tip was observed in 94% of cases. Four patients (7.6%) developed a non-union but only two complained of pain. Arthrodesis with power staple fixation minimizes bone resection and postoperative immobilization (mean 28 days) because of the good stability following this procedure.

Adult↗

Nodular fasciitis of the hallux: difficulties in diagnosis.

Nodular fasciitis or proliferative fasciitis is currently classified as a tumor-like hyperplastic lesion of soft tissues. Histological characteristics of this lesion have often caused diagnostic problems since it can be mistaken for a malignant mesenchymal neoplasm. To highlight this we report a case of nodular fasciitis that was difficult to diagnose because of its atypical radiographic and clinical features.

Adult↗

[Biomechanical changes in and lesions of the lumbosacral spine in horse riding. Magnetic resonance assessment].

Spinal injuries account for 5-15% of sport-related traumas. Equestrian sports are considered, together with rugby, motor sport and diving, the riskiest sport for severe spinal injuries. We investigated the biomechanical changes and repeated microtraumas in equitation. We examined with MR the lumbar spines of 12 professional horsewomen and horsemen, 18-51 years old (mean: 33.4 years), belonging to F.I.S.E. (the Italian Federation for Equestrian Sports) and classified as Olympic riders, Senior and Young European riders. An 0.3-T resistive and an 0.2-T permanent magnets with dedicated surface coils were used. We also examined a control group of non-professional healthy volunteers homogeneous by age. MR findings were classified as follows: 1) changes in normal bending and angles of the lumbar spine; 2) injuries and changes in lumbar disks; 3) changes in spinal ligaments; 4) vertebral body injuries. MR was very sensitive in the assessment of all lumbosacral components in all the athletes; besides yielding useful findings to integrate with clinical results, MR also has a predictive value relative to both the continuation of sports activity and the possible damage at the end of it.

Adolescent↗

Operative laparoscopy in the management of ovarian cancer.

Advances in operative laparoscopic techniques have made possible the extension of this technology to the treatment of women with ovarian cancer. We present a detailed case series of eight patients with ovarian cancer who underwent a total of 11 operative laparoscopies for treatment of ovarian cancer ranging in stage from IA to IIIC. Three patients underwent initial laparoscopic staging and therapeutic debulking procedures. In three other cases that were incompletely staged via laparotomy, laparoscopy was used to complete the staging. Interval laparoscopic tumor debulking combined with second-look laparoscopy was performed in four cases. We describe our experience with these new applications of evolving techniques with particular regard to potential advantages, disadvantages, and complications. This detailed preliminary case series suggests the need for prospective clinical studies to establish the safety and efficacy of the approach.

Adult↗

Urinary tract endometriosis treated by laparoscopy.

OBJECTIVE: To evaluate the efficacy of the laparoscopic approach for the diagnosis and treatment of severe urinary tract endometriosis. DESIGN: Retrospective review of 28 cases of severe urinary tract endometriosis. SETTING: Center for Special Pelvic Surgery, a tertiary referral center. PATIENT(S): Between October 1989 and September 1994, we treated 28 women who had deeply infiltrating urinary tract endometriosis (bladder, 7, ureter, 21). INTERVENTION(S): All procedures were performed laparoscopically. MAIN OUTCOME MEASURE(S): Postoperative urinary function, pain relief, and complications. RESULT(S): Those who had vesical endometriosis underwent partial cystectomy and primary repair. Partial ureteral obstruction was found in 17 women; 10 underwent ureterolysis and excision of endometriosis, and 7 had partial wall resection. Four patients with ureter involvement had complete obstruction. Three underwent partial resection and ureteroureterostomy, and one had ureteroneocystostomy. The rate of ureteral endometriosis in the present series is higher than that reported previously. CONCLUSION(S): Severe infiltrative endometriosis of the bladder and the ureter can present without specific symptoms and can cause silent compromise of renal function. We demonstrated that the laparoscopic approach is safe and effective in the diagnosis and treatment of this entity.

Adult↗

Osteoid osteoma of the carpus. Case reports and a review of the literature.

Osteoid osteoma mainly affects long bones, and is rarely observed at the hand. The authors report three cases of osteoid osteoma in the carpus (one case in the scaphoid, one in the triquetral, one in the capitate), treated by removal of the entire nidus. No bone grafting or intercarpal arthrodesis was necessary. There were no recurrences.

Adult↗