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Biomedical subjects

A Rocca

Publications and source records attributed to A Rocca.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Echographic aspects of renal tuberculosis].

In this study the Authors examine the utility of the ultrasonographic investigation in the preoperative evaluation of 22 patients submitted to nephrectomy for tubercular lesions, comparing the informations obtained from this procedure with the histologic report. The renal ultrasonography execute with a Toshiba 3.5 Mhz probe, has been utilized to value morphology, volume, parenchymal echostructure and hydronephrosis. According to the Author's series, the ultrasonography has shown a 100% sensitivity permitting to well value the presence of parenchymal lesions and hydronephrosis. As regards the tubercular renal injuries the ultrasonography is non-specific because it does not allow to have pathognomonic images. The results obtained from the U.S. are overlapping to the Results Related from the literature for abdominal CT. The Authors argue that U.S., rapid and economical investigation is an efficient complement to the urography for an exhaustive preoperative evaluation of patients suffering from renal Tuberculosis.

Humans↗
PubMed1995

Role of light chain variable region in myeloma with light chain deposition disease: evidence from an experimental model.

Light chain deposition disease (LCDD) results from a propensity of some human monoclonal L chains to form tissue deposits. We designed an experimental model for in vivo expression of human kappa L chain sequences in mice and compared a somatically mutated LCDD chain with a closely related control kappa chain, both encoded by the unique V kappa IV gene. Mice secreting the LCDD chain but not those producing the control chain showed deposits with a distribution similar to that observed in patients. These data show that discrete changes in V region sequences can play a major role in tissue deposition of human L chains.

Amino Acid Sequence↗
PubMed1995

Sequences of V kappa L subgroup light chains in Fanconi's syndrome. Light chain V region gene usage restriction and peculiarities in myeloma-associated Fanconi's syndrome.

Certain monoclonal Ig light chains (LC) are responsible for marked disturbances of proximal tubule cell functions (Fanconi's syndrome, FS). In patients with FS, intracellular crystal-like inclusions containing LC determinants are commonly found in plasma cells, macrophages, and renal tubular cells. In an attempt at understanding the pathogenesis of myeloma-associated FS, we recently determined the first complete primary sequence of a kappa-LC (CHEB) responsible for the disease. We now report on the primary structure of three other kappa-LC of the V kappa l variability subgroup associated with FS (TRE, TRO, and DEL). After PCR amplification, cDNA encoding these LC were sequenced. CHEB, TRE, and TRO LC genes were found to be highly homologous to the same germline gene O2/O12. These patients had numerous intracellular crystals, whereas the fourth patient, DEL, had no detectable crystals. The LC from the latter patient was homologous to another germline gene, O8/O18. Comparison of these LC sequences to previously reported LC of the V kappa l subgroup allowed identification of a number of unusual amino acid substitutions in the V region that had rarely or never been previously described at the corresponding positions. Some of these unusual substitutions affect highly conserved amino acids located either in an external loop (residue 30) or in inner (residues 48 and 55) and outer (positions 63 and 72) beta-sheets that may be important for the structure and binding properties of the kappa-chains. These and several other substitutions, some of them shared with amyloidogenic kappa-LC, could induce conformational alterations and represent a determinant pathogenic factor.

Amino Acid Sequence↗
PubMed1995

Protease resistance and binding of Ig light chains in myeloma-associated tubulopathies.

Kidney tubule dysfunction and lesions are frequent complications of myeloma, related to unknown properties of the monoclonal light chain. We have analyzed protease sensitivity and binding properties of urinary light chains from four patients with Fanconi's syndrome, 12 with cast nephropathy, and four control patients without myeloma-associated tubulopathy. All light chains were normal-sized, monomeric and/or dimeric, and none was N-glycosylated. Kinetic studies of light chain digestion by pepsin and the lysosomal enzyme cathepsin B showed the generation of a protease-resistant 12 kDa fragment, corresponding to the V domain of the kappa chain in the four Fanconi's syndrome patients; in two out of four the V domain was also completely resistant to trypsin. Western and dot blots revealed similar patterns of reactivity of light chains from patients with the Fanconi's syndrome towards other light chains. Properties of cast-nephropathy light chains were more heterogeneous but clearly differed from those of Fanconi's syndrome: (i) 9 out of 12 were of the lambda-type; (ii) only four yielded a transient 12 kDa fragment after cathepsin B digestion, but all showed some resistance to proteolysis of the entire molecule or a fragment thereof to at least one protease, at variance with control light chains; (iii) they displayed various patterns of reactivity with other light chains; (iv) 7 out of 12 reacted specifically with Tamm-Horsfall protein (THP) by ELISA, in contrast with those of Fanconi's syndrome. In one patient who presented with cast nephropathy and the Fanconi's syndrome, the light chain exhibited both partial resistance of the V kappa domain to cathepsin B and the highest reactivity with THP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

[Reconstruction of the skin of the lower eyelid by orbito-nasolabial flap].

The orbitonasolabial flap has been known for a long time. The author considers that it has an important place for the cutaneous reconstruction of the lower lid. The surgical anatomy of the naso-labial area is reviewed before presenting a detailed technical description. This flap was used in 26 cases of repair of defects, usually following resection of a lower lid skin carcinoma. Advantages and drawbacks of this flap, dedicated to the reconstruction of the lower lid skin, are analysed, before a comparative study of other flaps. This method of reconstruction is simple, effective, and can be performed in a one-stage operation. It can therefore be proposed in elderly people and its application can be extended.

Adult↗
PubMed1995

Relevance of intravenous cocaine use in relation to prevalence of HIV, hepatitis B and C virus markers among intravenous drug abusers in southern Italy.

The purpose of this study was to analyze the relationship between intravenous (i.v) drug use practices and the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in 146 heterosexual male i.v. drug users (IVDUs) attending a methadone-maintainance treatment program in Catanzaro, Southern Italy. One hundred and forty-six heterosexual male IVDUs attending a methadone-maintainance treatment program in Catanzaro were interviewed in order to obtain the following information: age, number of drug injections (calculated by multiplying the mean number of daily injections by 365 and then by the number of years of injections), number of injection equipment-sharing partners in the last year, number of sexual partners in the last year and possible IV cocaine use. Their sera were studied for the presence of antibodies to HIV, HBV and HCV by commercial enzyme-linked-immuno-sorbent assays run in duplicate. HIV positive samples were confirmed by Western Blot assay. Sixteen per cent of IVDUs were anti-HIV positive, 40% were anti-HBc positive and 68% were anti-HCV positive. Twenty-three per cent were seronegative and 12% were seropositive for all 3 viral markers. Multiple logistic analysis of HIV, HBV and HCV seropositivities in relation to age, number of drug injections, i.v. cocaine use and presence of injection equipment-sharing partners in the last year, showed that: a) older age (more than 27 years) was significantly associated with all 3 viral infections (mainly with HIV); b) i.v. cocaine use was associated with HBV, but even more with HIV; c) injection equipment-sharing partners in the last year was directly associated with HCV and inversely with HIV. No significant association was observed with the number of drug injections and the number of sexual partners. In conclusion, this study: a) demonstrates a difference of prevalence for HIV, HBV and HCV serum markers in this group of IVDUs from Catanzaro, Southern Italy; b) underlines the importance of i.v. cocaine use in the spreading of HIV; c) emphasizes the need of preventive strategies.

Adolescent↗
PubMed1994

The effect of intron sequences on expression levels of Ig cDNAs.

Several cDNA expression vectors were constructed and tested by stable transfection into a murine lymphoid cell line in order to compare secretion rates of a human immunoglobulin (Ig) light chain (LC). When the cDNA was under transcriptional control of the SV40 promoter and enhancer and preceded by the SV40 19S late mRNA intron, a weak LC production was detected. Secretion rate was not improved by replacing the SV40 promoter and enhancer by a combination of a murine Ig heavy chain (HC) gene promoter and enhancer even with insertion of additional Ig enhancers. In contrast, replacement of the 19S intron by a large intron derived from a human Ig HC gene and containing the intronic enhancer dramatically increased the secretion rate. High-level production was also obtained with the same enhancer-containing intron placed downstream from the LC cDNA. Stable transfectants were obtained that secreted the human LC in amounts comparable to those obtained with Ig genes. Our results suggest that the SV40 19S late mRNA intron used in several expression vectors is not appropriate when the purpose is to produce large amounts of antibody molecules. By providing transcriptional, splicing and polyadenylation signals, the presently described vectors will be useful for easy cloning and high-level expression in lymphoid cells of cDNAs or PCR products encoding antibody molecules.

Animals↗
PubMed1993

Cross-reactivity among evolutionarily distant major histocompatibility complex class I molecules (HLA-B27 and H-2Kk) revealed by xenoreactive T lymphocytes.

A set of mouse HLA-B27-reactive cytotoxic T lymphocyte clones were found to recognize the HLA-B27 molecule in an H-2-unrestricted manner, i.e. independently of any mouse major histocompatibility complex (MHC) molecule. The reactivity patterns of these clones on HLA-B27 variants (positive only on HLA-B*2702 and HLA-B*2701) allowed the identification of residues N77 and A81 of the HLA-B27 molecule as important for their reactivity. The location of these residues in the peptide-binding groove (specificity pocket F) suggested that the reactivity of the clones is dependent on HLA-B27-bound peptide(s). However, several other class I molecules sharing these residues (N77 and A81) were not recognized, indicating that other residues might also be involved. One of the clones was found to display an interesting cross-reactivity with allogeneic H-2Kk molecules, sharing N77 and A81 with HLA-B*2702. Sequence comparison suggested the involvement of residue H9, located in specificity pocket B of the peptide-binding groove, and revealed some similarity of pockets B in HLA-B27 and H-2Kk. The structural basis of such T cell-mediated MHC cross-reactions across species barriers is discussed.

Amino Acid Sequence↗
PubMed1993

Combined modality treatment for primary gastrointestinal non-Hodgkin's lymphoma: the Milan Cancer Institute experience.

BACKGROUND: The study analyzes clinical-pathologic features, treatment and outcome of all patients with primary lymphoma of the gastrointestinal tract (GI-NHL) seen during the past two decades at the Milan Cancer Institute. SUBJECTS AND METHODS: Clinical and histopathological data from 135 patients presenting with GI-NHL and disease localized within the abdomen were reviewed. Of these, 114 (84%) presented with limited disease (stage I and II), while 21 patients were found to have disease involvement of other abdominal organs (i.e., liver, pancreas, peritoneum) or more than one gastrointestinal site and were therefore classified as stage IV. Seventy-three percent presented with lymphoma in the stomach, 15% in the small intestine and 9% in the large bowel, while in 5 cases multiple localizations of the gastrointestinal tract were documented. Median age was 50 years, with one-fourth of patients older than 60 years. According to the revised Kiel classification for GI-NHL, 61% of patients presented with pure high-grade lymphoma, 9% high-grade NHL associated with residual low-grade lymphoma, and 30% had low-grade NHL. Nine percent presented with bulky disease, 5% with elevated LDH and 21% with a Karnofsky performance status (PS) < or = 80. RESULTS: Laparotomy with radical (108 patients) or palliative (15 patients) intent was performed in all patients who were not deemed at high risk of complication from major surgery. Complete removal of all measurable tumor was feasible in 101 patients, with no difference relative to primary site. Surgical morbidity and mortality were 11% and 2%, respectively. Overall, 83% of patients were treated with chemotherapy. Patients who did not receive systemic chemotherapy included 12 managed with surgery alone and 10 who received only postoperative irradiation mainly because of low-grade lymphoma with superficial disease. Of patients with limited disease, 99% achieved complete tumor remission. After a median follow-up of 73 months, 13 of 113 patients have relapsed, mostly (70%) outside the gastrointestinal tract. The actuarial 10-yr. freedom from progression (FFP) and overall survival (OS) were 84% and 86%, respectively. Aside from age, no other factor revealed a statistically significant impact on outcome. There was only a trend in favor of low-grade histology (FFP 97% vs. 79%), that failed to reach statistical significance. Of patients with advanced abdominal disease, 48% achieved complete remission with chemotherapy with or without prior surgical debulking. Actuarial 10-yr. FFP and OS were 44% and 42%, respectively. In this subset, tumor burden and LDH levels represented the most important prognostic factors affecting outcome. CONCLUSIONS: This retrospective study underscores the good results obtained in a wide and unselected population of patients with limited-stage primary GI-NHL following a combined-modality approach that included surgical debulking and systemic chemotherapy for most patients. Surgery alone can be considered adequate treatment for patients with low-grade NHL disease that does not infiltrate beyond the submucosa. Patients with advanced GI-NHL show a long-term outcome similar to that of patients with advanced NHL arising outside the gastrointestinal tract.

Aged↗
PubMed1993

Primary structure of a variable region of the V kappa I subgroup (ISE) in light chain deposition disease.

Although structural abnormalities of monoclonal immunoglobulin light chains (LC) are suspected to play a determinant role in non-amyloid light chain deposition disease (LCDD), this condition is as yet poorly documented at the molecular level, since only three sequences have been reported to date. In a case of myeloma-associated LCDD, the patient's urine contained an unglycosylated kappa Bence Jones protein made up of dimers and monomers with an apparent molecular mass of 25,000 which was assigned to the V kappa I subgroup by N-terminal amino acid sequencing. The complete variable region sequence of the monoclonal kappa chain produced by the malignant plasma cells was amplified by polymerase chain reaction (PCR) using small amounts of material obtained by bone marrow aspiration. The sequence of three independently amplified cDNA clones derived from a normal-sized kappa messenger RNA was identical to that of the urinary kappa chain. The kappa mRNA had an overall normal structure made up of a V kappa I sequence rearranged to J kappa I. Several unusual features of the variable region (the first complete V kappa I sequence reported in LCDD) included three substitutions that introduced hydrophobic residues at spatially close positions. The strategy associating N-terminal sequence determination and cDNA cloning by PCR could help in accumulating new sequence data and improving our understanding of LCDD pathogenesis.

Amino Acid Sequence↗
PubMed1993

Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas.

PURPOSE: A single-center, prospective, nonrandomized trial was conducted to evaluate therapeutic results of a short-term program of chemotherapy followed by locoregional radiotherapy in stage I or II intermediate/aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1985 to 1990, 183 consecutive patients with a diagnosis of NHL (Working Formulation [WF] E through J excluding Burkitt's type), Ann Arbor stage I or II, and no more than three sites of disease involvement were treated with four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (six cycles in partial responders). Radiation therapy to initial sites of disease involvement (40 to 44 Gy) and to proximal uninvolved nodal region (36 Gy) was delivered shortly after completion of the chemotherapy program. RESULTS: The complete remission (CR) rate was 98% at the end of combined therapy. Diagnostic excision of all measurable disease was performed in 33% of patients. In the remaining patients, 87% achieved CR with chemotherapy and 11% with radiation therapy, while three patients failed to achieve CR. After a median follow-up of 51 months, 26 patients have relapsed and 25 have died. The 5-year relapse-free and total survival rates were 83%. Aside from age older than 60 years, no other factor such as histology, stage, extranodal disease, bulky lymphoma, or abnormal lactic dehydrogenase (LDH) could predict for treatment outcome. There was a trend toward higher relapse rate for patients achieving CR at the time of radiation therapy (31%) as opposed to patients achieving CR with chemotherapy (15%) or with initial surgery (10%). Treatment was well tolerated and no deaths due to acute toxicity were observed. CONCLUSION: For patients who present with limited-stage, aggressive NHL, a short course of CHOP chemotherapy followed by locoregional irradiation is safe, highly effective, and curative for most. Therefore, at the present time this approach can be regarded as standard therapy for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Lingual schwannoma. Apropos of 2 clinical cases].

In the light of two cases of benign schwannomas of the tongue, including one particularly large tumour, the authors review the clinical and histological features and natural history of these tumours. Their rarity may explain the limited knowledge concerning these tumours and the long interval prior to treatment, resulting in technical difficulties due to their volume. Surgical enucleation is generally easy to perform. The prognosis is excellent after resection, as malignant transformation is exceptional.

Adult↗
PubMed1992

Localization of the conformational alteration of MHC molecules induced by the association of mouse class I heavy chain with a xenogeneic beta 2-microglobulin.

Changes in the antigenicity of major histocompatibility complex (MHC) class I molecules resulting from the association of bovine beta 2-microglobulin (beta 2-m) with mouse class I heavy chains were investigated. Mice (H-2b) were immunized with syngeneic Concanavalin A (Con A) blasts induced in the presence of fetal calf serum (FCS) in conditions allowing exchange between mouse and bovine beta 2-microglobulin (beta 2-m). Spleen cells from hyperimmunized mice were fused with myeloma cells and two monoclonal antibodies which required for their reactivity the presence of FCS have been further studied. One of them (CAB 297) recognized a determinant of bovine beta 2-m which is present on free molecules in solution as well as when they are associated with either mouse or bovine class I heavy chains. In contrast, the second monoclonal antibody (CBB 70) did not react with free bovine beta 2-m molecules, nor with beta 2-m associated with bovine class I heavy chains. It did react with cells of some H-2 haplotypes (b, f, p and r) but only when their class I heavy chains are associated with bovine or with human beta 2-m. Therefore, expression of the CBB 70 defined antigenic determinant requires both xenogeneic beta 2-m and class I heavy chain of a given H-2 molecule. In order to precisely localize the antigenic determinant defined by this monoclonal antibody and therefore the region altered by the association of class I heavy chain with xenogeneic beta 2-m, we made use of exon shuffled class I molecules. The results indicate that changes induced by the association of bovine beta 2-m with H-2 class I heavy chain affect the conformation of the alpha 2 domain. These studies illustrate that MHC class I molecules exhibit a considerable conformational flexibility which could influence their ability to bind and present various peptides to the T-cell receptor.

Animals↗
PubMed1992

Protection against Chlamydia psittaci in mice conferred by Lyt-2+ T cells.

A murine model was used to study the respective roles of L3T4+ and Lyt-2+ T cells in protection against Chlamydia psittaci. Donor mice were intravenously (i.v.) infected with 1 x 10(5) plaque-forming units (PFU) per mice of live C. psittaci. One month after inoculation, splenic cells from donors were transferred into syngenic recipients (5 x 10(7) cells/mouse). As measured by splenic colonization on Day 6 after i.v. challenge (1 x 10(5) PFU/mouse), transfer with primed (untreated) cells conferred a 3 log protection in this model. In vitro treatment, before transfer, of splenic cells with anti-Lyt-2 monoclonal antibody (mAb) and complement, markedly impaired the protection in comparison with control mice transferred with primed untreated cells, whereas treatment with anti-L3T4 mAb did not reduce the transferred protection. Resistance to a reinfection with C. psittaci was also studied after selective in vivo depletion of L3T4+ and Lyt-2+ T cells. One month after primary infection, mice were treated with anti-L3T4 or anti-Lyt-2 mAb and challenged thereafter (i.v., 1 x 10(5) PFU). The splenic colonization on Day 6 after challenge demonstrated that treatment with anti-Lyt-2 mAb impaired resistance against a subsequent infection with C. psittaci. Treatment with anti-L3T4 mAb in vivo had no effect on protection, as previously described in vitro. The mechanisms by which Lyt-2+ T cells could participate in the elimination of bacteria were discussed.

Animals↗