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Biomedical subjects

A Carbone

Publications and source records attributed to A Carbone.

At least 451 records · Page 25Linked to original sources

Effectiveness of a rapid immunohistologic method for tumor cell origin analysis.

A rapid immunohistologic method is described to analyze the possible cell origin of a given neoplasm during surgery by using selected examples of monoclonal and polyclonal antibodies (anti-cytokeratins, anti-vimentin, anti-leukocyte common antigen, and anti-keratin). This rapid (26-28 min) procedure, consisting of a two-step immunoperoxidase method, did not differ in terms of intensity and specificity of the immunoreaction from the control procedure for which conventional longer times of incubation and washing were used. The results demonstrate the feasibility and effectiveness of the procedure.

Antibodies, Monoclonal↗

Splenic irradiation in chronic lymphocytic leukemia. A 10-year experience at a single institution.

A group of 38 patients with a median age of 70 years and chronic lymphocytic leukemia (CLL) were treated using a cobalt 60 U or a 6-MeV linear accelerator. A direct field or two opposite fields covered the palpable spleen area in most patients. 100 cGy were administered weekly for a total dose of 10 Gy, given over 10 weeks. The stage arrangement (according to Rai) for the 32 evaluable patients was as follows: Stage I: 11 patients, Stage II: nine patients, Stage III: three patients, and Stage IV: nine patients. Patients in Stages I and II were treated when symptomatic. Twenty-five patients (78%) achieved hematologic response (HR), defined as normalization of the differential leukocyte count, of the total blood cell count, and of bone marrow infiltration. However, no complete response according to the standard criteria of response has been obtained. The median response time of HR was 7 months (range, 1.5 months to greater than 120 months). The overall median survival time from the start of splenic irradiation (SI) was 40 months. More than 50% splenomegaly reduction was obtained in 63% of patients, whereas no benefit was verified in the lymphadenopathy. The incidence of second tumor was 29%. Fourteen patients benefited from a further 21 SI cycles. SI does not result in a complete remission and therefore cannot modify the course of CLL. This treatment is most advisable for elderly patients with predominant bone marrow lymphocytosis, for patients with previous extensive chemotherapy or radiotherapy, and for patients with poor marrow reserve. Moreover, because of the absence of toxicity subsequent treatment is not compromised.

Aged↗

Reed-Sternberg cells and their cell microenvironment in Hodgkin's disease with reference to macrophage-histiocytes and interdigitating reticulum cells.

Fifty-eight paraffin-embedded lymph node biopsies from patients with Hodgkin's disease (36 nodular sclerosis, 14 mixed cellularity, five lymphocyte depletion, and three lymphocyte predominance) were immunostained with a panel of monoclonal (anti-Leu-M1, antileukocyte common antigen) and polyclonal (to lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and S-100 protein) antibodies by using the avidin-biotin immunoperoxidase technique. Both the immunostaining features of the Reed-Sternberg (R-S) cells and their variants, and the numbers of immunostained accompanying cells morphologically corresponding to macrophage-histiocytes (M-H) and to interdigitating reticulum cells (IRC) were analyzed. Variable numbers of R-S cells and their variants were positive for Leu-M1 in 83% of the cases, for alpha 1-antitrypsin in 40%, for alpha 1-antichymotrypsin in 30%, and for leukocyte common antigen in 3.4%; they were constantly negative for lysozyme and S-100 protein. Whereas the average numbers of accompanying cells immunostained for Leu-M1 were very low, the numbers of S-100-positive IRC were relatively high in all the Hodgkin's subtypes. The average numbers of M-H were lower (P less than 0.1 for lysozyme; P less than 0.001 for alpha 1-antichymotrypsin) in the nodular sclerosis than in the other pooled subtypes. In the nodular sclerosis subtype, however, R-S cells and their variants that stained positive for Leu-M1 appeared to express more frequently the lineage markers of M-H (alpha 1-antitrypsin and/or alpha 1-antichymotrypsin). These data appear to suggest that there is not an apparent qualitative correspondence between the immunostaining features of the cellular microenvironment composed of M-H and IRC and the features of the R-S cells.

Antigens, Differentiation, T-Lymphocyte↗

Proliferative activity in human urologic malignancies: a preliminary study.

Cellular proliferative activity was evaluated by the determination of 3H-thymidine labeling index (LI) in 20 specimens of human urologic malignancies (13 renal cell carcinomas and 7 transitional cell bladder carcinomas). Very low LI values were found in renal cell carcinomas, with a median value of 0.28%. Slightly higher proliferative activities were observed in bladder carcinomas, with a median LI value of 1.96%. No significant correlations were found between proliferative activity and pathologic stage or histologic grading in renal cell carcinomas. Although the number of bladder carcinomas evaluated does not allow any definite conclusion, an increase in LI values was found from in situ to invasive carcinoma and from tumors at stage I to tumors at stage III.

Aged↗

Practical importance of routine paraffin-embedded bone marrow biopsy in multiple myeloma.

Paraffin-embedded bone marrow biopsy specimens obtained prior to (37) or after (25) therapy from 62 patients with multiple myeloma (MM) were analyzed with particular reference to infiltration pattern, extent of infiltration, and myeloid to myeloma tissue percentage ratio (MMR) to verify their mutual relationships and clinicopathologic relevance. Fifty-nine biopsies were evaluable for infiltration pattern (diffuse in 27, interstitial in 25, and nodular in 7). Diffuse and interstitial patterns were more common (P less than 0.025) in stage III and stage I patients, respectively. A higher (P less than 0.001) mean serum paraprotein level was found in patients with the diffuse pattern than in those with the interstitial pattern. The average extent of infiltration by myeloma cells in the residual myeloid tissue was higher (P less than 0.001) and a high extent (75% or more) was more frequently (P less than 0.005) seen in diffuse than in interstitial pattern cases. The average MMR value was lower (P less than 0.001) and a MMR value less than 1 was more frequently (P less than 0.005) seen in the diffuse pattern group than in the interstitial pattern group. All these differences were present also when a separate analysis was performed for treated and untreated patients. It seems that a diffuse histologic pattern, as opposed to interstitial, would significantly predict a bone marrow extent of infiltration of 75% or more, a MMR lower than 1, a higher serum paraprotein level, and a clinical stage III. Bone marrow biopsy appears thus to play a role in providing parameters of prognostic relevance in MM also in the course of the disease. Prospective studies are needed to establish whether histologic pattern has an independent prognostic value.

Biopsy↗

Glucocorticoid receptors and corticosensitivity of human thymocytes at discrete stages of intrathymic differentiation.

Human thymus is composed of several discrete compartments. Stage III thymocytes, located mainly in the medulla, stain brightly with anti-T3 monoclonal antibody; stage II thymocytes, located in the cortex, are T3- but react with T6 antibodies. The earliest identifiable intrathymic cell (stage I) expresses the sheep erythrocyte glycoprotein T11 but not T6 or T3 antigens. Within the thymus a phenotypically heterogeneous pool of proliferating lymphoblasts is present. This capacity to proliferate without in vitro activation is mainly attributable to thymocytes unable to respond to mitogens and expressing the cortical T6 marker. Both T3+ and T3-T6- cells respond to mitogen. However, in order to exhibit maximal proliferative responses, T3+ but not T3-T6- thymocytes require the addition of exogenous IL 2. Thymocyte subsets at distinct stages of intrathymic differentiation were then analyzed for glucocorticoid (GC) receptor content by using a whole cell assay with 3H-triamcinolone acetonide as tracer. The least mature T3-T6- thymocyte subset contained the highest levels of GC receptors . T3+ thymocytes exhibited a receptor content higher than that found in T6+ cells and similar to that reported for peripheral blood lymphocytes. Apart from the number, the GC receptor sites in all thymocyte subsets were similar in their affinities, kinetic characteristics, specificity for steroids, and ability to undergo translocation from cytoplasm to nucleus, and they behave in all these respects like binding sites of GC receptors in lymphoid and other cells. Independently of both phenotype and GC receptor content, all in vivo activated thymocytes (i.e., spontaneously proliferating cells) were similarly sensitive to the steroid inhibitory action in vitro. Both in the presence and in the absence of exogenous IL 1 or IL 2, the PHA-induced mitogenesis of T3-T6- cells was less inhibited by GC than that of T3+ thymocytes. Exogenous IL 1 and IL 2 were equally effective in removing, although not completely, the GC inhibition on T3-T6- proliferative responses to PHA. Relative to T3+ cell mitogenesis, only exogenous IL 2 was able to antagonize the steroid inhibitory action. The capacity observed in vitro of GC to differentially affect the proliferative potential or the cell viability of thymocytes belonging to functionally distinct subsets suggests that these hormones could regulate the intrathymic maturative pathways. Finally, although at present the physiologic relevance of the highest expression of GC receptors in intrathymic precursor cells remains unclear, the receptor density may be considered a marker of differentiation for the T lymphoid lineage.

Antigens, Differentiation, T-Lymphocyte↗

Selective depletion of the OKT 4+ 4B4+ subset in lymph nodes from HIV+ patients.

We have used 4B4 and 2H4 monoclonal antibodies in conjunction with OKT 4 to quantify T cell subsets in lymph node suspensions from human immunodeficiency virus (HIV) positive subjects with lymphadenopathy syndrome. The data indicate that the reduced OKT 4:OKT 8 ratio was due to a depletion of the OKT 4+ 4B4+ subset. In contrast, there were no differences compared to reactive controls, considering the OKT8+ subpopulation. These alterations may be related to the immunological deficiency associated with HIV infection.

Acquired Immunodeficiency Syndrome↗

Non-Hodgkin's lymphomas in the elderly: prospective studies with specifically devised chemotherapy regimens in 66 patients.

The results of 2 consecutive and prospective trials with specifically devised chemotherapy regimens in elderly patients (pts) with non-Hodgkin's lymphoma (NHL) are reported. Between August 1979 and September 1984, 66 pts aged 70 or older (median 75 years) with NHL entered 2 consecutive trials, the former with single agent teniposide 100 mg/m2 i.v. weekly (41 pts), the latter with etoposide and prednimustine (E + P), 100 mg/m p.o. for 5 days every 21 days (25 pts). Forty-five pts were previously untreated, 21 previously treated. Forty-seven pts were of the intermediate and high grade groups according to the Working Formulation; 19 pts were of the low grade; 57 pts were stages III and IV, 9 pts were stages I and II. The median performance status was 70 (range 30-100). The objective response rate in the 66 evaluable pts is 53% with 38% CR; the 3-year overall, disease-free and CR survivals are 21, 12 and 40% respectively. The objective response rate in the 45 previously untreated pts is 58% with 42% CR; the 3-year overall, disease-free and CR survivals are 24, 16 and 58% respectively. The overall toxicity was mild. Severe toxicity (grade III and IV according to WHO criteria) was observed only in 16/498 courses (3.2%), with 1 toxic death (grade IV leucopenia). We experienced the usefulness of a properly orientated clinical approach to elderly pts with NHL. We suggest that a combination regimen like E + P, suitable for oral administration, may be safely employed in a large fraction of pts with NHL.

Aged↗

Widespread codistribution of glycoprotein gp 115 and elastin in chick eye and other tissues.

Frozen sections of chick tissues were exposed to affinity-purified monoclonal antibodies raised against chick gp 115 and to affinity-purified antibodies raised against chick tropoelastin to study the distribution pattern of the corresponding antigens by the avidin-biotin immunoperoxidase technique. Laminin and fibronectin antibodies were used for comparison. Gp 115 and tropoelastin antibodies localized to the same structure in several of the tissues examined. The endothelial membrane of the cornea and Bruch's membrane in the choroid were positive, while the corneal epithelial membrane was negative. Both antibodies displayed a peculiar punctate reactivity in the corneal stroma and a very fine fibrillar pattern in the conjunctiva and at the corneal-scleral junction. Liver, heart and large vessels, striated muscle and skin showed a similar pattern both for tropoelastin and gp 115 antibodies. Few differences were seen in the distribution of the reactivity: the pericellular matrix of intestinal smooth muscle cells was stained by gp 115 but not by tropoelastin antibodies. However, the reactivity of gp 115 and tropoelastin antibodies was similarly distributed in the lung smooth muscle cell clusters. The peritubular matrix in the kidney did also not react with tropoelastin antibodies as did the brain intraparenchymal vessels; whereas gp 115 antibody reactivity was present in both sites. We interpret these lack of apparent codistribution in some tissues as a variation in the relative availability of the target antigen for the reaction with the antibody and not as a consequence of a qualitative difference in the distribution of gp 115 and tropoelastin. By the use of anti gp 115 monoclonal antibodies that do not cross-react, and presumably recognize different epitopes, it was shown that some but not all antibodies, react with brain intraparenchymal blood vessels; whereas the pattern of distribution in other tissues was the same. This suggests that in vessels with an undetectable level of elastin, certain epitopes of gp 115 molecule might not be recognized as a result of being masked by other components or by a different conformation of the molecule.

Animals↗

Medium tumor antigen of polyomavirus transformation-defective mutant NG59 is associated with 73-kilodalton heat shock protein.

Affinity-purified medium T antigen encoded by NG59, a nontransforming mutant of polyomavirus, is specifically associated with a protein of 72,000 daltons (72K protein). Medium T antigens of wild-type polyomavirus and the transformation-competent mutant dl8 are not associated with the 72K protein. Instead, they form a complex with another protein of 61,000 daltons. Several lines of evidence suggest that the medium T antigen-associated 72K protein is equivalent to the abundant and constitutive 73K heat shock protein. First, on two-dimensional polyacrylamide gels the 72K protein migrated with the same pI (5.6) as did the 73K heat shock protein. Second, the 72K protein was immunoprecipitable with antibodies against heat shock proteins. Third, when digested with V8 protease, the 72K protein gave rise to the same pattern of fragments as did the 73K heat shock protein.

Animals↗

S-100 protein immunostaining in teratomatous well-differentiated tissues.

The presence and distribution of S-100 protein were studied in a case of ovarian teratoma using avidin-biotin complex immunoperoxidase method. S-100 immunoreactivity within the well-differentiated teratomatous tissues appeared to mirror that of their normally developed human counterparts, although we could unexpectedly detect S-100 immunoreactivity in bone osteoblasts and osteocytes, and in tooth germ odontoblasts. Choroid plexus-like formations present in the teratoma were also positive. Our results suggest that the presence of S-100 protein might be associated with a basic cell function regardless of the presence of a physiologically end-developed human organism.

Female↗

A case of extra-osseous osteosarcoma.

The authors report a case of extra-osseous osteosarcoma of the thigh. They review the literature and emphasize the rarity of this highly malignant neoplasm. It was treated by wide surgical excision associated with adjuvant radiotherapy and chemotherapy. A month later a metastasis appeared in the lung which was not amenable to treatment. The differential diagnosis and histological features are discussed.

Aged↗

S-100 protein, fibronectin, and laminin immunostaining in lymphomas of follicular center cell origin.

Forty-nine paraffin-embedded biopsy specimens of involved nodal and extranodal tissue (bone marrow, spleen, and liver) from 13 patients with follicular center cell lymphomas (FCCL) and 14 with small lymphocytic lymphomas (SLL), including 11 cases with chronic lymphocytic leukemia, were tested for S-100 protein immunoreactivity. Analysis for fibronectin and laminin immunoreactivities was limited to the lymph node biopsy specimens. In FCCL, S-100-positive dendritic reticulum cells (DRCs) were found in 23 of the 26 tissue specimens examined, regardless of the involved sites and the growth pattern. Cases with completely or predominantly follicular pattern were usually associated with a spherical meshwork pattern of S-100-positive DRCs; in the FCCL specimens with a diffuse pattern (lymph nodes and bone marrow) as well as in the specimen areas with a minimally follicular tumor pattern, S-100-positive DRCs were consistently fewer in number and composed loosely aggregated nests. No S-100-positive DRCs were found in all the biopsy specimens in SLL. Concerning fibronectin and laminin immunostainings, results showed that no differences were present between areas of follicular and diffuse neoplastic growth and that the neoplastic growth of FCCL maintained for each antiserum the same distribution pattern as that seen in normal follicles. Analysis of the microenvironmental components as revealed with antisera used in the current study--particularly with anti-S-100 protein antiserum--appears to be a useful adjunct for the identification of FCCL in paraffin-embedded biopsy specimens, especially in extranodal sites.

Dendritic Cells↗