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A Vacca

Publications and source records attributed to A Vacca.

At least 199 records · Page 11Linked to original sources
PubMed1987

Penetration and binding of radiolabeled anti-carcinoembryonic antigen monoclonal antibodies and their antigen binding fragments in human colon multicellular tumor spheroids.

The binding and penetration of two 125I-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) and their F(ab')2 and Fab fragments were measured in multicellular spheroids of poorly (HT29) and moderately well differentiated (Co112) human colon adenocarcinomas which express different amounts of CEA. Spheroids cultured in vitro model tumor microenvironments where poor vascular supply may modulate antigen expression and accessibility. The two MAb studied, 202 and 35, were shown previously to react with different CEA epitopes and to have high affinities of 1.2 and 5.8 X 10(9) M-1, respectively. MAb 202 has also been shown to cross-react with antigens present on human granulocytes and normal epithelial cells from human lung and pancreas. Specific binding of intact MAb and fragments of both antibodies was demonstrated for both types of human colon carcinoma spheroids compared to mouse colon carcinoma (CL26) and mammary tumor (EMT6/Ro) spheroids. Total binding of MAb and fragments was greater (1.5- to 2.5-fold) after 4 h compared to 1 h of exposure; the amount of binding compared to control IgG1 was 5- to 30-fold greater after 1-h incubation and 15 to 200 times greater after 4 h. This binding was stable as demonstrated by short and long wash experiments at 37 degrees and 4 degrees C. The binding of F(ab')2 and Fab fragments of the anti-CEA MAb 35 to spheroids of human colon Co112 was almost 2-fold greater than that of the intact MAb. However, for MAb 202, the binding of intact MAb and F(ab')2 was greater than that of Fab fragments. In addition the binding of both intact and F(ab')2 fragments of MAb 202 was greater than that obtained with MAb 35. Specific binding of both antibodies to HT29 spheroids, which express less CEA, was decreased for MAb and fragments of both 202 and 35. Autoradiography and immunoperoxidase experiments were performed to determine the penetration of MAb and fragments after incubation with intact spheroids. Comparisons were made with labeled MAb directly applied to frozen sections of spheroids. F(ab')2 and Fab fragments of both antibodies were bound at the surface of intact spheroids and penetrated to eight to ten cells, but the intact MAb were localized mainly at the spheroid surface and the outer one to three cell layers. There was much less binding at the surfaces of HT29 compared to Co112 spheroids. An enzyme immunoassay using MAb 35 and 202 demonstrated that Co112 spheroids produced about 8-fold more CEA/mg of cell protein than did monolayer cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1987

Tuberculosis in pregnancy--implications for antenatal screening in Australia.

Two cases of tuberculosis have been seen over the past two years in southeast Asian women who had recently emigrated to Australia and who attended a single maternity hospital in Brisbane. One patient died of tuberculous meningitis and the other had an asymptomatic tuberculous pleural effusion. Both cases illustrate some of the difficulties in the diagnosis of extrapulmonary tuberculosis, particularly in pregnant women, and the low level of awareness of this condition. Antenatal screening for tuberculosis is not performed as a routine in Australia. Pregnant women who have emigrated recently from areas of high prevalence constitute a group at increased risk for tuberculosis who should be screened selectively with tuberculin tests and chest x-ray examinations.

Adult↗
PubMed1986

Subcellular and extracellular localization of specific binding sites for triphenylethylene antiestrogens in human breast cancer.

MCF-7 human breast cancer cell homogenates and subcellular organelles were submitted to isopycnic centrifugation on Percoll gradients to investigate the subcellular localization of triphenylethylene antiestrogen specific binding sites (AEBS). Electron microscopy revealed that gradient fractions coincident with the migration of [3H]tamoxifen-AEBS complexes were homogeneously represented by rough and smooth endoplasmic reticulum. Eighty percent of AEBS were localized in the endoplasmic reticulum [45,000 +/- 4,000 sites/cell, mean +/- S.D.), while 20% of these sites were also found in the nuclear fraction (12,000 +/- 1,000 sites/cell, mean +/- S.D.). A similar subcellular distribution of AEBS was observed in human breast cancer bioptic specimens. No differences in [3H]tamoxifen binding affinity between microsomal and nuclear AEBS were observed in MCF-7 and bioptic breast cancer. No major differences in microsomal AEBS levels were observed in the limited number of estrogen receptor-positive or -negative breast cancer specimens we have studied, whereas estrogen receptor-negative samples had higher levels of nuclear AEBS with respect to estrogen receptor-positive tumors. The presence of AEBS was also detected in the human serum of healthy and tumor-bearing subjects. The affinity and the binding specificity of serum AEBS were similar to those of intracellular AEBS. No differences in the levels of serum AEBS were observed between healthy and tumor-bearing subjects [19 +/- 4 and 22 +/- 4 pmoles/ml (mean +/- S.D.) respectively. Human serum AEBS did not appear to be associated to lipoproteins, whereas it migrated as a 5.5 S sedimenting molecule.

Binding Sites↗
PubMed1986

Immunochemical characterization of two antigens recognized by new monoclonal antibodies against human colon carcinoma.

Two different monoclonal antibodies (MAb), called L-D1 and L-C5, were produced after immunization with either intact cells or the methanol phase of glycolipid extracts, respectively, from the same human colon carcinoma line, LoVo. As determined by an antibody-binding radioimmunoassay (RIA) on intact cells, MAb L-D1 and MAb L-C5 were highly reactive with all five colon carcinoma lines tested and with only one out of the 21 cell lines of various tissue origin tested. No reactivity of either MAb was observed with peripheral blood lymphocytes, granulocytes, or erythrocytes from healthy donors of various blood groups. Both MAb were tested in competitive binding experiments with an anti-CEA MAb from our laboratory (CEA 35) and with two previously described anti-colon carcinoma MAb from the Wistar Institute called 1083-17-1A (17-1A) and NS-19.9. In competitive binding experiments, MAb L-D1 was inhibited by MAb 17-1A and reciprocally, whereas MAb L-C5 was not inhibited by any of the other MAb tested. MAb L-D1 precipitated a major protein band with an apparent molecular weight (MW) of 41 kilodaltons (kD); interestingly, MAb 17-1A, which was reported to react with an uncharacterized antigen, precipitated the same protein band of 41 kD. This was confirmed with immunodepletion experiments. Furthermore, after treatment of the colon carcinoma cell line with tunicamycin, both MAb L-D1 and 17-1A precipitated a protein band of 35 kD. This shift of 6 kD suggests that the glycoprotein recognized by these 2 MAb contains two to three N-linked carbohydrate side chains. MAb L-C5 precipitated a group of three to four protein bands ranging from 43 to 53 kD that were not modified by tunicamycin treatment. A preliminary study conducted by using immunoperoxidase labeling on frozen sections of primary colon carcinoma showed that the two new MAb react strongly with these tumors, but also weakly with the normal adjacent mucosa, as did the other anti-colon carcinoma MAb tested.

Animals↗
PubMed1986

Expression on human thymocytes of the idiotypic structures (Ti) from two leukemia T cell lines Jurkat and HPB-ALL.

The expression on a significant number of thymocytes of idiotypic structures (Ti) restricted to HPB-ALL or Jurkat cells is demonstrated. As many as 2-4% of thymocytes were stained with anti-Ti HPB-ALL or anti-Ti Jurkat monoclonal antibodies, when analyzed by flow microfluorometry. Immunohistochemical localization studies performed on frozen thymus specimens of either fetal or pediatric origin indicated a scattered distribution of Ti-positive cells in both the cortex and the medulla. From lysates of 125I-labeled pediatric thymocytes, anti-Ti HPB-ALL and anti-Ti Jurkat monoclonal antibodies precipitated disulfide-linked heterodimers comparable to those precipitated from 125I-labeled HPB-ALL or Jurkat cells as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.

Antibodies, Monoclonal↗
PubMed1986

Monoclonal antibodies against idiotypic determinant(s) of the T cell receptor from HPB-ALL cells induce IL2 production in Jurkat cells without apparent evidence of binding.

Two monoclonal antibodies (mAb) directed against idiotypic determinants of the T cell receptor (anti-Ti) from HPB-ALL cells induce interleukin 2 (IL2) production in Jurkat T cells without evidence of binding to these cells as judged by fluorescence-activated cell sorter (FACS) analysis, indirect antibody-binding radioimmunoassay and direct binding studies with 125I-labeled mAb. The IL2 response induced by these mAb observed both in the presence and absence of phorbol myristate acetate was in the range of that obtained when Jurkat cells were stimulated with phytohemagglutinin or anti-T3 mAb (Leu 4). The idiotypic specificity of the two anti-HPB-ALL Ti mAb was demonstrated by several criteria. Both mAb bound specifically to HPB-ALL cells as determined by radioimmunoassay or FACS analysis but not with 8 other T cell lines. The anti-HPB-ALL Ti mAb precipitated a disulfide-linked heterodimer of 85 kDa only from 125I-labeled HPB-ALL cells and not from other cell lines tested. Incubation of HPB-ALL cells with anti-T3 abrogated the expression of T3 and induced co-modulation of the idiotypic structures detected by the two anti-HPB-ALL Ti mAb. Conversely, incubation of HPB-ALL cells with either one of the anti-Ti mAb abrogated the expression of T3 and of the idiotypic structures. Our results suggest that mAb with an apparent unique specificity for the receptor of the immunizing T cell line HPB-ALL can activate Jurkat cells by a very weak cross-reaction with these cells, which is not detectable by conventional binding tests.

Animals↗
PubMed1986

Follow up of babies delivered in a randomized controlled comparison of vacuum extraction and forceps delivery.

Babies delivered in a randomized controlled comparison of vacuum extraction vs. forceps delivery were reassessed at 9 months of age. There were no statistically significant differences between the two groups as regards head circumference, weight, or head circumference to weight ratio, nor in the results of hearing and vision tests. The reasons for hospital readmission, pediatric follow-up and parents' and health visitors' worries appeared to be unrelated to the mode of delivery in nearly all cases. The finding in the original trial that neonatal jaundice was more common following vacuum extraction was reinforced by an additional case of jaundice in the vacuum extractor group which had necessitated readmission to hospital.

Child Development↗
PubMed1986

Calmodulin antagonism and growth-inhibiting activity of triphenylethylene antiestrogens in MCF-7 human breast cancer cells.

The triphenylethylene antiestrogen tamoxifen has been shown previously to inhibit both calmodulin and protein kinase C activities, which are involved in the control of cell proliferation. We have studied the effect of several derivatives of the triphenylethylene antiestrogen family on the inhibition of both calmodulin-dependent cyclic adenosine 3':5'-monophosphate-phosphodiesterase activity and proliferation of breast cancer cells cultured with 0.5 microM estradiol in order to prevent interaction of these drugs with the estrogen receptor. We have observed that hydroxylation of the triphenylethylene molecule significantly decreases its ability to inhibit the calmodulin-dependent phosphodiesterase activity in vitro. Furthermore, the growth-inhibiting activity of several antiestrogens and other calmodulin antagonists [R24571, trifluoperazine, N-(6-aminohexyl)-5-chloronaphthalene-1-sulfonamide, and N-(6-aminohexyl)-1-naphthalenesulfonamide] correlated with their antagonistic effects on calmodulin activity. The level of activity was determined as follows: R24571 greater than tamoxifen = N-demethyltamoxifen = nafoxidine greater than 4-hydroxytamoxifen greater than 3,4-dihydroxytamoxifen = trifluoperazine greater than N-(6-aminohexyl)-5-chloronaphthalene-1-sulfononamide greater than metabolite A greater than N-(6-aminohexyl)-1-naphthalenesulfonamide. On the other hand both protein kinase C-activating and -inhibiting drugs (phorboltetradecanoate-13-acetate and tamoxifen, respectively) have a synergistic inhibitory effect on the growth of MCF-7 cells. Our data suggest that antiestrogen interactions with calmodulin and not protein kinase C may play a role in mediating the drug-induced estrogen-independent inhibition of breast cancer cell growth.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Treatment of multiple myeloma: a randomized study of three different regimens.

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Cyclic lysozyme administration as a tool for immunopotentiation in patients with multiple myeloma.

Fourteen patients with multiple myeloma (MM) were given chemotherapy courses for 7 days followed by 21-day intervals, combined with an immunomodulating treatment, namely lysozyme (LZM), 2 g daily for three weeks every other interval. Some parameters of cell-mediated immunity (total-E-rosettes, monocyte and polymorphonuclear leukocyte chemotaxis, skin tests) as well as humoral immunity (serum Ig levels, electrophoresis, immunoelectrophoresis) were evaluated comparatively in the intervals with and in those without LZM administration. A significant increase in total-E-rosettes and monocyte chemotaxis was observed in about half of the patients studied, this enhancement being accompanied by a reduction in both frequency and severity of viral and bacterial infections. No side-effects ascribable to LZM were recorded in any of the patients.

Adjuvants, Immunologic↗
PubMed1984

Immunoglobulin secretion by peripheral blood and bone marrow B cells in patients with multiple myeloma. Studies by the reverse haemolytic plaque assay.

The reverse haemolytic plaque assay (RHPA) was used to enumerate circulating and bone marrow (BM) immunoglobulin secreting cells (ISC) in patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), as well as in normal controls. Significantly greater quantities of plaque forming cells (PFC) secreting the same isotype of the serum M component were detected in the peripheral blood of MM patients than in the blood of MGUS patients or normal subjects. Comparative analysis of the numbers of monoclonal PFC in both peripheral blood (PB) and BM at diagnosis usually showed a higher number as well as more precocious chemotherapy-induced variations of ISC in the BM compartment than in the PB. Although large individual variations were observed during follow-up studies of MM patients, persistently increased or decreased levels of monoclonal PFC were often found to accompany (and sometimes to precede by months) the phases of relapse or remission, respectively. Similarly to IgG-MGUS patients, a distorted ratio of IgG kappa to IgG lambda secreting cells was consistently detected in patients with smouldering MM, although the total number (IgG kappa plus IgG lambda) of ISC appeared within normal limits. It is suggested that, in addition to other clinical and laboratory criteria, the RHPA may be of value in the diagnosis and follow-up of patients with monoclonal gammopathies.

Aged↗
PubMed1983

Portsmouth operative delivery trial: a comparison vacuum extraction and forceps delivery.

A total of 304 women, for whom operative delivery was considered necessary in the second stage of labour, were randomly assigned to delivery by vacuum extraction or forceps. Of those allocated to forceps a higher proportion of babies were actually delivered with the allocated instrument; however, the caesarean section rate was also higher in this group. Maternal trauma, use of analgesia and blood loss at delivery were significantly less in the group allocated to vacuum extraction. Vacuum extraction did, however, appear to predispose to an increase in mild neonatal jaundice. More serious neonatal morbidity was rare in both groups and the trial was of insufficient size to rule out a clinically important differential effect of the two instruments on these measures of outcome. Another trial is now needed to address this still open question more rigorously.

Adult↗
PubMed1980

Puerperal sepsis in Port Moresby, Papua New Guinea.

Because puerperal sepsis is the second most common cause of maternal death in Papua New Guinea some aspects of its aetiology and prevention have been investigated. 91% of 125 women with puerperal fever were found to have post-partum uterine infection. The anaerobes Bacteroides and Peptostreptococcus singly or together, were the commonest causes, while Streptococcus pyogenes was the predominant aerobic species. Antibiotic sensitivity patterns were established, and chloramphenicol was found to be the most active agent against anaerobic and most aerobic strains. Endocervical cultures obtained from 103 ante-partum and 50 afebrile post-partum women demonstrated all the species associated with post-partum genital infection in this study. An analysis of the records of all patients was made to determine the redisposing factors associated with puerperal fever; only operative delivery was found to be significant, especially when it followed prolonged labour. Metronidazole given to 72 women before induction of labour was associated with puerperal fever in 4%, compared with 21% in matched controls.

Bacteroides Infections↗