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Biomedical subjects

M Forni

Publications and source records attributed to M Forni.

At least 73 records · Page 4Linked to original sources

Establishment of an EBV-positive lymphoblastoid cell line that grows as a lymphoma in nude mice and expresses membrane CD2 molecules.

We describe a human lymphoblastoid cell line (LCL), called ZS, that originated spontaneously from the cultures of gamma-irradiated (50 Gy) peripheral-blood mononuclear cells of a normal donor. When injected subcutaneously in sublethally irradiated, splenectomized and anti-asialo-GM1-treated nude mice, ZS cells invaded the lymph nodes, that appeared 10 to 50-fold enlarged in all of the mice tested. Furthermore, ZS cells expressed a typical T-cell surface structure, the CD2 molecule, detectable by a variety of different anti-CD2 monoclonal antibodies (MAbs). However, other T-cell markers were not found, with the possible exception of a truncated messenger of the beta chain of the T-cell receptor and ZS cells could be identified as B cells since they (i) expressed a battery of markers of the resting and activated B cells, (ii) displayed a monoclonal rearrangement of the IgH chain locus and (iii) synthesized IgM K molecules. The Epstein-Barr virus (EBV) genome was detected in ZS cells in approximately ten copies per cell by DNA hybridization techniques. Furthermore, the cells were positive for EBV nuclear antigens (EBNA). Western blotting analysis of EBV encoded antigens demonstrated clear differences with those present in the B 95.8 virus-producer cell line, indicating that ZS cells were not infected by EBV in vitro and that they already harbored the virus in vivo. ZS cells formed colonies in vitro with a high cloning efficiency and displayed chromosomal abnormalities in all of the mitoses (karyotype 47, xy, +13, -14, 8p+, 21p+, +m). In spite of these malignant features, ZS cells expressed the full range of EBV latent proteins as usually do "normal" LCSs and did not have any of the chromosomal abnormalities that juxtapose the c-myc oncogene to one of the genes coding for immunoglobulin molecules.

Animals↗

Report of a cavernoma of the cauda equina and review of the literature.

Subdural intramedullary and extramedullary cavernous angiomas are rare vascular malformations. A case of cavernoma of the cauda equina affecting a 46-year-old man is reported. He presented with low back and sciatic pain. This is the fourth case of cavernoma of the cauda equina in the literature. The available literature on intramedullary (28 cases) and extramedullary (9 cases) cavernomas is reviewed.

Cauda Equina↗

Increased tight junction width in two children with Ménétrier's disease.

Protein-losing enteropathy (PLE) and edema are usually the most prominent clinical features in children with Ménétrier's disease. However, the changes in gastrointestinal mucosa that can cause PLE have not been described yet in children. We studied by electron microscopy the mucosa of the gastric fundus, which is the site where macroscopic changes are most prominent, in two children with Ménétrier's disease. We found that tight junction width was increased to 10.5 +/- 0.94 nm (mean +/- 1 SD) in one child and to 9.7 +/- 0.7 in the other. Tight junction width returned to normal when PLE and edema subsided. These ultrastructural changes were similar to those described in adults with the disease, although the clinical course of Ménétrier's disease is very different in adults and in children. Both patients showed evidence of cytomegalovirus (CMV) infection, as indicated by increasing IgG antibodies against the virus or recovery of the virus in the urine. Although Helicobacter pylori was found in the antral mucosa of one patient, the clinical course of the disease was not related to this microorganism. We conclude that increased tight junction width plays a role in PLE seen in Ménétrier's disease in children and that CMV, rather than Helicobacter pylori, is associated with the disease.

Adolescent↗

Serum pepsinogen I and gastrin concentrations in children positive for Helicobacter pylori.

Serum pepsinogen I, serum gastrin concentration, and inflammatory scores were measured in a population of 71 children undergoing upper gastrointestinal endoscopy for investigation of upper abdominal pain. Forty four were initially colonised with Helicobacter pylori. The indices were measured before treatment (in 71 children), one month (in 41 children), and six months (in 21 children) after stopping treatment. Before treatment there was a significant correlation between serum pepsinogen concentration, total inflammatory score, and H pylori state, but no correlation between serum gastrin concentrations and H pylori state. Similarly, the total inflammatory score and serum pepsinogen concentrations were significantly correlated. There was no such correlation in children negative for H pylori. After treatment the inflammatory score improved in those patients in whom H pylori had been eradicated. There was also a significant fall in serum pepsinogen I and serum gastrin concentration in those patients in whom H pylori had been eradicated. These results were similar to those found six months after treatment had been stopped. These findings suggest that the serum pepsinogen I concentration could be considered a useful marker for gastritis and can be used as an index of severity of gastritis in H pylori positive subjects. The measurement of serum gastrin concentrations does not give useful information.

Adolescent↗

Treatment of childhood peptic oesophagitis with famotidine or alginate-antacid.

Both antacids and H2 receptor antagonists have a potential role in treating peptic oesophagitis associated with acid reflux. The aim of this study is to assess the efficacy and tolerability of famotidine and alginate-antacid in children with endoscopically documented peptic oesophagitis. We compared clinical, endoscopic and histological response to alginate-antacid (1 tablet to be chewed 30 min after each meal and at bed time) or famotidine (1 mg/kg before supper at 7 pm) in 49 children (mean age 9 years, 34 males). Twenty-four of them were randomly allocated to alginate-antacid treatment (group A), twenty-five to famotidine (group B). Both treatments were protracted for six months and endoscopy was then repeated. Symptoms disappeared in 43.4% and improved in 47.8% of children of group A and disappeared in 91.6% of those of group B (p less than .05). Mean time for symptom disappearance was 17 weeks for group A and 5 weeks for group B (p less than .01). After six months, at endoscopy oesophagitis was healed in 43.4% in group A and in 41.6% of group B, the difference between the two groups was not significant, however the improvement of endoscopic grades induced by famotidine was significantly better (p less than .05). Histology showed a healed peptic oesophagitis in 52.2% of the children in group A and in 70.8% of group B (p less than .001). No toxicity was observed with either treatment. We conclude that famotidine is superior to alginate-antacid in treating peptic oesophagitis associated with acid reflux, since it induces a better symptomatic response and a greater improvement of endoscopic lesions.

Adolescent↗

Perilymphatic injections of cytokines: a new tool in active cancer immunotherapy. Experimental rationale and clinical findings.

Various strategies for local immunotherapy performed by using lymphokines and lymphocytes are presented. In experimental mice models, the antitumor reaction elicited through the injection of little amounts of IL-2 and gamma-IFN at the tumor growth site is significantly enhanced by the concurrence of lymphocytes from tumor bearing mice artificially admixed to challenging tumor cells. These lymphocytes act as initiator or helper cells that elicit both a local and a systemic long lasting immune reaction by the release of additional lymphokines. The reaction activated mostly involves draining lymph nodes, where multiple reaction mechanisms are induced. The local injection of cocktails of molecularly defined lymphokines can also mimic the helper action of lymphocytes and trigger a similarly effective anti-tumor reaction. A set of pilot clinical trials with IL-2 or gamma-IFN injected perilymphatically were initiated in patients with advanced primary or recurrent localized tumors of the head and neck and the bladder. This treatment appears to elicit a local reaction by activating a few pathways of patients immunoreactivity, whose efficiency may well be high, as shown by the tumor inhibition often observed.

Amino Acid Sequence↗

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

Abdomen↗

A new childhood T-cell lymphoma established in nude mice and in vitro.

A T-lymphoma cell line was established from a lymph node biopsy of a boy currently alive in complete remission. Neoplastic cells from this biopsy did not grow in vitro, whereas they formed a progressively growing s.c. tumor in splenectomized and sublethally irradiated nude mice and became serially transplantable in splenectomized and sublethally irradiated nude mice with a stable latency time. After the fourth transplant, cells were stored in liquid nitrogen and referred to as ST-4 cells. ST-4 cells display a membrane phenotype and a karyotype similar to that of the biopsy cells. After thawing, ST-4 cells grow both in splenectomized and sublethally irradiated nude mice and in vitro. They do not secrete interferon or interleukin 2, do not have natural killer activity, and do not respond to mitogen or alloantigen stimulation. The stable features of these T-lymphoma cells and the availability of normal autologous lymphocytes from the patient make this in vivo system quite unique and of importance for studies in tumor immunotherapy.

Animals↗

Interleukin 2 activated tumor inhibition in vivo depends on the systemic involvement of host immunoreactivity.

Daily local administration at the tumor challenge site of 10 injections of 10 U of recombinant interleukin 2 (IL 2) obtained from different factories induces a consistent, though limited inhibition of the growth of CE-2, a poorly immunogenic methylcholanthrene-induced tumor. By contrast, almost complete tumor inhibition is observed when these injections are performed in mice challenged with tumor cells admixed at 1:5 cell ration with nylon wool column purified lymphocytes obtained from tumor-bearing animals. The host immune system plays a fundamental role in this lymphokine-activated tumor inhibition (LATI), which is derived from the local combination of IL 2 and nonreactive lymphocytes. When the host is sublethally irradiated, or the reactivity of L3T4 and Asialo GM1 lymphocytes is suppressed by in vivo antibody treatment, in fact, LATI no longer takes place. Daily injections of antibody to murine interferon-gamma or cyclosporin A have the same effect, indicating that lymphokine release plays an important role in the recruitment of host reactivity. The morphological data show that when LATI is taking place the tumor challenge area becomes infiltrated by mononuclear cells and granulocytes (mostly eosinophils), which establish close contacts with each other and with tumor cells as determined at ultrastructural analysis. Tumor draining lymph nodes display marked expansion of cortical and paracortical areas. Lymphocyte proliferation, interferon-gamma release and cytotoxicity against CE-2 and YAC-1 target cells are greatly enhanced during LATI. Contralateral lymph nodes and the spleen also show a slight increment of these functions. In mice challenged with CE-2 tumor cells only and receiving daily IL 2 injections, these reaction functions (with the exception of interferon-gamma secretion) are also enhanced, though to a lesser extent than during LATI and only in tumor-draining lymph nodes. Last, the growth of a second contralateral tumor challenge is significantly impaired during or after LATI, showing that a persistent and effective systemic reactivity can be quickly induced in this way.

Animals↗

Surgery as part of a combined modality approach for inflammatory breast carcinoma.

From November 1977 to February 1984 21 patients with inflammatory breast carcinoma (IBC) were treated in a prospective, nonrandomized study with initial chemotherapy, consisting of a combination of chlorambucil, methotrexate, 5-fluorouracil, and doxorubicin. Modified radical mastectomy was performed after three courses of chemotherapy followed by another six courses of the same chemotherapy. Locoregional radiotherapy concluded the treatment program. All patients responded clinically to the initial chemotherapy. Modified radical mastectomy provided a direct histologic control of the effectiveness of the treatment and, in case of tumor persistence, allowed cytoreduction. No scarring problems were observed and postoperative chemotherapy could be administered without any delay. Radiotherapy was decisive for locoregional tumor control which was obtained in all patients who were treated strictly according to the protocol. Dermal lymphatic involvement represented in this series of clinical inflammatory breast carcinoma no pejorative feature and positive hormone receptors failed to be of predictive value for response to treatment. Considerably variable tumor persistence after initial chemotherapy and the results relative to local tumor control advocate surgery as part of a combined modality approach for inflammatory breast carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Duodenitis in children: clinical, endoscopic, and pathological aspects.

In a retrospective study of 320 gastroduodenoscopies performed on children in the last 2 years, 32 cases of duodenal damage, either isolated or associated with esophagitis, gastritis, or both, were selected. Twenty matched children with dyspeptic symptoms but an endoscopically normal duodenum were chosen as controls. Histological sections of fiberoptic biopsy specimens were submitted to double-blind examination by two observers: only four fulfilled accepted criteria for histological duodenitis. The concordance between endoscopic and histological results in our patients was 13.8%. No changes of duodenal endoscopic appearance predictive of duodenitis were identified. In 8 more cases (6 patients and 2 controls) the histological examination showed an isolated lymphocyte and plasma cell infiltration of the lamina propria without any additional damage. We called this picture "minimal change duodenitis" and considered it as a variation of normal. In 17 patients and 11 controls, basal and maximal acid outputs were calculated and no significant differences were found. We concluded that duodenitis in children may be present, although rare, and its diagnosis requires histological examination of duodenal mucosa.

Adolescent↗

Serum CA 125 in epithelial ovarian cancer. A longitudinal study.

Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level greater than 35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels less than 35 U/ml, whereas all the patients with no change or with a progressive disease had levels greater than 35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (greater than 35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.

Adenocarcinoma↗

Tumour inhibition by interleukin-2 at the tumour/host interface.

Until recently, lymphokines were regarded suspiciously as 'ill-defined factors'. Today, however, some of them have been clearly defined in both structural and functional terms. The interleukin-2 (IL-2) molecule and its specific membrane receptors have been the subject of particular attention. Endogenous IL-2 has proved to be an important signal for the activation and expansion of various cell-mediated immunity functions, while exogenous IL-2 has been used to activate numerous cell functions, both in vitro and in vivo, as well as in tumour immunotherapy, both alone or combined with lymphocytes previously activated in vitro (lymphokine-activated killer cells). Adoptive transfer of these cells together with high doses of IL-2 is particularly promising from the clinical standpoint, though by no means free from problems. IL-2 can also be employed in small doses locally in the presence of non-activated lymphocytes from tumour bearing mice to induce a local reaction that subsequently becomes systemic and can lead to the rejection of incipient tumours. Various host immune cells, primarily eosinophils and lymphocytes are involved in this reaction, which can also give rise to tumour-specific immune memory. In this way, the host immune system, despite its inevitable defeat in the first battle against a tumour, may acquire an important role in the long war that lies ahead.

Animals↗

Interferon-activated tumor inhibition in vivo. Small amounts of interferon-gamma inhibit tumor growth by eliciting host systemic immunoreactivity.

Ten international units (IU) of recombinant (r) or natural (n) murine interferon (MuIFN)-gamma were used for the in vivo immunotherapy of a chemically induced fibrosarcoma (CE-2) of BALB/c mice. In vitro, doses of r-IFN-gamma below 100 units have a marginal antiproliferative effect on CE-2 cells and do not induce expression of H-2d class-II antigens, whereas they do increase that of class-I antigens. In vivo, 10 daily injections of 10 IU of r- or n-MuIFN-gamma at the challenge site provide significant protection against increasing doses of CE-2 tumor cells. This protection was enhanced when non-reactive T-lymphocytes from CE-2 tumor-bearing mice were admixed at a 10:1 ratio with the CE-2 tumor cells. Combined lymphocyte and r-MuIFN-gamma treatment also inhibited the growth of already established tumors when it was started before these reached a mean diameter of 5 mm. Tumor inhibition depends upon activation of the host immune system. The antitumor activity of r-MuIFN-gamma and T-lymphocytes was null when mice were first irradiated with 450 rads. Moreover, host leukocytes massively infiltrated the area of tumor growth and the small r-MuIFN-gamma doses injected daily activated various host immunoreactivity mechanisms.

Animals↗