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Biomedical subjects

P Ramani

Publications and source records attributed to P Ramani.

14 recordsLinked to original sources

Abdominal inflammatory myofibroblastic tumours in children.

Inflammatory myofibroblastic tumours (inflammatory pseudotumours) occurring at intra-abdominal sites in children have rarely been described. This paper reports three patients with this tumour, two of whom presented with fever, anaemia and an abdominal mass, the third with chronic duodenal obstruction. All had experienced significant weight loss. At operation, each had a large fibrous tumour (7-18 cm in diameter) originating from the transverse mesocolon, small bowel mesentery and duodenum respectively. Intraoperative frozen section histological examination in one patient was misinterpreted as a sarcoma. All the lesions were judged to have been completely excised, but one was ruptured during operation and the patient subsequently developed recurrent tumour nodules. Abdominal inflammatory myofibroblastic tumours are rare. They may be suspected before operation but their clinical, radiological and pathological features may be confused with those of malignancy. Complete excision is necessary to avoid local recurrence.

Child

Restrictive dermopathy: a disorder of fibroblasts.

Restrictive dermopathy is a rare, lethal genodermatosis, characterized by a thin, tightly adherent skin which causes a dysmorphic facies, arthrogryposis and respiratory insufficiency. The recorded cases to date show a remarkable phenotypic similarity. Thinning of the dermis and the arrangement of collagen in parallel bundles appear to be constant findings. We have found many dead and degenerating fibroblasts in the dermis on ultrastructural examination, and have demonstrated their poor growth in vitro. Studies of collagen from a skin sample showed a marked increase in mature cross-links, indicating a decrease in skin collagen turnover. These findings suggest a primary disorder of fibroblasts, and may explain the apparent arrest in growth and differentiation of the skin which appears to be important in the pathogenesis of this rare condition.

Bone and Bones

Evaluation of endothelial markers in detecting blood and lymphatic channel invasion in pT1 transitional carcinoma of bladder.

In a study of 40 patients with high-grade (G2 and G3) transitional cell carcinoma of bladder invading the lamina propria--stage pT1, retraction artifact was often misdiagnosed as vascular/lymphatic tumour invasion. Vascular/lymphatic infiltration was diagnosed in five cases based on haematoxylin and eosin stained sections, but confirmed in only two of these using immunohistochemical techniques to demonstrate endothelial markers. Of the latter, these preparations demonstrating von-Willebrand factor and binding the monoclonal antibody QBEND/10 were technically superior to those in which Ulex europaeus agglutinin 1 was used. It is unlikely that the demonstration of vascular/lymphatic infiltration, a rare feature, will prove of value in defining prognostic groups for treatment.

Antibodies

Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver.

Antibodies, Monoclonal

QBEND/10, a new monoclonal antibody to endothelium: assessment of its diagnostic utility in paraffin sections.

The immunoreactivity of a new monoclonal antibody to endothelium. QBEND/10, in formalin-fixed, paraffin-embedded sections from a variety of vascular and lymphatic tumours is described and compared to that of two other endothelial markers, von Willebrand factor and Ulex europaeus agglutinin, type 1. All the benign tumours of blood vascular origin showed immunoreactivity whereas only five out of eight lymphangiomas demonstrated a weak focal reaction with QBEND/10. Primitive lumina in epithelioid and spindle cell haemangioendotheliomas were highlighted in all the cases. Tumour cells in angiosarcoma forming vasoformative areas and solid areas showed immunopositivity to QBEND/10 in 17/23 and 13/24 cases respectively, and complementary immunoreactivity for von Willebrand factor was observed. Proliferating vessels and the majority of spindle cells in Kaposi's sarcoma were positive in all 40 cases. Only one of 54 cases of carcinoma showed luminal reaction to QBEND/10. However, 17 of 45 spindle cell tumours displayed a positive reaction. QBEND/10 is an additional marker for demonstrating endothelial differentiation and has some advantages over currently available antibodies.

Antibodies, Monoclonal

Action of recombinant alpha interferon against experimental and spontaneous metastases in a murine model.

The therapeutic potential of rHuIFN-alpha A/D, a hybrid human IFN molecule with equal activity on murine cells, was studied in experimental and spontaneous metastatic models of a murine colon carcinoma COLON 26. rHuIFN-alpha A/D inhibited experimental pulmonary metastases of COLON 26 and prolonged the survival of BALB/c mice. Dose scheduling, survival and tumour-cell clearance studies showed that the first 5 days were critical in the inhibition of pulmonary metastases. However, it is unlikely that lung NK cells were involved in the anti-metastatic effect of rHuIFN-alpha A/D because inhibition of pulmonary metastases and a decrease in radio-labelled tumour-cell survival was seen in BALB/c mice depleted selectively of their NK cells by prior treatment with rabbit antiasialoGMI serum. Although rHuIFN-alpha A/D stimulated NK-cell activity in BALB/c mice, it was ineffective in abrogating the NK suppressant action of rabbit anti-asialoGMI serum on murine lung NK cells. Thus, IFN may mediate its early antimetastatic effect via a mechanism independent of NK-cell stimulation. IFN also inhibited the development of lung metastases from s.c. COLON 26 tumors in normal, NK-depleted and T-cell-deficient mice.

Animals

Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice.

Therapy with human lymphoblastoid interferon HuIFN-alpha(N1), or recombinant human interferon gamma, rHuIFN-gamma, inhibited experimental pulmonary metastases of the human melanoma cell line, DX3-azac, in BALB/c nude mice and significantly prolonged survival. The human IFNs had no effect on nude mouse lung and spleen NK cell activity, lung macrophage activity, haemoglobin or white cell counts. HuIFN-alpha(N1) had no effect on the levels of the IFN induced enzyme 2-5A synthetase in nude mouse lungs although the rHuIFN-gamma caused some elevation. In addition, clearance of radiolabelled DX3-azac cells was identical in control or human IFN treated mice, and there was no histological evidence of an increase in immune effector cells associated with the metastatic lesions in treated mice. Human IFN therapy did not affect the state of differentiation of the melanoma cells in vivo as measured by melanin content, but both IFNs inhibited the development of colonies of DX3-azac cells in vitro. We conclude that in this model system IFNs have direct anti-proliferative effects on metastatic cells.

Animals

Enhanced metastases of a mouse carcinoma after in vitro treatment with murine interferon gamma.

We have studied the influence of interferons (IFNs) on the metastatic potential of mouse colon adenocarcinoma, COLON 26, cells. Pre-treatment of the cells in vitro for 24 hr with recombinant murine IFN-gamma (rMuIFN-gamma) significantly increased the number of lung tumour nodules when cells were injected i.v. into immunocompetent BALB/c mice and BALB/c nude mice. However, when MuIFN-gamma-pre-treated cells were injected into beige (NK-deficient) nude mice or anti-asialoGM 1 (asGM 1)-serum-treated BALB/c mice (NK-depleted) no enhancement of metastatic potential was seen. Pre-treatment of COLON 26 cells with recombinant human IFN-alpha A/D (Bg1 I), an IFN with equal activity on human and mouse cells, did not significantly enhance their subsequent metastases in immunocompetent or immunodeficient mice. In fact, there was a small but significant decrease in the number of tumour nodules in the lungs of beige nude and asGM 1-treated mice. The effects of rMuIFN-gamma on COLON 26 cells did not appear to be related to an alteration in MHC expression. COLON 26 cells constitutively express H-2D and H-2K antigens and both IFNs had equal enhancing (approx. 2-fold) activity on the expression of these antigens at the doses used in this experiment (10(3)U/ml). We conclude that pre-treatment with rMuIFN-gamma renders COLON 26 cells resistant to in vivo NK-cell lysis via a mechanism that does not involve changes in MHC expression.

Adenocarcinoma

Demonstration of HSV-I antigen in patients with oral cancer by immunofluorescence and immunoperoxidase techniques.

Biopsies from one hundred and seventy five patients suffering from carcinoma of the oral cavity were examined for the presence of Herpes simplex virus Type 1 (HSV-1) antigen, using Immunofluorescence (Direct and indirect) and immunoperoxidase techniques. Seventy-seven percent of the biopsies showed significant fluorescence, while 71% showed positivity with immunoperoxidase staining. There was no correlation either in the degree of fluorescence or in the intensity of peroxidase staining with clinical stage of the disease. Normal oral biopsies showed 30% and 20% positivity in immunofluorescence and immunoperoxidase respectively. In the case of oral cancer cells, the fluorescence was very much diminished when HSV-1 antiserum was absorbed with specific homologous virus-infected Vero cells.

Animals

The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice.

A recombinant human hybrid alpha interferon (rIFN-alpha A/D) with antiviral, immunomodulating and cell-growth-inhibitory activity on murine cells strongly inhibited the development of experimental pulmonary metastases of the Colo 26 adenocarcinoma in BALB/c mice. Twenty-one days after i.v. injection of 5 X 10(4) cells, 8/8 control mice had greater than 200 lung tumour nodules whereas 1/6 mice receiving 500 ng rIFN-alpha A/D had one lung tumour nodule and the other 5 mice were tumour-free. Equally strong inhibition was seen in immunodeficient BALB/c nu/nu (athymic) and beige nu/nu (athymic and NK-deficient) mice. Scheduling experiments in vivo showed that the most important time of IFN treatment was from the day of tumour cell injection to day 5, although statistically significant reductions in lung tumour nodule number and lung weight were seen even when IFN treatment was started 7 days after cell injection. rIFN-alpha A/D was cytostatic to Colo 26 in vitro, causing 50% or more inhibition of cell growth or colony number at IFN levels that could be achieved in the sera of IFN-treated mice. Although rIFN-alpha A/D stimulated NK-cell activity in BALB/c mice, Colo 26 cells were resistant in vitro to such cells whether from control or IFN treated mice.

Adenocarcinoma