T-2 toxin effect on rat aorta: cellular changes in vivo and growth of smooth muscle cells in vitro.

Rats were injected intraperitoneally with T-2 toxin and their aortas were studied by light and electron microscopy. The growth of smooth muscle cell explants taken from the tunica media of aortas of similarly treated animals was observed. A single large dose (2 mg/kg) or four injections of 0.3 mg/kg T-2 toxin caused damage and occasional necrosis of endothelial cells, accumulation of basement membrane-like material in the intima, and swelling and activation of smooth muscle cells in the tunica media. Three or more weeks after the last injection of 0.3 mg/kg T-2 toxin the endothelial cells were normal but an excess of fragmented intimal basement membrane-like material persisted and smooth muscle cells were still activated. Outgrowths from explants of aortic tunica media taken within 1 week of the last dose of T-2 toxin showed marked inhibition of smooth muscle cell growth. Three or more weeks after the toxin, the explants showed significantly increased outgrowths. These findings suggest that T-2 toxin causes early endothelial and smooth muscle cell injury accompanied by inhibition of smooth muscle cell growth in culture. This is followed by stimulation of the proliferative capacity of smooth muscle cells in vitro. If a similar mechanism is operative in vivo, it could explain the chronic vascular changes observed after limited exposure to T-2 toxin.

Lung nonresponsiveness produced in guinea pigs by aerosolized antigen. I. Nonresponsiveness is not antigen specific.

Nonresponsiveness to aerosolized antigen induced by repeated exposure of guinea pigs to either bovine serum albumin (BSA) or ragweed (RW) aerosols was not antigen specific, since induction of lung sensitization with the same, as well as heterologous antigen, was prevented. However, prior lung sensitization to an antigen was maintained in spite of subsequent treatment with aerosolized antigen. In this case treatment with aerosolized antigen could abrogate sensitization of the lung to all subsequent antigens. Chopped lung pieces could not be passively sensitized by antisera to homologous or heterologous antigens unless they were previously treated at low pH. High levels of conventional and homocytotropic antibody were demonstrated in nonresponder animals. Nonresponsiveness induced by fed antigen, however, was antigen specific, and elevated homocytotropic antibody levels were not present. Aerosol-induced nonresponsiveness appears to be a local phenomenon which involves a blocking of the pulmonary mast cells by immune complexes or other blocking factors so that they can no longer respond to antigen challenge.

Plasma exchange in six patients with advanced cancers of the head and neck.

Six patients with advanced squamous cell cancers of the head and neck, with serum IgA greater than or equal to 400 mg/dl and IgE less than or equal to 1000 IU/ml, underwent a trial of six 2-liter plasma exchanges over a 2-3-week period. Disease progressed in patients 1, 2, and 4, who died on days 44, 72, and 159. The tumor in patients 3 and 6 regressed significantly, repeatedly in patient 3 over each of four courses of apheresis. Tumor recurred in both patients after cessation of treatment, and they died at days 420 and 79. Patient 5, with inoperable disease, received full-dose radiotherapy immediately following the course of apheresis, and showed complete response in the primary lesion and a major response in the extensive lymph node metastases, dying on day 421 of apparently unrelated causes. Serum IgE in the three patients experiencing tumor regression rose paradoxically during plasmapheresis. Only patient 3 had an elevated level of soluble E-receptor suppressor factor prepheresis; the serum of patient 6 was lymphocytotoxic prepheresis but this activity decreased or disappeared during each of the exchanges studied. Controlled trials are now indicated.

T8 chronic lymphocytic leukemia. A distinctive disorder related to T8 lymphocytosis.

A case of T chronic lymphocytic leukemia (CLL) was first suspected on histologic and cytochemical examination of a splenectomy specimen. Later the patient became frankly leukemic with an E+/T3+/T8+/T4- phenotype. From our case and other reported cases of T-CLL studied with monoclonal antisera, the authors conclude that there are significant clinical and morphologic differences between T4 CLL and T8 CLL. In contrast to T4 CLL, T8 CLL characteristically presents with relatively low lymphocyte counts, little organ involvement, and often only discreet bone marrow involvement, and has a long clinical course. The leukemic cells are often large and have abundant cytoplasm with azurophilic granules. Similar features in cases reported as T8 lymphocytosis with neutropenia lead us to consider both entities part of a spectrum of the same disorder.

Peripheral T-cell lymphoma: a clinicopathologic study of nine cases.

The clinicopathologic features of nine cases of peripheral T-cell lymphoma were analyzed. Although the youngest patient was 18 years old, the median age was 59.8 years. They usually presented with widespread disease and had an aggressive course. Seven have died with a median survival of 10.9 months. Five cases were of mixed cell type, sharing certain histopathologic features that we believe are characteristic of peripheral T-cell lymphomas. Three cases were of large cell type; one was a small cell (PDL) type. This latter patient lived symptom-free without treatment for over 3 years, despite stage III disease. Another patient, whose tumor had nodular sclerosis-like fibrosis, is in complete remission two years after chemotherapy for stage III B disease. Because peripheral T-cell lymphoma is morphologically heterogeneous, it may be clinically heterogeneous as well. We believe that classification according to a modified Rappaport system may clarify possible variations in biologic behavior.

Antigen aerosols induce lung nonresponsiveness.

Guinea pigs intranasally dusted with ragweed pollen (RW) for one month went into anaphylaxis in ragweed extract aerosol (RWEA). Animals which received RWEA pretreatment for one month before nasal dusting with RW pollen were nonresponsive to RWEA. The purpose of this study was to define the mechanism of nonresponsiveness. The protocol for producing either sensitivity or nonresponsiveness was applicable to another antigen, bovine serum albumin (BSA). Antibody blocking passive cutaneous anaphylaxis (PCA) in passively sensitized animals was demonstrable in BSA nonresponder serum. However, the blocking antibody probably was not responsible for the nonresponsiveness because BSA nonresponder serum was also able to sensitize passively the skin and lungs of normal recipients. Also nonresponsiveness was not due to the swallowing of antigen because feeding antigen inhibited synthesis of sensitizing antibody and precipitating antibody both of which were present in high titers in nonresponders. Sensitive guinea pig lungs contained nearly twice as much histamine as normal and nonresponder lungs. However, normal and nonresponders went into anaphylaxis at the same time in an aerosol of compound 48/80. These results suggest that the mechanism of nonresponsiveness produced by pretreatment with antigen aerosols might be due to a modification in antigen reactivity of the lung mast cells rather than to alterations in the mediators of anaphylaxis.

Prognostic indicators in chemotherapy for head and neck carcinoma: alkaline phosphatase levels.

Serum alkaline phosphatase (AP), total bilirubin, total protein, serum albumin, and serum glutamic oxaloacetic transaminase (SGOT) were determined in 55 patients with biopsy proven carcinoma of the head and neck prior to their induction chemotherapy with cis-platinum and bleomycin. Of the 55 patients, 40 (73%) exhibited either a complete or partial response (tumor mass decreased by over 50%) to the chemotherapy. Responses were noted more frequently in patients with elevated AP levels. Nine of the 10 patients (90%) with AP levels greater than 100 mU/ml experienced a major response; whereas, only 8 of 16 patients (50%) with AP levels less than 60 mU/ml demonstrated a favorable response to the chemotherapeutic agents. The source of the elevated AP levels has not yet been established. Possible sources include liver, bone, kidney, intestinal mucosa, or the tumor itself. Total bilirubin, total protein, serum albumin, and SGOT levels did not differentiate the responders from the non-responders as accurately as did the AP levels.

Comparison of the PCA titer and aerosol microshock time in guinea pigs made sensitive to ragweed.

Guinea pigs were sensitized either by intranasal dusting with ragweed (RW) pollen or by intranasal instillation of RW extract and subsequently challenged with a RW extract aerosol. It was relatively easy to determine the microshock time for animals which responded between 0 and 10 minutes. Sera from these sensitive guinea pigs were tittered by passive cutaneous anaphylaxis tests. Data from these two assays showed a semilogarithmic relationship with a correlation coefficient of -0.934.

Suppression of anaphylactic reactions in guinea pigs by previous treatment with ragweed aerosol.

Guinea pigs subjected to intranasal dusting with ragweed (RW) pollen or intranasal instillation of RW extract (RWE) showed anaphylactic reactions when subjected to RW extract aerosol (RWE). These animals, however, did not respond to an aerosol of RW whole pollen. Animals which received the RWEA treatment prior to nasal dusting with RW pollen showed no subsequent anaphylactic reactions when exposed to RWEA. Both the aerosol-sensitive and the aerosol-nonresponsive animals exhibited high titers of homocytotropic antibodies to RWE. In addition, the aerosol-nonresponsive animals also had precipitating antibodies of IgG type. The state of nonresponsiveness did not appear to be due to the precipitating antibodies, since this condition could not be passively transferred by sera and blocking antibody activity was not demonstrable.

Peliosis of the spleen.

Peliosis of the spleen is a rare condition that accompanies peliosis hepatis. Two cases are presented, and a detailed morphologic description is given. The lesions are confined to the red pulp and appear to arise by progressive distention of splenic sinuses, with eventual thrombosis and organization. Peliotic involvement of the spleen is probably more common than realized and can have serious clinical implications.

Lack of correlation between growth characteristics, agglutinability by plant lectins and the malignant phenotype.

Wheat germ agglutinin and Concanavalin A were found to agglutinate a variety of normal hamster cells as well as a number of lines of transformed or tumor cells. The normal cells included preparations from embryos and neonatal organs, and the spontaneous line, BHK-21 C13. In order to explore more fully the situation in regard to the BHK cells, three sublines were isolated and studied. A "flat revertant" selected by FUdR treatment grew to diminished saturation density and failed to produce colonies in soft agar in contrast to the parent line, which did. Yet, it was only minimally less tumorigenic and less agglutinable than the parent line. Lines derived from one and four consecutive in vivo tumor passages showed increased tumorigenicity and growth in soft agar when compared to the parent line. Although the first passage line showed increased saturation density, the saturation density of the fourth passage line was similar to or less than that of the parent cells. Agglutinability of these lines was not significantly increased. These results indicate that, in contrast to widely accepted beliefs, tumorigenicity may correlate poorly with growth characteristics and agglutination by plant lectins.