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Biomedical subjects

L Rice

Publications and source records attributed to L Rice.

At least 73 records · Page 4Linked to original sources

Effect of whole-body hyperthermia on cell survival, metastasis frequency, and host immunity in moderately and weakly immunogenic murine tumors.

The effects of whole-body hyperthermia (WBH) on animal tumors and on metastasis frequency were studied. The tumors were a chemically-induced fibrosarcoma, FSa-I, which is moderately immunogenic and a spontaneously arisen fibrosarcoma, FSa-II, which is very weakly immunogenic. The WBH was given at 42.5 degrees in an incubator which had an auxiliary heater for accurate temperature control. Animal core temperature reached 41.5 degrees in 30 min. The lung colony assay revealed that the WBH for 60 min given at 24 hr after i.v. injection of single cells gave no lethal damage to either FSa-I or -II tumor cells. A significant inhibition of tumor growth was found when large tumors were given three daily WBH treatments. The frequency of lung metastasis was enhanced when large weakly immunogenic FSa-II tumors were treated by WBH, although no increase in the frequency was observed for FSa-I tumors of any size. Local hyperthermia did not significantly increase the metastasis rate of both tumors. These results suggest that the WBH might be useful for a treatment of large immunogenic tumors. However, the WBH is not a choice of treatment for possible micro-metastases.

Animals↗

Granulomatous infections complicating hairy cell leukemia.

Of 14 patients with hairy cell leukemia (HCL), four developed opportunistic granulomatous infections: blastomycosis, coccidioidomycosis and two Mycobacterium kansasii. The former two pathogens have not been reported with HCL, while M. kansasii infections appear to be common. While most reviews stress susceptibility to pyogenic bacteria and the predisposing role of iatrogenic factors, three of our patients were infected prior to any therapy. Thus, disease-related factors predispose to these granulomatous infections. Granulocytopenia and monocytopenia were present; the latter was not often corrected by splenectomy. There was impaired granuloma formation, with all infectious lesions appearing histologically as focal microabscesses containing few macrophages. Awareness of the frequency of opportunistic intracellular infections with early consideration of invasive diagnostic procedures to establish specific etiologic diagnosis may greatly prolong survival for many HCL patients.

Agranulocytosis↗

Angioimmunoblastic lymphadenopathy with hypogammaglobulinemia. Possible role of monocyte suppression.

A patient wit angioimmunoblastic lymphadenopathy had low serum immunoglobulin values and no antibodies to injected immunogens. This occurred despite the proliferation of polyclonal B cells. T cells were deficient in number and in lymphoproliferative responses, but their helper and suppressor functions were maintained. Ia-antigen bearing leukocytes from the patient stimulated poorly in mixed leukocyte culture. In vitro immunoglobulin synthesis by mononuclear leukocytes form the patient was severely impaired. These leukocytes actively suppressed immunoglobulin synthesis by normal cells from healthy subjects in co-culture. The responsible cell had characteristics of a monocyte. The suppression was selective for humoral immunity and was manifest despite normal numbers of monocytes. It appears that heterogeneous immunoregulatory abnormalities can underlie the syndrome of angioimmunoblastic lymphadenopathy. Furthermore, monocyte suppressor abnormalities may be implicated in clinical disease phenomena.

Aged↗

Erythrocytosis and marked leukocytosis in overlapping myeloproliferative diseases.

We describe two patients who had similar features of erythrocytosis and marked leukocytosis but who were subsequently classified as having chronic myelogenous leukemia and polycythemia vera, respectively, using leukocyte alkaline phosphatase scores and cytogenetic studies to detect the Philadelphia chromosome. The patient diagnosed as having polycythemia vera had a leukocyte count of 164,000/cu mm, which remained at similar levels when the patient was not in remission. We believe this is the first well documented case of PV with a leukocyte count above 150,000/cu mm.

Adult↗

Suppression of lymphocyte responses by monocytes with untreated and treated multiple myeloma.

Studies were performed on 15 untreated and 14 treated patients with multiple myeloma. The monocyte content was normal in blood but elevated in mononuclear leukocytes (MNL) from treated but not untreated patients (p less than 0.001). This correlated with the severity of lymphopenia in blood (p less than 0.01). Three patterns of immunoglobulin(Ig) synthesis emerged. (1) Most untreated patients showed normal polyclonal responses to pokeweek mitogen. (2) Of 12 treated patients, the 8 whose MNL included greater than 30% monocytes had subnormal Ig responses to pokeweek mitogen. Ig synthesis increased when adherent cells that suppressed Ig synthesis were depleted. Suppression in vitro bore no relationship to polyclonal immunoglobulin levels in serum. (3) Three patients had early blood invasion by plasmacytoid cells. Their MNL spontaneously released large amounts of the Ig class of their serum gammopathies. Proliferative responses to phytohemagglutinin by MNL from all patients were reduced, in part due to monocytoid cell suppression and in part to intrinsic T-cell hyporesponsiveness. B- and T-cell responses in vitro are sometimes suppressed with myeloma. This is related to elevated monocyte percentages in MNL preparations. This excess of monocytes is a function of lymphopenia secondary to therapy, rather than the primary malignant process itself. No evidence was found that suppression by monocytes is qualitatively altered by myeloma or its treatment.

Antibody Formation↗

Acquired Pelger-Huët nuclear anomaly with tuberculosis.

Karel Pelger described an abnormality of granulocyte nuclear segmentation in the context of advanced tuberculosis, but G. Huët questioned this association. It is now recognized that the Pelger-Huët nuclear anomaly (PHNA) can be either hereditary or acquired with systemic diseases, commonly hematologic dysplasias. An association with tuberculosis has never been well verified. The man described in our study had cachexia, high fevers, severe hypoproliferative anemia, and acquired PHNA. At autopsy, an overwhelming tuberculosis was discovered in the absence of any other underlying disease. Acquired PHNA may serve as a diagnostic and prognostic indicator in tuberculosis.

Bone Marrow↗

Thermal resistance in a spontaneous murine tumour.

Resistance to subsequent hyperthermia as a result of prior heating was investigated using a spontaneous murine tumour implanted into the feet of C3H/Sed mice. Tumours were treated by immersing the tumour-bearing foot into a constant-temperature hot water bath set at 45.5 degrees C and were given single and split doses of heat. Response was assessed using a tumour-growth time assay. Three aspects of thermally-induced resistance were particularly considered: the time course of development and decay; the importance of the magnitude of the priming dose and the influence of the size of the tumour at the time of treatment. Substantial resistance was induced in this tumour by short priming doses at 45.5 degrees C, rising rapidly 1-2 days after the first treatment and then starting to decay. There was no significant difference in the kinetics of thermal resistance induced in tumours treated at 4mm and those treated at 8 mm in size, although the large tumours were more sensitive to single doses of heat. Increasing the magnitude of the priming dose of heat resulted in an increase in the magnitude of resistance to the second dose. The results of this study are compared with results of similar studies in this and other laboratories using murine normal tissues and cells in culture. Possible clinical implications are considered.

Animals↗

Spectrum of immunodeficiencies with Hodgkin's disease.

The role of six suppressor mechanisms upon T and B cell responses was studied on 17 untreated patients with Hodgkin's disease. Proliferative hyporesponsiveness to mitogen was greatly impaired in 8 of the 13 patients. 10 of these patients had an excessive degree of suppression by cells that adhered to foreign surfaces. Suppression by adherent cells correlated with impairment of proliferative responses and, in some instances, suppression was largely inhibited with indomethacin. Likewise, adherent cells suppressed immunoglobulin synthesis. A correlation was evident between suppression of T and B cell responses by adherent mononuclear leukocytes from individual patients. This suppression coincided with elevated percentages of monocytes in the patient mononuclear cell preparations. This excess of monocytes was not the result of a circulating monocytosis. The monocyte excess may have been acquired during isopyknic cell separation. A second form of suppression was observed in 5 of the 11 patients affected by a lymphocyte that neither adhered to glass wool nor required preactivation. It did not inhibit allogeneic lymphocytes, which contrasts with the suppressor abnormality of monocytoid cells.

Adolescent↗

The radiosensitivity of a murine fibrosarcoma as measured by three cell survival assays.

The radiation sensitivity of a weakly immunogenic spontaneous fibrosarcoma of the C3Hf/Sed mouse (designated FSa-II) was assessed by three in vivo cell survival methods: end-point dilution (TD50) assay, lung colony (LC) assay, and agar diffusion chamber (ADC) assay. The hypoxic fraction of this tumour was also determined by the ADC method. Although there was a good agreement of the cell survival data between the ADC and LC methods, the TD50 method yielded a considerably less steep cell survival curve. Beneficial aspects and limitations of each assay are discussed. In addition, the use of the ADC method for the growth of xenogeneic cell lines and a preliminary experiment with human tumour cells in non-immunosuppressed hosts suggest that this method may be a valuable adjunct for studying the growth and therapeutic responses of human tumour cells.

Agar↗

Three suppressor systems in human blood that modulate lymphoproliferation.

Three suppressor system of T lymphocyte proliferation found in normal blood were characterized. The adherent cell suppressor system (ACSS) is effected by a steroid and radioresistant monocyte that survives well in culture. The prostaglandin-related suppressor system (PgSS) is effected by a similar cell but is distinct from the ACSS in terms of magnitude of suppression, effective monocyte concentration, and carrageenan or indomethacin sensitivity. The induced suppressor system (ISS) is effected by a T lymphocyte that is partially radiosensitive and loses activity after 24 hr in culture. Although the ISS is unaffected by age, ACSS and PgSS activity is, overall, higher among elderly than among young adult subjects. Activation of these three suppressor systems does not require cell replication. They are not restricted by histocompatibility barriers.

Adult↗