Max R. Proffitt

Congestive cardiomyopathy and illness related to the acquired immunodeficiency syndrome (AIDS) associated with isolation of retrovirus from myocardium.

Excerpt Most clinical signs and symptoms reported in persons infected with the human immunodeficiency virus (HIV) are due to opportunistic infections or malignancies that flourish in the presence o...

Small noncleaved B cell burkitt-like lymphoma with chromosome t(8;14) translocation and epstein-barr virus nuclear-associated antigen in a homosexual man with acquired immune deficiency syndrome

This case report describes new manifestations of the acquired immune deficiency syndrome (AIDS) in a promiscuous homosexual man. Investigation of upper gastrointestinal bleeding in the patient lead to discovery of a high-grade, small, noncleaved cell (Burkitt-like) gastroduodenal lymphoma with visceral and extralymphatic extension. Specific phenotyping of the lymphoma revealed that it was a monoclonal B cell lymphoma of mu kappa isotype. An in vitro cell line was established that was Epstein-Barr virus nuclear-associated antigen-positive. The lymphoma cells displayed a t(8;14) translocation similar to endemic African Burkitt lymphoma. Epstein-Barr virus genomes were identified in the lymphoma and an axillary lymph node biopsy specimen by molecular hybridization. These data strongly suggest that Epstein-Barr virus actively infected this patient. However, he showed normal Epstein-Barr virus-specific serologic responses, indicating an immune defect against the virus.

Interferon γ production by human intestinal mucosal mononuclear cells

Immune (γ) Interferon is a substance produced by immunologically activated mononuclear cells. Besides its antiviral activity, interferon γ has a crucial role in immunoregulation, by acting directly upon lymphocytes and monocytes, and interacting with other soluble mediators of the immune response. Studies of the interferon system in inflammatory bowel disease have been limited, and little information is available on the generation of interferon during immunological events occurring in the human gut. To investigate the capacity of intestinal mucosal mononuclear cells to produce interferon γ, lamina proprial mononuclear cells, isolated from Crohns disease, ulcerative colitis, and control patients, were incubated with interleukin 2 or phytohemagglutinin, and the amounts of interferon γ present in the culture supernatants were measured by a virus cytopathic effect inhibition assay. Under identical stimulatory conditions, culture supernatants of cells derived from actively involved mucosa of inflammatory bowel disease specimens contained two- to fivefold less interferon γ than those of cells from control tissue. However, the amount of interferon γ present in supernatants of cells from uninvolved inflammatory bowel disease mucosa was similar to that found in control supernatants. These results indicate that, in patients with active Crohns disease and ulcerative colitis, mononuclear cells produce decreased amounts of interferon γ in the intestinal mucosa. The exact significance of these findings is unclear, but because of the importance of interferon γ in a variety of cell-mediated immune phenomena, its impaired availability might be relevant to the pathogenesis of inflammatory bowel disease.Immune (gamma) interferon is a substance produced by immunologically activated mononuclear cells. Besides its antiviral activity, interferon gamma has a crucial role in immunoregulation, by acting directly upon lymphocytes and monocytes, and interacting with other soluble mediators of the immune response. Studies of the interferons system in inflammatory bowel disease have been limited, and little information is available on the generation of interferon during immunological events occurring in the human gut. To investigate the capacity of intestinal mucosal mononuclear cells to produce interferon gamma, lamina proprial mononuclear cells, isolated from Crohns disease, ulcerative colitis, and control patients, were incubated with interleukin 2 or phytohemagglutinin, and the amounts of interferon gamma present in the culture supernatants were measured by a virus cytopathic effect inhibition assay. Under identical stimulatory conditions, culture supernatants of cells derived from actively involved mucosa of inflammatory bowel disease specimens contained two- to fivefold less interferon gamma than those of cells from control tissue. However, the amount of interferon gamma present in supernatants of cells from uninvolved inflammatory bowel disease mucosa was similar to that found in control supernatants. These results indicate that, in patients with active Crohns disease and ulcerative colitis, mononuclear cells produce decreased amounts of interferon gamma in the intestinal mucosa. The exact significance of these findings is unclear, but because of the importance of interferon gamma in a variety of cell-mediated immune phenomena, its impaired availability might be relevant to the pathogenesis of inflammatory bowel disease.

Acute Infection with the Human Immunodeficiency Virus (HIV) Associated with Acute Brachial Neuritis and Exanthematous Rash

Clinical descriptions of acute or primary infection with the human immunodeficiency virus (HIV) are rare. Among cases previously reported, most describe an acute illness resembling infectious mononucleosis. We describe the case of a 32-year-old homosexual man with an acute illness associated with strong serologic evidence of a primary infection with HIV. This case illustrates two new clinical features: an acute, bilateral brachial neuritis, and a vesicular, pustular exanthematous and enanthematous rash. Studies of HIV-related serologic results show differential sensitivities for enzyme-linked immunosorbent assay, Western blot, immunofluorescence, and viral antigen techniques in the acute phase of HIV infection. There appears to be significant clinical heterogeneity of the acute phase of HIV infection.

Enhancement of mouse natural killer cell activity by thyroxine.

Abstract In vivo administration of thyroxine (T 4 ) to CBA/J, C3H/HeN, and B 6 C 3 F 1 mice resulted in enhanced splenic and peritoneal natural killer (NK) cell activity against YAC-1 lymphoma target cells in vitro . T 4 treatment did not augment splenic or peritoneal NK activity in A/J, BALB/c, C57BL/6, or DBA/2 mice. Natural killer cells from T 4 -treated mice did not lyse P815 cells and were not removed by treatment with anti-Thy 1.2 + complement. Effector cell binding to target cells was not altered following T 4 treatment. CBA/J mice treated with T 4 also exhibit enhanced in vivo NK activity compared with untreated mice as demonstrated by rapid clearance of [ 125 I]iodo-2′-deoxyuridine-labeled YAC-1 lymphoma cells. The augmentation of NK activity as a result of T 4 treatment is reversible and is not accompanied by increased serum interferon levels. Spleen cells from T 4 -treated mice incorporate more [ 3 H]thymidine and [ 3 H]uridine in comparison to spleen cells from control animals. Treatment of mice with 131 I did not enhance splenic or peritoneal NK activity. These data suggest that thyroid hormones can augment mouse NK activity and this modulation is most likely due to changes in the metabolic properties of NK cells.

A murine leukemia virus yield-reduction semi-microassay for interferon

Interferon (IF) treatment of murine cells chronically producing infectious leukemia virus results in a decreased yield of extracellular virus. We have utilized this principle to develop a useful semi-microassay for IF. The assay incorporates the desirable features of both virus yield-reduction and plaque-reduction assays, yet has few of the undesirable features associated with many IF assays. Being a semi-micro assay, it is amenable to the screening of multiple samples for IF and is economical with respect to cell culture materials, reagents and amount of sample required for testing.

Kaposi's sarcoma, angioimmunoblastic lymphadenopathy, and antibody to HIV-1 p24 antigen in a patient nonreactive for HIV-1 with use of ELISA

1. Biro L, Price E, Brand A. Cryosurgery for basal cellcarcinoma of the eyelids and nose: five-year experience. J AM ACAD DERMATOL 1982;6:1042-7. 2. Domonkos AN. Treatment of eyelid carcinoma. Arch DermatoI1965;91:364-71. 3. Zacarian SA. Cryosurgeryfor skin cancer and cutaneous disorders. St Louis: CV Mosby, 1985:96-102. 4. Kuflik EG. Cryosurgery forcarcinomaof the eyelids: a 12year experience. J DermatolSurg Oncol 1985;11 :243-6.

Comparison of plasmagel with LeucoPREP™-Macrodex methods for separation of leukocytes for virus isolation

Plasmagel (Cellular Products, Inc., Buffalo, NY), which can separate both polymorphonuclear leukocytes (PMN) and mononuclear cells from other blood components, and LeucoPREP (Becton Dickinson Immunocytometry Systems, Mountain View, CA), which can separate mononuclear cells from other blood components, were used to harvest leukocytes from whole blood for the purpose of virus isolation. Macrodex was combined with the later, in a second step, for recovery of PMN. Of 90 peripheral blood specimens examined, cytomegalovirus was recovered from 10: in six by both methods, in three from Plasmagel prepared cells only, and in one from cells from the LeucoPREP-Macrodex preparation only. Total leukocyte counts, differential counts, and leukocyte viability did not differ significantly for the two methods. Plasmagel provided an efficient, inexpensive means of harvesting leukocytes from whole blood for virus isolation.

The immune response to a chemically induced fibrosarcoma

SummaryA clone of C3H10T 1/2 fibroblasts transformed in vitro with the carcinogen 3-methylcholanthrene readily produced tumors when as few as 103 cells were injected into immunocompetent adult syngeneic mice. A non-transformed clone of the same parentage did not produce tumors. Because the cell-mediated immune response has an important role in inhibiting the growth of tumors, we have compared the ability of both these transformed and non-transformed fibroblasts to stimulate and to act as targets in cell-mediated cytotoxicity (CMC) assays. This model is unique in that studies of the immune response to tumors rarely have or utilize appropriate normal controls. When both types of irradiated fibroblasts were used as stimulators in vitro, neither syngeneic nor allogeneic effector spleen cells capable of efficiently lysing the tumor fibroblasts were generated. In contrast, the normal fibroblasts could both stimulate and be lysed by allogeneic cytolytic T cells (CTL). However, the tumor fibroblasts could be lysed by allogeneic effector spleen cells that had been sensitized to C3H/He spleen cells. These results suggest that the expression of alloantigenic determinants necessary for stimulating a CMC response may vary substantially among ‘normal’ cell types. They further indicate that the tumor cells are not resistant to lysis by appropriately stimulated effector cells. Thus, they must express antigenic determinants necessary for immune lysis and they do not inhibit the functional expression of cytolytic cells once generated. Consequently, tumor growth in vivo may be dependent, in part, upon a failure of the syngeneic hosts immunocompetent cells to respond appropriately to the tumor cells. Additional data are provided which suggest that this failure is attributable in large part to immunosuppressive properties of the tumor cells.

Cell-mediated immune functions, interleukin 2 and interferon production by high leukemia incidence mutant (hr/hr) mice of the HRS/J strain

Homozygous hr/hr mice of the HRS/J strain have a high incidence of lymphoma not seen in congenic hr/+ littermates. The suggestion has been made that a helper T cell defect in the immune system of the homozygotes may account for this. To further examine the immune status of these mice, we compared the ability of spleen cells of mice of both types to stimulate, as well as to generate, allogeneic cell-mediated cytolytic responses and to produce a soluble mediator of such responses. In addition, both types of mice were tested for their ability to produce interferon (IFN) or to have their splenic natural killer cell (NK) levels augmented by polyriboinosinic-polyribocytidylic acid (poly rI-rC). We found that the spleen cells of young or aging mice of either type were able to stimulate the generation of alloreactive cytotoxic cells, but they did not inappropriately stimulate the generation of syngeneic cytotoxic cells. Similarly, spleen cells of both types of mice produced a T helper cell-derived growth factor (interleukin 2) involved in the proliferation of cytolytic cells and generated a classical cell-mediated lympholysis (CML) response to alloantigen-bearing cells. Finally, spontaneous NK cell levels, as well as poly rI-rC augmented IFN and NK cell levels, were similar in both types of mice. Thus, it appears that if defects in the immune system are solely responsible for the high incidence of lymphoma in hr/hr mice, the defects involve components or regulatory aspects of that system that have yet to be defined.