Cheryl M. Reichert

Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer

We describe here the preliminary results of the systemic administration of autologous lymphokine-activated killer (LAK) cells and the recombinant-derived lymphokine interleukin-2 to patients with advanced cancer. This regimen was based on animal models in which the systemic administration of LAK cells plus interleukin-2 mediated the regression of established pulmonary and hepatic metastases from a variety of murine tumors in several strains of mice. We treated 25 patients with metastatic cancer in whom standard therapy had failed. Patients received both 1.8 to 18.4 X 10(10) autologous LAK cells, generated from lymphocytes obtained through multiple leukaphereses, and up to 90 doses of interleukin-2. Objective regression of cancer (more than 50 per cent of volume) was observed in 11 of the 25 patients: complete tumor regression occurred in one patient with metastatic melanoma and has been sustained for up to 10 months after therapy, and partial responses occurred in nine patients with pulmonary or hepatic metastases from melanoma, colon cancer, or renal-cell cancer and in one patient with a primary unresectable lung adenocarcinoma. Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Further development of this approach and additional patient follow-up are required before conclusions about its therapeutic value can be drawn.

Hepatitis B Virus Infection in the Acquired Immunodeficiency Syndrome

Excerpt The acquired immunodeficiency syndrome has become a major phenomenon during the last 3 years. Recent data from several sources suggest that the syndrome may be a result of infection with a ...

Disseminated Bilateral Chorioretinitis due to Histoplasma capsulatum in a Patient with the Acquired Immunodeficiency Syndrome

A 31-year-old white male homosexual was healthy until March 1984, when he developed Pneumocystis carinii pneumonia, which resolved with treatment. In April 1984 he developed fever, followed by hepatosplenomegaly, headaches, blurred vision, pancytopenia and pulmonary infiltrates. On June 11, intracytoplasmic yeast were noted within leukocytes on a peripheral blood smear, and amphotericin B was started. The patient developed progressive respiratory and renal insufficiency and died on June 13, 1984. Autopsy histopathology demonstrated disseminated histoplasmosis and Histoplasma capsulatum was cultured from numerous tissues. Ocular histopathologic examination using special fungal stains and electron microscopy revealed numerous budding yeasts characteristic of Histoplasma capsulatum in the choroid, retina and central retinal vein. Their identification as H. capsulatum was confirmed by immunofluorescent staining.

Antitumor effect of recombinant tumor necrosis factor-α against murine sarcomas at visceral sites: tumor size influences the response to therapy

SummaryWe examined the antitumor efficacy of rTNF-α administration on established tumor at two visceral sites, lungs and liver. Treatment of B6 mice harboring multiple (>100 foci of ≤0.5 mm diameter) 10-day pulmonary macrometastases from the MCA-106 sarcoma, with dosages of rTNF-α (5–10 μg, single dose i. v.) that caused hemorrhagic necrosis and regression of a 6 mm MCA-106 s. c. tumor, had no impact on the number (or size) of lung nodules. Similarly, rTNF-α failed to show an antitumor effect in B6 mice with advanced day 8 or 10 multiple (>100 foci of ≤0.5 mm diameter) hepatic metastases at single i. v. doses up to 20 μg, as measured by either enumeration of residual liver nodules or survival. B6 mice injected s. c. with MCA-106 sarcoma and treated with rTNF-α as a single i. v. dose on day 0, 3, 5, or 7 experienced marked tumor regression only after the day 7 rTNF-α injection, when the tumor had achieved a size of 5–6 mm in diameter. Since tumor size appeared important for rTNF-α susceptibility in vivo, we next induced a single hepatic tumor of the MCA-106 sarcoma by the direct injection of cells into the left lobe of the liver and treated these mice at day 10 when the nodule had achieved a size of 5–6 mm in diameter. Increasing doses of rTNF-α (up to 8 μg) given as a single i. v. injection resulted in increasingly greater reductions in hepatic tumor as well as significant survival benefit of the treated mice. Sites of regressing hepatic tumor exhibited central necrosis accompanied by polymorphonuclear leukocytes and lymphocytes. Collectively, these results show that rTNF-α administration can mediate a significant antitumor effect on visceral tumor and suggest that tumor size is an important factor in rTNF-α susceptibility not only for tumors growing at s. c. sites but also for those established at visceral sites.

Delayed hemorrhage after percutaneous liver biopsy

Clinically significant hemorrhage immediately after percutaneous liver biopsy is an uncommon, although well-recognized risk of the procedure. However, hemorrhage from the biopsy site delayed a day or more after the procedure is a seldom-appreciated potential complication. Delayed hemorrhage from the liver biopsy site may go unsuspected; in fact, the patient may no longer be under direct medical surveillance. We describe two cases of such delayed hemorrhage which we attribute to intrahepatic hematoma at the site of biopsy. Neither patient had a prebiopsy contraindication to the procedure. One patient suffered a fatal intraperitoneal hemorrhage 15 days after liver biopsy, the other a massive, but nonfatal intrahepatic hemorrhage 41 hours after the procedure. In the first patient, a hemorrhagic diathesis developed in the immediate period after biopsy; no predisposition to hemorrhage could be identified in the latter patient, even retrospectively. The admittedly rare possibility of delayed hemorrhage should be considered whenever a liver biopsy is performed.

Two monoclonal antibodies highly specific for the blood group N determinant

Two monoclonal IgM antibodies, 179K and 35/5F, obtained following immunization of mice with A2,MN or O,MN human erythrocytes, agglutinate NN and MN red cells strongly, and MM erythrocytes weakly. As shown by hemagglutination inhibition and solid phase ELISA, both antibodies are highly specific for the blood group N determinant. They react with N glycoprotein, its amino-terminal glycopeptides and with Ss glycoprotein (glycophorin B), which carries the blood group N determinant. They fail to react with M glycoprotein, M glycoprotein-derived glycopeptides, or with internal glycopeptides derived from N glycoprotein. Reaction of the antibodies with N glycoprotein is abolished by desialylation, periodate oxidation/borohydride reduction, orN-acetylation of the glycoprotein. Thus, the antibodies are specific for an epitope which includes sialylated oligosaccharide chain(s) and is located in the region of the amino-terminal leucine residue of N glycoprotein. MMU− erythrocytes, lacking both blood group N and Ss glycophorin are non-reactive. Agglutination of MMU+ erythrocytes by the anti-N antibodies occursvia interaction with glycophorin B and correlates with the Ss phenotype of red cells MM,S erythrocytes are usually more strongly, agglutinated than MM,ss cells. The agglutination of MM erythrocytes decreases markedly as the pH is increased from 6 to 8, while agglutination of NN red cells is much less affected by shifts in pH over this range. As a result, both monoclonal antibodies are highly anti-N specific typing reagents when the agglutination assay is carried out at pH 8.

Kaposi's Sarcoma of the Head and Neck in the Acquired Immune Deficiency Syndrome

Since 1981 a new syndrome of acquired immune deficiency (AIDS) has been recognized. Male homosexuals, male and female intravenous drug abusers, and recipients of blood products (i.e., hemophiliacs) appear to be the populations at risk. The syndrome has been manifested by community-acquired opportunistic infections and/or Kaposis sarcoma (KS). Otolaryngologic manifestations of AIDS are not infrequent. Thirteen AIDS patients at the National Institutes of Health with KS of the head and neck region are presented. All 13 patients were homosexual or bisexual males. Nine initially presented with KS, five with KS of the head or neck. As a group the patients demonstrated lesions involving the oropharyngeal, tracheobronchial, and gastrointestinal regions. Their clinical course and complications are presented in detail. The mortality rate in this subgroup of AIDS patients is extraordinarily high (62%), with an average longevity of 11 months following initial diagnosis.

An erythrocyte Pr auto‐antibody with sialoglycoprotein specificity in a patient with purine nucleoside phosphorylase deficiency

A warm auto‐antibody with specificity in the Pr blood group system was demonstrated in the serum and red cell eluate of a patient with purine nucleoside phosphorylase (NP) deficiency. The antibody reacted with all cells tested except En(a‐) red cells which lack glycophorin A, the major erythrocyte sialoglycoprotein. However, anti‐Ena was ruled out by absorption of the antibody with En(a‐) red cells. The antibody demonstrated similar serologic characteristics to Pra antibodies, except that those previously described were inactive with protease‐ treated red cells, while in this case, reactivity was destroyed by papain and ficin but maintained in the presence of trypsin. Inhibition analysis with purified glycoprotein fragments localized the predominant reactive antigen on the MN sialoglycoprotein between amino acid residues 40 and 61. Serologic tests demonstrated its presence in decreased amount on at least one other erythrocyte membrane structure. The serum from another patient with NP deficiency contained an autoantibody similar to the one described here. It may be of interest to explore the association of auto‐antibodies to erythrocyte sialoglycoprotein antigens in NP and other immune deficiency states.