Eliezer Benjamini

Chemoimmunotherapy for canine lymphosarcoma

Thirty‐two dogs with naturally occurring multicentric lymphosarcoma were randomly assigned to one of two treatment groups. One half of the animals received combination chemotherapy plus vitamin injections (controls) while the other half received identical chemotherapy plus injections of chemically‐modified tumor cell extract in Freunds complete adjuvant (vaccinates). Clinical staging revealed no bias between groups but showed that prognosis could be closely correlated with the severity of disease at initial presentation. Twenty dogs (62%), including 11 vaccinates and 9 controls, responded favorably to chemotherapy and were evaluated for length of first remission and total survival time. Both parameters were significantly longer in vaccinated dogs than in controls. These data suggest that immunological stimulation may be a helpful adjunct to conventional therapy in selected types of cancer when immunological principles are observed.

Antibody‐dependent cell‐mediated cytotoxicity in treated and nontreated cancer patients

Antibody‐dependent cell‐mediated cytotoxicity (ADCC) exhibited by peripheral blood leukocytes was used as a criterion for assessing immune competence of groups of noncancerous individuals and of treated and untreated cancer patients. The results show that, as a group, leukocytes of nontreated cancer patients exhibited significantly lower ADCC than that exhibited by leukocytes of noncancerous individuals. However, the ADCC of leukocytes from cancer patients under treatment approximated that of normals. Thus, using ADCC as criterion, the results indicate that as a group, cancer patients under treatment tend to exhibit restored immune competence.

TUMOR VACCINES FOR IMMUNOTHERAPY OF CANINE LYMPHOSARCOMA

Canine hemolymphatic disease is a group of neoplasms that are frequently encountered in the veterinary practice. Priester and Mantel l reported that it was the fourth most common neoplasm in the dog. Lymphosarcomas (malignant lymphoma) comprise the majority of hemolymphatic tumors, whereas granulocytic leukemia is relatively rare in the dog. Dorn et aL8 reported an incidence of lymphosarcoma of 241 100,000 dogs in a defined population in two California counties. There is increased frequency of the disease with age. Canine malignant lymphoma is usually seen as a generalized lymphatic disease. In a series of 146 dogs with lymphosarcoma from our clinic, 84% had a generalized lymph node involvement. The liver and spleen were involved, respectively, in 54 and 62% of all the animals. Involvement of just the organs of the abdomen or of the thorax or the skin accounts for 14% of our 146 cases. Most of the lymphosarcoma animals presented to our clinic are in advanced stages of disease, usually in stages I11 and IV according to the criteria of Squire et aL3 Until recently, lymphosarcoma was classified as an untreatable fatal disease of dogs. There are little data in the literature that provide information that pertains to spontaneous remissions and to survival after diagnosis in untreated dogs. Unfortunately, most dogs with lymphosarcoma are euthanized, so data from the literature and from our own experience with untreated animals are scarce. Nevertheless, it is recognized that without treatment, dogs rarely survive beyond 30 days after clinical diagnosis (TABLE 1). A report from Scotland indicated a longer duration of life, but the survival time was calculated from the time the owners first noted signs of illness rather than from time of established diagnosis by a veterinarian. However, even there, the mean survival time was less than 2 months. Of 91 dogs presented to our clinic with lymphosarcoma and not treated, owners requested that 5 1 be immediately euthanized. Seventeen were hospitalized for clinical work-up. These dogs died with a mean time of 2.5 days. Seventeen other dogs in less advanced disease were sent home without treatment. The latter group survived from 5 to 133 days, with an approximate mean of 30 days (TABLE 1 ) .

Immunological specificity of antibodies to morphine and their effect on the electroencephalographic activity of morphine.

Abstract Rabbit antibodies to morphine were induced by immunization with morphine conjugated to bovine gamma globulin. The relative reactivity of the antibodies with morphine and twelve other opiates was ascertained in vitro by the capacity of the opiates to inhibit the reaction between antibodies and [14C] internally labelled morphine. Of the opiates tested, codiene, heroin and dihydromorphinone exhibited binding similar in magnitude to that of morphine; meperidine, normorphine, nalorphine, dextromethorphan, methadone, fentanyl, cyclazocine, levallorphan, and naloxone exhibited greatly reduced or no binding with antibodies. These findings indicate that the methyl group on the tertiary amine and the furan ring are crucial for the antigenic specificity of the molecule. Experiments on the passive transfer of the rabbit immune globulins into electrode implanted rats subsequently challenged with morphine, demonstrated the capacity of the transferred globulins to attenuate the electroencephalogram (EEG) effect of morphine. The attenuation was characterized by the absence of the maximum effect or phase 4 of the EEG continuum, induced by administration of 20 mg/kg morphine. Globulins obtained from rats following a single administration of 20 mg/kg morphine sulphate exhibited specific binding with morphine which was demonstrable at 16 days and 32 days following injection. The development of globulins capable of binding morphine, parallels the previously reported development of physiological tolerance to the drug induced by a single administration of 20 mg/kg morphine sulphate.

Bluetongue virus-17 fusion protein NS1 expressed in Escherichia coli by pUC vectors

The cDNA coding for the major nonstructural protein, NS1, of bluetongue serotype 17 (BTV-17) was cloned previously. Using pUC plasmids, we have successfully expressed the NS1 protein in Escherichia coli as a LacZ-NS1 fusion protein. The recombinant NS1 protein reacted with rabbit anti-BTV-17 antiserum, and was thus immunologically indistinguishable from the native BTV-17 NS1 protein. This was the first bluetongue viral protein to be produced in a bacterial system.