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Biomedical subjects

J Brenner

Publications and source records attributed to J Brenner.

At least 37 records · Page 2Linked to original sources

BLV-infected lymphocytes exhibit two patterns of expression as determined by Ig and CD5 markers.

Lymphocytes were defined by their cell surface markers, Ig and CD5 in three groups of cows naturally infected with bovine leucosis virus (BLV). Lymphocytes were enumerated and groups were designated BLV seropositive with persistent lymphocytosis (BLV + PL +), BLV seropositive without persistent lymphocytosis (BLV + PL-) and BLV negative. The competence of peripheral blood mononuclear cells (PBMC) from the tested cows to express these two markers was determined by the double staining immunofluorescence procedure. Cows which developed persistent lymphocytosis (PL) as a result of BLV infection consequently underwent massive proliferation of B lymphocytes which express both Ig and CD5 antigens. In contrast, cows which were defined as BLV positive and PL negative showed a remarkable decrease of CD5 + Ig-, CD5- Ig+ and CD5+ Ig+ cells and also in the total number of lymphocytes. We suggest that BLV infection affects bovine lymphocytes through two different pathways of expression which might be related to the genetic properties of the target cells.

Animals

Immunization of chickens with live Newcastle disease vaccine adjuvanted with oil.

Chickens of various ages and breeds were vaccinated subcutaneously with Newcastle disease live-in-oil vaccines. These vaccines were prepared immediately prior to the vaccination by mixing the lyophilized live vaccine with the oil adjuvant, which was kept at room temperature. The live-in-oil vaccines were shown to be 30-50 times more effective in efficacy tests than either the same vaccines reconstituted in water or killed-in-oil vaccines. In addition to its biological advantage, the method of preparation of live-in-oil vaccine saves the expensive space of cold storage and shipment necessary for conventional killed-in-oil vaccines.

Adjuvants, Immunologic

Vaccination of chickens with live fowl pox (FP) vaccine in oil.

Live fowl pox (FP) vaccine was adjuvanted in oil just prior to the subcutaneous (SC) vaccination of one day old chicks and adult chickens. The birds were challenged by the wing web (WW) method and absence of "takes" were considered as protection. On 21 day post challenge, 90%-100% of the chicks or chickens were protected while on day 9 post challenge 60% were protected. Full protection of the live-in-oil adjuvanted vaccine is probably somewhat delayed as compared to protection endowed by the liquid vaccine. Incorporation of live FP vaccine in two different kinds of commercial Newcastle disease (ND) killed vaccine in oil, was shown to endow full protection following SC administration.

Adjuvants, Immunologic

A lactogenic-immune-deficiency-syndrome in cows: unexplained phenomenon.

The majority of adult cows in a certain dairy herd, were found to have very low levels of immunoglobulins (Igs) in their colostrum. This phenomenon was defined by us as Lactogenic-Immune-Deficiency-Syndrome (LIDS). The mean IgG levels were 44.5 and 57.2 mg ml-1 respectively (on two different occasions) as compared to that of a control group which was 103.4 mg ml-1. The levels of Igs in the colostra of heifers from the same herd were found to be higher than those of adult cows. The degree of LIDS was found to be closely related to the age of cows in the herd. The low levels of Igs in the colostra were not directly linked to their concentrations in the sera of the affected cows. The relatively low amount of IgA in the affected colostra suggests that the local production in the lymph tissue associated with the mammary glands is impaired as well. In order to investigate the etiology of the phenomenon, tests were carried out to reveal whether bovine leucosis virus (BLV) infection or immune complexes were involved in the pathogenesis of LIDS. The results were negative. The etiology of LIDS remains for the time being unknown.

Animals

Circulating immune complexes in bovine leukemia virus (BLV)-infected cattle.

Circulating immune complexes (ICs) were detected in the sera of bovine leukemia virus (BLV)-seropositive cattle. Immune complexes were precipitated in 2.5% polyethylene glycol (PEG) and further dissociated. Bovine leukemia virus antigens, IgG and IgM molecules were detected after solubilization in the presence of sodium dodecyl sulphate, and quantitated by enzyme-linked immunosorbent assay (ELISA) assays. Mean values of IgG and IgM in BLV-containing ICs did not significantly differ from those obtained from ICs originating from BLV-seronegative animals. However, differences were found in the composition of ICs from older BLV-positive animals as compared to those obtained from young animals. The ratio of IgG/IgM was 5.02 in animals aged 5-10 years, while this ratio was 11.66 in animals of less than 5 years of age and 10.19 in controls. This might indicate a possible increase in the contribution of IgM molecules to the structural composition of ICs in BLV-infected cattle as related to age or stage of infection.

Aging

The riddle of the uvula.

Since ancient times, the uvula has been a subject of interesting and contradictory observations. On the one hand, it was regarded as having a functional role in speech and in immunology, but on the other hand it was regarded as a potentially hazardous organ, possibly responsible for sudden infant death syndrome. None of these hypotheses, however, has been proved. In a previous study on patients undergoing uvulopalatopharyngoplasty, we suggested that the most important function of the uvula is connected with the muscularis uvula. Its function could be related to drinking while bending over. This previous assumption was that the uvula is a phylogenetic remnant from mammals that drink while bending their neck downward. In the present study, the soft palate of eight different mammals was macroscopically and microscopically studied and compared. Of all animals in the study, a small underdeveloped uvula was found only in two baboons. We found that the human uvula consists of an intermix of serous and seromucous glandular masses, muscular tissue, and large excretory canals. The serous and seromucous glands are absent in the other mammals. Thus, the uvula is a highly sophisticated structure, capable of producing a large quantity of fluid saliva that can be excreted in a short time. Both uvula and speech serve to differentiate human beings from animals. Our conclusion is that the uvula is possibly an accessory organ of speech, and may be another marker of human evolution that differentiates man from other mammals.

Animals

The fat content of milk from dairy cattle infected with bovine leukosis virus.

Two groups of cows infected with the bovine leukosis virus (BLV) were kept on two different diets and the fat content of their milk was assayed. The results were compared with those obtained from two comparable groups of BLV-free cows. The cows in each group were of similar ages, those in the groups on the poorer diet being 1-4 months post partum, while those on the richer diet were 5-7 months post partum. The mean percentage of fat in the milk from uninfected cows on the poorer diet was 2.94 while that from the similar infected cattle was 3.06. Uninfected cows on the richer diet produced milk containing 3.39% fat, while those that were infected produced milk containing 3.30% fat. No statistical differences in milk fat production were observed between the BLV seropositive and seronegative cows.

Animals

Effect of two novel inhibitors of the human immunodeficiency virus protease on the maturation of the HIV gag and gag-pol polyproteins.

The ability of two novel synthetic compounds to inhibit the HIV protease-mediated processing of HIV-1 precursor polyproteins was investigated in an in vitro gag-protease mixed lysate assay system and in an assay using recombinant baculoviruses engineered to express the HIV-1 gag and pol genes in cultured insect cells. With the in vitro mixed lysate assay we have shown that both compounds at 1 microM can completely inhibit the HIV-1 and HIV-2 protease-mediated release of p24 from the HIV-1 gag precursor at pH 5.5 and pH 7.0. In the intracellular baculovirus system these compounds were shown to inhibit the protease-mediated maturation of gag and also the excision of the protease moiety from its precursor.

Animals

Use of milk samples and monoclonal antibodies directed against BLV-p24 to identify cattle infected with bovine leukemia virus (BLV).

An indirect double-antibody sandwich (IDAS) enzyme-linked immunosorbent assay (ELISA) using milk samples was developed to identify cows infected with bovine leukemia virus (BLV). Two monoclonal antibodies (McAbs) were used. One, which was directed against BLV core protein p24, was used to coat ELISA plates; the other was used to prepare a horseradish peroxidase (HRP) conjugate directed against bovine immunoglobulin. The IDAS-ELISA detected antibodies directed against BLV-p24 in 97% of the milk samples collected from known seropositive cows identified by the agar gel precipitation test (AGTP). Even when milk samples were diluted 1:50, 93% of the seropositive cows were identified. Only 0.43% of the 4000 milk samples collected in The Netherlands reacted nonspecifically. Nonspecific binding disappeared, however, when these samples were diluted 50 times in BLV-negative milk. In a comparative evaluation of BLV test-kits in various European laboratories, our IDAS-ELISA using McAb directed against p24 was one of the most sensitive.

Animals

The implication of BLV infection in the productivity, reproductive capacity and survival rate of a dairy cow.

The objective of the present study was to find out whether BLV infection, known to cause immunodisturbances in cows, might also bring about decreased productivity, reproductive rate and a shorter life span. More than 100 pairs of dairy cows, and a whole population of 3000 milch cows, were studied for this report. The findings revealed that a BLV-positive cow had a shorter life span than both its seronegative counterpart and the entire milch cow population. It also produced a total of 3.5% less milk and had a mean of 48 more days open than did the BLV-negative cow. The differences in survival rate were highly significant, while, at a level of 5%, those of productivity and reproductive rate were not. The implications of these findings are discussed. A highly significant correlation was also shown between BLV infection and the persistence of Trichophyton verrucosum infection in cows. The presented data indicate that BLV infection might affect the immune system of a cow to such a degree that it ceases to be productive enough to be kept within a herd. Thus it is usually culled before any severe symptoms of disease emerge.

Animals

Effect of shock waves on suspended and immobilized L1210 cells.

L1210 mouse leukemia cells have been exposed to different doses of shock waves generated by underwater spark discharge at 18 kV in an experimental lithotripter (XL1, Dornier). Histological and flow cytometric investigations revealed severe damage and a LD50 of about 420 shock waves when the cells were treated as suspensions. Cells immobilized in gelatine, however, were unaffected, indicating that secondary effects are responsible for the cellular damage. Possible mechanisms such as cavitation, jets, and shear forces are discussed.

Animals

The possible enhancement of parvovirus vaccination on the mortality rate of diseased dogs.

A survey was conducted by using questionnaires dealing with morbidity and mortality of young dogs. Seventy-one clinical evaluations of diseased dogs were included in this survey. The cases were divided into 3 groups according to their vaccination history: 1. dogs vaccinated with the parvovirus and distemper live modified vaccine; 2. dogs vaccinated with the killed parvovirus vaccine; 3. non-vaccinated dogs. Statistical analysis of the information obtained by analyzing the questionnaires gave the following results: The survival rate of the non-vaccinated and killed parvovirus vaccine-vaccinated dogs was significantly higher than that of the dogs which were vaccinated by the live modified vaccine. No such difference was encountered between groups 2 and 3. This finding, once more, supports the notion that the live modified parvovirus vaccine may have an immunosuppressive property.

Animals

Cisplatin. A phase II evaluation in previously untreated patients with soft tissue sarcomas.

A Phase II trial of moderately high-dose cisplatin (120 mg/m2 with mannitol diuresis) was conducted in 26 previously untreated patients with soft tissue sarcomas. One partial response (major response rate, 4%) and two minor responses were seen. Severe nausea and vomiting and transient increases in the serum creatinine level were the most common side effects of treatment. Cisplatin has minimal activity as a single agent in patients with soft tissue sarcoma.

Adult

A comparison of low- and high-dose cisplatin-based combination chemotherapy as initial postoperative treatment in advanced ovarian adenocarcinoma.

Cyclophosphamide, Adriamycin, and cisplatin were given as the initial postoperative treatment to 35 patients with Stages II through IV ovarian cancer of epithelial origin during two time periods. During the first period the dose of cisplatin was 60 mg/m2 and during the second period it was 120 mg/m2, while the dose of cyclophosphamide and Adriamycin remained unchanged. No differences with regard to survival, progression-free interval, rate, and outcome of second-look laparotomy between 18 consecutive patients who received the low-dose and 17 consecutive patients who received the high-dose cisplatin were observed. The complication rate was significantly higher in the high-dose treatment group. Low-dose cisplatin-based combination chemotherapy seems therefore to be the preferable initial postoperative treatment.

Antineoplastic Combined Chemotherapy Protocols

Abdominopelvic irradiation for stage II-IV ovarian carcinoma patients with limited or no residual disease at second-look laparotomy after completion of cisplatinum-based combination chemotherapy.

Abdominopelvic irradiation was given to 18 stage II-IV ovarian carcinoma patients who completed cisplatinum-based combination chemotherapy, were in complete clinical remission, and who underwent second-look laparotomy. The survival as well as the progression-free interval (PFI) was significantly longer in patients with a negative second-look laparotomy than in those with limited residual disease at this operation. Abdominopelvic irradiation was not effective in patients with limited residual disease at second-look laparotomy (3 year survival--34.3% and median PFI from second-look laparotomy--4.8 months). Even in patients with a negative second-look laparotomy the median PFI was only 13 months from this operation and the 3-year survival was 87.5%. The results were similar to other comparable series in which no treatment was administered to patients with a negative second-look laparotomy.

Adult

Humoral and cellular responses in calves experimentally infected with bovine leukemia virus (BLV).

In order to elucidate whether infection by Bovine Leukemia Virus (BLV) might induce an immunodeficient state, we inoculated sixteen calves with BLV. The calves were followed up for two years and were tested for humoral and cellular responses using various parameters, namely the appearance of antibodies to the BLV antigens, the changes in the numbers of lymphocytes involved, and the ratio between the two main populations of lymphocytes. Antibodies to the BLV antigens were of both the IgG and the IgM classes of immunoglobulins. The levels of antibodies of the IgM class were higher than those of IgG. There was a temporary decrease of reactive antibodies to the BLV antigens, to below detectable levels, during the 14-24 weeks post infection. A significant decrease in the level of plasma IgM was found in all BLV infected calves exhibiting lymphocytosis, while the level of IgG in the plasma of all experimental calves did not diverge significantly from the initial values, throughout the experiment. BLV infection was followed by lymphocytosis of B-cells in most infected calves, which persisted for the whole course of the experiment, while a decrease in the population of T-cells in peripheral blood was observed for a period of several months in all infected calves.

Animals

Effect of treatment on fertility and sexual function in males with metastatic nonseminomatous germ cell tumors of testis.

The effects of therapy on the sexual ability and fertility of sixty-seven patients with nonseminomatous germ cell tumors of the testis were analyzed. Ten of 38 patients had subfertile sperm counts before therapy. Normal ejaculation was preserved in only 7/61 patients who underwent retroperitoneal lymph node dissection. In five of these patients, sperm analysis was done after chemotherapy; all had complete azoospermia. An effort to restore ejaculation with imipramine yielded only minimal response in 4/9 patients who received this drug. No major long-term effects on the libido were observed.

Adolescent

A comparison of postoperative radiotherapy with postoperative chemotherapy in stage II-IV ovarian cancer patients.

A retrospective comparison between 28 stage II-IV ovarian cancer patients who received postoperative abdominopelvic irradiation and 15 such patients who received postoperative cis-platinum, Adriamycin, and Cytoxan chemotherapy was made. In both treatment groups there was a trend for a longer progression-free interval and 3-year survival in patients with residual tumor masses of less than 2 cm in diameter. In these patients there was also a trend favoring radiotherapy. However, all differences were not significant. Criteria for the choice of either modality of postoperative therapy of ovarian cancer patients remain to be determined. Nevertheless, the efficacy of both modes of treatment does not differ greatly.

Antineoplastic Combined Chemotherapy Protocols