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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 361 records · Page 20Linked to original sources

Anti-tumor immunity in B-lymphocyte-deprived mice. III. Immunity to primary Moloney sarcoma virus-induced tumors.

Tumor induction and immunity to tumors were studied following the injection of Moloney sarcoma virus (MSV) into mice whose B-lymphocyte functions had been suppressed by the chronic administration of anti-IgM antibodies. Two preparations of MSV were used; one which gives rise to tumors which uniformly regress in normal adult mice, and another which elicits progressively growing tumors in the majority of recipients. The tumor incidence, mean tumor size, and tempo of regression were not modified by treatment with anti-IgM. However, whereas tumors induced by the regressor virus were all rejected in 19 NRG-treated and 29 untreated recipients, continued growth was obtained in 2 of 23 B-lymphocyte-deprived mice. Furthermore, in 9 additional mice from this group, apparent rejection was followed by tumor recurrence at the site of the initial tumor. Continued growth was accompanied by widespread metastasis. These tumors were freely transplantable to normal syngeneic recipients. Metastasis and transplantability were also detected in 7 of 24 anti-IgM-treated mice given progressor virus, but were not seen in the control animals. Recurrence and metastasis was obtained despite the presence of high levels of specific cytotoxic T lymphocytes in the spleen. It is concluded that B lymphocytes or their products play an essential role in host protection against MSV-induced tumors.

Animals↗

Mechanisms controlling differentiation and function of antigen-presenting macrophages.

We have briefly reviewed our studies on the mechanisms controlling the differentiation and activation of peritoneal antigen-presenting cells. We demonstrated that the peritoneal population is composed of two main subsets of cells, only one of which participates actively in primary antigen presentation. The latter is missing in athymic mice and seems to differentiate under the influence of the shortlived, cortisone-resistant subpopulation of thymocytes. The maturation of the peritoneal macrophages is subjected also to an additional inducing effect, that of the spleen. Macrophages from splenectomized donors are impaired both with respect to antigen presentation to naive and to primed lymphocytes, and with respect to phagocytosis of "opsonized" bacteria. The mature antigen-presenting cell is subjected to activating signals deriving from the Fc-bound Ig molecule. This is mediated via a tetrapeptide, tuftsin, which is cleaved off the CH2 portion of the Ig and activates the immunogenic effect of the antigen-pulsed macrophage.

Animals↗

Effect of an opiate antagonist (naloxone) on the gastric acid secretory response to sham feeding, pentagastrin, and histamine in man.

We studied the effect of the opiate antagonist naloxone on the human gastric acid secretory response to three secretory stimulants: sham feeding, pentagastrin, and histamine. Intravenous naloxone (40 micrograms/kg/hr) significantly inhibited the acid secretory response to sham feeding without affecting the serum gastrin response to sham feeding. Naloxone also significantly reduced pentagastrin- and histamine-stimulated acid secretion. These studies indicate that naloxone reduces acid secretion in response to all stimulants of acid secretion yet tested in humans.

Adult↗

Parietal cell vagotomy in a surgical training program.

Parietal cell vagotomy was performed in 48 patients at the Parkland Memorial Hospital and the Dallas Veterans Administration Hospital between April 1977 and January 1981. The maximum follow-up time was 50 months and the average was 28 months. Seventy-five percent of the patients were followed for more than 1 year. There were no operative deaths. Four patients (8.3 percent) had persistent postoperative side effects including two documented ulcer recurrences (4.2 percent). Acid secretion studies were reviewed to characterize the longterm effect of parietal cell vagotomy. These studies demonstrated marked postoperative reductions in gastric acid secretion. The results of this study suggest that with the simplified technique described in this paper, parietal cell vagotomy can be performed with minimal mortality and morbidity by surgical residents under direct staff supervision.

Adolescent↗

Adjunctive therapy with interstitial irradiation for prostate cancer.

Thirty patients with clinically localized adenocarcinoma of the prostate underwent simultaneous staging pelvic lymphadenectomy and interstitial irradiation. Patients were followed for eighteen to forty-five months with regard to progression of disease and development of long-term complications. Upstaging to Stage D1 by virtue of discovering pelvic node involvement was noted in 16 patients (53.3 per cent). Subsequent disease progression (defined as development of bone or soft tissue metastasis) was seen in 9 of 16 upstaged patients with an average time to progression of 12.2 months. Three Stage D1 patients have died with an average time to death of 19.6 months. Only 1 patient whose lymphadenectomy was negative has experienced disease progression, and none has died. Adjuvant chemotherapy (cyclophosphamide and doxorubicin hydrochloride) was given to 9 upstaged patients, in only 3 did disease progress. In contrast, in 6 of 7 upstaged patients not receiving chemotherapy metastatic disease developed, with an average time to progression of 10.3 months. In an attempt to improve local tumor control achieved by interstitial irradiation alone, 18 patients received additional external beam radiation therapy to the prostate, in doses ranging from 2,000 to 4,000 rad. There were sixteen long-term complications in the 30 patients, 75 per cent of which were seen in patients receiving added external beam irradiation.

Adenocarcinoma↗

Involvement of peritoneal macrophages and spleen stromal cells in X-irradiation-induced reticulum cell neoplasms in C57BL/6 mice.

Some correlation was observed between the occurrence of FA-positive PE-MO and spleen stromal cells (removed from X-irradiated RCN-bearing old-adult B6 mice) and the generation of RCN. No significant correlation was found between the viral content of lymphoid organs from the same mice and the occurrence of RCN. The main viral particle detected in lymphoid organs from radiation-induced RCN-bearing mice was the xenotropic virus. Ecotropic viruses were detected in a few spleens and Payer patches from such mice. These ecotropic viruses showed very poor lymphomagenic activity and required 400R X-ray as a cofactor. No dualtropic viruses were detected. However, inoculation of ecotropic (SFA2) helper virus to X-irradiated old-adult B6 mice, resulted in an efficient rescue of lymphomagenic viruses, enriched with phenotypically mixed, dualtropic viruses. Some of these DT viral preparations were cloned and seemed to consist mainly of xenotropic sequences. Thus, inoculation of helper viruses influenced the generation and selection of DT viruses. Such viral preparations, enriched with DT viruses, had a better lymphomagenic activity compared to endogenous ecotropic viruses, isolated from radiation-induced RCN-bearing mice. Indirect evidence suggested the involvement of a defective (xenotropic and possibly adjacent cellular genes) particle in lymphoma induction. To conclude, a possible mechanism for the development of radiation-induced RCN is suggested, emphasizing the role of MO in such a process.

Animals↗

Effect of splenectomy on the progression of postoperative pulmonary metastases of the 3LL tumor.

Surgical excision of the local intrafootpad tumor of the 3LL lung carcinoma is followed by accelerated growth of its lung metastases. When, however, splenectomy was performed concomitantly with tumor excision, the acceleration of lung metastases was prevented. In cases where excision of the local tumor took place when it reached large sizes, concomitant splenectomy did not prevent the accelerated growth of the lung metastases. If, however, at these stages of tumor growth splenectomy was performed 3 days prior to the excision of the tumor, it did prevent the accelerated growth of metastases. Intrafootpad reinoculation of tumor cells following tumor excision and splenectomy caused further reduction in metastatic growth. The results suggest that existence of two possible distinct mechanisms which control metastatic growth: the local tumor might exert non-immunologically, an inhibitory effect on its lung metastases, and the spleen, possibly via suppressor lymphocytes, may suppress an immune effector activity against the tumor metastases, an activity which is manifested following splenectomy.

Animals↗

Stage-dependent secretion of ABP by rat seminiferous tubules.

The secretion rate of the Sertoli-cell-specific androgen-binding protein (ABP), has been studied in isolated rate seminiferous tubules, where the stages of the spermatogenic cycle have been identified by a transillumination method. The secretion of ABP was highest in stages VII-XII, as determined by steady-state polyacrylamide-gel electrophoresis as well as by radioimmunoassay. More specifically, when the sensitive RIA technique permitted the assay of ABP secretion from a total amount of 10-30 mm of isolated tubules, it was found that maximal ABP secretion occurred at stages VIII-XI and minimal at stages IV-V. The present results show that the secretory activity of the Sertoli cells (ABP) is influenced by the type of germ cell at each cell association. It is postulated that the variation is Sertoli-cell secretory activity is of importance for the normal maintenance of spermatogenesis.

Androgen-Binding Protein↗

Analysis of the parameters relating to failures above the clavicles in patients treated by postoperative irradiation for squamous cell carcinomas of the oral cavity or oropharynx.

One hundred and two patients with squamous cell carcinoma of the oral cavity or oropharynx were treated from January 1955 through August 1976 with surgical excision followed by irradiation. Twelve patients had T2 lesions and 90 had T3 or T4 lesions. Failures above the clavicles were associated with disease present at the margins of resection, location of the recurrence close to the periphery, or outside of the irradiated portals. Failure in the neck essentially were a result of no elective irradiation. In patients with disease present at the margins of resection, there is a risk both of gross residual disease and hypoxic microscopic disease left behind; 4500 to 5000 rad is not adequate for a significant control rate. In situation where there is definite disease at the margin of resection, 6500 rad, or in specific situations, 7000 rad, should be given through reduced fields.

Carcinoma, Squamous Cell↗

Lactic dehydrogenase virus (LDV) impairs the antigen-presenting capacity of macrophages yet fails to affect their phagocytic activity.

The effect of acute infection of mice with lactic dehydrogenase virus (LDV) on two major functions of peritoneal macrophages was tested. Using a macrophage-dependent T cell proliferative assay to test the antigen-presenting capacity of LDV-infected macrophages we found that LDV impairs the capacity of antigen-presenting cells to trigger memory T lymphocytes. Endocytosis of antigen by LDV-infected macrophages was similar to that of uninfected cells. In addition, the proportion of intracellular antigen versus membrane-bound antigen in LDV-infected cells were similar to that observed in uninfected mice. It appears therefore, that the impaired immunogenic effect of LDV-infected macrophages results from reduced immunogenicity of the membrane-bound antigen. Testing the phagocytic activity of peritoneal macrophages we found that the uptake of radiolabeled antibody-coated sheep erythrocytes or bacteria (E. coli) by infected cells was similar to that by uninfected macrophages. In addition, LDV failed to affect the ability of peritoneal macrophages in a nitroblue tetrazolium reduction reaction which serves as an alternative parameter for measuring phagocytic activity. Our results support the assumption that LDV, which probably propagates in the cells of the reticuloendothelial system, impairs some of the immunogenic functions of macrophages and thereby affects macrophage-dependent immune responses.

Animals↗