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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 415 records · Page 23Linked to original sources

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↗

An immune response against the alloantigens of the 3LL Lewis lung carcinoma prevents the growth of lung metastases, but not of local allografts.

3LL tumor cells inoculated intra footpad grow locally both in syngeneic and in allogeneic recipients. Yet, spontaneous lung metastases appear only in syngeneic animals or in mice which share with the tumor strain of origin both the D-end of the H-2b haplotype and the genetic background. The lack of lung metastases in allogeneic recipients is not due to tissue restrictions for tumor growth, since intravenous injections of tumor cells resulted in local primary lung tumors. The growth rate of primary intra footpad tumors or pulmonary tumors in syngeneic mice is similar to that in congenic resistant recombinant mice. From a local intra footpad tumor in BALB/c mice, 3LL cells migrate out and reach the lungs but are arrested there, since grafts of lungs from such mice onto (BALB/c X C57BL/6)F1 resulted in tumor growth. Since spontaneous metastases developed in chimeric (C3HeB X C57BL/6)F1----C3HeB mice, it appeared that immunogenetic restrictions prevent the growth of spontaneous 3LL metastases in allogeneic recipients. Further support for the notion of allograft rejection of lung metastases derived from experiments demonstrating the generation of metastases in nu/nu ICR mice but not in nu/+ heterozygous ICR animals. It thus appeared that the local allograft of the 3LL tumor elicits a reaction which prevents the growth of its metastases. This was further supported in experiments in which intravenous inoculation of 3LL cells to allogeneic recipients from which the local tumor was removed did not produce lung tumors.

Animals↗

Preservation of brush border transport systems for proline and alpha-methyl-D glucoside from rat, dog, and human kidney.

The effects of freezing renal tissue from rat, dog, and man on the time course of uptake of proline and alpha-methyl-D-glucoside by subsequently isolated brush border membrane vesicles was examined and compared with uptake patterns by membranes isolated from tissue that had never been frozen. The overshoot phenomenon was used as the critical criterion for viability of the transport systems. Membranes isolated from frozen rat and dog kidney possessed intact transport systems for proline and alpha-methyl-D-glucoside capable of producing normal or even enhanced overshoot patterns. Freezing human kidney prior to membrane isolation resulted in severe impairment of the vesicle transport capabilities. Freezing a crude membrane suspension, however, allowed the subsequent purification of only partially intact systems.

Animals↗

Differences in immunogenicity between the local tumor 3LL and its metastasis-derived line as detected by sensitization with antigen-fed macrophages.

Macrophages fed with solubilized membrane extracts of the Lewis lung carcinoma 3LL were used to sensitize normal spleen cells in vitro. The injection of these spleen cells into the foot pad of normal syngeneic recipients 5-7 days prior to the inoculation of a lethal tumor dose into the same foot pad resulted in a significant reduction in the rate of growth of the local tumor. Moreover, the intraperitoneal injection of the sensitized spleen cells into tumor-bearing mice 6 days prior to tumor amputation caused a considerable decrease in the postoperative lung metastasis. In contrast, spleen cells sensitized in a similar manner on monolayers of macrophages fed with solubilized extracts of the metastasis-derived 3LL (M-3LL) line failed to induce such efficient host protection against either the local growth or the metastasis of 3LL.

Animals↗

High-performance liquid chromatography of phospholipids with UV detection: optimization of separations on silica.

Chromatography of phospholipids was performed on silica columns with detection by absorbance at 205 nm using mixtures of hexane--isopropanol--water in which the role of water and isopropanol in elution was investigated. One system was developed which provided adequate separation of most major phospholipid species. However, lipids with several ionizable groups were not well separated and gave multiple broad peaks. A second system was developed utilizing sulfuric acid for ion suppression. The behavior of phospholipids in this system was found to be dependent on the presence of quaternary ammonium, amino, or hydroxyl groups. Except for plasmalogen, phospholipids were recovered intact. This system was optimized to provide baseline resolution of essentially all phospholipid species commonly found in mammalian tissues.

Animals↗

Amino acid uptake by isolated renal brush border membrane vesicles in various buffers.

The uptake of amino acids by isolated rat renal brush border membrane vesicles in a modified Krebs-Ringer bicarbonate buffer and a phosphate buffer was compared to the uptake in the standard membrane vesicle buffer, Tris-Hepes-mannitol. The uptake in the modified Krebs-Ringer bicarbonate buffer was similar to that in the Tris-Hepes-mannitol buffer. Removal of the ionic constituents other than NaCl and NaHCO3 in the modified Krebs-Ringer bicarbonate buffer (KCl, CaCl2, KH2PO4 and MgSO4) did not affect the amino acid uptake by the isolated membrane vesicles. The timed uptake of proline under sodium gradient conditions in a phosphate buffer had a markedly dampened overshoot. Kinetic analysis of the initial rate of proline uptake in a phosphate buffer compared to a Tris-Herpes-mannitol buffer showed two entry systems for proline in each buffer with similar Km values, but the maximal rate of transport (V) for each system in the phosphate buffer was much lower than that in the Tris-Hepes-mannitol buffer. From these data, phosphate buffer does not appear to be a suitable medium for the study of amino acid uptake by isolated brush border membrane vesicles.

Amino Acids↗

Cystinuria in the maned wolf of South America.

Of 42 maned wolves in zoos or live-trapped in Brazil, 34 had excessive cystine in their urine. Renal clearance studies of five of the affected wolves revealed a variable defect for the reabsorption of cystine and dibasic amino acids. The renal tubular handling of other solutes including glucose, phosphate, sodium, potassium, and uric acid was considered normal. Urinary calculi composed of cystine were found in four wolves and proved fatal in three of them. With the exception of the high incidence in this species, this hereditary disease resembles the disorder described in dogs and humans.

Amino Acids↗

Laser photovaporization of endometrium for the treatment of menorrhagia.

As an alternative to hysterectomy in patients with excessive bleeding, the endometrium was destroyed by means of the neodymium-YAG laser. The photovaporization was done under direct vision through a hysteroscope. Twenty-two patients have been treated, all but one successfully, i.e., little or no menstrual flow. The human uterus having a thick myometrium was found to be ideal for this modality. To suppress endometrial regeneration further, each patient was placed on a regimen of danazol for 2 to 3 weeks prior to and after the procedure. Hysterograms after laser photovaporization showed variable degrees of uterine contraction, scarring, and adhesion formation. Biopsies of the endometrial surface up to 20 months following the procedure showed no evidence of inflammation other than foreign body giant cell reaction around carbon particles. Minimal endometrial regeneration occurred.

Adult↗

Synthesis and secretion of alkaline phosphatase in vitro from first-trimester and term human placentas.

The synthesis and secretion of alkaline phosphatases in vitro by human placental tissue incubated in organ culture were studied. First-trimester placenta synthesizes and secretes two different alkaline phosphatase isoenzymes (heat-labile and heat-stable), whereas in term placenta nearly all the alkaline phosphatase synthesized and secreted is heat-stable. The specific activities of alkaline phosphatases in first-trimester and term placental tissue remain constant throughout the time course of incubation. In the media, specific activities increase with time. Hence, alkaline phosphatase synthesis seems to be the driving force for its own secretion. The rates of synthesis de novo and of alkaline phosphatases were measured. The specific radioactivities of the secreted alkaline phosphatases were higher than the corresponding specific radioactivities in the tissue throughout the entire incubation period. The intracellular distribution of the alkaline phosphatase isoenzymes was compared.

Alkaline Phosphatase↗

Cystine uptake by rat renal brush-border vesicles.

Uptake of L-cystine by brush-border membrane vesicles isolated from rat renal-cortical tissue was time-dependent and occurred in the absence of cystine reduction. A significant capacity for vesicular binding of cystine was observed. The amount bound increased with time of incubation and could be displaced by thiol reagents. At early time points, cystine uptake measured the transport of cystine into the intravesicular space. Total cystine uptake was mediated by multiple transport systems, including a low-Km high-affinity component which was shared by lysine, arginine, ornithine and glutamine and on which hetero-exchange diffusion of lysine and cystine was demonstrated.

Amino Acids↗