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Biomedical subjects

A Santoni

Publications and source records attributed to A Santoni.

At least 163 records · Page 9Linked to original sources

Sequential metabolic events and morphological changes during in vivo large granular lymphocyte activation and proliferation.

Interferon (IFN) and IFN inducers are known to boost natural killer (NK) activity in vivo and in vitro. In vivo enhancement of NK activity results from activation of preexisting NK cells as well as from an increased number of large granular lymphocytes (LGL), with a portion of them undergoing cell division. Our study was addressed to analyze the sequence of metabolic events occurring within the LGL population of Fischer rats treated with poly(I:C), as an IFN inducer. The increase in cytotoxic activity and LGL number in the peripheral blood already reached maximal levels by 12 hr after poly(I:C) injection, remained on a plateau 24 to 48 hr later, then slightly decreased on Day 4, and returned to control levels by Day 6. A similar kinetics was observed for RNA synthesis. In contrast DNA synthesis first increased at 24 hr, peaked at 48 hr, then decreased on Day 4, and was not detectable on Day 6. Percoll fractionation resulted in 92-97% of LGL in fraction 1, and cells in this fraction accounted for the increase of cytotoxicity as well as for newly synthesized RNA and DNA. However, LGL recovered on Day 1 or 2 after poly(I:C) stimulation displayed quite heterogeneous morphology, and a number of mitotic configurations were seen on Day 2 within the LGL population. Our results indicate that the boosting of NK activity by poly(I:C) is always associated with an increase in LGL numbers, the enhanced lytic capacity is associated in vivo with new RNA synthesis by the NK cells, and only in a later phase NK cell proliferation may account for the increase in LGL numbers.

Animals↗

Effect of prolonged administration of low doses of dietary retinoids on cell-mediated immunity and the growth of transplantable tumors in mice.

A study was conducted on the activity exerted by prolonged dietary supplementation with progressive amounts of retinoids on cell-mediated immune responses and the growth of transplantable tumors in mice. A few groups of BALB/c mice received 0 (group C), 50 (group A 50), 200 (group A 200), 500 (group A 500), and 1,000 (group A 1000) IU retinol palmitate/mouse/day in drinking water for 150 days. At progressive intervals mice from each group were tested for proliferative responses to concanavalin A (Con A), Escherichia coli lipopolysaccharide, interleukin-2, and interferon-gamma release to Con A. Ten mice from each group were also challenged with the 90-100% tumor-inducing dose of 3 distinct transplantable tumors. At the end of the experiment the principal organs were histologically examined, and the accumulation of vitamin A was evaluated. In groups A 200, A 500, and A 1000, an increase in the proliferative responses and production of lymphokines as compared to those in group C occurred after 60-90 days, but vanished after 150 days. The takes of the 3 tumors were impaired when the challenges were performed on days 75 and 150. This enhancement of distinct functions of cellular reactivity and resistance to transplantable tumors showed a linear relationship with the amount of supplemental retinol palmitate for the first 60-90 days. After 150 days, however, these enhancement effects vanished or tended to decrease.

Animals↗

[Primary cervico-facial amylosis. Apropos of a case].

Diagnosis in a case of primary localized amylosis of the sinuses and cervical nodes was from the discovery of nasal obstruction with conductive hearing loss and cervical nodes. Biopsy confirmed the presence of amyloid deposits in the maxillary sinuses mucosa and the cervical nodes. This case illustrates the value of typing of the amylosis, rectal biopsy and investigation to detect a myeloma, thus providing confirmation of a primary localized amylosis. A literature review confirmed the rarity of this localization of amyloidosis.

Adult↗

Modulation of natural killer activity in mice by prolonged administration of various doses of dietary retinoids.

Groups of BALB/C mice received a diet supplement of 0 (group C), 200 (group A 200), 500 (group A 500), and 1,000 (group A 1,000) IU retinol palmitate (RP)/mouse/day in drinking water for 450 days. At progressive time intervals, mice from each group were tested for natural killer (NK) activity and for the percentage of large granular lymphocytes (LGL) in the spleen. In groups A 200, A 500 and A 1,000, a dose-dependent increase in NK activity was evident 50 days after the beginning of RP supplementation and was accompanied by a parallel increase of LGL number in the spleen. In group A 1,000, the increase of spontaneous or Poly I:C-induced cytotoxicity persisted until day 160. By contrast, inhibition of Poly I:C-induced NK cytotoxicity was found in this group at day 450.

Age Factors↗

Reactivity of anti-asialo GM1 serum with tumoricidal and non-tumoricidal mouse macrophages.

All peritoneal macrophage (pM phi) populations studied exhibited some binding of the anti-asGM1 serum as assessed by flow cytometry. The levels of reactivity varied quantitatively among populations, depending on the combination of eliciting and activating agents employed prior to the harvest of pM phi. Resident pM phi contained a very small percentage (4%) of cells that were strongly asGM1+. Any treatment of these cells that induced them to become stimulated or activated increased the percentage of highly asGM1+ cells. Treatments that enhanced anti-asGM1 binding including eliciting pM phi with proteose peptone (16% asGM1+) or Brewer's thioglycollate medium (66% asGM1+), treatment with the activating biological response modifiers (BRMs) MVE-2 (12% asGM1+) and P acnes (18% asGM1+), or treatment with both peptone + MVE-2 (37% asGM1+) or peptone + poly IC/LC (33%). Increased expression of anti-asGM1 was accompanied by some increase in the reactivity of the various pM phi populations to treatment with anti-asGM1 serum. This conclusion was based on the reduced viabilities of cells treated with both an eliciting agent and an activating agent prior to in vitro treatment with anti-asGM1 + C, as well as by reductions in cytolytic activity of pM phi elicited with peptone and activated by MVE-2, following anti-asGM1 treatment in vitro or administration in vivo. Conversely, the cytolytic activity of resident pM phi activated in vivo by MVE-2 or heat-killed P acnes, agents that induced relatively small increases in the percentage of asGM1+ cells, was resistant to the effects of in vivo and/or in vitro treatment with doses of anti-asGM1 serum that inhibit NK activity. These results indicate that stimulation of pM phi by eliciting or activating agents can increase the level of expression of asGM1. This increased expression of asGM1 may be a useful marker for some aspects of macrophage heterogeneity, but increased expression is not necessarily directly related to expression of tumoricidal activity. In fact, the results of this study demonstrate that anti-asGM1 serum can be used for specific depletion of NK activity in vivo in normal mice and in mice treated with at least some BRMs. However, the results also demonstrate that the use of eliciting agents, particularly thioglycollate, or eliciting agents in conjunction with activating agents can cause pM phi to become reactive with anti-asGM1 serum.

Animals↗

Changes in number and density of large granular lymphocytes upon in vivo augmentation of mouse natural killer activity.

NK activity of mice as well as humans and rats has been clearly associated with large granular lymphocytes (LGL). To better understand the effects of interferon (IFN) and IFN inducers on natural killer (NK) cells, we have compared the LGL in the spleens of normal and boosted mice. Cells were fractionated by centrifugation on discontinuous Percoll density gradients, and each fraction was tested for NK activity against YAC-1 targets and for the presence of LGL. In vivo treatment with C. parvum (0.7 mg/mouse, i.p., day-3), MVE-2 (25 mg/kg, i.p., day-3), poly I:C (4 mg/kg, i.p., day-3), or IFN (10(5) U/mouse, i.p., day-1) resulted in a marked augmentation and a change of distribution of cytotoxic activity. Most of the NK activity of boosted spleen cells was associated with lower density fractions 1 and 2, whereas active normal spleen cells had somewhat higher density (fractions 2 and 3). In parallel to their increased reactivity, the boosted spleens had a marked increase in the percentage of LGL, particularly in fractions 1 and 2. The augmented activity appeared to be mediated by the LGL, because treatment with anti-asialo GM1 or anti-Thy-1.2 plus complement reduced NK as well as the number of LGL. These results indicate that IFN-mediated boosting of NK activity in the spleen is due to an increase in the lower density LGL, as well as to an increase in the function of preexisting NK cells.

Adjuvants, Immunologic↗

Lymphokine-activated tumor inhibition in vivo. I. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth.

CE-2 is a chemically induced tumor of low immunogenicity in syngeneic BALB/c mice. Nylon wool columns eluting lymphocytes from the spleen of mice bearing clinically evident (5-mm mean diameter) CE-2 tumors (CE-2 TB lymphocytes) do not react with CE-2 cells in vitro, nor are they able to affect their growth in vivo in a Winn-type neutralization assay at 5:1 lymphocyte:tumor cell ratio. However, they become able to inhibit CE-2 tumor growth when 20 U of interleukin 2 (IL 2) in 0.4 ml are injected daily for 10 days at the challenge site. In contrast, mice injected with CE-2 cells and IL 2 only display tumor takes and growth that are not significantly different from those in controls challenged with CE-2 cells alone. This lymphokine-activated tumor inhibition (LATI) is not a peculiarity of the CE-2 tumor-host combination, because different tumors can be inhibited in this way and various TB lymphocytes can initiate it. In these experiments, IL 2-rich 25,000 to 30,000 m.w. fractions were obtained routinely from the culture supernatants of a clone of EL-4 thymoma stimulated with phorbol myristic acetate. Equally active IL 2-rich preparations were obtained from rat spleen cells stimulated with concanavalin A, or from MLA 144 gibbon lymphosarcoma spontaneously releasing IL 2. Treatment of CE-2 TB lymphocytes with various antibody and C, with 2000 rad gamma-irradiation, or fractionation on Percoll density gradients suggested that radioresistant functions of Thy-1.2+, Lyt-1.2+, Lyt-2.2- and of asialo GM1+ cells are independently involved in LATI induction. These lymphocytes inhibit tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor destruction. CE-2 tumor inhibition by LATI leaves a specific delayed-type hypersensitivity and an immunologic memory, resulting in rejection of a second lethal CE-2 challenge in a significant number of mice.

Adenocarcinoma↗

Alloantigen-activated lymphocytes from mice bearing a spontaneous "nonimmunogenic" adenocarcinoma inhibit its growth in vivo by recruiting host immunoreactivity.

Nylon wool columns eluting lymphocytes from the spleen of mice bearing a clinically evident spontaneous, nonimmunogenic adenocarcinoma of recent origin (TS/A) do not display cytotoxic response, release of lymphokines, and proliferation in vitro against TS/A cells, nor do they inhibit TS/A tumor growth in a Winn-type neutralization assay in vivo. After 5-day co-culture with allogeneic spleen cells from mice differing at multiple minor histocompatibility antigens only, these lymphocytes are still noncytolytic against TS/A cells, whereas they release interferon-gamma, mediate delayed-type hypersensitivity (DTH) reactions, and inhibit TS/A tumor growth in the Winn assay. In the Winn test, alloactivated lymphocytes from TS/A tumor-bearing mice are more effective than those from normal mice on a per cell basis. The induction of this TS/A tumor inhibition ability depends on the presence in the cultures of Thy-1+ lymphocytes. The presence of Lyt-2+ lymphocytes is also important, whereas that of asialo GM1+ is not. The TS/A inhibition in vivo by alloactivated lymphocytes mostly depends on Thy-1+, Lyt-2- and asialo GM- lymphocytes, even though a few Thy- cells are also very efficient tumor inhibitors. The alloactivated lymphocytes inhibit TS/A tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor rejection. TS/A tumor rejection leaves a specific DTH and an immunologic memory resulting in rejection of a second lethal TS/A challenge in a significant number of mice.

Adenocarcinoma↗

[Pefloxacin: clinical experience].

Pefloxacin was given as the single drug (except in one case) to twenty-seven patients with a variety of infections (bone and/or joint: 8; respiratory tract: 6; urinary tract: 5; bacteremia: 4; meninges: 3; other: 1). The following bacteria were isolated: P. aeruginosa: 11; Enterobacteriaceae: 10; Acinetobacter: 3; Staphylococci: 3 (including 2 methicillin-resistant strains), and Streptococcus faecalis: 2. Pefloxacin was given in a daily dosage of 800 mg in 20 patients and 1 200 to 1 600 mg in 7. All pathogens proved susceptible, in varying degrees. 21 patients recovered. Three incomplete results and three failures were observed. No significant side effects were recorded except for development of three mucosal candidiasis and two transient rashes. The authors put special emphasis on the value of pefloxacin in bone and meningeal infections.

Acinetobacter Infections↗

Physiological and pathological influences of central nervous system on the immune system: a critical appraisal.

There is considerable evidence of intricate links between central nervous and immune systems. This paper makes a critical assessment of these relationships. Recent experimental data on hypothalamic influences on Natural Killer activity in mice have been presented and the problems met with in defining causal nexuses discussed. Some information on immune reactivity in patients with mental disorders has briefly been reviewed.

Animals↗

[Pseudomonas aeruginosa bacteriaemia: new clinical and therapeutic aspects ].

Fifty one cases of Pseudomonas aeruginosa bacteriaemia observed during the last 12 years are reported. Thirty five patients were over fifty years old; 92 p. cent were admitted for several days and about 50 p. cent were in post-operative period. A previous antibiotherapy and an impaired status are promotive factors. The respiratory or peritoneal origins are the most frequent. All patients were feverish; 24 have had an infectious shock which was inaugural in 12 cases. Seven pneumonitis, 3 endocarditis, one pericarditis and 2 osteitis were observed. An ecthyma gangrenosum was noted in three patients. Mortality was 70 p. cent. Comparison between recovered and died patients improved bad prognosis of old age, post operative period, neoplasic, previous organica weakness and pulmonary or peritoneal origins. Used alone, colimycin has seemed to be more effective than aminosid antibiotics; but their association with betalactamins was better. An in vitro study of the susceptibility of 100 Pseudomonas aeruginosa strains has proved the interest of piperacillin and cefsulodin; azlocillin, cefoperazone and ceftriaxone are just less effective.

Aged↗

Suppression of natural killer (NK) activity by splenic adherent cells of low NK-reactive mice.

Adherent cells with the ability to inhibit NK activity were found in the spleens of young 8-week-old SJL/J mice. Such suppressor cells were also found in the spleens of other low-NK-reactive strains, but not in the spleen of age-matched high-NK-reactive strains. These suppressor cells had the characteristics of macrophages, since they were plastic- and nylon-adherent, phagocytosed latex and iron particles, and were resistant to treatment with anti-Thy-1.2 serum plus complement. Their inhibitory activity appeared to be due to their production and/or release of soluble suppressive factor(s). Their suppressor activity was similar to that of pyran copolymer-activated macrophages, which were previously shown to be suppressive for cytotoxicity by NK cells. We suggest here that macrophages may be involved in the physiological regulation of NK activity and may contribute to the low NK activity in some strains of mice.

Animals↗

Suppression of activity of mouse natural killer (NK) cells by activated macrophages from mice treated with pyran copolymer.

Treatment of young mice with pyran copolymer caused a substantial decrease in natural killer (NK) cell activity at 7 days. The decrease in cytotoxicity was associated with the presence of splenic suppressor cells, capable of inhibiting in vitro the NK activity of spleen cells from normal mice. The suppressor cells appeared to be macrophages, being plastic-adherent, phagocytic and radioresistant, and lacking demonstrable Thy 1.2 antigen. Sonicates or culture supernatants of adherent spleen cells from pyran-treated mice were also able to inhibit NK activity, suggesting that suppressor cells act by release of soluble factors.

Animals↗