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Biomedical subjects

P Tandon

Publications and source records attributed to P Tandon.

At least 73 records · Page 4Linked to original sources
PubMed1990

Systemic administration of kainic acid increases GABA levels in perfusate from the hippocampus of rats in vivo.

The ventral hippocampi of male, Fischer-344 rats were implanted with microdialysis probes and the effects of systemically administered kainic acid (KA) (8 mg/kg, s.c.) on the in vivo release of amino acids were measured for four hours after administration. In order to measure GABA release in vivo, gamma-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase, was injected intrahippocampally prior to perfusion. GVG pretreatment resulted in measurable levels of GABA in the perfusate without significant effects on the release of aspartate, glutamate, glutamine, glycine or taurine. Following GVG pretreatment systemic administration of KA produced a time-dependent increase in GABA, as well as all other amino acids except glutamine, which was initially decreased. These results show for the first time that systemically administered KA increases extracellular GABA levels, an effect previously reported only in vitro. These data suggest that prior to destruction of GABA-containing interneurons in the hippocampus, there is an increased activity of those GABA interneurons reflected as an increase in extracellular GABA levels.

Amino Acids↗
PubMed1989

Colchicine-induced alterations in receptor-stimulated phosphoinositide hydrolysis in the rat hippocampus.

Intradentate administration of colchicine has been reported to affect the cholinergic muscarinic system in the hippocampus, causing a reduction in quinclidinylbenzilate binding sites and an increase in choline acetyltransferase activity. Since the cholinergic muscarinic system is coupled to the formation of inositolphosphates in the brain, the effect of intradentate administration of colchicine on the agonist-induced turnover of inositollipid was studied in rats. The animals were sacrificed 12 weeks after injection, and the hippocampi removed and sliced. [3H]Inositol was incorporated into slices in the presence of lithium, and carbachol, a cholinergic muscarinic receptor agonist, was used to study the stimulated turnover of inositollipids. Hippocampal slices taken from colchicine-treated rats showed an increased carbachol-stimulated accumulation of inositolmonophosphate. Thus, intradentate colchicine appears to alter the signal transduction process for the muscarinic cholinergic receptor in the hippocampus, a change that may be associated with compensatory processes following damage to the hippocampus.

Animals↗
PubMed1989

Cytopathological changes in human cervix and endometrium following prolonged retention of copper-bearing intrauterine contraceptive devices.

Since 1971, cytological evaluation of cervical smears and endometrial aspirates was carried out in 604 women wearing CuT200 intrauterine contraceptive devices (IUDs) for periods ranging from 6 mo to 15 yr. No cases of cervical neoplasia or endometrial carcinoma were encountered, even after continuous use of the device for 15 years. Dysplastic cervical smears were, however, found in 45 postinsertional smears, and endometrial hyperplasia was detected in seven aspirates; in no cases was the dysplasia or hyperplasia higher than of moderate degree. Thirty-nine of the 45 women with postinsertional dysplastic smears were followed for 3-4 yr; in no case did the lesion progress to a higher grade or to frank malignancy. However, persistence and recurrence of dysplasia were seen in 10 women, necessitating removal of the IUDs. The incidence of cervical dysplasia and endometrial hyperplasia was found to be much higher when the IUDs had been changed than when the original devices were worn continuously. The rate of removal of IUDs because of persistent or recurring dysplasia was also much higher in the former group. Since no pregnancies were reported in any of the women wearing the original device for as long as 15 yr, we do not advocate the practice of changing the device at the end of 3 yr for maintaining contraceptive efficacy as recommended by the manufacturers; instead, we recommend the uninterrupted retention of the original device for periods not longer than 5 yr in view of occurrence of endometrial hyperplasia in two 6-yr wearers.

Adult↗
PubMed1989

Characterization of receptor-coupled phosphoinositide hydrolysis in the rat hippocampus after intradentate colchicine.

Lesions produced by intradentate hippocampal administration of colchicine have been reported to produce several time-dependent behavioral and neurochemical changes, including a possible change in the signal transduction process for the cholinergic muscarinic receptor. To characterize further the effects of colchicine on receptor-coupled hydrolysis of phosphoinositides, colchicine was injected stereotaxically into the dentate gyrus of rats at a dose of 2.5 micrograms/site. The animals were killed 1, 3, or 12 weeks after injection and the hippocampi removed and sliced. [3H]Inositol was incorporated into slices, and various receptor agonists known to stimulate inositol phosphate (IP) metabolism were studied. Colchicine administration altered agonist-stimulated turnover in the hippocampus in a time-dependent manner. This hyperstimulation was receptor-mediated, because it was blocked by pirenzepine. The hyperstimulation of turnover was observed also with norepinephrine and serotonin. Colchicine had no effect on IP turnover in vitro. The effect of the colchicine lesion was observed only in the hippocampus, because no change in cholinergic muscarinic receptor-stimulated phosphatidylinositol turnover was observed in the cortex. These studies indicate that intradentate administration of colchicine produces a compensatory change in the signal transduction process in the hippocampus detectable 12 weeks after the lesion.

Animals↗
PubMed1989

Ultrastructural reappraisal of endometrial glandular changes in women wearing Cu-T200 device for longer duration.

The present communication deals with the effects of Copper-T200 Sq mm intrauterine device on the endometrial glands in the women using it for a longer duration i.e. up 8 years. The ultrastructural changes in the lining endometrial glands were studied during both non-ovulatory and ovulatory phases of the menstrual cycle. The ultrastructural studies demonstrated significant progressive changes in the lining endothelial cells of endometrial glands. The findings showed marked accumulation of glycogen in the cells in secretory phase of the endometrial cycle. Ultrastructural changes in glandular lining cells were more pronounced in women using Cu-IUCD for 4-8 years having distorted morphology with disrupted cell organelles, swollen mitochondria, irregular pattern of microvilli, deposition of electron dense material on cell surface and narrowing of glandular lumen.

Adult↗
PubMed1989

Ultrastructural changes in parietal cells in iron deficiency anemia.

Eighteen patients with iron deficiency anemia (IDA) and 14 age and sex matched control subjects were studied with regard to ultrastructural changes in parietal cells. The control subjects had normal hemoglobin and serum iron levels and endoscopic examination of the upper gastrointestinal tract. Thirteen cases of iron deficiency anemia had chronic superficial gastritis on light microscopy. Ultrastructural abnormalities in the parietal cells, such as indented or pyknotic nucleus with irregular outline, grossly distorted canalicular system, abnormal large empty spaces in the cytoplasm and paucity of mitochondria, were demonstrated in all IDA patients but not in controls. The presence of superficial gastritis and ultrastructural changes were not related either to hemoglobin or serum iron levels in the IDA group.

Adolescent↗
PubMed1988

Fetal hippocampal cell suspensions ameliorate behavioral effects of intradentate colchicine in the rat.

Colchicine, a neurotoxin that preferentially destroys dentate gyrus granule cells and mossy fibers, was injected into the hippocampus of adult rats. Three weeks later, the rats were tested for colchicine-induced hypermotility after which they received fetal hippocampal explants. Locomotor activity was retested three weeks later, after which the rats were trained over a period of four weeks on a food-reinforced, spatial, working memory task in an 8-arm radial maze. Fetal hippocampal explants were found to attenuate significantly the colchicine-induced hypermotility and spatial learning deficits. Histological observations showed the presence of surviving hippocampal explants in both the lesioned and the control rat brains, suggesting that the presence of viable implants facilitates the recovery of behavioral function in rats with spatial memory deficits.

Animals↗
PubMed1986

Synergism of recombinant human interferon gamma with liposome-encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes.

Freshly isolated human peripheral blood monocytes from healthy volunteers are not cytotoxic to allogeneic A375 melanoma cells, but they were rendered tumoricidal by incubation in vitro with either liposomes containing 5 micrograms/mumol phospholipid of muramyl tripeptide phosphatidylethanolamine (liposome-MTP-PE; optimal dose, 500 nmol/ml) or recombinant human interferon gamma (rIFN-gamma; optimal dose, 100 U/ml). A combination of sub-threshold concentrations of liposome-MTP-PE (50 nmol/ml) and rIFN-gamma (1 or 10 U/ml) also induced significant tumor-cell killing, indicating that the effects of rIFN-gamma and liposome-MTP-PE in monocyte activation are synergistic. In contrast to rIFN-gamma, recombinant IFN-alpha and IFN-beta had additive effects with liposome-MTP-PE in human monocyte activation. Since recombinant human IFN-gamma has a synergistic effect with liposome-MTP-PE in monocyte activation, unlike IFN-alpha or IFN-beta, and liposome-MTP-PE as well as rIFN-gamma is available at standardized concentrations, this combination could be of clinical value in the treatment of disseminated malignant disease.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

A dried preparation of liposomes containing muramyl tripeptide phosphatidylethanolamine as a potent activator of human blood monocytes to the antitumor state.

Studies were performed on the activation of human blood monocytes to the antitumor state by a dried preparation of multilamellar vesicle (MLV) liposomes in which synthetic muramyl tripeptide phosphatidylethanolamine (MTP-PE) was inserted directly into the liposome membrane. Dried liposomes composed of synthetic phospholipids [phosphatidylcholine (PC) and phosphatidylserine (PS) in a molar ratio of 7:3] were prepared by lyophilization. Dried liposome-MTP-PE was found to be superior in several ways to free desmethyl muramyl dipeptide (norMDP) or conventional liposome-MTP-PE, prepared immediately before use. First, dried liposome-MTP-PE was stable and strongly activated monocytes when stored for over 3 months in a freezer at -20 degrees C or even in suspension at 4 degrees C. Second, human monocytes in suspension, as well as in the adherent form, were activated to the tumoricidal state by interaction for at least 4 h with the dried preparation of liposome-MTP-PE. Third, monocytes activated with the dried liposome-MTP-PE or conventionally prepared liposome-MTP-PE maintained their tumoricidal activity for a longer period (4 days) than those activated with free norMDP. These results indicate that the dried preparation of liposome-MTP-PE can be stored for a long time, has a reproducible effect that can be standardized and should be valuable for in situ activation of human monocytes to the tumoricidal state, which is associated with eradication of cancer metastases.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Synthesis, structure, and antitumor activity of N-salicyloyl-N'-(2-furylthiocarbonyl)hydrazine and its copper(II) complex.

N-Salicyloyl-N'-(2-furylthiocarbonyl)hydrazine (H2sfth) and its Cu(II) complex [Cu(sfth)] were prepared and characterized by physicochemical studies. The IR and ESR spectral studies imply dibasic tetradentate behavior of the ligand bonding through "thiolo" sulfur, enolic oxygen, and hydrazinic nitrogens in a polymeric structure. The electronic spectrum of the complex indicates a square-planar geometry around Cu(II). Maximum antitumor activity was observed when 25 mg/kg dose levels of H2sfth and Cu(sfth) were injected intraperitoneally in mice bearing either solid fibrosarcoma or ascites Dalton's lymphoma. However, H2sfth appeared to possess better antitumor activity as demonstrated by higher T/C (percent) values than those observed for Cu(sfth). The appearance of lymphocytes, leukocytes, and macrophages within the tumor mass 2-6 days after treatment are indicative of involvement of the host's immune system.

Animals↗
PubMed1986

Inflammatory lesions of the basal ganglia and thalamus: review of twenty-one cases.

We report a series of 21 patients with basal ganglia and thalamic granulomas or abscesses treated over 7 years. Among them, 15 were tubercular, 5 were pyogenic, and 1 was fungal. Pyogenic abscesses, usually hematogenous, also occurred secondary to osteomyelitis of the skull and chronic otitis media. The fungal abscess developed in a nonimmunocompromised patient with no intercurrent malignancy. Evidence of tuberculosis elsewhere in the body was detected in only 7 patients with tuberculomas. The computed tomographic (CT) image morphology characterizing an abscess or a tuberculoma was present in all except 2 patients with tuberculomas. The fungal abscess resembled a malignant glioma. The only hospital mortality occurred in a deeply unconscious patient with a thalamic pyogenic abscess. A 12-month or longer follow-up in 16 patients showed that 3 continued to be handicapped neurologically, and 2 died 13 and 16 months later, respectively. We conclude that inflammatory lesions at these sites are not uncommon and that CT scans are diagnostic in the great majority. Doubtful diagnosis merits stereotactic aspiration or biopsy of the lesion. Satisfactory results follow adequate medical therapy.

Adolescent↗
PubMed1986

[Induction of tumoricidal properties in human monocytes by synergism between interferon-gamma and liposome-entrapped muramyl tripeptide].

Human blood monocytes from healthy volunteers, separated by centrifugal elutriation, were not cytotoxic to allogeneic A 375 melanoma cells. The monocytes were rendered tumoricidal by incubation for 24 h with natural interferon-alpha and beta or recombinant interferon-alpha A and alpha A/D (more than 100 U/ml) or with interferon-gamma (more than 1 U/ml). Liposome-MTP-PE at concentrations of more than 50 nmol/ml also induced tumoricidal activity of monocytes. When a combination of subthreshold concentrations of these IFNs and liposome-MTP-PE were added to monocyte cultures, IFN-alpha and beta acted additively in monocyte activation, while IFN-gamma acted synergistically. The synergism for monocyte activation required that monocytes be incubated first with IFN-gamma and then with liposome-MTP-PE. These findings suggest that the synergistic effect of IFN-gamma and liposome-MTP-PE can decrease the necessary clinical doses of these agents for malignant diseases, and may have therapeutic availability in the treatment of metastatic cancer in humans.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

[Augmentation of natural killer (NK) cell activity in human blood lymphocytes by a new synthetic acyltripeptide (FK-565) and its derivatives].

Natural killer (NK) activities of human blood lymphocyte populations that were depleted of monocytes by centrifugal elutriation, were significantly augmented by in vitro treatment with synthetic acyltripeptide (FK-565) at concentrations ranging from 10 micrograms/ml to 100 micrograms/ml in medium. Of FK-565 and its eight derivatives, FR-39868 was the most effective in potentiating human NK cell activity, and caused NK cell-mediated cytotoxicity against K-562 target cells even at a minimal concentration of 1 microgram/ml. The significant levels of cytotoxicity, increased with increasing NK cell/target ratio. These results indicate that acyltripeptide and its derivatives should be useful in enhancing natural host defense against neoplasias in vivo.

Adjuvants, Immunologic↗
PubMed1986

Lack of production of interleukin 1 by human blood monocytes activated to the antitumor state by liposome-encapsulated muramyl tripeptide.

Previously human blood monocytes were shown to become tumoricidal when treated in vitro with lipopolysaccharide, muramyl dipeptide analogue, or liposomes containing muramyl dipeptide analogue. In this study the ability of human blood monocytes activated to the antitumor state by these macrophage activators to produce interleukin 1 (IL-1) was examined. Blood monocytes separated by centrifugal elutriation did not release IL-1 into the culture supernatant but elaborated IL-1 maximally within 24 h after treatment with lipopolysaccharide or desmethyl muramyl dipeptide. In contrast, they did not elaborate IL-1 when rendered tumoricidal by muramyl tripeptide phosphatidylethanolamine (MTP-PE) encapsulated in multilamellar vesicle liposomes composed of phosphatidylcholine and phosphatidylserine in a molar ratio of 7:3. IL-1 rich supernatants that induced thymocyte proliferation were not adsorbed or destroyed by the liposomes, and addition of supernatants from cultures of monocytes treated with liposome-MTP-PE to IL-1 rich supernatants did not inhibit thymocyte proliferation. MTP-PE in liposomes composed of phosphatidylserine or phosphatidylcholine or both in various molar ratios also did not induce IL-1 production by monocytes. These results indicate that MTP-PE encapsulated in liposomes may be useful in in situ activation of human blood monocytes to the antitumor state for destruction of clinical micrometastases because MTP-PE encapsulated in liposomes does not stimulate production of IL-1, which is responsible for undesirable side effects such as fever and granulomatous reactions.

Acetylmuramyl-Alanyl-Isoglutamine↗