Biomedical subjects

G Soma

Publications and source records attributed to G Soma.

At least 19 recordsLinked to original sources

PubMed1997

Structural characterization of lipid A obtained from Pantoea agglomerans lipopolysaccharide.

Lipopolysaccharide isolated from Pantoea agglomerans showed higher priming and triggering activities for macrophages in terms of tumor necrosis factor production than other lipopolysaccharides. To identify the difference in biological activities of lipopolysaccharide of Pantoea agglomerans from other lipopolysaccharides on the basis of structure, we determined the structure of the lipid A part, which is the biological center of lipopolysaccharides, by quantitative analysis, nuclear magnetic resonance spectroscopy and mass spectrometry. Lipopolysaccharide of Pantoea agglomerans is constructed with at least two kinds of lipid A of different levels of acylation. One is of the same type as that of Escherichia coli with hexa-acyl lipid A and the other is the Salmonella minnesota type with hepta-acyl lipid A.

Bacterial Proteins↗

PubMed1996

Mechanistic analysis of high antitumor effect of intradermal administration of lipopolysaccharide from Pantoea Agglomerans.

Lipopolysaccharide from Pantoea Agglomerans (LPSp) has a remarkably high antitumor activity even against poorly immunogeneic tumors when given by intradermal injection combined with cyclophosphamide (CY). We have extended this study to gain an insight into the mechanism of this antitumor effect, and especially into the induction of cell mediated immunity. In immunohistological studies, extensive necrosis and marked infiltration of the inflammatory cells at the tumor were observed after intradermal injection of LPSp combined with CY, but not after CY alone or after no treatment. The cells around the tumors were mostly neutrophils and macro phages (Mac 1+); T cells (CD4+, CD8+) were also present. The serum levels of cytokines, induced after intradermal injection of LPSp, were determined and compared with intravenous administration of LPSp or recombinant TNF-SAM2. TNF-alpha, IL-1, IL-6 and GM-CSF were measured by ELISA as a marker of cytokine induction. The peak level of TNF-alpha induced by intradermal injection of LPSp was about 5000 pg ml-1, which was considered relatively small since this level was observed even in clinical trial. There seems to be a longer period of release of TNF-alpha after an intradermal injection than after an intravenous injection. This may produce the remarkably high antitumor effect of the intradermal injection. The antitumor effect of intradermal administration combined with CY was evaluated in nude mice to clarify the role of T cells in high antitumor activity. In this experiment, antitumor activity was found to be much less in BALB/c nu/nu mice without regression, while complete regression was frequently observed in syngeneic mice, showing the crucial role of T cells in this treatment. These observations suggest that intradermal administration of LPSp in combination with CY continuously releases and induces not only extensive necrosis of the tumor but also cell mediated antitumor immunity, which may be indispensable for complete regression of the tumor. Clinical application of this treatment for advanced cancer patients is in progress.

Animals↗

PubMed1996

Surgical experience of total anomalous pulmonary venous connection with mid-term follow-up in a developing country.

OBJECTIVE: To illustrate the incidence, the different age group, varied clinical presentation, incremental risk factors for surgery and follow-up results from this part of the world. EXPERIMENTAL DESIGN: Retrospective study with follow-up from 3 months to 5 years. SETTING: Institutional practice with hospitalised care. SELECTION PROCEDURE: Hospitalised patients with a diagnosis of total anomalous pulmonary venous connection. INTERVENTIONS: All patients who were diagnosed to have total anomalous pulmonary venous connection underwent corrective surgery. RESULTS: There were 20 hospital deaths postoperatively. The mean follow-up was 1.9 year. Logistic regression analysis identified age group, timing of surgery, associated anomalies preoperative symptoms, anatomical type of lesion, pulmonary artery hypertension, duration of ventilation, low cardiac output as risk factors for surgery. The mean survival time was 4-8 years. CONCLUSION: Mortality continues to be higher from this part of the world due to severe malnourishment, late presentation. Sociodemographic factors also play a major role in affecting surgical outcome apart from the identified risk factors for surgery.

Cardiac Surgical Procedures↗

PubMed1995

Molecular cloning of a cDNA that encodes the precursor to several exogastrula-inducing peptides, epidermal-growth-factor-related polypeptides of the sea urchin Anthocidaris crassispina.

Complementary DNA clones for exogastrula-inducing peptides (EGIPs) of the sea urchin Anthocidaris crassispina, which are related to epidermal growth factor (EGF), were obtained from a cDNA library of late gastrula embryos using, as probe, the partial cDNA for one of the EGIP (EGIP-D) obtained by the reverse-transcription PCR method. The longest cDNA was composed of 1662 bp, and encoded a protein of approximately 36 kDa with a region that resembled a signal sequence. The deduced protein contains the sequences of EGIP-C, EGIP-D, and EGIP-A in that order, followed by the sequence for an unidentified EGIP-like polypeptide. When expressed in Escherichia coli as a fusion protein with beta-galactosidase, the product for the cDNA was specifically recognized by a rabbit antibody raised against EGIP-D that had been purified from embryos. Characteristic amino acid residues were found around the N-terminus and the C-terminus of each EGIP sequence, suggesting a specific processing mechanism for the generation of the individual EGIPs from the precursor. RNA-blot analysis revealed the presence of EGIP mRNA in unfertilized eggs. The level of this mRNA decreased gradually after fertilization, began to increase dramatically after the onset of gastrulation, and continued to increase through the pluteus stage. Genomic Southern-blot analysis suggested that this gene is present as a single copy. A homology search showed that the EGIP cDNA has a similarity to the cDNA for SpEGF2 which was cloned as a gastrula-specific gene in another sea urchin, Strongylocentrotus purpuratus.

Amino Acid Sequence↗

PubMed1995

Inducibility of endogenous tumor necrosis factor by tumor cells from colorectal tumor patients at Dukes stage C as a novel prognostic factor following curative operation.

PURPOSE: It is well known that tumor cells secrete endogenous tumor necrosis factor (en-TNF) as a cytokine when stimulated with lipopolysaccharide (LPS). We, therefore, analyzed the biologic role of en-TNF secreted by tumor cells themselves to learn the prognosis of patients and the susceptibility of tumors to biologic response modifiers in particular. METHODS: Patients with Dukes C colorectal tumors were studied after curative operation to determine the inducibility of en-TNF by their primary cultured cells in response to LPS. RESULTS: Irrespective of the known clinicopathologic factors of the tumors, en-TNF was produced in 21 of a total of 44 patients. The group of patients with clear en-TNF production showed a significantly lower incidence of recurrence and/or metastasis and a higher survival rate than the group without en-TNF production, suggesting a strong correlation between patient prognosis and inducibility of en-TNF. CONCLUSION: Inducibility of en-TNF by tumor cells themselves can be a novel prognostic factor for patients with colorectal tumor, especially of Dukes Stage C.

Biomarkers↗

PubMed1995

Hemodynamic evaluation of recombinant human tumor necrosis factor (TNF)-alpha, TNF-SAM2 and liposomal TNF-SAM2 in an anesthetized dog model.

We have evaluated the hemodynamic effects of systemically administered recombinant human tumor necrosis factor (TNF)-alpha, TNF-SAM2 and liposome-bound TNF-SAM2 in an anesthetized mongrel dog model. A dose of 10 micrograms TNF protein/kg of each formulation was injected in a peripheral vein and mean systemic arterial pressure (SAP), heart rate (HR) and cardiac output (CO) were measured. TNF-alpha induced a marked drop in SAP in all three dogs (mean decrease = 59.3 +/- 5.2 mm Hg; to 61.5% of baseline; p = 0.008); whereas TNF-SAM2 caused a smaller and transient drop in SAP in four dogs (mean decrease = 25.5 +/- 10.1 mm Hg; to 81.2% of baseline; p = 0.086). In three dogs administered liposome-bound TNF-SAM2, which retains antitumor activity in vivo, a net slight hypertensive phase and sustained elevated CO occurred, followed by a return to an essentially normotensive state (101.0% of baseline SAP). This model demonstrates that the principal acute systemic toxicity of TNF, i.e., hypotension, can be markedly attenuated by liposomal formulation of a second-generation TNF.

Animals↗

PubMed1994

Antinociceptive effect of lipopolysaccharide from Pantoea agglomerans on streptozotocin-induced diabetic mice.

The antinociceptive effect of lipopolysaccharide from Pantoea agglomerans (LPSp) in streptozotocin-induced diabetic mice was examined. Although subcutaneous (s.c.) administration of LPSp produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of LPSp in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by beta-funaltrexamine, a selective mu-opioid receptor antagonist. These results suggest that LPSp produces a marked antinociceptive effect in diabetic mice through the activation of delta- and kappa-opioid receptors.

Analgesics↗

PubMed1994

Constitutive expression of TNF-alpha and -beta genes in mouse embryo: roles of cytokines as regulator and effector on development.

1. Using the RT/PCR method, we examined mRNA expression of several inflammatory factors in mouse embryos during mid-late embryonal development. mRNAs of tumor necrosis factor (TNF)-alpha, TNF-beta, their receptors (TNF-RI, TNF-RII), transforming growth factor (TGF)-beta, were expressed constitutively in most of the embryonic tissues. 2. While mRNAs of other factors, interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granurocyte-colony stimulating factor (G-CSF), leukaemia inhibitory factor (LIF), and interferon (IFN)-gamma were only limitedly expressed. 3. The mRNAs of several complement components (C2, C3, C4, C5) and receptors (CR1, CR2) were also detected. Among them, the expression of C3 and CR1 were prominent. These results strongly support our idea that inflammation-like system play an important role to regulate embryogenesis.

Animals↗

PubMed1994

Effects of a lipopolysaccharide from Pantoea agglomerans on the cocaine-induced place preference.

A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified, and its effect on the cocaine-induced place preference was examined in rats. Cocaine (4 mg/kg, i.p.) produced a significant place preference. Administration of LPSp (5-1000 micrograms/kg, i.p.) alone resulted in neither preference nor aversion for either the drug- or saline-associated place. However, pretreatment with LPSp (500 and 1000 micrograms/kg, i.p.) abolished the place preference that had been induced by cocaine. Furthermore, treatment with LPSp (500 micrograms/kg, i.p.) abolished cocaine (20 mg/kg, i.p.)-induced locomotor enhancement in mice. These results suggest that while LPSp itself may possess neither reinforcing nor locomotor enhancing effects, it blocks both the reinforcing and the locomotor enhancing effects of cocaine. Therefore, LPSp might be useful in pharmacotherapy for prevention of recurrent cocaine abuse.

Animals↗

PubMed1994

Antitumor effect of exogenous/endogenous TNF (EET) therapy with cyclophosphamide on C6 glioma in rat.

We earlier reported that endogenous TNF could be induced in mice as well as in patients by successive administration of exogenous TNF as a primer and OK-432 as a trigger, and we termed this exogenous/endogenous TNF (EET) therapy. We studied the effect of EET therapy with cyclophosphamide (CY) on tumor-transplanted rats. In order to induce endogenous TNF, 5 x 10(5) U/kg of recombinant human TNF-S(AM2) (rTNF; 5.6x10(6) U/mg protein) was injected intravenously (iv) as a primer followed by injection of 25 KE/kg of OK-432 as a trigger. TNF activity induced in serum was about 500 U/ml. Only 1 U/g of TNF was detected in the brain. To evaluate the antitumor effect, C6 glioma cells (1.6 x 10(4) cell/5 microliters) was transplanted into the brain. On day 7 of the transplantation, the rats were administered iv with CY (75 mg/kg), treated with EET therapy 7 days thereafter, and survival days were checked. No clear difference in survival days was observed between the rats treated with the EET and the control group. Three rats out of 6 treated with CY survived for more than 40 days, and all the rats treated with the combination of CY and EET continued to survive. The histological examination on day 44 revealed necrotic changes at the tumor lesions in all of the surviving rats, and the animals were evaluated as completely cured. These results suggest that applied treatment based on the EET therapy will be also effective against malignant brain tumors.

Animals↗

PubMed1994

Suppression of hyperalgesia in streptozotocin-induced diabetic mice by a lipopolysaccharide from Pantoea agglomerans.

The ability of a lipopolysaccharide from Pantoea agglomerans (LPSp) to relieve hyperalgesia was examined by observing its inhibition of the decrease in the threshold for nociceptive perception, as determined by the tail-pinch test, in streptozotocin-induced diabetic mice. Subcutaneous injection of LPSp suppressed hyperalgesia in streptozotocin-induced diabetic mice and also exerted a therapeutic effect on hyperalgesia in these animals. The present data suggest that LPSp may be effective in relieving the pain associated with diabetic neuropathy.

Animals↗

PubMed1993

Fc gamma receptor-mediated biological activities of human leukemic cell lines and their modulation by transforming growth factor-beta 1 and interleukin 6.

Previously we reported that transforming growth factor-beta 1 (TGF-beta 1) remarkably enhanced the differentiation of human leukemic cell lines, HL-60 and THP-1, in the presence of 1 alpha,25-dihydroxyvitamin D3 (VD3) and also that it induced Fc receptor for immunoglobulin G (Fc gamma R), type IIIB, in the presence of retinoic acid (RA). The present study revealed that TGF-beta 1 enhanced the Fc gamma RI- and Fc gamma RII-mediated antibody-dependent cellular cytotoxicity (ADCC) of the cells differentiated in the presence of VD3 and RA. However, production of active oxygen molecules was suppressed by TGF-beta 1. On the other hand, IL-6 stimulated production of active oxygen molecules and ADCC of the cells treated with VD3 and tumor necrosis factor-alpha (TNF-alpha). Furthermore, the levels of cell surface Fc gamma RI and Fc gamma RII were not clearly correlated with the ADCC. The TGF-beta 1/VD3-treated HL-60 cells were able to synthesize mRNAs for TGF-beta 1 and TNF-alpha, although TNF-alpha protein was not detectable. These results suggest that TGF-beta 1 has a bifunctional role, either stimulatory or inhibitory, in the modulation of macrophage activities through Fc gamma Rs and that IL-6 stimulates certain macrophage activities in mature cells.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1993

Gangliosides can activate human alternative complement pathway.

The alternative complement pathway (ACP) in vertebrates is known to be important in inflammatory reactions, and to be activated by foreign substances such as bacterial lipopolysaccharide (LPS) and zymosan, although to date no intrinsic activators have been identified except complement receptor type 2. From the point of the structural similarity of LPS to ganglioside, we have investigated gangliosides which are abundantly present in animal cells for their activity on the human ACP. All of seven gangliosides tested were found to activate this pathway in a manner depending on the number of sialic acids and neutral sugars contained in the molecules. A dose-response study suggested a correlation of the threshold in ganglioside concentration with its critical micelle concentration. Gangliosides may thus serve as an intrinsic activator for ACP in animals, thereby leading to inflammation. The possibility of the participation of sialidase in complement activation is also discussed.

Complement Pathway, Alternative↗

PubMed1992

Expression of transcripts of complement components and their receptors during differentiation of embryonal carcinoma cell lines.

Based on our previous finding that TNF-alpha and TNF-beta can be expressed constitutively during early embryonal development [1], we extended our work to identify factors which are generally known to take part in inducing inflammation in adults. They can be regarded as candidate molecules involved in ontogenic inflammation during embryonal development. In this study, we chose the factors which are constituents of either a classical or an alternative pathway of a complement system and found that mRNAs corresponding to those of C2, C3, C4, C5 and to those of receptors CR1 and CR2 were expressed. Among them, mRNA expression of C3, C4, and CR1 was especially constitutive. Contrary to these observations, expression of two kinds of scavenger receptors (SR-I, SR-II) proved to be negative. In this report, the framework of ontogenic inflammation as a regulatory mechanism in embryonal development at the molecular level is discussed.

Animals↗

PubMed1992

Homeostasis as regulated by activated macrophage. VI. Protective effect of LPSw (a lipopolysaccharide from wheat flour) against acute infection by Toxoplasma gondii in mice.

An oral administration of partially purified LPSw, a lipopolysaccharide (LPS) from wheat flour, at a concentration of 20 ng/ml in drinking water beginning 1d after infection significantly decreased mouse mortality and prevented animal weight loss in acute infection with Toxoplasma gondii. Whereas 71% (5/7) of mice in a control group that did not receive LPSw died of toxoplasmosis, only 14% (1/7) of mice treated with LPSw died (p less than 0.05). The administration of LPS purified from Bordetella pertussis also significantly decreased the mortality of infected mice. LPS from Escherichia coli and synthetic lipid A (LA-15-PP(506)), however, did not show a significant decrease in mortality.

Acute Disease↗

PubMed1992

Homeostasis as regulated by activated macrophage. VII. Suppression of serum cholesterol level by LPSw (a lipopolysaccharide from wheat flour) in WHHL (Watanabe heritable hyperlipidemic) rabbit.

The effect of LPSw (a lipopolysaccharide from wheat flour) on cholesterol catabolism was examined using WHHL (Watanabe heritable hyperlipidemic) rabbit, which is an experimental model of familial hyperlipidemia. The serum cholesterol level of the animal decreased by the addition of LPSw to drinking water. Following cessation of the addition of LPSw to the drinking water, the cholesterol level was decreased for 30 to 40d and then gradually elevated. The serum level of apolipoprotein B, which is a constituent of apolipoprotein of low density lipoprotein (LDL), also decreased in accord with serum cholesterol at a nearly coincident rate. Conversely, the level of apolipoprotein A-I, which is a constituent of apolipoprotein of high density lipoprotein (HDL), did not change, nor did HDL-cholesterol. Furthermore, the atherosclerosis risk factor, expressed as the ratio of apolipoprotein B to apolipoprotein A-I, was decreased by LPSw administration.

Animals↗

PubMed1992

Homeostasis as regulated by activated macrophage. VIII. LPSw (a lipopolysaccharide from wheat flour) can regulate bone resorption of chick embryo.

The effect of LPSw (a lipopolysaccharide from wheat flour) on the bone resorption of 18-d chick embryonic calvaria was examined in an organ culture following the method of Raisz. Bone was prelabeled in culture medium containing 45Ca and chased in a cold medium. On addition of test samples, labeled calcium was released indicating the grade of bone resorption. LPSw (10-100 ng/ml) stimulated bone resorption, showing an effect comparable to parathyroid hormone (PTH) (1 U/ml). PTH at 1 U/ml decreased the total amount of calcium and phosphorus, while LPSw did not. LPSw is thus assumed to stimulate bone resorption more actively than PTH.

Animals↗

PubMed1992

Homeostasis as regulated by activated macrophage. IX. Enhancement effect of LPSw (a lipopolysaccharide from wheat flour) on hen egg-laying and breaking strength of eggshell.

Oral administration of LPSw (a lipopolysaccharide from wheat flour) given at 60 micrograms/hen/d in drinking water, markedly enhanced eggshell strength. The monthly percentage of eggs laid with a shell strength of more than 4 kg to the total number of eggs was 32% in the group given LPSw in drinking water while it was 12% in the control group given plain water. At the same time, LPSw caused a 30% enhancement of total monthly number of eggs laid over that of control.

Animals↗