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Biomedical subjects

J Samuel

Publications and source records attributed to J Samuel.

At least 19 recordsLinked to original sources
PubMed1999

Encapsulation of plasmid DNA in biodegradable poly(D, L-lactic-co-glycolic acid) microspheres as a novel approach for immunogene delivery.

A plasmid DNA encoding bacterial beta-galactosidase gene was encapsulated in poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. Plasmid DNA extracted from PLGA microspheres retained both structural and functional integrity as evidenced by its restriction endonuclease digestion pattern and its ability to transfect COS-1 cells in vitro. PLGA microspheres protected plasmid DNA from digestion by deoxyribonuclease I (DNase I) in vitro. The encapsulation efficiency of plasmid DNA and its release rate depended on the molecular mass of PLGA. Lastly, J-774A macrophages phagocytosed PLGA microspheres loaded with plasmid DNA. Co-encapsulated monophosphoryl lipid A increased the rate of phagocytosis. These results suggest that biodegradable PLGA microspheres can deliver intact and functional plasmid DNA at controlled rates. Thus, PLGA microspheres may be used to jointly deliver genes and other biologically active molecules, e.g., immunomodulators, to antigen presenting cells.

Animals↗
PubMed1998

Immunogenicity and antitumor activity of a liposomal MUC1 peptide-based vaccine.

A human MUC1-transfected mouse mammary adenocarcinoma cell line (GZHI) was used to develop both subcutaneous and intravenous tumor models. A vaccine formulation comprised of a 24 mer (human MUC1) synthetic peptide encapsulated with monophosphoryl lipid A adjuvant (MPLA) in multilamellar liposomes was tested for immunogenicity and anti-tumor activity. A low dose of the human MUC1 peptide (5 microg) administered in liposomes provided excellent protection of mice in both tumor challenge models. The protective antitumor activity mediated by the liposome formulation correlated with anti-MUC1-specific T-cell proliferation, gamma-interferon (IFN-gamma) production and IgG2a anti-MUC1 antibodies, suggesting a type 1 (T1) T-cell response. In contrast, lack of protection in mice immunized with negative control vaccines correlated with IgG1 anti-MUCI antibody formation, low or no anti-MUC1 IgG2a and low antigen-specific T-cell proliferation, consistent with a type 2 (T2) T-cell response to the tumor.

Amino Acid Sequence↗
PubMed1998

Induction of anti-idiotypic humoral and cellular immune responses by a murine monoclonal antibody recognizing the ovarian carcinoma antigen CA125 encapsulated in biodegradable microspheres.

The use of biodegradable poly(DL-lactic-co-glycolic acid) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses was investigated using a murine monoclonal antibody B43.13 that recognizes the human ovarian cancer antigen CA125. Immunization of mice with mAb B43.13 encapsulated in poly(DL-lactic-co-glycolic acid) microspheres resulted in enhanced humoral and cellular immune responses compared with mAb B43.13 alone or mAb B43.13 mixed with microspheres. The antibody responses could be further enhanced by the co-encapsulation of mAb B43.13 with monophosphoryl lipid A, a non-toxic adjuvant, in microspheres. Anti-idiotypic humoral responses were shown to result in Ab2 antibodies mimicking the nominal antigen CA125 and Ab3 antibodies recognizing CA125. Further, microsphere delivery of mAb B43.13 also resulted in induction of T cell responses involving T2 cells reactive with mAb B43.13 epitopes and T3 cells recognizing CA125. These results indicate that microsphere delivery of Abl can induce both humoral and cellular anti-idiotypic responses relevant to cancer antigens. This raises the possibility of the use of such formulations for anti-idiotypic induction immunotherapy for cancer.

Animals↗
PubMed1998

Ovalbumin peptide encapsulated in poly(d,l lactic-co-glycolic acid) microspheres is capable of inducing a T helper type 1 immune response.

An ovalbumin (OVA) peptide, consisting of residues 323-339, was incorporated into poly(d,l lactic-co-glycolic acid) (PLGA) microspheres and administered to mice. It was hypothesized that microencapsulation of the peptide in PLGA microspheres would avoid the need for traditional adjuvants and bias the immune response towards a type 1 T helper (Th1) response. An immunomodulator, monophosphoryl lipid A (MPLA), was incorporated into the microspheres to determine its efficacy in enhancing a Th1 response. The specificity of the immune response was determined using a T cell proliferation assay. The type of T helper response was determined by analysis of the cytokine secretion profiles of the proliferating T cells. Following s.c. immunization, the results revealed a T cell-specific immune response for the encapsulated OVA peptide both with and without MPLA. The cytokine profiles revealed high levels of IFN-gamma with very low levels of IL-4 and IL-10, suggesting a Th1 response. Furthermore, incorporation of MPLA in the peptide loaded PLGA microspheres resulted in an increase in the production of IFN-gamma. Hence, peptide-loaded PLGA microspheres are capable of eliciting a specific Th1 immune response, which may be further enhanced in the presence MPLA.

Amino Acid Sequence↗
PubMed1998

Use of encapsulated single chain antibodies for induction of anti-idiotypic humoral and cellular immune responses.

The use of biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses has been investigated using a single chain antibody scFv-pDL10, which recognizes the human ovarian cancer antigen CA125. Immunization of mice with scFv-pDL10 encapsulated in PLGA microspheres resulted in enhanced humoral and cellular immune responses when compared to scFv-pDL10 alone. Induced anti-idiotypic antibodies (Ab2) which mimic the original antigen CA125 compete with CA125 for the epitope. A cellular response (T2 induction) was also observed. These results raise the possibility of anti-idiotypic antibody induction by a single chain antibody, encapsulated in biodegradeble microspheres, as a potential vaccine for ovarian carcinoma.

Animals↗
PubMed1998

Delivery of MUC1 mucin peptide by Poly(d,l-lactic-co-glycolic acid) microspheres induces type 1 T helper immune responses.

Synthetic peptides corresponding to the variable tandem repeat domain of the cancer-associated antigen MUC1 mucin are candidates for cancer vaccines. In our investigation mice were immunized via subcutaneous injection with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres containing a MUC1 mucin peptide. It was hypothesized that microencapsulation of the MUC1 mucin peptide would prime for antigen-specific Th1 responses while avoiding the need for traditional adjuvants and carrier proteins. Furthermore, an immunomodulator, monophosphoryl lipid A (MPLA), was incorporated into the peptide-loaded PLGA microspheres based on its ability to enhance Th1 responses. The results revealed T cell specific immune responses. The cytokine secretion profiles of the T cells consisted of high levels of interferon-gamma with undetectable levels of interleukin-4 and interleukin-10. Moreover, incorporation of MPLA in the MUC1 peptide-loaded PLGA microspheres resulted in an increase in interferon-gamma production. The antibody response was negative for IgM and IgG in the absence of MPLA; however, in the presence of MPLA antibody production was negative for IgM with a minimal IgG response consisting of IgG2a, IgG2b, and IgG3. Based on the antibody and cytokine profiles, it was concluded that MUC1 mucin peptide-loaded PLGA microspheres are capable of eliciting specific Th1 responses, which may be enhanced through the use of MPLA.

Amino Acid Sequence↗
PubMed1998

Use of a liposome antigen delivery system to alter immune responses in vivo.

It has been reported that a certain peptide encompassing residues 129-140 of the hepatitis B virus core antigen (HBcAg) leads to a Th2-type response in C57BL/10 mice. We postulated that by formulating the peptide in liposomes along with an immune modulator known as MPLA the immune response could be directed toward a Th1-type response. If these liposomes could deliver the peptide along with MPLA to antigen presenting cells, then the immune response generated could be polarized to a Th1 response. The type of immune response initiated after immunization with the peptide HBcAg (126-140) in different formulations was determined by an ex vivo T cell proliferation assay and by analysis of the cytokine profile of the proliferating T cells. A group of C57BL/6 mice immunized with peptide plus MPLA in a liposome formulation displayed a strong T cell proliferative response. The T cell subset was identified as Th1 based on the cytokine profile. The cytokine profiles showed significant production of interferon-gamma (IFN-gamma, a Th1-type cytokine) and extremely low levels of interleukin-4 (IL-4, a Th2-type cytokine). The control group of C57BL/6 mice immunized with peptide plus alum showed a very low level of T cell proliferation, and no increase was seen in IFN-gamma or IL-4 production. These data signify that a Th1-type response occurred in mice treated with peptide in a liposome formulation but not in mice treated with the control formulation.

Adjuvants, Immunologic↗
PubMed1997

A myosin-derived peptide C109 binds to GLUT4-vesicles and inhibits the insulin-induced glucose transport stimulation and GLUT4 recruitment in rat adipocytes.

The yeast-based two-hybrid screening of a human cardiac myocyte cDNA library revealed a peptide, C109 that interacted with the C-terminal cytoplasmic domain of GLUT4 (GLUT4C). cDNA-deduced amino acid sequence of C109 was identical to the human cardiac muscle myosin heavy chain beta isoform sequence 1469-1909. GST-fusion protein of C109 (GST-C109) bound synthetic GLUT4C-peptide in vitro, but not GLUT1C-peptide. GST-C109 avidly bound to the GLUT4-vesicles isolated from basal rat adipocytes but not those isolated from insulin treated adipocytes. Furthermore, the incorporation of C109 into rat adipocytes greatly reduced the plasma membrane GLUT4 level and the 3-O-methyl D glucose flux in host cells without affecting total cellular GLUT4 content. These findings suggest that myosin or a myosin-like protein plays a key role in insulin-regulated movement of GLUT4 to the plasma membrane in rat adipocytes.

Adipocytes↗
PubMed1996

Comparison of percutaneous and surgical tracheostomies.

OBJECTIVE: To compare the safety and efficacy of percutaneous dilational tracheostomy (PDT) with surgical tracheostomy (ST). DESIGN: Prospective randomized trial. SETTING: Public urban teaching hospital. PATIENTS: Twenty-six patients were randomized to undergo PDT and 27 patients to ST. RESULTS: The time from randomization into the study until tracheostomy was performed was 28.5 +/- 27.9 h in the PDT group and 100.4 +/- 95.0 h in the ST group (p < 0.001). PDT was performed in 8.2 +/- 4.9 min vs 33.9 +/- 14.0 min for ST (p < 0.0001). There was no significant difference in intraprocedural complications between the groups. Postprocedural complication rates were 12% for PDT and 41% for ST (p = 0.008). CONCLUSION: PDT is superior to ST logistically. PDT can be performed at the bedside eliminating the risk of patient transport. Because operating room scheduling is not necessary, PDT can be performed earlier once the decision to do a tracheostomy is made, which will improve ICU utilization. PDT is a faster procedure to perform and has fewer postprocedural complications.

Female↗
PubMed1995

Development of active specific immunotherapeutic agents based on cancer-associated mucins.

As a result of aberrant glycosylation, cancer-associated mucins expose to the immune system certain carbohydrate, peptide, and possibly glycopeptide epitopes that are not exposed on the normal mucins. This provides the basis for our development of synthetic carbohydrate, peptide, and glycopeptide-based ASI agents corresponding to the cancer-associated mucin epitopes. Our studies on ASI formulations based on carbohydrate structures such as TF and STn have demonstrated their ability to induce immune response relevant to the native epitopes on the cancer cells in animal models and in cancer patients. Further, such immune responses were able to mediate cancer rejection in an animal model. Similar studies on peptide epitopes of a cancer-associated mucin, MUC1, have also shown the ability of the synthetic antigen to induce anticancer immune responses in an animal model. Ongoing studies on the carbohydrate and peptide epitopes would allow us to define the most important target structures on cancer-associated mucins that can selectively stimulate cancer-specific immune responses. Our long-term goal is to develop multiepitopic glycopeptide ASI formulations capable of stimulating strong CMI responses against common carcinomas.

Animals↗
PubMed1995

Relationship between clinical manifestations of footrot and specific DNA products of Dichelobacter nodosus amplified through PCR.

A total of 141 Dichelobacter nodosus isolates from 46 merino sheep farms with various clinical forms of footrot was examined by the gelatin gel test and the polymerase chain reaction (PCR) using virulent (Vf2 and Vr2) and benign (Bf and Br) specific primers. Isolates from sheep with virulent and high intermediate footrot usually produced relatively thermostable proteases, but a decreasing proportion of the isolates from sheep with medium and low intermediate or benign footrot had thermostable proteases, as determined by the gelatin gel test. The amplification by PCR of a major band of 857 bp by Vf2 and Vr2 was often associated with isolates from the more virulent forms of footrot whereas the presence of a major band of 1300 bp by Vf2 and Vr2 and/or a band of 609 bp by Bf and Br was associated with isolates from less virulent forms of footrot. Nevertheless, the virulent and benign gene regions represented by Vf2 and Vr2 and Bf and Br are only two of the many factors involved in determining the virulence of D nodosus. As a result the relationship observed between the clinical manifestations of footrot and specific DNA products amplified by PCR was not complete.

Animals↗
PubMed1995

Toxic effects of the novel protein UpI from the sea anemone Urticina piscivora.

UpI is a basic protein, with molecular mass (approximately 28 kDa) and a pI > 9.4, isolated from the sea anemone Urticina piscivora. It is a potent cardiac stimulatory protein with the partial amino acid sequence D1ENEN5LYGPN10ENKAK15AKDLT20AGASY25LTKEA30GCTKL35QAGCT40MYQAY45N [1]. The toxic effects of UpI and the crude extract from which it was isolated have been investigated on three tumour cell lines: KB, L1210, and HEL 299 cells. UpI, however, was less potent on each cell line than the crude extract. Since previous experiments had shown extracts of U. piscivora to be haemolytic on erythrocytes of rat, guinea pig and dog, the haemolytic action of UpI was investigated. It was found to be a potent haemolysin on erythrocytes of rat, guinea pig, dog, pig and human, causing haemolysis on erythrocytes of each species tested at concentrations as low as 10(-10) M. Haemolysis was inhibited in a concentration-dependent manner by the phospholipid sphingomyelin but not cholesterol. Using scanning electron microscopy, it is now being shown that UpI produces significant structural damage to membranes of erythrocytes from rat and guinea pig. It proved to be a potent ichthyotoxin. These data suggest that sea anemone toxin not only possess different pharmacological activities but that UpI, one of the active constituents, could be responsible for the different pharmacological effects exhibited by the crude extract.

Amino Acid Sequence↗
PubMed1995

[Left ventricular thrombosis complicating systemic lupus erythematosus].

The authors report an isolated pediculated thrombus in the left ventricle of a young 14 year old girl with systemic lupus erythematosus with antiphospholipid antibodies without any other cardiovascular abnormality, especially ventricular wall motion abnormalities. After surgical ablation of the thrombus, the patient was followed up to avoid recurrence. This type of cardiac lesion (ventricular thrombosis without underlying myocardial disease) is exceptionally rare. Echocardiographic follow-up after surgical ablation showed no recurrence of thrombosis after four years.

Adolescent↗
PubMed1995

Incidence of intermediate syndrome in organophosphorous poisoning.

Seventy two patients admitted to the Intensive Care Unit following ingestion of organophosphorus compounds were studied prospectively with two different doses of pralidoxime (PAM). One group received 1 gm immediately after admission and no further PAM and the other group received infusion of PAM, 1 gm 8 hourly for four days (total 12 gms). The incidence of type II paralysis or intermediate syndrome was 47%. We observed a higher incidence in the 4 days of infusion of PAM group (61%) (20 patients) as compared to the single Bolus dose group (39%) (13 patients). Relative risk 1.48 (confidence interval = 0.9-2.4).

Adult↗