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Biomedical subjects

S Nair

Publications and source records attributed to S Nair.

At least 19 recordsLinked to original sources
PubMed1992

Class I restricted CTL recognition of a soluble protein delivered by liposomes containing lipophilic polylysines.

CD8+ cytotoxic lymphocytes recognize peptides derived from endogenous antigens complexed with class I major histocompatibility complex while CD4+ helper cells recognize peptides from exogenous antigens bound to class II MHC molecules. A soluble protein can be introduced into the class I pathway of antigen processing and presentation using an appropriate vehicle to deliver the antigen into the cytosol. Cationic liposomes containing lipophilic polylysine readily form complexes with an anionic, soluble protein ovalbumin. Mouse thymoma EL4 cells incubated with such complexes can be sensitized for killing by OVA-specific CTL effector cells. This method of target sensitization by a soluble antigen is more sensitive than the osmotic loading method previously reported.

Animals↗
PubMed1992

Molecular cloning and analysis of an eIF-4A-related rat liver nuclear protein.

In this paper, we report the cloning and analysis of a cDNA encoding a protein of M(r) congruent to 47,000 (p47), which is localized to the nucleus of rat hepatocytes. The cDNA showed 37% overall sequence identity with a mouse translation initiation factor, eIF-4A, which belongs to a family of putative ATP-dependent RNA helicases. We raised polyclonal antibodies against the fusion protein and by indirect immunofluorescence on primary cultures of hepatocytes have demonstrated that p47 is located in the nucleus. Although only approximately 27% of hepatocytes showed this nuclear staining, most of the nuclei in proliferating transformed cell lines such as 3T3, PtK-1, and Hela were fluorescently labeled. Studies on serum-starved cells in culture indicated that p47 was expressed in a cell cycle-dependent manner. Northern analyses demonstrated that the levels of p47 mRNA were high in fetal liver and dropped significantly after birth to low levels in adult liver. Our data suggest that p47 is developmentally regulated in rat liver at the mRNA level.

Amino Acid Sequence↗
PubMed1992

Analysis of gene expression in single live neurons.

We present here a method for broadly characterizing single cells at the molecular level beyond the more common morphological and transmitter/receptor classifications. The RNA from defined single cells is amplified by microinjecting primer, nucleotides, and enzyme into acutely dissociated cells from a defined region of rat brain. Further processing yields amplified antisense RNA. A second round of amplification results in greater than 10(6)-fold amplification of the original starting material, which is adequate for analysis--e.g., use as a probe, making of cDNA libraries, etc. We demonstrate this method by constructing expression profiles of single live cells from rat hippocampus. This profiling suggests that cells that appear to be morphologically similar may show marked differences in patterns of expression. In addition, we characterize several mRNAs from a single cell, some of which were previously undescribed, perhaps due to "rarity" when averaged over many cell types. Electrophysiological analysis coupled with molecular biology within the same cell will facilitate a better understanding of how changes at the molecular level are manifested in functional properties. This approach should be applicable to a wide variety of studies, including development, mutant models, aging, and neurodegenerative disease.

Animals↗
PubMed1992

In vivo cytotoxic T lymphocyte induction with soluble proteins administered in liposomes.

The in vivo induction of a CTL response usually requires that Ag be endogenously synthesized so that appropriate processing can occur. In most of the few examples where successful CTL induction was reported with proteins and peptides, unacceptable adjuvants or means of Ag formulation were used. In the present report, liposomes were used to incorporate the soluble proteins OVA and beta-galactosidase. This simple and convenient to use approach, which requires minimal amounts of Ag, results in priming for a CD8+ CTL response and the establishment of immunologic memory. The liposome approach may not only prove a convenient means of inducing CTL responses in vivo but may also be useful to study the mechanisms of Ag processing.

Animals↗
PubMed1992

Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial.

Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro.

Effective immunity to many infectious agents, particularly viruses, requires a CD8+ cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually not processed appropriately to induce CTL. In the present report, we have demonstrated that a potent primary CTL response against a soluble protein can be achieved by delivering antigen in pH-sensitive liposomes to dendritic cells (DC) either in vivo or in vitro. Since the pH-sensitive liposome delivery system is efficient and easy to use, the approach promises to be valuable both in the study of basic mechanisms in antigen processing, and as a practical means of immunization.

Animals↗
PubMed1992

Implications for the pathogenesis of aneurysm formation: metastatic choriocarcinoma with spontaneous splenic rupture. Case report and a review.

We report a case of ruptured intracranial aneurysm from metastatic choriocarcinoma in a patient presenting with intracerebral hemorrhage. Operative evacuation of the hematoma with clipping of a distal right middle cerebral artery aneurysm was performed. Postoperatively, the patient developed hypovolemic shock from spontaneous splenic rupture. Histopathologic examination of the cerebral aneurysm showed choriocarcinoma invading the vessel wall. Metastatic choriocarcinoma should be considered in the differential diagnosis of intracerebral or subarachnoid hemorrhage in women of child-bearing age.

Adult↗
PubMed1992

Interferon-induced reversible acute renal failure with nephrotic syndrome.

Although there has been considerable experience with interferons in clinical trials during the past decade, acute renal failure as a side effect of interferon treatments has rarely been reported. We report a case in which acute renal failure with nephrotic syndrome was associated with therapy with two types of interferons. We note incomplete return of renal function upon withdrawal of therapy.

Acute Kidney Injury↗
PubMed1992

Renal transplant sonography: correlation of Doppler and biopsy results in cellular rejection.

Seventy-one patients with allograft dysfunction had concomitant Doppler sonography and percutaneous biopsy. Forty-one had biopsy proven acute cellular rejection and eight had acute cellular rejection in combination with acute tubular necrosis. Real time ultrasonic appearance and various parameters of Doppler waveform were studied and compared with 30 controls who had a long period of stable function with no previous episodes of rejection or acute tubular necrosis (ATN). Morphological appearances were unhelpful in diagnosing rejection. A resistive index greater than 0.8 in the study group was highly specific for dysfunction but could not differentiate between acute rejection and ATN. However, two patients in the control group of normal transplants had a resistive index of 0.83. An early to mid diastolic notch was highly specific for acute rejection but of low sensitivity. It may be the only Doppler indication of cellular rejection and may be present when the resistive index is in the normal range.

Adolescent↗
PubMed1992

Inhibition of bone DNA and collagen production by surface-associated material from bacteria implicated in the pathology of periodontal disease.

Gentle extraction of oral bacteria implicated in the pathogenesis of periodontal disease, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, or Eikenella corrodens, with saline removes the extracellular components while leaving the bacteria intact. This readily-solubilized surface-associated material (SAM) has been demonstrated to significantly inhibit DNA and collagen synthesis by murine calvaria at concentrations as low as 10 ng/ml. DNA and collagen synthesis in isolated calvarial osteoblasts were also inhibited by these SAM preparations with similar dose responses. The inhibitory effect of these bacterial expolymers was blocked by 1 microM indomethacin. The potent inhibitory actions on bone synthesis of the SAM from these bacteria may contribute to the alveolar bone loss found in patients with periodontal disease.

Aggregatibacter actinomycetemcomitans↗
PubMed1992

Abnormal intracerebral thallium localization in a bacterial brain abscess.

A 56-yr-old man with a prior history of renal cell carcinoma had moderately intense abnormal localization of 201Tl-chloride in a solitary brain lesion which was discovered to be a bacterial abscess. The organisms isolated by culture included Actinomycosis odontolyticus, Peptostreptococcus and Hemophilus aphrophilus. Because of the clinical presentation, MRI characteristics and thallium scintigraphic findings, the lesion had been felt to represent either a primary or a metastatic neoplasm. This case illustrates the need for caution in the interpretation of thallium brain scintigram.

Bacterial Infections↗
PubMed1992

Liposomes as antigen delivery systems in viral immunity.

Since their first description, liposomes have been put to a wide variety of uses. Encapsulation or incorporation of antigens into liposomes markedly enhances the immunogenicity of the antigen. The type of immune response elicited by the liposome is found to depend on their chemical and structural properties. Immunization with viral glycoproteins encapsulated in liposomes has resulted in enhancement of the humoral response seen as a rise in the serum antibody levels which is several fold higher than that elicited by free antigen alone. Furthermore, liposome encapsulation of peptide antigens which are poor immunogens by themselves not only increases the immunogenicity of the peptide but also play an important role in delivery. The adjuvant effect afforded by liposomes can be further enhanced by the concomitant encapsulation of adjuvants like lipid A or muramyl tripeptide-phosphatidylethanolamine. Formation of liposomes with special characteristics such as pH sensitivity has resulted in the use of liposomes to deliver soluble antigen to the cytosol where it can undergo class I pathway of processing and presentation. Therefore liposomes could provide valuable tools to further understand the pathways of antigen processing and the requirements for induction of cell mediated immunity.

Animals↗
PubMed1991

Flow cytometric monitoring of glutathione content and anthracycline retention in tumor cells.

We have used an enzymatic (spectro-photometric) and a flow cytometric (GSH-MBCL) method to compare the glutathione (GSH) content of doxorubicin sensitive (P388) and resistant (P388/R-84) murine leukemic and human lung cancer cells. The flow cytometric analysis revealed that GSH-MBCL conjugate formation was dependent on glutathione-S-transferase (GST) activity. The human solid tumor cell lines exhibited extensive heterogeneity, high GSH content, and GST activity. In contrast to the enzymatic method, the flow cytometric method did not accurately reflect the 95% reduction in GSH content of cells treated for 24 h with 100 microM BSO. Possible reaction of MBCL with other sulfhydryl groups (other than GSH) in BSO-treated cells may be responsible for this discordance. We have also shown the feasibility of using dual parameter flow cytometry to monitor cellular anthracycline (daunorubicin) retention and GSH-MBCL conjugate fluorescence in human tumor cells. These two parameters, which measure drug retention and cellular detoxification, are believed to be the important determinants of chemoresistance in tumor cells.

Adenocarcinoma↗
PubMed1991

Radical proposal for the treatment of malignant astrocytoma.

The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles.

Astrocytoma↗
PubMed1991

Cloning and expression in Escherichia coli of a recA homologue from Mycobacterium tuberculosis.

A 3.8 kb PstI fragment of Mycobacterium tuberculosis was cloned in a recA-deleted Escherichia coli by selecting transformants with increased EMS resistance. The cloned fragment restored homologous recombination in Hfr crosses and conferred resistance to long wave (302 nm) but not short wave (254 nm) UV light. E. coli containing the 3.8 kb PstI fragment produced a 38-40 kDa protein which cross-reacted with antibodies raised against the E. coli RecA protein. The cloned DNA thus probably encodes a RecA homologue.

Antibodies, Bacterial↗
PubMed1991

Respi-Care. An innovative home care program for the patient with chronic obstructive pulmonary disease.

The purpose of the present study was to evaluate the effectiveness of a hospital-based home care program for a group of patients with severe COPD. Respi-Care was a multidisciplinary home care program administered by Norwalk Hospital in cooperation with the public health nursing departments of the city of Norwalk and the town of Wilton, Conn. The overall goal of Respi-Care was to provide more comprehensive home care services to patients previously requiring frequent hospitalizations by combining the advantages of hospital resources and community agencies through a unique cooperative effort. Preprogram and on-program data were collected on the following variables for the 48 months of Respi-Care operation: hospitalizations; hospital days; emergency room visits; home care services; and the costs of these services. Costs of operating the Respi-Care program were included in on-program data. Seventeen subjects completed 320.5 months on Respi-Care. Each subject was matched to an equal length of time prior to entering the program, for a total of 641 months analyzed. There were 88 preprogram hospitalizations for the group; hospitalizations while participating in Respi-Care dropped to 53 (p = 0.022; paired t statistics). On-program hospital days showed a significant decrease, from 1,181 preprogram days to 667 on-program days (p = 0.024). Emergency room visits decreased from 105 before the program to 64 during the program (p = 0.017). Costs of care also decreased. Costs for hospitalizations, emergency room visits, and home care fell from $908,031 to $802,999, resulting in a $105,032 savings or $328 per patient per month.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Intracranial cystic meningioma.

Two cases of intracranial cystic meningiomas are reported. Neuroradiological and intraoperative diagnoses in both cases were cystic astrocytoma. However routine biopsy during the intra-operative period and an accurate interpretation during frozen-section will establish the diagnosis of cystic meningioma. Complete excision of cyst wall of the meningioma during the surgery will minimise the incidence of recurrence of these benign tumours.

Adult↗