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Biomedical subjects

S Nair

Publications and source records attributed to S Nair.

At least 217 records · Page 12Linked to original sources
PubMed1993

Recognition by and in vitro induction of cytotoxic T lymphocytes against predicted epitopes of the immediate-early protein ICP27 of herpes simplex virus.

The identification of herpes simplex virus type 1 (HSV-1) proteins and the minimal epitopes within these proteins which serve as targets for cytotoxic T lymphocytes (CTL) remains an important goal for the development of effective vaccine strategies. In this report, an H-2Kd allele-specific peptide-binding motif was used to locate putative CTL epitopes in the HSV-1 immediate-early protein ICP27, a protein previously identified as a major CTL target in the BALB/c mouse. Peptides 1 (amino acids 322 to 332) and 2 (amino acids 448 to 456) synthesized to represent two separate predicted CTL epitopes in ICP27 were able to sensitize target cells in vitro for recognition by HSV-1-specific CTL. Moreover, using a recently developed system to generate primary CTL responses in vitro, both peptides induced primary CTL which reacted with target cells expressing HSV-1. This system allowed us to verify the activity of two CTL epitopes in the ICP27 protein and holds promise as a rapid way of identifying immunogenic peptides from any protein molecule.

Animals↗
PubMed1993

Induction of primary, antiviral cytotoxic, and proliferative responses with antigens administered via dendritic cells.

Cytotoxic T lymphocytes (CTL) play an essential role in recovery from viral infections, but induction of CTL responses with nonreplicating antigens is difficult to achieve. Exogenous antigens, such as viral proteins and peptides, normally induce CD4+ T-cell responses unless appropriately delivered to the major histocompatibility complex class I antigen presentation pathway. In vitro studies performed to address this issue revealed a similar scenario, and primary CTL induction with nonreplicating antigens has rarely been reported. This study demonstrated primary antiviral CTL induction in vitro with exogenous antigens delivered in vivo to dendritic cells. This study also evaluated the efficacy of glycoprotein B peptide (free or encapsulated in liposomes), peptide-tripalmitoyl-S-glyceryl cysteinyl conjugate (acylpeptide), and glycoprotein B protein encapsulated in pH-sensitive liposomes as antigen delivery vehicles. Our results show that higher levels of cytotoxicity against herpes simplex virus type 1 resulted from exposure of dendritic cells to peptide-tripalmitoyl-S-glyceryl cysteinyl in liposomes. Macrophages treated in a similar manner were not effective stimulators for primary CTL induction. Our data have relevance to the understanding of mechanisms of antigen processing and presentation and the design of antiviral vaccines.

Animals↗
PubMed1993

Renal osteodystrophy of the cervical spine: neurosurgical implications.

Renal osteodystrophy describes the changes in bone physiology seen in renal failure. Traditionally, these changes resulted in mild neurological sequelae that were effectively managed medically. Despite the often severe destruction seen on x-ray, surgical therapy has not been reported extensively. With increasing numbers of long-term hemodialysis survivors, however, a newly recognized erosive spondyloarthropathy with extensive bony destruction is seen more frequently. These changes can mimic the radiographic appearance of osteomyelitis, not an uncommon sequela of hemodialysis patients; therefore, this diagnosis must be considered. Although renal osteodystrophy can be seen throughout the spine, reports of significant cervical spine involvement are uncommon. We present our experience with six cases of renal osteodystrophy of the cervical spine requiring surgical intervention for instability or cord compression. Osteomyelitis was present in two of the patients. The pathophysiology and radiographic characteristics of renal osteodystrophy and the incidence of osteomyelitis are discussed. Fusion techniques, including the use of anterior and posterior internal and external stabilization, are presented. These patients represent a therapeutic challenge for the neurosurgeon, given the underlying bone pathology.

Adult↗
PubMed1993

Prebiopsy localization of nonpalpable breast lesions.

Radiologically guided localization procedures are indicated pre-operatively when breast lesions are nonpalpable. The results of 42 percutaneous hookwire localizations over a period of 3 years are described. Of the total, 7 (17%) were found to be malignant. Biopsy was indicated by mammographically detected mass in 48%, by microcalcifications in 40% and by microcalcifications with an associated mass in 12%.

Adult↗
PubMed1993

Cellular distribution of hexa and trivalent chromium in Pseudomonas aeruginosa.

Binding of Cr to P. aeruginosa whole cells increased with an increase in positive charge of the chromium complexes used. Distribution of Cr bound from aqueous solutions of potassium dichromate--a Cr(VI) salt and basic chromium sulphate (BCS)--a Cr(III) salt [used for tanning which has 25% of Cr2O3 on weight basis and is of 33% basicity (one hydroxyl/Cr atom)] was more in soluble fraction (protein and nucleic acids) than in insoluble fraction (lipids, polyphosphates, polysaccharides, lipopolysaccharides and mucopeptides). Electron spin resonance spectrum of the cells exposed to hexavalent chromium revealed the presence of Cr(III) ion demonstrating a reduction of the same by the Pseudomoas. The infrared spectra of chromium exposed cell envelopes support that protein carboxylic sites and proteins are involved in binding Cr(III) and predominantly lipids in Cr(VI). Bound chromium could be removed chemically and the cells could then be reused as a biosorbent.

Cell Fractionation↗
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↗