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Biomedical subjects

R Murali

Publications and source records attributed to R Murali.

At least 19 recordsLinked to original sources
PubMed1995

Mutagenesis of the putative alpha-helical domain of the Vpr protein of human immunodeficiency virus type 1: effect on stability and virion incorporation.

vpr is one of the auxiliary genes of human immunodeficiency virus type 1 (HIV-1) and is conserved in the related HIV-2/simian immunodeficiency virus lentiviruses. The unique feature of Vpr is that it is the only nonstructural protein incorporated into the virus particle. Secondary structural analysis predicted an amphipathic alpha-helical domain in the amino terminus of Vpr (residues 17-34) which contains five acidic and four leucine residues. To evaluate the role of specific residues of the helical domain for virion incorporation, mutagenesis of this domain was carried out. Substitution of proline for any of the individual acidic residues (Asp-17 and Glu-21, -24, -25, and -29) eliminated the virion incorporation of Vpr and also altered the stability of Vpr in cells. Conservative replacement of glutamic residues of the helical domain with aspartic residues resulted in Vpr characteristic of wild type both in stability and virion incorporation, as did substitution of glutamine for the acidic residues. In contrast, replacement of leucine residues of the helical domain (residues 20, 22, 23, and 26) by alanine eliminated virion incorporation function of Vpr. These data indicate that acidic and hydrophobic residues and the helical structure in this region are critical for the stability of Vpr and its efficient incorporation into virus-like particles.

Amino Acid Sequence↗
PubMed1995

Malignant teratocarcinosarcoma of the sphenoid sinus.

We have presented the first reported case of malignant teratocarcinosarcoma arising in the sphenoid sinus treated successfully with surgery and radiation therapy. The patient shows no signs of recurrence 5 years after surgery. The combined head and neck/neurosurgical approach using complete rhinotomy and medial maxillectomy with transsphenoid/transethmoid approach is advocated for sphenoid sinus tumors of this type.

Carcinosarcoma↗
PubMed1994

The refined crystal structure of hexon, the major coat protein of adenovirus type 2, at 2.9 A resolution.

The crystal structure of hexon, the major coat protein from adenovirus type 2, has been refined at 2.9 A resolution. Hexon is a homo-trimer (molecular mass 3 x 109,077 Da) and crystallizes in the cubic space group P2(1)3, with a cell edge of 150.5 A. There are four molecules in the unit cell so that the crystallographic asymmetric unit contains one subunit of the trimer. The electron density in most regions is well-defined and 880 amino acid residues, of the 967 in this unusually long polypeptide chain, have been located and fitted. The N terminus (1 to 43) and three internal stretches (192 to 203, 270 to 291 and 444 to 453) are not defined, and a stretch (168 to 207) with unclear side-chain density is modelled as poly(Ala/Gly). The current refined model, consisting of 6943 non-hydrogen protein atoms and 85 water molecules, yields an R-factor of 19.9% for 18,176 reflections in the resolution range 5.0 to 2.9 A. The model has reasonable geometry with root-mean-square deviations from ideal bond lengths of 0.022 A and angle-related 1-3 distances of 0.056 A. The overall shape of the trimeric hexon molecule is unusual and may be divided into a pseudo-hexagonal base rich in beta-structure, and a triangular top formed from three long loops containing some secondary structure. The base contains two similar pedestal domains, P1 and P2, each of which is a flattened eight-stranded beta-barrel with the "jelly-roll greek key" topology characteristic of other viral coat proteins. P1 and P2 are related by an approximate 6-fold operation about the molecular 3-fold axis so that six barrels form the walls of the tubular hexon base. The hexon bases form close-packed p3 arrays on each facet of the icosahedral adenovirus virion. Unlike other viral capsids, the barrel axes are almost perpendicular to rather than parallel with the capsid surface. The hexon top, which consists of intimately interacting loops emerging from P1 and P2 in the base, has a triangular outline and so does not exhibit the pseudo-symmetry of the base. The structure of the hexon trimer shows how economically it meets the demands of its function as a stable protective viral coat, reveals the significance of the special features in its unusual amino acid sequence, and explains its biochemical and immunological properties. The molecule is hollow, with a large central cavity, and so has a high effective volume for its mass.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1994

Crystallization and preliminary X-ray analysis of human alpha-galactosidase A complex.

Human alpha-galactosidase A (alpha-D-galactoside galactohydrolase; EC 3.2.1.22), the glycosylated lysosomal enzyme deficient in Fabry disease, has been crystallized as a complex with the inhibitor N-6-aminohexanoyl-alpha-D-galactopyranosylamine. The "hanging drop" method of vapor diffusion was used to grow crystals from solutions containing 50 mM sodium phosphate (pH 4.0 to 4.5), 120 to 170 mM ZnCl2 and 8 to 10% polyethylene glycol 3350. X-ray diffraction data collected from these crystals indicate that the crystals belong to the orthorhombic space group C222(1) with cell dimensions of a = 93.8 A, b = 141.1 A and c = 184.4 A. The crystals diffract to a resolution of 3 A and native data have been collected to 3.5 A resolution. Assuming one dimer per asymmetric unit with a total molecular mass of 110 kDa (with oligosaccharide chains), the Matthews' coefficient is Vm = 2.77 A3/dalton corresponding to a solvent content of 55% (v/v). The self-rotation function reveals that a non-crystallographic 2-fold axis relates the subunits of each dimer.

Crystallization↗
PubMed1994

Sequence and structural analysis of murine adenovirus type 1 hexon.

The genomic region encoding the major capsid protein (hexon) of murine adenovirus type 1 (MAV-1) has been isolated and sequenced. The sequence predicts a 908 residue MAV-1 hexon protein and is flanked by a portion of the upstream pVI gene and the downstream endoproteinase gene. The order of these genes and their location in the middle of the genome are the same as those found in other adenoviruses sequenced to date. Multiple sequence alignment with the other five known hexon protein sequences reveals an overall residue identity of 51% and residue conservation of 66%. In comparison with human adenovirus type 2 (Ad2), MAV-1 hexon has major deletions between residues 141 to 170, 270 to 284 and 446 to 455. Since these regions in the Ad2 hexon are partially exposed on the outer surface of the virion, they may represent type-specific antigenic determinants. The MAV-1 hexon sequence has been modelled using the known three-dimensional structure of the Ad2 hexon. The variable regions in which the mutations, deletions and insertions occur are located in the l1 and l2 loops of the molecule that form the protruding hexon towers on the external surface of the virion.

Amino Acid Sequence↗
PubMed1992

Spinal cord claudication from amyloid deposition.

We describe the clinical course of an 81-year-old woman who was evaluated for worsening symptomatology of spinal cord claudication. Diagnostic studies revealed mild lumbar canal stenosis at L3-4, severe stenosis at L4-5 with a myelogram-CT scan demonstrating a complete block at this level mainly a result of a hypertrophied ligamentum flavum. At surgery, the ligamentum was found to be thickened and to be causing severe compression of the dural tube. Pathologic studies of the excised ligamentum flavum revealed extensive amyloid protein deposition. The amyloid was not further classified with further medical evaluation and followup failing to identify any conditions associated with local or systemic amyloidosis.

Aged↗
PubMed1991

Effect of temperature on the myoglobin-facilitated transport of oxygen in skeletal muscle.

An analysis of thermal effects on the facilitative transport of oxygen in skeletal muscle fibers is presented. Steady-state mass and energy transport balances are written and solved analytically or numerically using a finite-difference procedure. It is shown that no significant spatial thermal gradients exist due to internal reactions or bulk conduction effects across a muscle fiber. At typical muscle conditions, it is predicted that increased global temperature reduces the fraction of oxygenated myoglobin, increases local oxygen concentrations, and increases the percentage of oxygen flux attributed to oxy-myoglobin. The maximum supportable oxygen consumption rate, mO2max, is defined as the highest consumption rate sustainable without developing anoxic regions at the center of the fiber. By considering only temperature sensitive effects within fibers, mO2max is found to increase slightly with temperature at low temperatures. This increase is due to thermal effects on the diffusion coefficients as opposed to effects associated with the kinetics of the myoglobin-oxygen reaction. If the simulations include the temperature effect associated with oxygen solubility in blood plasma, mO2max decreases with temperature. A sensitivity analysis was performed by varying the values of relevant parameters. The maximum consumption rate was least affected by parameters associated with the kinetic and equilibrium constants and most affected by the diffusion coefficients and the concentration of myoglobin.

Animals↗
PubMed1991

Cervical spine diastematomyelia in adulthood.

Adult cervical diastematomyelia is a rare malformation and is usually associated with posterior element anomalies. A case of isolated cervical diastematomyelia, which was initially thought to be a herniated cervical disc, is described. Diagnosis and surgical management are discussed.

Adult↗
PubMed1991

Neurovascular relationships of the root entry zone of lower cranial nerves: a microsurgical anatomic study in fresh cadavers.

The study describes the microsurgical neurovascular relationships of the root entry zone of lower cranial nerves in 23 cadavers. The vessel type, frequency of contact and site of contact on the root entry zone were analysed. Three types of vascular patterns (Types I-III) were found. Facial nerve: frequency of contact 31.8%; arterial contact 92.9%, Type I (lying across) 78.9%; anterior inferior cerebellar artery in 84.6%. Glossopharyngeal nerve: frequency of contact 23.9%; arteries 54.5%, veins 45.5%; posterior inferior cerebellar artery in 83.3% and Type II (loop) 50.1%. Vagus nerve: frequency of contact 26.1%, arteries 58.3%. Types II and III (passing through) formed 42.9% each. Hypoglossal nerve: frequency of contact 78.2%; vertebral artery 88.9%. No 'grooving' on any nerve was seen. Hence, 'contact' by a vessel at the root entry zone may not be significant in the etiology of lower cranial rhizopathies.

Adolescent↗
PubMed1990

Role of tryptophan repeats and flanking amino acids in Myb-DNA interactions.

The c-myb protooncogene codes for a sequence-specific DNA-binding protein that appears to act as a transcriptional regulator and is highly conserved through evolution. The DNA-binding domain of Myb has been shown to contain three imperfectly conserved repeats of 52 amino acids that constitute the amino-terminal end. Within each repeat, there are three tryptophans that are separated by 18 or 19 amino acids and are flanked by basic amino acids. To determine the role of tryptophans and the flanking basic amino acids in the DNA-binding activity of Myb proteins, we have selectively mutagenized individual tryptophans as well as some of the amino acid residues that flank these tryptophans. Replacement of these tryptophans with glycine, proline, or arginine abolished the DNA-binding activity whereas replacement with other aromatic amino acids or leucine or alanine did not appreciably affect this activity. On the other hand the replacement of two amino acids, asparagine and lysine, that flank the last tryptophan with acidic amino acids completely abolished their DNA-binding activity. These results are consistent with a model we present in which the tryptophans form a hydrophobic scaffold that plays a crucial role in maintaining the helix-turn-helix structure of the DNA binding domain. Basic and polar amino acids adjacent to these tryptophans seem to participate directly in DNA binding.

Amino Acid Sequence↗
PubMed1990

Primary neuroendocrine (Merkel cell) carcinoma presenting in the calvarium: case report.

A case of a primary neuroendocrine carcinoma arising in the calvarium and involving the bone, dura, and underlying brain is presented. The histopathology and immunohistochemical staining characteristics of tumor were consistent with those of Merkel cell tumor. The natural history and histopathology of this tumor are discussed, along with the possible explanation for the origin of this tumor in the calvarium.

Aged↗
PubMed1989

Chronic lymphocytic leukemia with hypothalamic invasion.

Headaches and a state of confusion developed in a patient with chronic lymphocytic leukemia (CLL). A computed tomography (CT) scan of the head showed a hyperdense lesion in the hypothalamus with obstruction of the foramina of Monro. Leukemic cells with monoclonal lambda B-cell markers were identified in the ventricular fluid at the time of surgical decompression. Similar cells were identified in the peripheral blood. This lesion has not been described as a complication of CLL, a disease that, unlike other leukemias, rarely has central nervous system manifestations.

Aged↗
PubMed1989

Fragments of lipoma ascending to the brain.

A 37-year-old woman underwent microsurgical resection of a "lipodermoid" tumor of the conus medullaris. Preoperative evaluation demonstrated an incidental finding of multiple small hypodense lesions in the cerebral ventricles and basal cisterns on cranial computed tomography. It is hypothesized that these lesions represent rostral subarachnoid embolization of flecks of fat from the conus lesion. Evidence supporting this hypothesis is presented.

Adult↗
PubMed1989

The adenovirus type 40 hexon: sequence, predicted structure and relationship to other adenovirus hexons.

The gene encoding the major capsid protein (hexon) of human adenovirus type 40 (Ad40) has been isolated and sequenced. Comparison of the predicted amino acid sequence of the Ad40 hexon with the corresponding polypeptide of the human enteric adenovirus, Ad41, reveals an overall identity of 88%. The majority of the changes in sequence are located in two areas, amino acids 131 to 287 and 390 to 425. Regions in the hexon protein that vary between Ad40 and Ad41 (subgroup F) were the same regions that varied between Ad2 and Ad5 (subgroup C) suggesting that these areas of the protein represent type-specific antigenic determinants. Other areas were conserved within members of a subgroup but varied between subgroups. Fitting of the Ad40 hexon sequence to the known three-dimensional structure of the Ad2 hexon demonstrates that the variable regions are located in the 1(1), 1(2) and 1(4) loops that form the surface of the virion. Of major significance is the absence in Ad40 of the highly acidic region present in both Ad2 and Ad5. In Ad2 this region stretches down into the D-strand of the beta-barrel forming the P1 domain. Molecular modelling indicates that the amino acids in Ad40 which correspond to the acidic region of Ad2 can also be accommodated in the eight-stranded beta-barrel, thereby maintaining the integrity of the barrel. Since the acidic region is also absent from the hexon of Ad41, the sequence of amino acids that replaces the acidic residues may be responsible for some of the distinctive biological properties of the subgroup F adenoviruses.

Adenoviruses, Human↗
PubMed1989

Neurosurgical considerations in headaches.

The anatomic pathways for headaches are reviewed. Headaches from increased intracranial pressure, brain tumors, empty sella syndrome, spinal tap, infections of the brain and its coverings, collagen vascular disease, subarachnoid hemorrhage, trauma, and cervical spine disease are discussed.

Bacterial Infections↗