Biomedical subjects
S Natarajan
Publications and source records attributed to S Natarajan.
A new curved vitreous cutter for managing phakic retinal detachment with proliferative vitreoretinopathy.
In the presence of proliferations anteriorly, adequate excision of the vitreous base is essential. To enable a good vitreous base excision, removal of lens often becomes necessary as it may be damaged while attempting to remove peripheral vitreous. To avoid damage or the need to remove the crystalline lens we have used a new modified curved vitreous cutter along with a wide angle observation system binocular indirect ophthalmomicroscope (BIOM). Use of BIOM during vitreous surgery enables easy viewing of the retinal periphery without the need for scleral depression. Sclerotomies are made as for any regular three-port vitrectomy procedure and the vitrectomy is carried out using the curved vitreous cutter, including the vitreous base, avoiding damage to the crystalline lens. The modified curved vitreous cutter is helpful in removing the peripheral vitreous without damaging the crystalline lens, giving the patient the advantage of intraocular lens implantation at a later date.
The effect of keyboard keyswitch make force on applied force and finger flexor muscle activity.
The design of the force-displacement characteristics or 'feel' of keyboard keyswitches has been guided by preference and performance data; there has been very little information on how switch 'feel' alters muscle activity or applied force. This is a laboratory-based repeated measures design experiment to evaluate the effect of computer keyboard keyswitch design on applied finger force and muscle activity during a typing task. Ten experienced typists typed on three keyboards which differed in keyswitch make force (0.34, 0.47 and 1.02 N) while applied fingertip force and finger flexor electromyograms were recorded. The keyboard testing order was randomized and subjects typed on each keyboard for three trials, while data was collected for a minimum of 80 keystrokes per trial. No differences in applied fingertip force or finger flexor EMG were observed during typing on keyboards with switch make force of 0.34 or 0.47 N. However, applied fingertip force increased by approximately 40% (p < 0.05) and EMG activity increased by approximately 20% (p < 0.05) when the keyswitch make force was increased from 0.47 to 1.02 N. These results suggest that, in order to minimize the biomechanical loads to forearm tendons and muscles of keyboard users, keyswitches with a make force of 0.47 N or less should be considered over switches with a make force of 1.02 N.
Large-cell change of hepatocytes in cirrhosis may represent a reaction to prolonged cholestasis.
Large-cell change of hepatocytes (LCC), also called liver cell dysplasia of large-cell type, is a set of cytologic changes comprising nuclear and cytoplasmic enlargement, nuclear pleomorphism, and multinucleation. This entity is encountered frequently on histologic or cytologic examination of specimens obtained from livers with a variety of chronic diseases and originally was thought to have a premalignant nature. Accumulating evidence, however, now suggests that LCC is merely a reactive change. Having often observed LCC in liver specimens with chronic biliary tract disease, that is, in livers where cholestasis preceded hepatocyte injury, we surmised that LCC may be a result of prolonged cholestasis. To determine whether there was any association between LCC and cholestasis, we examined microscopically a series of 400 nodules from 40 consecutive adult cirrhotic livers, resected on transplantation, and graded LCC and cholestasis semiquantitatively. LCC was present diffusely in cirrhotic nodules of 25 specimens (62.5%). Nine additional specimens (22.5%) had focal mild LCC. Usually, LCC and cholestasis occurred together, in the same cirrhotic nodules and in the same areas of nodules. There was a statistically significant association between the presence and grade of LCC and those of cholestasis (p < 0.0001; chi-square test). Within etiological categories of cirrhosis (chronic hepatitis; n = 28; alcoholic liver disease; n = 6; biliary disease: n = 6), the significance was maintained. We conclude that, in cirrhosis of different etiologies, LCC may represent a reactive change that results from prolonged cytoplasmic cholestasis.
Adenomatoid tumor of the heart: report of a case.
We report a case of an adenomatoid tumor involving the heart. The lesion was found incidentally at the time of cardiac surgery, measured 1.0 cm, and was poorly demarcated from the adjacent myocardium. Microscopically, the tumor consisted of aggregates of relatively large, epithelioid cells that coalesced to form tubular spaces and occasionally branched into anastomosing channels. The neoplastic cells were strongly immunoreactive with antibodies against cytokeratin. The pathologic features of this unusual cardiac tumor are diagnostic of an adenomatoid tumor, a relatively rare benign neoplasm of mesothelial origin usually found in association with the genital tract. Although rare cases of adenomatoid tumors found outside of the genital tract have been described, including two recently reported pleural tumors, it has not been described to involve the heart.
Functional and structural roles of the highly conserved Trp120 loop region of glucoamylase from Aspergillus awamori.
The functional role of a loop region, highly conserved among glucoamylase and other starch hydrolases which also includes the essential Trp120 of Aspergillus awamori, is investigated. Residues 121-125 of A. awamori glucoamylase were singly substituted, and their individual effects on catalytic activity and thermal stability were determined. The Arg122-->Tyr mutation displayed opposing effects for shorter and longer maltooligosaccharide substrates, K(m) decreasing for shorter substrates but increasing for longer substrates. The Pro123-->Gly mutation decreases the thermal stability of glucoamylase by 19 degrees C with little effect on activity. The Gln124-->His substitution decreases k(cat) for all substrates 10-15-fold. Gly121-->Thr and Arg125-->Lys had only minor effects on glucoamylase activity. While Arg122-->Tyr, Gln124-->His, and the previously constructed Trp120-->Phe [Sierks, M. R., Svensson, B., Ford, C., & Reilly, P. J. (1989) Protein Eng. 2, 621-625] glucoamylases have significantly reduced activity toward maltose hydrolysis, all mutations in the Trp120 loop region retain wild-type level activity toward alpha-D-glucosyl fluoride hydrolysis. The Trp120 loop region therefore plays a major role in directing conformational changes controlling the postulated rate-limiting product release step, even though only Trp120 is indicated to interact with acarbose in the crystal structure [Aleshin, A. E., Firsov, L. M., & Honzatko, R. B. (1994) J. Biol. Chem. 269, 15631-15639]. Side chains of residues 116, 120, 122, and 124 oriented in one direction play crucial roles in the enzyme mechanism, while side chains of residues 119, 121, 123, and 125, oriented in the opposite direction, play only minor roles.
Should percutaneous transluminal coronary angioplasty catheters be reused?
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Keyboard reaction force and finger flexor electromyograms during computer keyboard work.
This study examines the relationship between forearm EMGs and keyboard reaction forces in 10 people during keyboard tasks performed at a comfortable speed. A linear fit of EMG force data for each person and finger was calculated during static fingertip loading. An average r2 of .71 was observed for forces below 50% of the maximal voluntary contraction (MVC). These regressions were used to characterize EMG data in force units during the typing task. Averaged peak reaction forces measured during typing ranged from 3.33 N (thumb) to 1.84 N (little finger), with an overall average of 2.54 N, which represents about 10% MVC and 5.4 times the key switch make force (0.47 N). Individual peak or mean finger forces obtained from EMG were greater (1.2 to 3.2 times) than force measurements; hence the range of r2 for EMG force was .10 to .46. A closer correspondence between EMG and peak force was obtained using EMG averaged across all fingers. For 5 of the participants the force computed from EMG was within +/-20% of the reaction force. For the other 5 participants forces were overestimated. For 9 participants the difference between EMG estimated force and the reaction force was less than 13% MVC. It is suggested that the difference between EMG and finger force partly results from the amount of muscle load not captured by the measured applied force.
Endothelin analogs which distinguish vasoconstrictor and vasodilator ETB receptors.
[Pen 1,11, Nle7, Glu9, Ala18]-Sarafotoxin S6b (BMS-184696) and [Pen1,11, Nle7, Glu9, Leu18]-sarafotoxin S6b (BMS-184697) were synthesized with the aim of preparing ETB receptor antagonists. BMS-184696 was a potent ETA antagonist, an extremely potent vasoconstrictor ETB agonist, and a non-competitive vasodilator ETB antagonist with no agonist activity. BMS-184697 was a potent ETA antagonist, a potent vasoconstrictor ETB agonist, and a vasodilator ETB agonist with moderate potency. The ability of BMS-184696 to activate the vasoconstrictor ETB receptor but not the vasodilator ETB receptor, despite having high affinity binding to the vasodilator ETB receptor as evidenced by its antagonist activity, strongly suggests the existence of ETB receptor subtypes.
Inhibition of thrombin and SFLLR-peptide stimulation of platelet aggregation, phospholipase A2 and Na+/H+ exchange by a thrombin receptor antagonist.
A thrombin receptor has been described that is activated by thrombin cleavage generating a new N-terminus. The newly exposed SFLLR-containing "tethered-ligand" then activates the receptor. In these studies, we used 3-mercapto-propionyl-Phe-Cha-Cha-Arg-Lys-Pro-Asn- Asp-Lys-amide (Mpapeptide) as a thrombin receptor antagonist. This compound was capable of preventing both thrombin- and SFLLR-peptide-induced platelet aggregation with little effect on collagen-induced platelet aggregation. It also prevented thrombin- and SFLLRNP-induced calcium mobilization with little effect on thromboxane receptor-activated platelet Ca2+ mobilization. Platelet membrane GTPase could be activated by peptides that activated the thrombin receptor, and the thrombin receptor antagonist also prevented receptor-stimulated GTPase activity. Platelet phospholipase A2 (PLA2) activity (measured as the release of radiolabeled arachidonic acid) and Na+/H+ exchange activation were stimulated by alpha-thrombin and by SFLLR-containing peptides. Activation of both processes with low concentrations of thrombin required thrombin's anion-binding exosite, as they were not activated by similar concentrations of gamma-thrombin, and the alpha- and zeta-thrombin activation was blocked by peptides mimicking the C-terminal region of hirudin. Stimulation of PLA2 and Na+/H+ exchange by both thrombin and SFLLR-containing peptides was inhibited by the thrombin receptor antagonist Mpa-peptide. These results support the hypothesis that thrombin stimulation of PLA2 activity and Na+/H+ exchange occurs via activation of the thrombin tethered-ligand receptor. Moreover, these data are consistent with the tethered-ligand receptor mediating most actions elicited by low concentrations of alpha-thrombin involved in human platelet activation.
Cutaneous Mycobacterium kansasii infection: case report and review.
A case of cutaneous Mycobacterium kansasii infection is reported, and 28 similar cases are reviewed. Cutaneous infection may resemble sporotrichosis and is often associated with systemic illness, immunosuppression, skin pathology, or contact with contaminated water. Immunosuppressed patients with M. kansasii infection may present with atypical clinical features (such as cellulitis and seroma) and atypical histology (absence of granulomas), which may delay diagnosis and effective treatment. The incidence of disseminated M. kansasii infection, which has a worse prognosis, is higher among immunosuppressed patients. When M. kansasii infection is confined to the skin, the disease is usually indolent. Chemotherapy with a variety of agents, including traditional antituberculous agents as well as erythromycin, minocycline, and doxycycline, has been successful, although in vitro resistance to isoniazid and p-aminosalicylic acid is common. Reducing the dose of corticosteroids may be a beneficial adjunct to therapy for M. kansasii infection.
'Tethered ligand' derived pentapeptide agonists of thrombin receptor: a study of side chain requirements for human platelet activation and GTPase stimulation.
Proteolytic action of alpha-thrombin on human thrombin receptor results in cleavage of a portion of the N-terminus, thereby generating a 'tethered ligand' at the newly exposed N-terminus, which then activates the receptor in an intramolecular fashion. Agonist peptides incorporating the amino acid sequence of the newly exposed N-terminal portion of the cleaved receptor cause receptor activation without requiring prior cleavage of the receptor by thrombin. The pentapeptide amide Ser-Phe-Leu-Leu-Arg-NH2, which retains the N-terminal sequence of the 'tethered ligand' of the receptor, has been shown to be the minimum sequence to cause receptor activation. To understand the importance of the side chains of various residues within the pentapeptide amide, we carried out an extensive structure-activity study of the ability of peptides to stimulate gel-filtered platelet aggregation. In this study 106 pentapeptide amides were synthesized, utilizing naturally occurring L-amino acids, unnatural amino acids, D-amino acids and N-methyl amino acids for replacements. At position-1, charged residues (acidic or basic) were not tolerated, and the size and shape of the residue were important. Position-2 tolerated only aromatic residues. Position-3 accommodated various residues. A significant finding of this study was that two very different residues, [3-(2-naphthyl)]-L-alanine and L-arginine, when substituted for leucine residue at position-3, resulted in more active agonists. At position-4 aromatic and aliphatic residues were well tolerated, whereas basic and acidic residues were less tolerated. Position-5 mimicked position-3 in its ability to tolerate a wide range of residues.(ABSTRACT TRUNCATED AT 250 WORDS)
Postsurgical endophthalmitis: diagnosis and management.
Infectious endophthalmitis following intraocular surgery is a complication that could cause severe visual loss or loss of the eye. The categorisation of the event that led to intraocular infection will help the clinician to predict the infectious agent and begin appropriate therapy. Most of the cases of postsurgical endophthalmitis are seen following cataract surgery. It is important for all ophthalmologists, irrespective of specialisation and areas of interest, to be familiar with the management of endophthalmitis. This review briefly describes the facets of clinical and laboratory diagnosis, pathology, and management. While the different viewpoints in the management of endophthalmitis are mentioned in appropriate places, more attention is paid to present a rational approach to the management of endophthalmitis.
Granulomatous vasculitis in herpes zoster scars.
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Closure of a benign gastrocolic fistula on medical management.
Gastrocolic fistulae secondary to un-operated benign gastric ulcers are rare. We report a case of a large benign gastrocolic fistula diagnosed by colonoscopy, which was found to have healed over a short period of 3 weeks, while the patient was being prepared for surgery. He was on parenteral nutrition and intravenous cimetidine. The available literature is reviewed and an attempt is made to explain the closure of the fistula on medical treatment. A trial of medical management may be justified in patients with benign gastrocolic fistulae who are poor surgical risks.
Fetal compromise associated with extreme fetal bile acidemia and maternal primary sclerosing cholangitis.
BACKGROUND: Primary sclerosing cholangitis is a rare form of progressive biliary inflammation and fibrosis of unknown etiology that ultimately destroys the liver, leading to cirrhosis, liver failure, and death. Only one prior case has been reported in pregnancy. CASE: Our patient had the diagnosis of primary sclerosing cholangitis made 2 years before conception. Her course was remarkable for retroplacental hemorrhage at 14-16 weeks and preplacental hemorrhage at 28-34 weeks, with fetal growth retardation, spontaneous premature rupture of the membranes, meconium-stained amniotic fluid, fetal bradycardia, and peripartal exacerbations of her disease. Most uniquely, however, in our case the fetal compromise was associated with an extreme elevation of the bile acid level to greater than 2000 mg/dL in the fetal circulation. CONCLUSION: The extreme elevation of fetal bile acidemia at levels greater than 40 times normal in our case may well represent the pathophysiologic link between aberrations of maternal bile acid metabolism during pregnancy and fetal compromise.
In vitro activity of the herpes simplex virus type 1 protease with peptide substrates.
Herpes simplex virus type-1 (HSV-1) protease is responsible for proteolytic processing of itself and the virus assembly protein ICP35 (infected cell protein 35). Two proteolytic processing sites within the protease have recently been identified between Ala247 and Ser248 and between Ala610 and Ser611. In this report we demonstrate that peptides corresponding to each of these cleavage sites are substrates for recombinant HSV protease-glutathione S-transferase fusion protein in vitro by high performance liquid chromatography analysis of cleavage reactions. Analysis of the products by fast atom bombardment-mass spectrometry confirmed that cleavage occurred at the expected position between the Ala and Ser residues of the substrate. Peptide cleavage was linear with respect to time and enzyme concentration and proceeded optimally at pH 8.0. A peptide that spans Ala99/Ser100 of the protease but does not correspond to a naturally occurring cleavage site was not a substrate for the protease in vitro confirming that sequence elements outside the conserved dipeptide sequence are required for substrate recognition and cleavage. Identification of P5-P8' as the minimal substrate peptide for the Ala610/Ser611 cleavage site revealed a requirement for residues flanking the conserved core P4-LVNA/S-P1' in substrate recognition and hydrolysis. Kinetic analysis with peptide P5-P8' yielded a Km of 190 microM and kcat of 0.2 min-1. Experiments with a panel of class-specific protease inhibitors were consistent with the protease being a member of the general class of serine proteases.
A 27 kd protein of E. coli promotes antitermination of replication in vitro at a sequence-specific replication terminus.
We have discovered a 27 kd protein of E. coli that binds to a terminator site (tau)-terminator protein (ter) complex and abrogates the replication fork-arresting activity of ter protein in vitro. The 27 kd protein also neutralizes the contrahelicase activity of ter protein, allowing dnaB helicase to unwind DNA past a tau-ter complex. The stimulatory activity of low levels of ter protein on helicase II is also abolished by the 27 kd protein. The binding of the 27 kd protein to a tau-ter complex does not appear to dissociate the ter protein from the DNA. Although the in vivo function of the 27 kd protein is unknown at this time, it has the major attributes of a novel replication antiterminator in vitro.