Biomedical subjects

J S Joseph

Publications and source records attributed to J S Joseph.

12 recordsLinked to original sources

PubMed2003

Occurrence of O-linked Xyl-GlcNAc and Xyl-Glc disaccharides in trocarin, a factor Xa homolog from snake venom.

Trocarin is a 46515-Da group D prothrombin-activating glycoprotein from the venom of the Australian elapid, Tropidechis carinatus. Amino acid sequencing and functional characterization of trocarin demonstrated that it is a structural and functional homolog of mammalian blood coagulation factor (F)Xa. In this study we show that, in contrast to mammalian Xa, which is not glycosylated, trocarin contains an O-linked carbohydrate moiety in its light chain and an N-linked carbohydrate oligosaccharide in its heavy chain. Mass spectrometry and sugar compositional analysis indicate that the O-linked carbohydrate moiety is a mixture of Xyl-GlcNAc-, GlcNAc-, Xyl-Glc- and Glc- structures linked to Ser 52. The N-linked carbohydrate on Asn 45 of the heavy chain is a sialylated, diantennary oligosaccharide that is located at the lip of the active site of the prothrombin activator.

Acetylglucosamine↗

PubMed2001

Tamulustoxin: a novel potassium channel blocker from the venom of the Indian red scorpion Mesobuthus tamulus.

We have characterized tamulustoxin, a novel 35-amino-acid peptide found in the venom of the Indian red scorpion (Mesobuthus tamulus). Tamulustoxin was identified through a [125I]toxin I screen, designed to identify toxins that block voltage-activated potassium channels. Tamulustoxin has also been cloned by RT-PCR, using RNA extracted from scorpion venom glands. Tamulustoxin shares no homology with other scorpion venom toxins, although the positions of its six cysteine residues would suggest that it shares the same structural scaffold. Tamulustoxin rapidly inhibited both peak and steady-state currents (18.9 +/- 1.0 and 37 +/- 1.1%, respectively) produced by injecting CHO cells with mRNA encoding the hKv1.6 channel.

Amino Acid Sequence↗

PubMed1999

Amino acid sequence of trocarin, a prothrombin activator from Tropidechis carinatus venom: its structural similarity to coagulation factor Xa.

Among snake venom procoagulant proteins, group II prothrombin activators are functionally similar to blood coagulation factor Xa. We have purified and partially characterized the enzymatic properties of trocarin, the group II prothrombin activator from the venom of the Australian elapid, Tropidechis carinatus (rough-scaled snake). Prothrombin activation by trocarin is enhanced by Ca2+, phospholipids, and factor Va, similar to that by factor Xa. However, its amidolytic activity on peptide substrate S-2222 is significantly lower. We have determined the complete amino acid sequence of trocarin. It is a 46,515-Dalton glycoprotein highly homologous to factor Xa and shares the same domain architecture. The light chain possesses an N-terminal Gla domain containing 11 gamma-carboxyglutamic acid residues, followed by two epidermal growth factor (EGF)-like domains; the heavy chain is a serine proteinase. Both chains are likely glycosylated: the light chain at Ser 52 and the heavy chain at Asn 45. Unlike other types of venom procoagulants, trocarin is the first true structural homologue of a coagulation factor. It clots snake plasma and thus may be similar, if not identical, to snake blood coagulation factor Xa. Unlike blood factor Xa, it is expressed in high quantities and in a nonhepatic tissue, making snake venom the richest source of factor Xa-like proteins. It induces cyanosis and death in mice at 1 mg/kg body weight. Thus, trocarin acts as a toxin in venom and a similar, if not identical, protein plays a critical role in hemostasis.

Amino Acid Sequence↗

PubMed1999

Amodal representation depends on the object seen before partial occlusion.

We demonstrate history-dependent effects in the amodal representation of partially occluded objects. The experience of seeing the fully visible objects before partial occlusion is shown to be influential in the way the objects are represented after occlusion has occurred. Using the method of ambiguous apparent motion correspondence to probe the extent of amodal continuation, bars of variable length were partly occluded by a moving rectangle. After a variable delay period, the part of the bars that remained visible underwent an apparent motion sequence. Subjects reported whether the perceived motion was horizontal or vertical. With a 1-s delay after occlusion, each of the five subjects tested showed a bias favoring motion in the direction of the elongated bars. These results indicate greater amodal continuation in the case of long bars after they have been occluded for an appreciable period of time. A control experiment varying the stereoscopic disparity of the occluder ruled out explanations based on two-dimensional effects, reinforcing the conclusion that the past history has a specific effect on amodal representations. With a delay of 2 s following occlusion, four of six subjects tested showed the history effect, indicating potentially longer durations for the effect, with individual differences in the duration. We conclude that the amodal representation of an object depends on the object seen before partial occlusion.

Humans↗

PubMed1998

Interferon-alpha treatment of posttransplant lymphoproliferative disorder in recipients of solid organ transplants.

Posttransplant lymphoproliferative disorder (PTLD) has been treated with decreased immunosuppression, antiviral medications, anti-B lymphocyte agents, radiation therapy, and/or chemotherapy. However, a standardized stepwise approach to treatment has not been previously evaluated. In the present study, 19 consecutive patients presenting to a single institution with newly diagnosed PTLD were treated according to a sequential protocol that consisted of (1) a reduction in immunosuppressive medications plus, if feasible, resection or definitive radiation therapy of localized disease, (2) interferon-alpha, and (3) systemic chemotherapy. Of the 3 patients presenting exclusively with localized disease, two were treated with resection of pulmonary parenchymal nodules and one was treated with radiation therapy to a paraspinous mass, without evidence of recurrence at a mean follow-up of 31 months (range, 8 to 46 months). Sixteen patients presented with PTLD not amenable to local therapy, and they were treated daily with 3x10(6) units/m2 subcutaneous interferon-alpha. Total regression of PTLD (defined as disappearance of the tumor mass by physical examination or computed tomography scanning) was found in 8 of 14 patients who received at least 3 weeks of interferon therapy. Interferon-alpha therapy was continued for 6 to 9 months in the eight patients judged to be responders. None of these patients have relapsed to date with the same neoplastic clone. Two patients, however, developed new neoplastic clones. Seven patients received systemic chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (n=1), EPOCH (etoposide, vincristine, and doxorubicin administered as a continuous infusion, with an intravenous bolus of cyclophosphamide and oral prednisone) (n=4), or EPOCH followed by DHAP (dexamethasone, cytarabine, and cisplatin) (n=2) after failure of interferon-alpha; five patients had a complete response. Only 1 of the 19 patients died of uncontrolled PTLD. These results suggest that the majority of solid organ transplant recipients who develop PTLD can be safely and successfully treated using a sequential approach to therapy.

Adult↗

PubMed1997

Attentional requirements in a 'preattentive' feature search task.

It is commonly assumed that certain features are so elementary to the visual system that they require no attentional resources to be perceived. Such 'preattentive' features are traditionally identified by visual search performance, in which the reaction time for detecting a feature difference against a set of distractor items does not increase with the number of distractors. This suggests an unlimited capacity for the perception of such features. We provide evidence to the contrary, demonstrating that detection of differences in a simple feature such as orientation is severely impaired by additionally imposing an attentionally demanding rapid serial visual presentation task involving letter identification. The same visual stimuli exhibit non-increasing reaction time versus set-size functions. These results demonstrate that attention can be critical even for the detection of so-called 'preattentive' features.

Attention↗

PubMed1997

Scaling effects in the perception of higher-order spatial correlations.

Human texture discrimination depends both on spatial-frequency content and on higher-order or multi-point correlations. Spatial-frequency discrimination exhibits a high degree of scale invariance over a range of several octaves, but the scaling behavior of sensitivity to higher-order correlation structure is unknown. We explored the scale dependence of texture discrimination for image ensembles which shared the same power spectrum, but differed in their higher-order correlations. Literally scaling the ensembles so that they occupy larger retinal regions results in discrimination performance that is largely independent of scale over a 3 octave range. Holding the display size constant and scaling the texture being sampled within the display over the same range produces performance that varies with scale appreciably. The ideal observer performance is computed, and the absolute efficiency is seen to be quite small, on the order of 10(-2)-10(-1). As the texture is scaled down, increasing the number of checks within the fixed display size, performance increases while the efficiency decreases. These dependencies remain when the stimulus onset asynchrony is increased from 50 to 500 msec. We created sets of textures which varied both in check number and correlation strength, for which ideal observer performance was equated. For the human observers, efficiency was significantly higher for textures with higher correlation strength, but fewer checks. These results are consistent with a model in which a fixed number of checks is processed in a scale-invariant manner, while the remainder of the display is processed much less efficiently.

Humans↗

PubMed1996

Involuntary attentional shifts due to orientation differences.

We tested the ability of orientation differences to cause involuntary shifts of visual attention and found that these attentional shifts can occur in response to an orientation "pop-out" display. Texture-like cue stimuli consisting of discrete oriented bars, with either uniform orientation or containing a noninformative orthogonally oriented bar, were presented for a variable duration. Subsequent to or partially coincident with the cue stimulus was the target display of a localization or two-interval forced-choice task, followed by a mask display. Naive subjects consistently showed greater accuracy in trials with the target at the location of the orthogonal orientation compared with trials with uniformly oriented bars, with only 100 msec between the cue and mask onsets. Discriminating these orientations required a stimulus onset asynchrony (SOA) of 50-70 msec. The attentional facilitation is transient, in most cases absent with a cue-mask SOA of 250 msec [corrected]. These results suggest that the preattentive character of some texture discrimination tasks with SOAs of only 100 msec is vitiated by the involuntary attentional shifts that are caused by orientation differences.

Adolescent↗

PubMed1994

A continuum of non-Gaussian self-similar image ensembles with white power spectra.

We introduce a scaling procedure that acts on visual textures to produce new textures having the same resolution, display size, and mean contrast power. We derive the form of the scaling fixed-point textures (image ensembles) resulting from repeated application of this scale transformation to the 'even' texture with an arbitrary amount of sporadic decorrelation. The result is a continuum of scaling fixed-point or 'self-similar' image ensembles, ranging from a strongly non-Gaussian white texture with higher-order spatial correlations at one extreme to Gaussian white noise at the other. The simple construction of a continuum of self-similar ensembles possessing phase correlations provides a tool for investigating human perception of structure in the absence of useful length scales. The fixed-point textures have luminance histogram differences, a direct result of their higher-order spatial properties. This suggests that scaling might afford an extension of our understanding of IID (independent identically distributed) texture discrimination (Chubb et al., J. Opt. Soc. Am. A 11, 2350-2374, 1994) to more general texture discrimination tasks in which spatial correlations play a role.

Form Perception↗

PubMed1992

Virtual intermediates in photosynthetic electron transfer.

We explore the possibility of virtual transfer in the primary charge separation of photosynthetic bacteria within the context of several types of experimental data. We show that the peak that might be expected in the virtual rate as electric fields vary the intermediate state energy is severely broadened by coupling to high-frequency modes. The Stark absorption kinetics data are thus consistent with virtual transfer in the primary charge separation. High-frequency coupling also makes the temperature dependence weak over a wide range of parameters. We demonstrate that Stark fluorescence anisotropy data, usually taken as evidence of virtual transfer, can in fact be consistent with two-step transfer. We suggest a two-pulse excitation experiment to quantify the contributions from two-step and virtual transfer. We show that virtual absorption into a charge transfer state can make a substantial contribution to the Stark absorption spectrum in a way that is not related to any derivative of the absorption spectrum.

Bacteria↗

PubMedDate not supplied

Procoagulant proteins from snake venoms.

Several procoagulant proteins from snake venoms have been isolated and characterized. They are either serine proteinases or metalloproteinases, which activate specific zymogens of coagulation factors and initiate the coagulation cascade. These procoagulant proteins are useful in treating various thrombotic and hemostatic conditions and contribute to our understanding of molecular details in the activation of specific coagulation factors. Recent studies have shown that the prothrombin activators with serine proteinase activity are structurally and functionally similar to mammalian coagulation factors. Their structural studies should provide us insight into prothrombinase complex formation. Here, we present an overview of snake venom procoagulant factors.

Animals↗

PubMedDate not supplied

Snake venom prothrombin activators homologous to blood coagulation factor Xa.

We have recently determined the complete amino acid sequence of trocarin, a group D prothrombin activator from the venom of Tropidechis carinatus (Australian rough-scaled snake). This proteinase is both functionally and structurally similar to mammalian blood coagulation factor Xa. It shows approximately 70% homology and possesses the characteristic Gla domain, two EGF domains and serine proteinase domain. To examine structure-function relationships, we generated a molecular model of trocarin based on a human factor Xa des-Gla crystal structure (1xka) as template. Based on known sites of interaction between mammalian factor Xa, factor Va and prothrombin, structure-function relationships of trocarin were explored. Unlike factor Xa, trocarin is glycosylated and has a large carbohydrate moiety at the entrance to its active site pocket. This might contribute to differences observed in the kinetics of hydrolysis of synthetic substrates by trocarin as compared to human factor Xa. A Ca(2+)-binding loop present in the heavy chain of factor Xa also seems to be lost in trocarin. In addition to its role in hemostasis, factor Xa shows other biological effects, including inflammation via its interaction with effector protease receptor-1 (EPR-1). Interestingly, the EPR-1 recognition site is distinctly different in trocarin, the functional consequences of which are being investigated.

Animals↗