PubMed Health⌕ Search

Biomedical subjects

P Nathan

Publications and source records attributed to P Nathan.

At least 19 recordsLinked to original sources
PubMed2006

The place of VEGF inhibition in the current management of renal cell carcinoma.

Vascular endothelial growth factor (VEGF) is overexpressed in around 80% of patients with clear cell carcinoma of the kidney owing to the inactivation of von Hippel Lindau gene activity. VEGF stimulates angiogenesis and acts as an autocrine growth factor. A number of different agents are now available which target VEGF and its signalling pathways. A significant body of evidence has accumulated demonstrating that antagonism of VEGF and its downstream pathways is clinically useful in a significant proportion of patients with metastatic clear cell carcinoma of the kidney. Enough data is now available to recommend that patients with metastatic clear cell carcinoma of the kidney should at some point during the course of their disease be offered entry into a clinical trial enabling exposure to a targeted inhibitor of VEGF or its signalling pathways. Assuming early clinical trial data is substantiated by ongoing registration studies, efforts should be made to minimise the time taken between licensing and general availability of these active agents.

Antibodies, Monoclonal↗
PubMed2001

Factors in prison suicide: one year study in Texas.

UNLABELLED: The goal of the study was to examine psychopathology and stressors suffered by suicide victims, and to describe the characteristics of the suicides in the Texas Department of Criminal Justice between June of 1996 to June of 1997. Data on 25 completed suicides were collected from the records department. RESULTS: The authors identified 60% of the suicide victims with a history of psychiatric disorders. Seventy-six percent had been diagnosed with psychiatric disorders while incarcerated. The most frequent psychiatric disorders were mood disorders (64%), psychotic disorders (44%), personality disorders (56%), and comorbidity with a history of presentencing alcohol and drug abuse was common. Most of the victims experienced chronic and/or acute stressors of acute trauma, disrupted relationship, sentence hearing, and/or medical condition. We concluded that important factors associated with increased risk of prison suicide include psychiatric disorders, comorbid substance abuse, a history of suicide attempt, and chronic and/or acute stressors.

Adult↗
PubMed2000

Volume transmission as a mechanism of time-dependent sensitization to antidepressant therapy.

Administration of certain drugs such as antidepressants have been shown to produce a phenomenon known as time-dependent sensitization, a process in which the acute effects of the drugs sensitize and grow over time. While both preclinical and clinical studies have demonstrated time-dependent sensitization, it is still uncertain how it occurs. It is possible that the mechanism by which time-dependent sensitization occurs may be via a type of transmission in the brain known as volume transmission. Signals released via this transmission have properties that may explain the process of time-dependent sensitization.

Antidepressive Agents↗
PubMed2000

Can the cognitive enhancing effects of ginkgo biloba be explained by its pharmacology?

Pre-clinical and clinical studies have shown that the extract of the leaves of Ginkgo biloba has modest therapeutic potential as a cognitive enhancing drug. The pharmacology of Ginkgo biloba is complex due to its multiple active constituents. While Ginkgo biloba's cognitive enhancing effects have been attributed to its platelet-activating factor antagonistic effects and its free-radical scavenger activity, recent evidence suggests it may have direct effects on the cholinergic system which might explain both its acute and chronic cognitive enhancing effects. Ginkgo biloba's direct cholinergic actions include reduction of scopolamine-induced amnesia, modulation of pre-synaptic choline uptake and acetylcholine release, upregulation of post-synaptic muscarnic receptors and indirect effects on cholinergic function by modulation of the serotonergic system. The overall pharmacodynamic effect of Ginkgo biloba is likely due to a combination of platelet activating factor antagonistic effects, free radical scavenging activity and modulation of cholinergic function.

Acetylcholine↗
PubMed2000

A cognitive-behavioural, group-based intervention for social anxiety in schizophrenia.

OBJECTIVE: The objective of this study was to investigate the efficacy of group-based cognitive-behavioural therapy (CBT) for social anxiety in schizophrenia. METHOD: Patients with schizophrenia (20) with comorbid social anxiety were randomly assigned to the group-based CBT or wait-list control condition. Pre-, post- and 6-week follow-up ratings included measures of social anxiety and avoidance, mood and quality of life. RESULTS: The intervention group improved on all outcome measures and the control group showed no change in symptomatology. CONCLUSIONS: Group-based CBT is effective in treating social anxiety in schizophrenia.

Adult↗
PubMed1999

The experimental and clinical pharmacology of St John's Wort (Hypericum perforatum L.).

Hypericum (St John's Wort) is a plant that has been used for centuries as a medicinal herb. Pre-clinical animals studies suggest that hypericum is effective in three major biochemical systems relevant for antidepressant activity, namely the inhibition of the synaptic re-uptake system for serotonin (5-HT), noradrenaline (NA) and dopamine (DA). It is the only antidepressant capable of inhibiting the re-uptake of 5-HT, NA and DA with similar potencies. The potencies for monoamine re-inhibition and chronic changes in receptors are also consistent with changes seen with known antidepressants. Behavioral studies suggest that hypericum is active in pre-clinical animal models of depression with comparable effects to known antidepressants. Supporting the pre-clinical pharmacology and efficacy, many clinical studies have shown that hypericum has superior efficacy compared to placebo and comparable efficacy to standard antidepressants in the treatment of mild-to-moderate depression. The advantage of hypericum over other antidepressants may result from its favorable side-effect profile. Although pre-clinical and short-term clinical studies demonstrate antidepressant activity, the lack of long-term use and efficacy, and the heterogeneity of patients, interventions, extract preparations from previous clinical studies suggests that more careful and controlled studies are needed to determine the long-term efficacy of hypericum in mild-to-moderate depression.

Animals↗
PubMed1998

Correlation of segmental carpal tunnel pressures with changes in hand and wrist positions in patients with carpal tunnel syndrome and controls.

We investigated pressures at 1 cm intervals along the carpal tunnel in 39 patients with carpal tunnel syndrome (CTS) and 12 controls. Pressures were measured for relaxed and gripping hand positions in combination with neutral, extended, and flexed wrist positions. Patient pressures exceeded control pressures, were below the previously reported 30 mmHg threshold for four of five locations in the relaxed neutral position and were typically greater in extension than in flexion. In the neutral position, both patient and control pressures were slightly above threshold levels just distal to the tunnel. Maximum intratunnel pressures were generally found in the central part of the tunnel and minimum pressures in the distal tunnel. Gripping hand pressures in the tunnel were lowest with the wrist flexed. In both controls and CTS patients, only in the neutral wrist and relaxed hand positions were pressures highest at the point where nerve conduction studies have indicated the nerve is most likely to be compromised (in the midpalm just distal to the distal margin of the carpal tunnel).

Adult↗
PubMed1996

The human IL-11 receptor requires gp130 for signalling: demonstration by molecular cloning of the receptor.

We describe the molecular cloning of a cDNA for the alpha chain of the human IL-11 receptor (IL-11R alpha) and demonstrate the requirement of either the human or mouse gp130 molecule for signalling. cDNA clones encoding IL-11R alpha were isolated from a bone marrow cDNA library using a fragment from the murine IL-11R alpha as a probe. The human receptor was predicted to consist of 422 amino acids and was found to share 84% identity with the murine protein. In the extra-cellular region it exhibited a single hemopoietin domain with conserved cysteine residues and WSTWS motif. The transmembrane region was followed by a short cytoplasmic tail which did not contain a tyrosine kinase domain. Interaction of the human IL-11R alpha with murine gp130 was demonstrated: expression of the human IL-11R alpha in murine M1 cells which constitutively express murine gp130 (and murine LIF receptor), resulted in the generation of specific high-affinity binding sites for IL-11 (Kd = 250 pM). In addition, expression of the human IL-11R alpha in these cells permitted the induction of macrophage differentiation in response to IL-11. These results suggested that the human IL-11R alpha chain was able to form a functional receptor complex in association with murine gp130. The requirement of gp130 for signalling was confirmed by expression of the human IL-11R alpha in Ba/F3 cells. BaF3 cells that expressed the human IL-11R alpha alone showed binding of radiolabelled IL-11 but no proliferative response. Introduction of human gp130 into these cells resulted in high-affinity IL-11 binding sites and IL-11 dependent cellular proliferation. Thus these results demonstrated the absolute requirement of gp130 for signalling.

Amino Acid Sequence↗
PubMed1995

Vasodilatory state of decompensated cirrhosis: relation to hepatic dysfunction, ascites, and vasoactive substances.

The objective of this study was to determine the relations between the hallmark circulatory finding of decompensated cirrhosis, a reduced systemic vascular resistance (SVR), and the indices of hepatic decompensation, the accumulation of ascites, and the concentrations of various vasoactive substances. At a university-affiliated teaching hospital, eighteen hospitalized patients with cirrhosis and 18 age- and sex-matched healthy subjects were used. This was a case-control study. Measurements included cardiac dimensions and indices derived from echocardiograms and Doppler studies, abdominal ultrasound estimates of ascites, indices of hepatic function, and various serum (S) and urinary (U) substances. Results showed that cirrhotics had increased left atrial and left ventricular dimensions, left ventricular mass, heart rate, cardiac output (CO), transvalvular velocities, and a decreased SVR. SVR was related to hepatic dysfunction, as reflected by an abnormal prothrombin time ratio (r = -0.64, p = 0.006), and also related to overall severity of liver disease as estimated by the Child-Pugh score (r = -0.53, p = 0.044). Although cirrhotics with ascites generally had a reduced SVR, estimates of ascites were directly related to SVR (r = 0.57, p = 0.03) and inversely related to CO (r = -0.53, p = 0.04). Concentrations of S and U digoxin-like immunoreactive substance (DLIS) were also increased, but the concentrations of S glucagon and estradiol were not elevated. The accumulations of S and U DLIS, S glucagon, and S estradiol were all related to hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Mood disorders in children with oppositional defiant disorder: a pilot study.

The nature and prevalence of comorbid mood disorders were explored in a group of 28 latency-age children diagnosed with oppositional defiant disorder. Findings are preliminary in nature but suggest that children with oppositional defiant disorder are at significant risk for low-grade depressive illness and that this may commonly be overlooked in the presence of their primary disorder's more overt symptoms.

Child↗
PubMed1993

Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.

The search for tumour-specific markers is one of the chief goals in cancer biology. We show that the translocation t(12;16)(q13:p11) in malignant myxoid liposarcoma can be a fusion of the CHOP dominant negative transcription factor gene with a novel gene, FUS, which can result in fusion of the FUS glycine-rich protein with the whole CHOP coding region. The data support the concept that protein fusion may commonly occur in solid tumours resulting in tumour-specific markers of potential clinical importance. The data also indicate the importance of transcription disruption in the pathogenesis of solid tumours.

Amino Acid Sequence↗
PubMed1992

Symptomatic angina secondary to coronary-subclavian steal syndrome treated successfully by percutaneous transluminal angioplasty of the subclavian artery.

Subclavian artery stenosis causing severely symptomatic angina in a patient with a previous left internal mammary artery bypass to the left anterior descending artery was treated successfully with percutaneous transluminal angioplasty. Baseline arteriography clearly revealed subclavian and coronary steal by evidence of competitive flow of nonopacified blood from the left vertebral artery. Although there was a difference of only 15 mm Hg between the right and left brachial arteries, there was a palpable difference in the upstroke of these pulses. The stenosis in the subclavian artery was successfully dilated with percutaneous transluminal angioplasty. Angiographic evidence of subclavian steal resolved following balloon dilatation, and the patient's angina was completely resolved.

Aged↗
PubMed1991

Varieties of sentence comprehension deficits: a case study.

In recent publications, Grodzinsky (1984, 1986, 1990) has offered a new theory of the disruption of sentence comprehension in so-called agrammatic aphasics. In these works Grodzinsky contends that his account, which is based in various ways on the formal apparatus of current syntactic theory (Chomsky, 1981), is an accurate and explanatory characterization of the preserved language of all those who present with both agrammatic sentence production and asyntactic sentence comprehension. We argue that this claim is not in accord with the facts. We present a detailed case study of the sentence comprehension performance of a patient who is clinically categorized as agrammatic. This patient's performance on full and truncated passives, and on subject- and object-cleft sentences fails each of Grodzinsky's predictions for these sentence types. We argue that whether there exists any patient who does exhibit the predicted performance pattern is also in serious doubt.

Aphasia, Broca↗
PubMed1988

Plasma proteolytic activity following burns.

Because a number of metabolic events which are triggered by proteolysis in the bloodstream are activated following trauma, net proteolytic activity (P.A.) in the plasma of 37 pediatric burned patients was measured. The P.A. assay involved incubating plasma with a radioiodinated protein substrate and counting the isotopic activity of the hydrolyzed fragments in the acid-soluble fraction. In patients, plasma P.A. increased in direct proportion to the extent of burn injury. To examine additional trends in plasma P.A. suggested by the patient P.A. data, we measured plasma P.A. in a burned rat model: circulating P.A. was significantly elevated at 6 hours and until at least 2 weeks postburn; infection with Pseudomonas and use of the proteolytic debriding agent, Travase, each further elevated this activity; the plasma P.A. was not directly derived from the burn site. We postulate that this elevated circulating P.A. triggers some of the pathologic as well as some physiologic sequelae which follow burn trauma.

Adolescent↗
PubMed1988

Identification of two new cell division genes that affect a high-molecular-weight penicillin-binding protein in Caulobacter crescentus.

Penicillin-binding proteins (PBPs) are membrane proteins associated with the synthesis of the bacterial cell wall. We report the characterization of 14 PBPs in Caulobacter crescentus, using in vivo and in vitro penicillin-binding assays and experiments to determine their possible role in cell division. New conditional cell cycle mutants were isolated by selecting cephalosporin-C-resistant mutants of the beta-lactamase strain SC1107 at 30 degrees C that are also defective in cell division at 37 degrees C. They fall into two classes, represented by strains PC8002 and PC8003. Strain PC8002 produced short cells arrested at all stages of cell division at 37 degrees C and was found to contain a high-molecular-weight PBP 1B which was temperature sensitive when assayed in vivo and in vitro. Strain PC8003 was blocked at an early stage of cell division and formed tightly coiled, unpinched filaments. This cephalosporin-C-resistant strain was also defective in PBP 1B, but only when assayed in vivo. PBP 1B behaved like a high-affinity PBP, and in competition assays, beta-lactams that induced filamentation bound preferentially to PBP 1B. These results and the phenotype of mutant PC8002 suggest that PBP 1B is required for cell division, as well as for cell growth, in C. crescentus. The behavior of strain PC8003 suggests that it contains a conditionally defective gene product that interacts in some way with PBP 1B at an early stage of cell division. None of the mutants showed an allele-specific PBP pattern when assayed in vitro at the nonpermissive temperature, but all of them displayed temperature-sensitive PBP 1C (102 kilodaltons) activity. Thus, it appears that PBP 1C is inhibited at 37 degree C as a consequence of filamentous growth.

Anti-Bacterial Agents↗