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Biomedical subjects

S Kapur

Publications and source records attributed to S Kapur.

At least 127 records · Page 7Linked to original sources
PubMed1996

Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor cell line, and EGF immunoreactive proteins are present at sites of metastasis in the stroma of lymph nodes and medullary bone.

Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at a frequency in excess of that which would be predicted by random tumor cell dissemination. In order to determine whether chemoattractants in these organs promote organ-specific metastasis, we utilized human cell lines derived from and/or related to these organs as sources of potential chemoattractants. Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1 (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1 prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition, secretory proteins from a human prostatic stromal cell line (hPS) and from the TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites represent organs of hematopoietic/lymphoid proliferation and activation, we undertook identification of specific cytokines present at these sites which may promote the chemomigration of prostate tumor cells. In this context, the cytokines interleukin-1 alpha, interleukin-2, interleukin-6, tumor necrosis factor-beta, transforming growth factor-beta, interferon alpha 2-a, and granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells through the Boyden chambers in a dose-dependent manner. Western blot analysis of secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1 identified EGF-immunoreactive proteins in all cases. In addition, EGF immunoreactivity was localized to the stroma of the human prostate, the osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line, and that EGF within the stroma of pelvic lymph nodes and medullary bone may act as a chemoattractant for prostate tumor cells, thereby facilitating the preferential formation of metastatic foci within these organs.

Bone Neoplasms↗
PubMed1996

Effects of self-generated sad mood on regional cerebral activity: a PET study in normal subjects.

This study investigated the cerebral regions modulated by self-generated sad mood in normal subjects. Eleven healthy men experienced a temporary sad mood by recalling sad personal memories. Two control states were used for comparison: a resting condition, and a condition involving the recall of affectively neutral personal events. Regional cerebral blood flow (rCBF) images were obtained using [15O]-H2O Positron Emission Tomography. A statistical comparison of the images during negative mood and neutral recall conditions revealed that sad mood was associated with a decrease in rCBF in the left dorsolateral prefrontal, left medial prefrontal, and left temporal cortex; no increase in activity was noted in this comparison. Our results are consistent with the noted left prefrontal decrease in metabolism found in depressed patients through a variety of methodologies; however, our results contrast with findings of increased left or bilateral prefrontal activity in transient induced negative mood states reported for women (George et al., 1995, Am J Psychiatry 152:341-341) and for mixed-gender (Pardo et al., 1993, Am J Psychiatry 150:713-719) subject groups. The study brings to light a number of methodological issues, including the crucial importance of the baseline condition used for the isolation of the emotional components of a given task.

Adult↗
PubMed1996

5-HT2 antagonism and EPS benefits: is there a causal connection?

This article examines the hypothesis that 5-HT2 antagonism ameliorates extrapyramidal side effects (EPS) induced by the blockade of D2 dopamine receptors by antipsychotics. Neuroanatomical and neurophysiological data confirm the existence of pathways whereby 5-HT2 antagonism may influence EPS. The experimental data in rodents is marginally positive, but shows that the net effect of 5-HT2 antagonism is dependent upon the precise conditions under which catalepsy is induced. The data in monkeys are mainly negative. Studies in patients who have received adjunct 5-HT2 antagonists in addition to typical neuroleptics lend some support the the hypothesis, but are not conclusive. It is reasoned that 5-HT2 antagonism plays no role in clozapine's freedom from EPS, but it may be responsible for risperidone's decreased propensity to cause EPS. The article concludes that there is support for a conditional role of 5-HT2 in decreasing EPS: 5-HT2 antagonists may delay the onset and decrease the severity of EPS but cannot totally eliminate its occurrence. The implications of these findings for the next generation of combined 5-HT2/D2 antagonists are discussed.

Animals↗
PubMed1996

The D2 receptor occupancy profile of loxapine determined using PET.

Positron emission tomography (PET) studies of typical neuroleptics suggest that 60% to 80% of striatal D2 occupancy may be sufficient for optimal clinical treatment of psychosis. Therefore, striatal D2 occupancy may be used as an index to determine the optimal dose range. Toward this end, we determined the in vivo D2 profile of loxapine, using [11C]-raclopride and PET. Seven patients selected from a clinical population were scanned while taking steady-state oral loxapine from 10 to 100 mg/day. Their D2 receptor occupancy was estimated by comparing them to age-matched data from neuroleptic-naive patients. The D2 receptor occupancy ranged from 52% to 90%, and there was a very strong relationship between dose and D2 occupancy, suggesting that 15 to 30 mg/day of loxapine would produce, the putatively optimal, 60% to 80% striatal D2 blockade. This dose range is much lower than that used in most clinical settings and points to the potential efficacy of loxapine at lower doses.

Administration, Oral↗
PubMed1996

The neural correlates of intentional learning of verbal materials: a PET study in humans.

The purpose of this study was to identify the brain regions invoked when subjects attempt to learn verbal materials for a subsequent memory test. Twelve healthy subjects undertook two different tasks: reading and encoding of word pairs, while they were being scanned using [15O]H2O positron emission tomography (PET). As expected, the encoding pairs were remembered much better (recall 39% vs. 8%; P < 0.001) than reading pairs in a subsequent memory test. The encoding scans, as compared to reading scans, showed activation of the left prefrontal cortex, the anterior cingulate cortex and the left medial temporal cortex. The left prefrontal activations were in two discrete regions: (i) a left anterior and inferior left prefrontal (Brodmann's areas 45, 46) which we attribute to semantic processing; and (ii) a left posterior mid-frontal region (BA 6, 44) which may reflect rote rehearsal. We interpret the data to suggest that when subjects use cognitive strategies of semantic processing and rote-rehearsal to learn words, they invoke discrete regions of the left prefrontal cortex. And this activation of the left prefrontal cortex along with the medial temporal region leads to a neurophysiological memory trace which can be used to guide subsequent memory retrieval.

Adult↗
PubMed1996

Serotonin-dopamine interaction and its relevance to schizophrenia.

OBJECTIVE: The therapeutic success of clozapine and risperidone has focused attention on the interaction between serotonin and dopamine systems as an avenue for superior therapeutics in schizophrenia. The authors review the neurobiological basis for this interaction and its clinical relevance. METHOD: The authors synthesized information from more than 100 published articles obtained through electronic and bibliography-directed searches. FINDINGS: The serotonin system inhibits dopaminergic function at the level of the origin of the dopamine system in the midbrain as well as at the terminal dopaminergic fields in the forebrain. Serotonergic antagonists release the dopamine system from this inhibition. This disinhibition of the dopamine system in the striatum may alleviate neuroleptic-induced extrapyramidal symptoms, and a similar disinhibition in the prefrontal cortex may ameliorate negative symptoms. However, the benefits of combined serotonergic-dopaminergic blockade may be observed in only a narrow dose range and may be lost with doses that produce suprathreshold dopaminergic blockade. CONCLUSIONS: Serotonergic modulation of dopaminergic function provides a viable mechanism for enhancing therapeutics in schizophrenia, but much remains unclear. Future research will have to establish the existence of this interaction in humans in vivo, specify the conditions under which it leads to optimal therapeutic benefits, and explore the possibility of using specific serotonergic treatments as flexible adjuncts to typical neuroleptics, rather than the present trend toward using single drugs with combined actions.

Animals↗
PubMed1996

High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET study.

OBJECTIVE: The purpose of this study was to determine the dopamine D2 receptor occupancy induced by low-dose haloperidol treatment in a prospective trial. METHOD: Seven patients with schizophrenia were treated with 2 mg/day of haloperidol for 2 weeks, and D2 receptor occupancy was measured by [11C]raclopride and positron emission tomography. RESULTS: The patients showed high levels of D2 occupancy (53%-74%); five of them showed substantial clinical improvement, and none showed important side effects. CONCLUSIONS: The findings demonstrate that low doses of haloperidol induce D2 receptor occupancies that are in the putative therapeutic range. In combination with recent empirical trials, these findings should encourage clinicians to initiate treatment of psychotic episodes with low (2-4 mg haloperidol equivalent) doses of typical neuroleptics, particularly for first-episode patients.

Adult↗
PubMed1996

Regulation of the anti-allograft response by targeting the CD2 antigen: a potential strategy for the creation of transplant tolerance.

Activated T cells playa central role in the rejection of histoincompatible organ allografts. Studies of trans- membrane signaling requirements ofT cells, by identifying molecular and cellular mechanisms ofT-cell activation, can lead to rational therapeutic strategies for the regulation of the anti-allograft response. A clear consensus exists that the primary signal for T-cell activation is generated as a consequence of the in- teractions among the T-cell receptor for antigen (TCR)I cluster designation 3 (CD3) complex and the antigenic peptide presented in the context of major histocompatibility complex (MHC) proteins expressed on the sur- face of the antigen-presenting cells (APCs). '-7 The TCR/CD3-dependent signaling is necessary but insufficient in itself to fully activate normal human primary (quiescent) T cells, and additional costimulatory signals are required for full activatiori.

Journal Article↗
PubMed1996

Host immune response in chlamydial cervicitis.

In order to study host immune responses to Chlamydia trachomatis infection in patients with chlamydial cervicitis, lymphoproliferative responses to purified protein derivative (PPD) and Chlamydia trachomatis antigen (elementary bodies) were studied in 15 patients and 10 normal control subjects. A significant lymphoproliferation of peripheral blood mononuclear cells (PBMC) was obtained with PPD and C. trachomatis antigen (P < 0.001) as compared to unstimulated PBMC showing that antigen-reactive T-cells are present in patients. There was no significant difference in the lymphoproliferation response to C. trachomatis in patients as compared to control subjects suggesting that the cell-mediated immune (CMI) response in peripheral blood is not altered in chlamydial cervicitis. Inhibition of IL-2 production in cervical secretions ranged from 44 to 84% in patients with chlamydial cervicitis while supernatants derived from PBMC stimulated with PPD failed to show inhibition. However, there was no inhibition of IL-2 production in secretion or supernatants stimulated with PPD in control subjects, thereby showing that local cell-mediated immunity is impaired in patients. Significant C. trachomatis specific IgA antibodies, in cervical secretions, were present in only three of 15 patients. C. trachomatis specific IgG, IgM and IgA were detected in the serum of most patients, suggesting that serum antibodies do not confer immunity at the local site. We conclude that although circulating antigen-reactive T-cells are present in chlamydial cervicitis patients, absence of protective antibody as well as impairment of local cell-mediated immunity may be responsible for alteration of the mucosal defence mechanism against chlamydial infection.

Adult↗
PubMed1995

Functional brain maps of retrieval mode and recovery of episodic information.

Positron emission tomography (PET) was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and those related to actual recovery of stored information (ecphory). Healthy young subjects recognized words that had been encoded with respect to meaning or the speaker's voice. Regardless of how the information had been encoded, recognition was associated with increased activation in regions in right prefrontal cortex, left anterior cingulate, and cerebellum. These activations reflect retrieval mode. Recognition following meaning encoding was specifically associated with increased activation in left temporal cortex, and recognition following voice encoding involved regions in right orbital frontal and parahippocampal cortex. These activations reflect ecphory of differentially encoded information.

Adult↗
PubMed1995

Dissociation of pathways for object and spatial vision: a PET study in humans.

A positron emission tomography (PET) study was conducted to determine which brain regions are differentially involved in visual object identification and object localization. Subjects engaged in a spatial task in which they matched the location of common objects, and an object task in which they matched the identity of common objects. In both tasks the stimulus arrangements used were of the same kind. Regional cerebral blood flow data showed that a right-sided region in the inferior parietal lobule was more activated during spatial than during object matching. In contrast, bilateral occipitotemporal regions, with the left more predominant, were more activated during object than spatial matching. These results provide support for Ungerleider and Mishkin's dual pathway model of vision and indicate important patterns of lateralization in the human visual system.

Brain↗
PubMed1995

Functional role of the prefrontal cortex in retrieval of memories: a PET study.

Retrieval of information from episodic memory involves the processes invoked by the attempt to remember (retrieval attempt) as well as processes associated with the successful retrieval of stored information (ecphory). Previous PET studies of memory have shown an activation of the prefrontal cortex in memory retrieval tasks, and we hypothesised that this activation represents retrieval attempt, not ecphory. This hypothesis was directly directed using [15O]H2 PET imaging in 19 healthy subjects who performed three matched tasks which involved different levels of retrieval attempt and ecphory. The results showed that retrieval attempt was associated with activation of the prefrontal cortex, right greater than left, while ecphory involved the posterior cortical regions. These findings illuminate the functional role of the different neuroanatomical regions involved in episodic remembering.

Adult↗
PubMed1995

Distinct neural correlates of visual long-term memory for spatial location and object identity: a positron emission tomography study in humans.

The purpose of the present study was to investigate by using positron emission tomography (PET) whether the cortical pathways that are involved in visual perception of spatial location and object identity are also differentially implicated in retrieval of these types of information from episodic long-term memory. Subjects studied a set of displays consisting of three unique representational line drawings arranged in different spatial configurations. Later, while undergoing PET scanning, subjects' memory for spatial location and identity of the objects in the displays was tested and compared to a perceptual baseline task involving the same displays. In comparison to the baseline task, each of the memory tasks activated both the dorsal and the ventral pathways in the right hemisphere but not to an equal extent. There was also activation of the right prefrontal cortex. When PET scans of the memory tasks were compared to each other, areas of activation were very circumscribed and restricted to the right hemisphere: For retrieval of object identity, the area was in the inferior temporal cortex in the region of the fusiform gyrus (area 37), whereas for retrieval of spatial location, it was in the inferior parietal lobule in the region of the supramarginal gyrus (area 40). Thus, our study shows that distinct neural pathways are activated during retrieval of information about spatial location and object identity from long-term memory.

Adult↗
PubMed1995

Encephalopathy with parkinsonian features in children following bone marrow transplantations and high-dose amphotericin B.

Encephalopathy, leukoencephalopathy, and secondary parkinsonism occurred in 3 children with refractory leukemia undergoing allogenic bone marrow transplantation (BMT) who were treated with high-dose amphotericin B for pulmonary aspergillosis or sinus aspergillosis that did not involve the nervous system. Treatment included high-dose cytosine arabinoside, cyclophosphamide, and total body irradiation prior to the BMT. The children developed a progressively worsening encephalopathy and parkinsonian features, characterized by resting tremor, cogwheel rigidity, and masklike facies. Neuroimaging studies showed cerebellar, cerebral, and basal ganglia atrophy, as well as frontal and temporal lobe white matter involvement. Two of the 3 patients recovered, although 1 has residual intellectual impairment. The third succumbed to non-central nervous system Epstein-Barr virus-lymphoproliferative disease and had autopsy-confirmed leukoenephalopathy.

Adolescent↗
PubMed1995

The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study.

Risperidone is a recently introduced neuroleptic distinguished by a decreased incidence of extrapyramidal side effects (EPS). The mechanism of its low EPS is unclear. Since it has been shown that EPS is related to the level of D2 receptor occupancy, we studied nine patients receiving 2-6 mg/day of risperidone using [11C]-raclopride PET scans in order to determine the in vivo D2 receptor binding characteristics of risperidone. The mean level of receptor occupancy was 66% at 2 mg; 73% at 4 mg; and 79% at 6 mg. Three patients, those with the highest receptor occupancies, exhibited mild EPS, though none required anitparkinsonian medications. Our results suggest that at doses of 4-6 mg the in vivo D2 receptor occupancy of risperidone is similar to that of typical neuroleptics and higher than that of clozapine. This would suggest that the EPS benefits of risperidone cannot be explained by a low D2 binding but may be related to its high 5-HT2 affinity. However, the emergence of EPS at higher levels of D2 receptor occupancy, in this study and in previous clinical trials, would suggest that risperidone's high 5-HT2 affinity provides only a relative protection from EPS. And once the D2 occupancy exceeds a certain threshold this 'relative' 5-HT2-mediated protection from EPS may be lost.

Adult↗
PubMed1995

Tumour necrosis factor-alpha-mediated dyscohesion of epithelial cells is associated with disordered expression of cadherin/beta-catenin and disassembly of actin filaments.

Tumour necrosis factor (TNF)-alpha induced, in a time- and dose-dependent fashion, dyscohesion (cell-cell dissociation) of the endometrial epithelial cells. TNF-alpha impaired the ability of cells to aggregate and to attain compaction. The cell-cell adherent junction is a specialized region of the plasma membrane where cadherin molecules act as adhesion molecules and actin filaments are densely associated with the plasma membrane through a well-developed plasmalemmal undercoat. Dyscohesion induced by TNF-alpha was associated with the disordered expression of cadherin/beta-catenin at the sites of cell-cell contact. In addition, within the time-frame that dyscohesion was induced, TNF-alpha down-regulated the expression of actin mRNA only at 100 ng/ml without modulating the overall amount of actin protein, its beta-isoform or the amount of ribosylated actin. However, TNF-alpha-mediated dyscohesion of epithelial cells was associated with loss of plasmalemmal undercoat as well as intracytoplasmic aggregates of F-actin and a simultaneous increase in G-actin. The effect of cytochalasin-B, which disrupts actin filaments on cell-cell binding, was less pronounced than the effect of TNF-alpha, suggesting that the effect of this cytokine on dyscohesion is not solely dependent on the disassembly of actin filaments. These findings show that the induction of disordered expression of adhesion molecules, as well as disassembly of actin filaments, are implicated in the dyscohesion induced by TNF-alpha.

Actins↗
PubMed1995

High-risk intrahospital transport of critically ill patients: safety and outcome of the necessary "road trip".

OBJECTIVE: Intrahospital transport of critically ill patients is often necessary for optimal patient care. However, transport of intensive care unit (ICU) patients within the hospital has been associated with a high rate of potentially detrimental complications. This study was designed to determine the occurrence rate of transport-related complications and to determine if these complications have any effect on patient morbidity and mortality. DESIGN: Prospective, cohort-matched study. SETTING: A 780-bed urban, university teaching hospital. PATIENTS: Seven hundred fifty-nine surgical ICU patients. INTERVENTIONS: One hundred seventy-five patients were transported out of the surgical ICU for diagnostic testing or operative interventions deemed necessary by their surgical or critical care team. MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores were determined 24 hrs after admission. Transport patients were stratified into low-risk and high-risk transport groups. Patients were considered a high-risk transport if they required positive end-expiratory pressure of > 5 cm H2O, a continuous infusion of dobutamine, or a continuous infusion of norepinephrine. The high-risk group was further stratified into three groups based on the number of defined treatment regimens required to maintain the patient during transport. The patients were then followed during their transport for any potentially detrimental complications, such as a need for an increased dose of vasoactive medications, loss of intravenous access, a need for additional ventilatory support, or cardiopulmonary arrest. APACHE-matched control cohorts were identified as patients who did not leave the surgical ICU. The overall occurrence rate of complications was similar in the two groups (low-risk group, 6.3%; high-risk group, 5.5%). The mortality rate for all transport patients was 28.6%, which was statistically higher (p < .01) than the mortality rate for all control patients (11.4%). However, there was no mortality as a direct result of a transport. The overall mortality rate (10.9%) of the low-risk group was not significantly different from the APACHE-matched controls (6.0%). The overall mortality rate (51.4%) in the high-risk group was significantly higher (p < .01) than the APACHE-matched controls, but was not statistically higher than predicted mortality (p = .416). Both the low-risk and the high-risk groups stayed in the surgical ICU three times as long as the APACHE-matched control cohorts. CONCLUSIONS: Intrahospital transport of critically ill patients is safe and carries a low risk of detrimental complications. Although patients requiring "high-risk" interventions experienced a higher mortality rate than did APACHE-matched controls, the increase in mortality does not appear to be directly related to the intrahospital transport. Patients requiring transport out of the surgical ICU are a more critically ill group of patients. These patients require a greater length of stay in the surgical ICU and may experience an increased mortality rate by virtue of the severity of their illness.

APACHE↗