Surviving childhood cancer: what next? Issues under consideration at the After Completion of Therapy (ACT) clinic in India.
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Adolescent↗
Biomedical subjects
S Goswami
Publications and source records attributed to S Goswami.
Childhood cancer survivors--living beyond cure.
Advances in diagnosis and treatment along with improved supportive care have contributed to the current survival rates for pediatric malignancies. Recent concept of a truly "cured child" in pediatric oncology envisages not only a biological cure of the disease but a child on par with peers in growth and development physically and in achievements and aspirations, both mentally and emotionally. Because of the young age of these survivors and their potential for longevity, the delayed consequences of therapy may have a serious impact on their lives and family at large than do the acute complications of the cytotoxic therapies that they had experienced. Though figures from India are not available, it has been estimated that, in USA, the prevalence of childhood cancer survivors is expected to increase from 1 in 900 persons among young adults to 1:250 persons by 2010. Although this constitutes a remarkable medical achievement, the late morbidity in this growing survivor population has become an area for concern. It is estimated that 50% of the survivors are likely to develop disabilities that alter the quality of life.
Adolescent↗
Courses of substance use and schizophrenia in the dual-diagnosis patients: is there a relationship?
BACKGROUND: Interrelationship of schizophrenia and substance use is complex and multifactorial. Examining the influence of various psychoactive substances on course of patients with pure dual-diagnosis schizophrenia may help to solve this riddle. AIM: To examine the relationship of the courses of substance use and schizophrenic symptomatology in substance abusing "dual-diagnosis" patients with schizophrenia. SETTINGS AND DESIGN: Outpatient Deaddiction and Treatment Center of a tertiary care hospital with a retrospective design. METHODS AND MATERIAL: Twenty-two substance abusing dual-diagnosis patients with schizophrenia were investigated regarding the course of substance use (abuse/dependence, use, non-use) and that of schizophrenia (psychotic, non-psychotic, in remission). A graphical representation of course of schizophrenia and substance abuse was made and their relationship studied by superimposition of respective graphs. STATISTICS: The Friedman two-way analysis of variance of ranks was applied to see the relationship between time spent by patients while on and off various substances. RESULTS: In five cases, the onset of schizophrenia preceded the onset of substance use. In seven out of 22 subjects, the schizophrenic exacerbation was clearly preceded by increase in substance abuse in the preceding two-twelve months. In none of the subjects decrease in substance use led to a decrease or increase in schizophrenic symptoms. CONCLUSIONS: Although substance use disorder preceded the onset of schizophrenic illness in the majority, and increase in substance abuse preceded schizophrenic exacerbation in one-third of dual-diagnosis patients, overall there was no evidence that the course of substance use was associated with that of schizophrenia after both disorders were diagnosed.
Adolescent↗
A novel dinuclear ruthenium complex bridged through a substituted phenazine ligand formed by ruthenium-promoted oxidative assembly of 1,3-diaminobenzene.
The reaction of [Ru(acac)3] (acac = acetylacetonate) with molten 1,3-diaminobenzene affords the crystalline monometallic compound [Ru(L1)-(acac)21 (1: L1 = N-(3'-aminophenyl)1,2-(3-amino)benzoquinone diimine) along with an unstable dimetallic compound [Ru2(mu-L2)(acac)4] (2: L2=N-4,6-bis(3'-aminophenyl)imino-3,5-diimino-hex-1-ene). Compound 2 transforms to a stable dimetallic compound [Ru2(mu-L3)(acac)4] (3: L3 = 2-amino-6(3'-aminophenyl)imino-9-imino-phenazine) in boiling 2-methoxyethanol. The above compounds are formed by ruthenium-mediated oxidative di- or trimerization of the diamine with the formation of several new C-N bonds. The products have been thoroughly characterized. FAB mass spectra, along with other physicochemical data, were used for their formulations. The compounds 1, 2, and 3 display intense peaks due to their parent molecular ions at m/z 512, 916, and 914, respectively. Final characterization of complex 3 was made by single-crystal X-ray structure determination. The structure of 3 confirmed the formation of three new C-N bonds and the bridging ligand L3 from 1,3-diaminobenzene. The conversion, 2 --> 3 is an oxidative ring-closure reaction, which is associated with dehydrogenation reactions. The monometallic compound 1, showed a reversible metal-based anodic response at 0.35 V. On the other hand, both the compounds 2 and 3 showed a pair of well-resolved metal-based anodic oxidations, for which the separation between the two successive anodic responses were high (>0.4 V). In addition, all of them showed multiple cathodic responses that were in the range -1.0 to -2.0 V.
Journal Article↗
Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens.
BACKGROUND: The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors. METHODS: In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells. RESULTS: Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%. CONCLUSIONS: The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining.
Adenocarcinoma↗
An atypical intronic deletion widens the spectrum of mutations in hereditary spastic paraplegia.
OBJECTIVE: To identify the genetic mutation responsible for autosomal dominant spastic paraplegia (HSP) in a large family with a "pure" form of the disorder. BACKGROUND: The disease locus in most families with HSP is genetically linked to the SPG4 locus on chromosome 2p21-p22. Some of these families have mutations in the splice-site or coding regions of the spastin gene (SPAST). METHODS: Linkage and mutational analyses were used to identify the location and the nature of the genetic defect causing the disorder in a large family. After the disease phenotype was linked to the SPG4 locus, all 17 coding regions and flanking intronic sequences of SPAST were analyzed by single-strand conformation polymorphism analysis (SSCP) and compared between affected and normal individuals. Direct sequencing and subcloning methods were used to investigate incongruous mobility shifts. RESULTS: The genomic sequence of SPAST showed a heterozygous four--base pair deletion (delTAAT) near the 3' splice-site of exon three in all 11 affected individuals but not in 21 normal family members or in 50 unrelated controls (100 chromosomes). CONCLUSIONS: This study identifies an atypical intronic microdeletion in SPAST that causes HSP and widens the spectrum of genetic abnormalities that cause the disorder.
Adult↗
Pharmacologic properties of brewery dust extracts in vitro.
STUDY OBJECTIVES: To study the effects of extracts of brewery dust on isolated guinea pig tracheal smooth muscle in vitro. DESIGN: Parallel pharmacologic intervention on guinea pig tracheal rings that were obtained from the same animal. SETTING: Mount Sinai School of Medicine, Department of Pulmonary Medicine. MATERIAL: The isolated guinea pig tracheal tissue of 18 guinea pigs. INTERVENTIONS: Pretreatment of guinea pig rings by mediator-modifying agents before challenge with the brewery dust extracts. MEASUREMENTS AND RESULTS: The effect of brewery dust extracts on isolated guinea pig tracheal smooth muscle was studied using water-soluble extracts of dust obtained from brewery materials, including hops, barley, and brewery yeast. Dust extracts were prepared as a 1:10 (wt/vol) aqueous solution. Dose-related contractions of nonsensitized guinea pig tracheas were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin and n-formyl-methionyl-leucyl-phenylalanine), but these agents were not thought to contribute directly to the constrictor effect of the dusts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with the following drugs known to modulate smooth muscle contraction: atropine; indomethacin; pyrilamine; LY171883; nordihydroguaiaretic acid; captopril; thiorphan; verapamil; and TMB8. The constrictor effects of the dust extracts were inhibited by a wide variety of agents, the patterns of which depended on the dust extract. Atropine consistently and strikingly reduced the contractile effects of these extracts. These observations may suggest an interaction of the extracts with parasympathetic nerves or, more directly, with muscarinic receptors. The inhibition of contraction by the blocking of other mediators was less effective and varied with the dust extract. CONCLUSIONS: We suggest that brewery dust extracts cause a dose-related airway smooth muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and, possibly, cholinergic receptors. This effect is not dependent on presensitization of the guinea pigs.
Animals↗
Troger's base molecular scaffolds in dicarboxylic acid recognition.
Artificial receptors (1-5) have been designed and synthesized from simple precursors. The chain length selectivity studies of dicarboxylic acids within the cavities of new fluorescent Troger's base molecular frameworks (1-3) have been carried out with a critical examination of their role of rigidity as well as flexibility in selective binding in comparison to receptor 5. The chiral resolution of the racemic Troger's base receptors (1 and 2) by chiral recognition with (+)- camphoric acid using hydrogen-bonding interactions has been studied.
Chemical Phenomena↗
1:1 hetero-assembly of 2-aminopyrimidine and (+)-camphoric acid
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Journal Article↗
Self-assembly of 2-pivaloyl-6-chloropterin
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Journal Article↗
Radiotherapy in carcinoma cervix.
The techniques of radiation treatment of cervical cancer with radium evolved empirically. During the last few decades a lot of technological breakthrough has occurred in the field of brachytherapy mainly due to revolutionary changes brought by computerisation. The difficulties encountered during intracavitary insertions and the practical problems have been discussed. The complications following acute and late reactions have also been discussed.
Brachytherapy↗
Pharmacologic effects of cocoa and rye flour extracts on isolated guinea pig trachea.
Confectionery workers are exposed to a wide variety of organic dusts and aerosols. Previous studies with workers in a confectionery plant working with cocoa and rye flour indicate that these workers are at risk of developing adverse respiratory symptoms and lung function impairment. The effects of cocoa and rye flour extract on isolated guinea pig tracheal smooth muscle were studied using water-soluble extracts from cocoa and rye flour obtained from the studied confectionery plant. Dose-related contractions of nonsensitized guinea pig tracheal rings were demonstrated using both cocoa and rye flour extracts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth muscle contraction: atropine, indomethacin, pyrilamine, nordihydroguaiaretic acid (NDGA), acivicin, bromophenacyl bromide (BPB), 3,4,5-trimethoxybenzoate 8-(N,N-diethylamino)octyl ester (TMB8), captopril, and capsaicin. Constrictor effects of the dust extracts were inhibited by these agents, the pattern of which depended on the dust extract. Atropine consistently and significantly reduced the contractile effects of both extracts. These observations suggest a release of parasympathetic mediators by these extracts or more directly an interaction with muscarinic receptors. In addition, the constrictor effect of cocoa and rye flour extracts was significantly, but only partially, reduced by indomethacin, pyrilamine, BPB, and TMB8. Acivicin also partially decreased the constrictor effect of cocoa extract. Pretreatment of tracheal tissue with capsaicin also decreased the constrictor effects of high concentrations of cocoa and rye flour extracts. Data suggest that cocoa and rye flour extracts cause a dose-related constriction of airway smooth muscle by non immunological mechanisms involving cholinergic pathways and airway mediators such as histamine and the products of the arachadonic acid cascade. This effect is not dependent on the presensitization of guinea pigs.
Air Pollutants, Occupational↗
Identification of a novel cardiac lineage-associated protein(cCLP-1): A candidate regulator of cardiogenesis.
We describe the isolation and characterization of a cDNA clone, called cCLP-1, that is a candidate for the previously described early cardiac-specific transcription factor BBF-1. BBF-1 binds the MEF2 (or element B) binding site within the cardiac myosin light chain 2 (MLC2) gene promoter. We used the element B sequence as a probe to screen an expression library constructed from mRNA obtained from the presumptive heart-forming regions of stage 6 chicken embryos. This yielded the cCLP-1 cDNA clone. Gel-shift analysis of stage 6 embryonic chicken protein extracts suggests that a protein that is recognized by the anti-cCLP-1 antibody binds to the same element B binding site to which BBF-1 binds. cCLP-1 mRNA was detected early in chicken development, prior to cardiac fate assignment at stage 4. The expression pattern of cCLP-1, based on whole mount in situ hybridization, coincides remarkably well with the established morphogenetic field of early heart formation. The nuclear localization of cCLP-1 is phosphorylation-dependent, suggesting that cCLP-1 may be a member of that class of transcription factors whose activity is regulated by cytoplasm to nucleus transport. Taken together, these data suggest that cCLP-1 may encode a novel transcription factor whose expression pattern is in agreement with that of the cardiogenic precursor cells of the early chicken embryo.
Amino Acid Sequence↗
Differential regulation of Bcl-2, AP-1 and NF-kappaB on cardiomyocyte apoptosis during myocardial ischemic stress adaptation.
Acute ischemia followed by prolonged reperfusion has been shown to induce cardiomyocyte apoptosis. In this report, we demonstrate that myocardial adaptation to ischemia induced by repeated cyclic episodes of short-term ischemia each followed by another short duration of reperfusion reduced cardiomyocyte apoptosis and DNA fragmentation. This was associated with the induction of the expression of Bcl-2 mRNA and translocation and activation of NF-kappaB. Another transcription factor, AP-1, remained unaffected by repeated ischemia and reperfusion, but exhibited significant upregulation by a single episode of 30 min ischemia followed by 2 h of reperfusion. This activation of AP-1 was inhibited by a scavenger of oxygen free radicals, DMTU. Thirty minutes ischemia and 120 min reperfusion downregulated the induction of the expression of Bcl-2 mRNA, but moderately activated NF-kappaB binding activity. This was associated with an increased number of apoptotic cells and DNA fragmentation in cardiomyocytes which were attenuated by DMTU. The results of this study indicate that Bcl-2, AP-1 and NF-kappaB differentially regulate cardiomyocyte apoptosis mediated by acute ischemia and prolonged reperfusion.
Animals↗
Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy.
In comparing the pathological state of cardiac hypertrophy with early embryonic growth and development of the primitive heart, important and informative aspects of mechanisms that underlie activation of the gene expression pattern become apparent. Interestingly, in both cases the muscle phenotypes share the expression of a 'fetal' gene expression program, raising the question whether the same genetic mechanism is being called upon by signals associated with the onsets of cardiogenesis and myocardial hypertrophy. A cell specific transcription factor, CLP-1, was recently identified in our laboratory that is likely to play a crucial role, in conjunction with other known regulatory factors, in early cardiac events leading to cardiogenic cell specification and differentiation. We have also identified a novel mechanism that involves activation of the Jak/Stat signaling pathway that is linked to the autocrine angiotensin-II loop associated with the hypertrophic response in cardiomyocytes. Since early cardiac cell development and the hypertrophic state involve the expression of the same battery of genes, one may speculate that common transcription factors may account for assembling a competent apparatus responsible for transcribing the genes. Our present studies are designed to investigate the potential role of these factors in control of both processes.
Adaptation, Physiological↗
Integrins inhibit angiotensin II-induced contraction in rat aortic rings.
Many extracellular matrix proteins contain the tripeptide sequence arginine-glycine-aspartate (RGD). This RGD motif is recognized by integrins, a family of adhesion receptors present on vascular smooth muscle cells. In the present study, we examined the ability of different RGD-containing peptides to affect the contraction of rat aortic rings in response to different agonists. We found that the peptide RGDS inhibited angiotensin-induced contraction in a dose dependent manner. In contrast, the peptides RGDW and RGES had no effect on angiotensin-induced contractility. We show that function-blocking antibodies to the integrins alphavbeta3 and alpha5beta1 also inhibit angiotensin-induced contraction. These effects were observed in the absence of an intact endothelium. In contrast, neither an antibody directed against the beta1 subunit nor the peptide RGDS had an effect on phenylephrine or 5-hydroxytryptamine-induced contraction. These data suggest that interactions of vascular smooth muscle with components of the surrounding extracellular matrix may influence the response of smooth muscle to agonists.
Angiotensin II↗
Effects of recycled paper dust extracts on isolated guinea pig trachea.
The effect of paper dust collected at two different locations in a paper recycling plant (PD1 and PD2) on isolated nonsensitized guinea pig tracheal smooth muscle was studied in vitro. Dust extracts were prepared as a 1:10 w/v aqueous solution. Dose-related contractions of guinea pig tracheal rings were elicited with both PD1 and PD2. Pharmacologic studies were performed with atropine (10(-6) M), indometacin (10(-6) M), pyrilamine (10(-6) M), LY171883 (10(-5) M), nordihydroguaiaretic acid (10(-5) M), and TMB8 (10(-5) M). The possible role of endogenous neuropeptides in this constrictor process was studied by depleting neural mediators with capsaicin (5 x 10(-6) M) before challenge with dust extracts. Constrictor effects were partially inhibited by a wide variety of the mediator blocking agents. The effects of both extracts were almost totally inhibited by the anticholinergic agent atropine, suggesting that a principal pathway mediating this response may involve the parasympathetic nervous system. The intracellular calcium-blocking agent TMB8 also induced a reduction of the contractile responses to PD1 and PD2 consistent with the well established role of intracellular calcium in smooth muscle constriction. Pretreatment with capsaicin significantly increased the contractile activity of paper dust extracts but only at the higher doses of these extracts. This suggests that the effect of paper dust is not initiated by the release of mediators stored in sensory nerves but that the prerelease of these mediators may enhance the constrictor effects of these dusts. We suggest that paper dust extracts cause dose-related airway smooth muscle constriction possibly associated with the release of cholinergic as well as other mediators. The constrictor effect does not require tissue presensitization or the release of neuropeptides from sensory nerves.
Animals↗
Interleukin-6-mediated autocrine growth promotion in human glioblastoma multiforme cell line U87MG.
Human glioblastoma multiforme cell lines, brain tumor biopsy tissue, and normal human fetal brain synthesize interleukin (IL)-6 and IL-6 receptor (IL-6R). Neither of these is expressed in human neurons or neuroblastoma cell lines in culture. Astrocytes from fetal brain grown in culture retain the ability to synthesize IL-6 but do not express IL-6R as inferred from RT-PCR and Southern blot studies. Coexpression of IL-6 and IL-6R in the glioblastoma cell line U87MG is confirmed by immunofluorescence staining. Both specific monoclonal antibodies against IL-6 and IL-6R and antisense oligonucleotide to IL-6 mRNA inhibit the growth of U87MG cells in culture, suggesting the existence of a functional autocrine growth loop. Anti-IL-6 antibodies also inhibit the growth of glioblastoma cell lines U373 and U118. The expression of IL-6 by human fetal astrocytes in culture is highly suggestive of its role as an oncofetal protein responsible for rapid proliferation of fetal and tumor cells but not cells of adult brain.
Animals↗