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Biomedical subjects

A Kurup

Publications and source records attributed to A Kurup.

At least 19 recordsLinked to original sources
PubMed2002

Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation.

Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.

Adolescent↗
PubMed2001

Searching for allosteric effects via QSARs.

A study of our database of 7,000 QSARs involving chemical-biological interaction uncovered 11 examples where the QSARs all contain inverted parabolas based on molecular refractivity. That is, biological activity first decreases with increase in MR and then increases. Two of the examples are for enzymes: cyclooxygenase and trypsin. The others are for various receptors. The results seem to be best rationalized by the larger compounds inducing a change in a receptor unit that allows for a new mode of interaction.

Allosteric Regulation↗
PubMed2001

QSAR of anticancer compounds. Bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides), bis(phenazine-1-carboxamides), and bis(naphthalimides).

QSAR have been developed for the anticancer activity (growth inhibition) of various tumor cells by bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides), bis(phenazine-1-carboxamides), and bis(naphthalimides). Of the seven QSAR, positive hydrophobic interactions are found in only two examples: bis(naphthalimides) versus human colon cancer cells. This is consistent with other QSAR of anticancer compounds where hydrophobic interactions are found to be unimportant.

1-Naphthylamine↗
PubMed2001

Possible allosteric effects in anticancer compounds.

We have found in this report, and an earlier one, that in a variety of instances an inverted parabolic relationship between biological activity and CMR or logP is observed. That is, activity first decreases as CMR or logP increases and then turns about and increases. This could be attributed to the ligands causing a change in the receptor structure. The present report considers QSAR for a variety of resistant and sensitive cancer cells.

Antineoplastic Agents↗
PubMed2001

Comparative QSAR: on the toxicology of the phenolic OH moiety.

In this report we consider the effect of substituents on phenol toxicity and show how the parameters used in Quantitative Structure-Activity Relationships (QSAR) can be used to draw mechanistic inferences of value in understanding the reasons behind the various types of toxicity. In particular, we are interested in gaining clearer insight into mechanisms via the Hammett-type parameters sigma, sigma(-), sigma(+) and octanol/water parti tion coefficients. Particular attention is given to the role of radical reactions and their role in attacking DNA to cause cancer or estrogenic toxicity.

Animals↗
PubMed2001

Infection of central nervous system by motile Enterococcus: first case report.

A 66-year-old man with four indwelling ventriculoperitoneal shunts for multiloculated hydrocephalus from a complicated case of meningitis a year before developed shunt infection based on a syndrome of fever, drowsiness, and cerebrospinal fluid neutrophil pleocytosis in the background of repeated surgical manipulation to relieve successive shunt blockages. The cerebrospinal fluid culture, which yielded a motile Enterococcus species, was believed to originate from the gut. This isolate was lost in storage and could not be characterized further. The patient improved with vancomycin and high-dose ampicillin therapy. He relapsed a month later with Enterococcus gallinarum shunt infection, which responded to high-dose ampicillin and gentamicin therapy. This is probably the first case report of motile Enterococcus infection of the central nervous system.

Aged↗
PubMed2000

Candida tropicalis pacemaker endocarditis.

A rare case of Candida tropicalis pacemaker endocarditis was diagnosed in a 77-year-old male who presented with lethargy. The organism was isolated from cultures of blood and vegetations on the tricuspid valve, interatrial septum and the pacing wire removed at surgery. The postoperative course was stormy and he succumbed to multiorgan failure.

Aged↗
PubMed1999

Quantitative structure-activity relationship study on some nonpeptidal cholecystokinin antagonists.

A quantitative structure-activity relationship (QSAR) analysis has been performed on a series of 1,4-benzodiazepine derivatives, which were found to act as antagonists of cholecystokinin (CCK), a gastrointestinal peptide hormone. The CCK acts with three different receptor subtypes termed as CCK-A, CCK-B, and gastrin receptor, which can be found in peripheral system, brain, and stomach, respectively. With all the three subtypes, the binding of the compounds is found to significantly depend on the lipophilicity of the compounds and their ability to form the hydrogen bonds with the receptor. However, the binding sites in CCK-A receptor seem to be slightly rigid as compared to those in CCK-B or gastrin receptor. The latter two appear to have similar binding features.

Animals↗
PubMed1999

The neurological manifestations of Nipah virus encephalitis, a novel paramyxovirus.

A novel Hendra-like paramyxovirus named Nipah virus (NiV) was the cause of an outbreak among workers from one abattoir who had contact with pigs. Two patients had only respiratory symptoms, while 9 patients had encephalitis, 7 of whom are described in this report. Neurological involvement was diverse and multifocal, including aseptic meningitis, diffuse encephalitis, and focal brainstem involvement. Cerebellar signs were relatively common. Magnetic resonance imaging scans of the brain showed scattered lesions. IgM antibodies against Hendra virus (HeV) were present in the serum of all patients. Two patients recovered completely. Five had residual deficits 8 weeks later.

Adult↗
PubMed1999

Meningoencephalitis caused by a novel paramyxovirus: an advanced MRI case report in an emerging disease.

Eleven abattoir workers in Singapore were infected in March 1999 by an outbreak caused by the Nipah virus. This newly discovered, Hendra-like paramyxovirus causes acute infection of the CNS. We present the magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) findings in a patient suffering from acute meningoencephalitis. Multiple small white matter lesions were detected on diffusion-weighted imaging (DWI) and T2-weighted images. There were no abnormalities detected on MRS. We believe this to be the first reported MRI findings in this novel zoonotic viral disease.

Abattoirs↗
PubMed1999

Disseminated Penicillium marneffei infection: a report of five cases in Singapore.

Penicillium marneffei has emerged as an important opportunistic pathogen in HIV-infected patients in Southeast Asia. We report the first 5 cases of P. marneffei diagnosed in Singapore. All the patients were HIV-infected and were either Thai nationals or had frequently travelled to Thailand. Fever, weight loss, anaemia and papular skin lesions were common clinical manifestations in our patients, all of whom had the organism isolated from blood. Skin biopsy specimens showed histological evidence of P. marneffei in 2 patients. In 1 patient each, the organism grew in cultures of specimens from bone marrow and respiratory secretions. Amphotericin B therapy followed by itraconazole were used in 3 of our 5 patients and was associated with good clinical response and outcome.

AIDS-Related Opportunistic Infections↗
PubMed1998

Characterization of the altered cutaneous reactivity of transgenic mice whose keratinocytes overexpress B7-1.

B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs that prevents the induction of T-cell clonal anergy and induces IL-2 production during antigen presentation. Tg mice whose epidermal KC overexpress B7-1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to 8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced ear-swelling responses to irritants that are not persistent. Exaggerated CHS was not reflected in the draining lymph node. T-lymphocyte proliferative responses after sensitization and local challenge with haptens, as there were no significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg mice had an alteration in the kinetics of in situ lymphokine transcripts compared to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2 weeks versus 24 h for NTg mice. RNase protection assays to detect inflammatory cytokine transcripts at hapten application sites indicated that B7-1 Tg mice responded to hapten application with increased TNF-alpha, IL-6, and TNF-beta transcripts compared to NTg mice. Thus, hapten-induced ear swelling in these Tg mice may be mediated by enhanced inflammatory cytokines during the early phase (1-14 days). IFN-gamma-producing lymphocytes may be responsible for the late phase of the ear-swelling response (14-42 days). These data indicate that B7-1 overexpression by KC in mouse skin directly or indirectly affects the nature of cutaneous inflammation induced by haptens and irritants.

Animals↗
PubMed1997

Genetically transferred central and peripheral immune tolerance via retroviral-mediated expression of immunogenic epitopes in hematopoietic progenitors or peripheral B lymphocytes.

BACKGROUND: Based on the hypothesis that IgGs are potent tolerogens and that immature lymphohematopoietic antigen-presenting cells (APC), and even mature peripheral B cells, may be effective APC for tolerance induction, we designed an immunoglobulin fusion protein retroviral expression vector to test the role of B cells in a novel gene therapy strategy for the transfer of immune tolerance. METHODS: An immunodominant epitope (residues 12-26 of the lambda repressor cI protein) was fused in frame to an IgG heavy chain in a retroviral vector, which was used to infect either bone marrow cells or activated peripheral B lymphocytes. These cells were transferred into syngeneic recipients, who were subsequently challenged with the 12-26 peptide in adjuvant. RESULTS: Bone marrow (BM) chimeras generated with retrovirally transduced bone marrow were shown to be profoundly unresponsive to the 12-26 peptide at both the humoral and cellular levels, but were competent to respond to an unrelated protein (lysozyme or PPD). Importantly, we also show that immunocompetent adult recipients infused with transduced mature, activated B lymphocytes, are rendered unresponsive by this treatment. Surprisingly, lymphoid-deficient BM progenitors from syngeneic SCID donors could also be transduced to produce tolerogenic APC. CONCLUSIONS: Our data suggest that activated B cells are sufficient to be effective tolerogenic APC in immunocompetent adult mice, but that nonlymphoid cells may also induce tolerance in reconstituted hosts. This approach for gene-transferred tolerogenesis has the potential to be maintained indefinitely, and it requires only knowledge of cDNA sequences of target antigens.

Amino Acid Sequence↗