Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthesis of optically pure (-)- and (+)-adenallene 2 and 3 is described. Racemic adenallene (1a) was subjected to deamination with adenosine deaminase monitored by HPLC using a Chiralcel CA-1 column to give (-)-adenallene (2) and (+)-hypoxallene (4). The latter compound was converted to acetate 5. The reaction of 5 with trifluoromethanesulfonic anhydride and pyridine followed by ammonolysis furnished acetate 6 or (+)-adenallene (3) depending on the solvent used in the last step. Acetate 5 was smoothly transformed to the 6-chloro derivative 7, but an attempted ammonolysis led only to racemization and decomposition. Single crystal X-ray diffraction established the R-configuration of (-)-enantiomer 2. The latter forms a pseudosymmetric dimer in the lattice with the adenine moiety in an anti-like conformation. The torsional angles of the allenic bonds show departures from 90 degrees (91 and 97 degrees, respectively) and rotameric preference of the hydroxymethyl groups is different in both molecules of the dimer. The R-enantiomer 2 inhibited the replication and cytopathic effect of human immunodeficiency virus (HIV-1) in ATH8 cell culture with an IC50 of 5.8 microM, whereas the S-enantiomer 3 was less active (IC50 > 200 microM). The enantioselectivity of the anti-HIV effect is significantly lower than that of 2',3'-dideoxyadenosine. Kinetics of deamination of R- and S-enantiomers 2 and 3 catalyzed by adenosine deaminase gave the following parameters: Km values of S-form 3 and R-form 2 were 0.41 and 0.52 mM with Vmax being 530 and 18.5 mumol/min, respectively [corrected]. Again,, a much lower level of enantioselectivity of deamination was observed than that of D- and L-adenosine. These results indicate (i) different enantioselectivity of enantiomers 2 and 3 as HIV inhibitors and adenosine deaminase substrates and (ii) both R- and S-enantiomers 2 and 3 can function as nucleoside analogues with varied enantioselectivity for different enzymes or receptors.
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PMID:(R)-(-)- and (S)-(+)-adenallene: synthesis, absolute configuration, enantioselectivity of antiretroviral effect, and enzymic deamination. 130 69

Short peptides often do not bind well to the plastic surface of microtitre wells in solid-phase immunoassays. To improve the reactivity of synthetic peptides coated on the solid phase, we have developed a highly sensitive, rapid and simple ELISA. This ELISA is based on the treatment of microtitre plates with Alcian blue prepared in acetic acid prior to coating the target peptide. With hyperimmune serum, this treatment increases the specific signal in such a manner that the detection of antibodies needs less antigen than with conventional ELISA. Moreover, the Alcian blue treatment was shown to be particularly effective for the detection of monoclonal antibodies against a synthetic peptide derived from the human immunodeficiency type 1 (HIV-1) vpu protein. These monoclonal antibodies that were not detected in conventional ELISA gave a positive signal up to a 1 in 1000 dilution after Alcian blue treatment of microtitre wells. This assay should be applicable to a variety of synthetic peptides and other types of molecules posing problems in assays requiring their immobilization on solid phases.
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PMID:Alcian blue-treated polystyrene microtitre plates for use in an ELISA to measure antibodies against synthetic peptides. 793 Jun 36

Sexually transmissible diseases (STD), caused by viruses are by far the most important ones, even though German legislation has ignored them up to now as STD. Anogenital herpes is easily diagnosed by means of monoclonal antibodies. This makes therapy available with acyclovir without delay in atypical cases or for example in persons with immunodeficiency. The therapy regimen usually is 5 x 200-400 mg/day. Recurrent herpes in high frequency and with severe pain may be successfully suppressed by 2-5 x 200 mg/day of acyclovir orally without serious side effects. This will not eliminate herpes viruses. Anogenital warts may look very different and occasionally cannot be detected before local application of 3% acetic acid. Histology is diagnostic. There are different strains causing diseases in men. Therapy of choice is destroying infected cells by CO2-laser coagulation. The incidence of hepatitis B in developed countries is decreasing slowly within the past years, this may partly be due to vaccines, that are available since the early eighties, producing immunity in about 95%. Treatment of chronic hepatitis with interferons seems to be beneficial. Infections with the human immunodeficiency virus (HIV) and their end stage disease AIDS are a growing problem all over the world. Interventions are possible with different nucleoside analogs, e. g. zidovudine (AZT), dideoxycytidine (DDC), dideoxyinosine (DDI). Up to now there is no agreement on when to start with one of the drugs and if or when to switch to combination therapy. Hopefully this may stabilize immunologic parameters and hold disease progression to some time.
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PMID:[Sexually transmitted diseases by herpes simplex, wart, hepatitis B, and human immunodeficiency virus]. 839 59

The protease encoded by the human immunodeficiency virus type 1 (HIV-1) was engineered in Escherichia coli as a construct in which the natural 99-residue polypeptide was preceded by an NH2-terminal methionine initiator. Inclusion bodies harboring the recombinant HIV-1 protease were dissolved in 50% acetic acid and the solution was subjected to gel filtration on a column of Sephadex G-75. The protein, eluted in the second of two peaks, migrated in SDS-PAGE as a single sharp band of M(r) approximately 10,000. The purified HIV-1 protease was refolded into an active enzyme by diluting a solution of the protein in 50% acetic acid with 25 volumes of buffer at pH 5.5. This method of purification, which has also been applied to the purification of HIV-2 protease, provides a single-step procedure to produce 100 mg quantities of fully active enzyme.
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PMID:Large scale purification and refolding of HIV-1 protease from Escherichia coli inclusion bodies. 839 90

Epidemiological hypotheses on disease etiology, generated by the observation of geographic distribution and time trends, can be confirmed or refuted by analytical investigations on specific risk factors. In the case of leukemias, lymphomas and myelomas, however, hypothesis generation is limited by the use of the ICD classification in mortality and incidence statistics. We compared recent incidence data in different parts of the world and at different times for leukemias, lymphomas and myelomas. The incidence rate of non-Hodgkin's lymphomas (NHL) is increasing in most Western countries, while trends for the other hematolymphopoietic malignancies are strikingly stable. To formulate hypotheses on the causes of this pattern would require a more appropriate classification of descriptive data. Excesses of non-Hodgkin's lymphomas have been observed in populations exposed to phenoxy-acetic acid herbicides, to insecticides and to organic solvents. Some of these exposures, in particular TCDD, which is a contaminant of phenoxy herbicides, DDT and chlorinated solvents, have been reported to alter cell-mediated immunity. The incidence of NHL is also increased among subjects with HIV infection and subjects undergoing heart or kidney transplantation, all of whom experience immunodeficiency. A hypothesis that has been put forward recently is that the NHL increase is related to increased exposure to sunlight, which has immunosuppressive effects. From a mechanistic point of view, one can hypothesize that NHL is caused by exposures that induce proliferation and immortalization of B-cells, followed by T-cell impairment entailing cell-mediated immune deficiency.
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PMID:Incidence and time trends for lymphomas, leukemias and myelomas: hypothesis generation. Working Group on the Epidemiology of Hematolymphopoietic Malignancies in Italy. 864 39

6-methoxy-2-benzoxazolinone (6-MBOA), a naturally occurring progonadal compound present in grasses with structural resemblance to melatonin, was tested for antifungal activity against Fusarium oxysporum, Rhizoctonia solani and Coprinus comatus. A variety of pineal products was also examined for the sake of comparison, including 5-methoxytryptamine, melatonin, 5-methoxytryptophol, 5-hydroxytryptamine, 5-methoxyindole-3-acetic acid and 5-hydroxytryptophol. The assay for antifungal activity was carried out in Petri plates containing potato dextrose agar. It was found that 6-MBOA most potently inhibited the growth of C. comatus, R. solani and F. oxysporum. When 6-MBOA and pineal indoles were tested for antibacterial activity against the bacterium Agrobacterium tumefaciens, 5-methoxyindole-3-acetic acid was found to be the most potent. 6-MBOA most potently inhibited human immunodeficiency virus-1 reverse transcriptase.
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PMID:Demonstration of antifungal and anti-human immunodeficiency virus reverse transcriptase activities of 6-methoxy-2-benzoxazolinone and antibacterial activity of the pineal indole 5-methoxyindole-3-acetic acid. 1210 2

The Z- and E-thymine and cytosine pronucleotides 3d, 4d, 3e, and 4e of methylenecyclopropane nucleosides analogues were synthesized, evaluated for their antiviral activity against human cytomegalovirus (HCMV), herpes simplex virus 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human immunodeficiency virus type 1 (HSV-1), and hepatitis B virus (HBV) and their potency was compared with the parent compounds 1d, 2d, 1e, and 2e. Prodrugs 3d and 4d were obtained by phosphorylation of parent analogues 1d or 2d with reagent 8. A similar phosphorylation of N4-benzoylcytosine methylenecyclopropanes 9a and 9b gave intermediates 11a and 11b. Deprotection with hydrazine in pyridine-acetic acid gave pronucleotides 3e and 4e. The Z-cytosine analogue 3e was active against HCMV and EBV The cytosine E-isomer 4e was moderately effective against EBV.
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PMID:Phosphoralaninate pronucleotides of pyrimidine methylenecyclopropane analogues of nucleosides: synthesis and antiviral activity. 1643 46

A CE method utilizing triple quadrupole electrospray (ES) MS (MS/MS) detection was developed and validated for the simultaneous measurement of nucleoside 5'-triphosphate and 5'-monophosphate anabolites of the anti-HIV (human immunodeficiency virus) didanosine (ddAMP, ddATP) and stavudine (d4TMP, d4TTP), among a pool of 14 endogenous 5'-mono-, di-, and triphosphate nucleosides. These compounds were spiked and extracted from peripheral blood mononuclear cells (PBMCs) which are the sites of HIV replication and drug action. An acetic acid/ammonia buffer (pH 10, ionic strength of 40 mM) was selected as running electrolyte, and the separation was performed by the simultaneous application of a CE voltage of +30 kV and an overimposed pressure of 28 mbar (0.4 psi). The application of pressure assistance was needed to provide stable ES conditions for successful coupling. The coupling was carried out with a modified sheath-flow interface, with one uninterrupted capillary (80 cmx 50 microm id; 192 microm od) in a dimension that fits into the ESI needle to get a stable ion spray. Some CE-MS parameters such as overimposed pressure, sheath-liquid composition, sheath-liquid and sheath-gas flow rates, ES voltage, and the CE capillary position were optimized in order to obtain an optimal sensitivity. The use of perfluorinated alcohols and acids in the coaxial sheath-liquid make-up (2,2,2-trifluoroethanol + 0.2 mM tridecafluoroheptanoic acid) appeared to provide the best MS sensitivity and improve the stability of spray. The linearity of the CE-MS and CE-MS/MS methods was checked under these conditions. Validation parameters such as accuracy, intraday and interday precision, and LOQs were determined in CE-MS/MS mode. Finally, the quantitation of d4T-TP and ddA-TP was validated in this CE-MS/MS system.
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PMID:Analysis and validation of the phosphorylated metabolites of two anti-human immunodeficiency virus nucleotides (stavudine and didanosine) by pressure-assisted CE-ESI-MS/MS in cell extracts: sensitivity enhancement by the use of perfluorinated acids and alcohols as coaxial sheath-liquid make-up constituents. 1678 81

An integrated metabolic model for the production of acetate by Escherichia coli growing on glucose under aerobic conditions was presented previously (Ko et al., 1993). The resulting model equations can be used to explain phenomena often observed with industrial fermentations, i.e., increased acetate production which follows from high glucose uptake rate, a low dissolved oxygen concentration, a high specific growth rate, or a combination of these conditions. However, several questions still need to be addressed. First, cell composition is growth rate and media dependent. Second, the macromolecular composition varied between E. coli strains. And finally, a model that represents the carbon fluxes between the Embden-Meyerhof-Parnas (EMP) and the hexose monophosphate (HMP) pathways when cells are subject to internal and/or external stresses is still not well defined. In the present work, we have made an effort to account for these effects, and the resulting model equations show good agreement for wild-type and recombinant E. coli experimental data for the acetate concentration, the onset of acetate secretion, and cell yield based on glucose. These results are useful for optimizing aerobic E. coli fermentation processes. More specifically, we have determined the EMP pathway carbon flux profiles required by the integrated metabolic model for an accurate fit of the acetic acid profile data from a wild-type E. coli strain ML308. These EMP carbon flux profiles were correlated with a dimensionless measurement of biomass and then used to predict the acetic acid profiles for E. coli strain F-122 expressing human immunodeficiency virus-(HIV(528)) beta-galactosidase fusion protein. The effect of different macromolecular compositions and growth rates between these two E. coli strains required a constant scaling factor for improved quantitative predictions.
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PMID:A metabolic model of cellular energetics and carbon flux during aerobic Escherichia coli fermentation. 1861 77

This case of microsporidiosis manifested as mutiple intracranial lesions separated in space and time, and neurological and radiological findings were improved with albendazole administration. A 33-year-old man presented with headache, fever, and dysphasia. His consciousness was clear. Neurological examination revealed acalculia, agraphia, and homonymous hemianopsia. He had a past history of febrile convulsive seizures of unknown cause until 14-years-old, but no history of immunodeficiency. T1-weighted magnetic resonance (MR) imaging showed a hypointense lesion with a hyperintense part, and ring-like enhancement with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA), in the left temporal lobe. T2-weighted and diffusion-weighted MR imaging showed the lesion surrounded by moderate hyperintense areas. He underwent gross total resection of the lesion. Histological examination demonstrated intracellular clusters of small basophilic spore-like bodies in the astrocytes, suggestive of microsporidia-infected astrocytes. However, immunohistochemical, polymerase chain reaction, and serological analyses failed to confirm the definitive diagnosis of microsporidiosis, so that he received no further treatment. Three years later, he presented with sensory disturbance in the left side of his face and left cerebellar ataxia, followed by fever, abnormal sensation in the left side of his face, and aggravated ataxia of the left upper and lower extremities on day 10 after admission. T1-weighted MR imaging with Gd-DTPA showed an enhanced lesion with irregular margin in the left cerebellar peduncle. T2-weighted MR imaging showed a diffuse hyperintense region around the lesion. Cerebrospinal fluid culture, serological analysis for autoimmune disease, and thoracic, abdominal, and pelvic computed tomography and 18F-fluorodeoxyglucose-positron emission tomography detected no abnormalities such as cancers or other lesions in the extracranial organs. No definitive diagnosis was obtained, but recurrence of microsporidiosis was the most probable cause. Administration of albendazole (600 mg/day) was started on day 15, because of rapid neurological and radiological deterioration. This treatment resulted in clinical improvement and disappearance of the lesion on MR imaging after daily administration for 4 weeks. He was discharged on foot with moderate sensory disturbance in the left side of the face and ataxia. Based on the clinical course and negative findings, the final diagnosis was microsporidiosis. This case suggests that microsporidiosis in the central nervous system can persist even in immunocompetent patients without involvement of any other organs, and that albendazole administration is likely to be effective.
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PMID:[Multiple intracerebral enhanced lesions strongly suspected to be microsporidiosis. A case report]. 1863 8


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