Mucosal leishmaniasis presenting as sinusitis and optic neuropathy.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
J Green
Publications and source records attributed to J Green.
The impact of disease management on outcomes and cost of care: a study of low-income asthma patients.
An asthma disease management program designed specifically for low-income patients experiencing significant adverse events can improve health outcomes substantially, while lowering costs. The Virginia Health Outcomes Partnership aimed to help physicians in a fee-for-service primary care case management program manage asthma in Medicaid recipients. Approximately one-third of physicians treating asthma in an area designated as the intervention community volunteered to participate in training on disease management and communication skills. This large-scale study discovered that the rate of emergency visit claims for patients of participating physicians who received feedback reports dropped an average of 41% from the same quarter a year earlier, compared to only 18% for comparison community physicians. Although only a third of the intervention community physicians participated in the training, emergency visit rates for all intervention community physicians nonetheless declined by 6% relative to the comparison community among moderate-to-severe asthma patients when data for participating and nonparticipating physicians were combined. At the same time, the dispensing of some reliever drugs recommended for asthma increased 25% relative to the comparison community. A cost-effectiveness analysis projected direct savings to Medicaid of $3 to $4 for every incremental dollar spent providing disease management support to physicians. The results of this study demonstrate the potential this program offers, especially for Medicaid programs in other states that want to improve the care of their primary care case management networks and, at the same time, manage costs.
Anti-Asthmatic Agents↗
The spectrum of "cerebral hyponatremia"--cerebral salt wasting syndrome in a patient with pituitary adenoma.
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Aged↗
Diagnostic quiz #38. Case no. 1. Central giant cell granuloma.
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Adolescent↗
Effects of nitrogen and phosphorus fertilization in a lowland evergreen rainforest.
A nutrient addition experiment was set up in August 1993 in a species-rich primary lowland dipterocarp forest in Barito Ulu, Central Kalimantan, Indonesia. The following treatments were applied: control, +N, +P and +NP. There were five blocks of four 50 m x 50 m plots with a separate treatment for each plot. Fine litterfall was measured on all the plots from 1 May 1994 for 12 months. Litterfall mass and phosphorus concentrations were significantly higher in all the fertilizer treatments compared with the controls. All trees (> or = 10 cm dbh) were measured in August 1993 and in August 1998, and there was no significant girth increment response to fertilization in dipterocarps or non-dipterocarps. Dipterocarps of the red meranti group showed a doubling of girth increment in the +NP treatment, however, the difference from the control fell short of significance.
Ecosystem↗
Health-related quality of life among renal-transplant recipients in Japan.
BACKGROUND: This study had four goals: (1) to evaluate an index of health-related quality of life (HQOL) among renal-transplant recipients in Japan, (2) to compare HQOL of renal-transplant recipients with that of the Japanese population as a whole, and (3,4) to study associations of HQOL with renal function and with the time since transplantation. METHODS: Questionnaires were distributed to 570 subjects. All were outpatients, were 16 years old or older, and were studied at least 1 year after they had received their latest renal transplant. HQOL was assessed with the Short Form 36-item health survey. Subjects' physicians provided data on renal function. Associations of HQOL with serum creatinine concentration and with the time since transplantation were evaluated by logistic regression. RESULTS: The response rate was 83%. Data from patients with diabetes and from those who had had at least two renal transplants were excluded; data from 395 recipients were analyzed. On the physical functioning, general health perception, vitality, and social functioning scales, the patients' scores were significantly lower than the Japanese national-norm scores. General health perception was particularly low. Serum creatinine concentrations were associated with general health perception, vitality, and social functioning. Longer times since transplantation were associated with better social functioning. CONCLUSIONS: Although social and physical functioning may improve after transplant surgery, a low self-rating of general health seemed to remain. The rarity of renal transplantation in Japan and other psychosocial factors may explain the low self-rating of general health in Japanese renal-transplant recipients.
Adolescent↗
Identification of a surface of FNR overlapping activating region 1 that is required for repression of gene expression.
A library of Escherichia coli fnr mutants has been screened to identify FNR (regulator of fumarate and nitrate reduction) variants that are defective repressors, but competent activators. All but one of seventeen variants had substitutions close to or within the face of FNR that contains activating region 1 (AR1). Activating region 1 is known to contact the alpha subunit of RNA polymerase to facilitate transcription activation. It is now evident that this face also has a role in FNR-mediated repression. Single amino acid substitutions at Lys54, Gly74, Ala95, Met147, Leu193, Arg197, or Leu239, and double substitutions at Ser13 and Ser145, Cys16 and Ile45, Tyr69 and Ser133, or Lys164 and Phe191, impaired FNR-mediated repression of ndh without greatly affecting activation from model Class I (FNR site at -71.5) and Class II (FNR site at -41.5) FNR-activated promoters. Although repression was impaired in a second group of FNR variants with substitutions at Leu34, Arg72 and Leu193, Phe92, or Ser178, transcription activation from the simple FNR-dependent promoters was severely reduced. However, expression from pyfiD (FNR sites at -40.5 and -93.5) and a derivative lacking the site at -93.5, pyfiD-/+, remained relatively high indicating that this second group have a context-dependent activation defect as well as a repression defect. The prediction that the substitutions affecting repression were likely to be in solvent exposed regions of FNR was supported by analysis of peptides produced by partial proteolysis of FNR. Thus, FNR-mediated repression at promoters with multiple FNR sites requires regions of FNR that are different from, but overlap, AR1.
Amino Acid Substitution↗
Self-similarity in the distribution and abundance of species
If the fraction of species in area A that are also found in one-half of that area is independent of A, the distribution of species is self-similar and a number of observed patterns in ecology, including the widely cited species-area relationship connecting species richness to censused area, follow. Self-similarity also leads to a species-abundance distribution, which deviates considerably from the commonly assumed lognormal distribution and predicts considerably more rare species than the latter. Because the abundance distribution is derived under the condition of self-similarity, it may be widely applicable beyond ecology.
Journal Article↗
Use of a pharmacophore model for the design of EGFR tyrosine kinase inhibitors: isoflavones and 3-phenyl-4(1H)-quinolones.
Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase together with published X-ray crystal data of quercetin (2) in complex with the Hck tyrosine kinase and of deschloroflavopiridol (3b) in complex with CDK2, a putative binding mode of the isoflavone genistein (1) was proposed. Then, based on literature data suggesting that a salicylic acid function, which is represented by the 5-hydroxy-4-keto motif in 1, could serve as a pharmacophore replacement of a pyrimidine ring, superposition of 1 onto the potent EGFR tyrosine kinase inhibitor 4-(3'-chlorophenylamino)-6, 7-dimethoxyquinazoline (4) led to 3'-chloro-5,7-dihydroxyisoflavone (6) as a target structure which in fact was 10 times more potent than 1. The putative binding mode of 6 suggests a sulfur-aromatic interaction of the m-chlorophenyl moiety with Cys 773 in the "sugar pocket" of the EGFR kinase model. Replacement of the oxygen in the chromenone ring of 6 by a nitrogen atom further improved the inhibitory activity against the EGFR kinase. With IC50 values of 38 and 8 nM, respectively, the quinolones 11 and 12 were the most potent compounds of the series. N-Alkylation of 11 did not further improve enzyme inhibitory activity but led to derivatives with cellular activity in the lower micromolar range.
Animals↗
The bovine Newbury agent-2 is genetically more closely related to human SRSVs than to animal caliciviruses.
The hypothesis that the enteric bovine calici-like virus Newbury agent (NA-2) belongs to the family Caliciviridae was examined by genome sequence analysis. Use of solid-phase immune electron microscopy allowed samples with good levels of virus to be identified and amplification of the genome was achieved by reverse transcription-polymerase chain reaction. Examination of a 216-amino-acid sequence in the RNA-dependent RNA polymerase gene and a 116-amino-acid sequence in the capsid gene showed that NA-2 had the closest deduced amino acid identity (77 to 80% for the polymerase region and 67 to 73% for the capsid region) to the morphologically indistinguishable human SRSVs (small round structured viruses) of genogroup 1, which are classified as members of the Caliciviridae. It had a weak relationship (<34.5% deduced amino acid identity) in both the polymerase and the capsid regions to animal caliciviruses, all of which have classical morphology. This is the first genomic data from a nonhuman virus with SRSV morphology. It confirms the hypothesis that the bovine enteric calici-like virus NA-2 is a member of the family Caliciviridae and endorses the observation to date that viruses with SRSV morphology are genomically distinct.
Amino Acid Sequence↗
Event-related potential changes in groups at increased risk for Alzheimer disease.
BACKGROUND: Individuals who have a family history (FH) of Alzheimer disease (AD) or who carry the apolipoprotein E epsilon4 allele are at increased risk for developing AD. Abnormalities in brain event-related potentials (ERPs) have been observed in patients diagnosed as having AD. OBJECTIVE: To determine whether groups of nonsymptomatic, middle-aged individuals at increased risk for AD exhibited ERP changes consistent with this disease. DESIGN: In a case-control study, ERPs were elicited using an auditory oddball paradigm, and a brief neuropsychological battery was administered. SETTING: University laboratory facilities. SUBJECTS: We compared age-matched and education-matched groups with a positive family history (FH+; n = 24) or a negative family history (FH-; n = 23) of AD. Within the FH+ group, subgroups were identified as either carriers of the apolipoprotein E epsilon4 allele (epsilon4+; n = 9) or noncarriers (epsilon4-; n = 8), and these subgroups were compared with the FH- group. MAIN OUTCOME MEASURES: The latency and amplitudes of P3, N2, and P2 components of the ERP were quantified and analyzed statistically. RESULTS: Compared with the FH- group, both the whole FH+ group and the FH+/epsilon4+ subgroup showed abnormal prolongation in the latency of the P3 component. In addition, the FH+/epsilon4+ subgroup showed abnormal prolongation in the latency of the N2 component. These changes were observed in the absence of neuropsychological deficits. CONCLUSIONS: The findings indicate that groups at increased risk for developing AD show ERP changes consistent with those observed in patients diagnosed as having AD. The results support accumulating evidence that AD has a preclinical phase and that early detection may be possible.
Alzheimer Disease↗
Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: A descriptive report from the Intergroup Rhabdomyosarcoma Studies (IRS)-II and - III. IRS Group of the Children's Cancer Group and the Pediatric Oncology Group.
BACKGROUND: This review of children and adolescents with nonorbital soft-tissue sarcoma of the head and neck was undertaken to describe late sequelae of treatment, as manifested primarily by problems with statural growth, facial and nuchal symmetry, dentition, vision and hearing, and school performance. PROCEDURE: Four hundred sixty-nine patients entered the IRS-II and -III protocols with localized, nonorbital soft-tissue sarcomas of the head and neck from 1978 through 1987. Their overall survival rate was 53% (250/469) at 5 years. Two hundred thirteen patients were surviving relapse-free 5 or more years after diagnosis, for whom there were serial height measurements at 2 or more years after initiation of therapy. Their median age at diagnosis was 5 years; the median length of follow-up was 7 years. All received multiple-agent chemotherapy, and all but 3 received irradiation to the primary tumor volume. Sixty-eight percent of the tumors arose in cranial parameningeal sites, 22% in nonparameningeal sites, and 10% in the neck. We reviewed flow sheets submitted to the IRS Group Statistical Office to ascertain which late sequelae were recorded. RESULTS: One hundred sixty-four patients (77%) had one or more problems recorded. One hundred ninety of the two hundred thirteen patients (89%) were under 15 years of age at study entry, and at follow-up 92 (48%) had failed to maintain their initial height velocity, which had decreased by more than 25 percentile points from the original value. Thirty-six of the one hundred ninety patients (19%) were receiving growth hormone injections. Hypoplasia or asymmetry of tissues in the primary tumor site was reported in 74 patients, and 13 underwent reconstructive surgery. Poor dentition or malformed teeth were noted in 61 patients. Impaired vision developed in 37 patients, owing primarily to cataracts, corneal changes, and optic atrophy. Thirty-six patients had decreased hearing acuity, and 9 were fitted with hearing aids; 5 of these 9 had received cisplatin. Thirty-five patients were noted to have problems learning in school. Four patients developed a second malignancy (two sarcomas, one carcinoma, one leukemia). CONCLUSIONS: Late sequelae affected the majority of these patients treated for soft-tissue sarcoma of the head and neck on IRS-II and -III. The potential impact of certain sequelae could be reduced by specific measures, such as surgical reconstruction and hormonal therapy. Late sequelae must be taken into account in designing future curative treatments.
Adolescent↗
The identical 5' splice-site acceptor mutation in five attenuated APC families from Newfoundland demonstrates a founder effect.
Inherited mutations of the APC gene predispose carriers to multiple adenomatous polyps of the colon and rectum and to colorectal cancer. Mutations located at the extreme 5' end of the APC gene, however, are associated with a less severe disease known as attenuated adenomatous polyposis coli (AAPC). Many individuals with AAPC develop relatively few colorectal polyps but are still at high risk for colorectal cancer. We report here the identification of a 5' APC germline mutation in five separately ascertained AAPC families from Newfoundland, Canada. This disease-causing mutation is a single basepair change (G to A) in the splice-acceptor region of APC intron 3 that creates a mutant RNA without exon 4 of APC. The observation of the same APC mutation in five families from the same geographic area demonstrates a founder effect. Furthermore, the identification of this germline mutation strengthens the correlation between the 5' location of an APC disease-causing mutation and the attenuated polyposis phenotype.
Adenomatous Polyposis Coli↗
Genomic characterisation of the large segment of a rabbit picobirnavirus and comparison with the atypical picobirnavirus of Cryptosporidium parvum.
The 2362 base pair sequence of the larger of the two double stranded RNA genome segments of a rabbit strain of picobirnavirus (PBV) has a major open reading frame (ORF) of 591 amino acids and two smaller ORFs of 55 and 155 amino acids. A clone of the segment did not hybridise with other viral bisegmented ds RNAs from faecal samples. There is no relationship in sequence or organisation between this PBV sequence and the bisegmented dsRNAs found associated with Cryptosporidium parvum. This suggests that there are at least two distinct classes of bisegmented dsRNA viruses or viral-like agents in faeces.
Animals↗
Comparison of specific and random priming in the reverse transcriptase polymerase chain reaction for genotyping group A rotaviruses.
This study describes an approach to the molecular typing of rotaviruses which requires only a single RNA extraction and reverse transcription (RT) reaction using random primers. Random-primed RT provides complementary DNA (cDNA) which can be used not only for G- and P-typing polymerase chain reactions (PCR), but also for the detection of other RNA viruses which may act as enteric pathogens. It is a sensitive and specific method that can detect 10 virus particles/ml of 10% faecal suspension provided the cDNA is amplified in a nested typing-PCR. Of 121 specimens positive for rotavirus by EM and analysed using this method, only 8% could not be G- or P-genotyped. The untyped samples were tested again performing the RT reaction with G- and P-specific primers, achieving a 5% increase in sensitivity. Comparing G-genotyping against G-serotyping, 92% were genotyped through random priming RT-PCR whereas only 64% were serotyped using G-serotype specific monoclonal antibodies (MAbs).
Aged↗
A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo.
The tyrosine kinase Src has been implicated in the process of osteoclast-mediated bone resorption. Here, we describe a novel class of Src inhibitors, substituted 5,7-diphenyl-pyrrolo[2,3-d]pyrimidines, and characterize one of them, CGP77675, in vitro and in models of bone resorption in vivo. In vitro, CGP77675 inhibited phosphorylation of peptide substrates and autophosphorylation of purified Src (concentration producing half-maximal inhibition [IC50] values 5-20 and 40 nmol/L, respectively). The compound was selective toward other protein kinases: the Src IC50 value was lower than those for Cdc2 (>500-fold), epidermal growth factor (EGF) receptor (7.5-fold), and vascular endothelial growth factor receptor (>50-fold), and for v-Abl (15-fold) and focal adhesion kinase (Fak) (>25-fold). The Src kinase family members Lck and Yes were inhibited with IC50 values 20-fold higher than or equal to Src. To measure the inhibition of cellular Src activity, we identified the major tyrosine-phosphorylated proteins in an Src-overexpressing cell line IC8.1 as Src, Fak, and paxillin. CGP77675 potently inhibited tyrosine phosphorylation of the Src substrates Fak and paxillin, but had much less effect on Src (IC50 values 0.3, 0.5, and 5.7 micromol/L). The phosphorylation of Src in IC8.1 cells reflected phosphorylation of the negative regulatory tyrosine 527 (Y527); thus, the inhibitor was selective against the Y527 C-terminal Src kinase Csk. In osteoblastic MC3T3-E1 cells, CGP77675 inhibited signaling induced by PDGF at the receptor level, but not signaling by EGF, basic fibroblast growth factor, insulin-like growth factor-1, and phorbol 12-myristate 13-acetate. The effect of CGP77675 on bone resorption was evaluated in vitro and in vivo. The parathyroid hormone-induced bone resorption in rat fetal long bone cultures was inhibited with an IC50 of 0.8 micromol/L. CGP77675 dose-dependently reduced the hypercalcemia induced in mice by interleukin-1beta and partly prevented bone loss and microarchitectural changes in young ovariectomized rats, showing that the protective effect on bone was exerted via the inhibition of bone resorption. Thus, specific Src family kinase inhibitors may be useful for the treatment of diseases associated with elevated bone loss.
3T3 Cells↗
Drink, illicit drugs and unsafe sex in women.
AIMS: To establish the extent and nature of linkages between illicit drug and alcohol use and sexual behaviour in women. PARTICIPANTS AND SETTING: One hundred women attending either a Genitourinary Medicine Clinic or a Family Planning Clinic. DESIGN: Respondents were interviewed using a semi-structured interview schedule covering the effect of drink/illicit drug use on the incidence of sex, on condom use, and on specific sexual activities, and deliberate use of drink/illicit drugs to affect sex. Interviews focused on the last three new male partners, from the beginning of the sexual relationship through its development. Data analysis was primarily qualitative, quantitative analysis was conducted where appropriate. RESULTS: There were few cases in which women reported that consumption of drink/illicit drugs caused them to engage in sexual behaviour which they would not have engaged in if they had not had drink/drugs. Associations between drink and illicit drugs and sexual behaviour were, mainly, either because encounters took place in social situations where drugs or drink were being consumed or because the woman used drink or drugs instrumentally to engage in desired behaviours. There was some evidence to suggest that greater use of drugs and alcohol might be part of a wider pattern of social behaviour including more sexual partners. CONCLUSIONS: The women's self-reported behaviour suggested that illicit drug and alcohol use in itself did not usually result in unsafe or undesired sexual behaviour.
Acquired Immunodeficiency Syndrome↗
Two operons that encode FNR-like proteins in Lactococcus lactis.
Global regulatory circuits of the type mediated by CRP and FNR in Escherichia coli were sought in Lactococcus lactis to provide a basis for redirecting carbon metabolism to specific fermentation products. Using a polymerase chain reaction (PCR) approach, two genes (flpA and flpB) encoding FNR-like proteins (FlpA and FlpB) with the potential for mediating a dithiol-disulphide-dependent regulatory switch, were identified. Transcript analysis indicated that they are distal genes of two paralogous operons, orfX-orfY-flp, in which the orfX and orfY genes were predicted to encode binding domain components of cation ATPases and storage proteins respectively. The corresponding promoters were each associated with a potential FNR site (TTGAT----ATCAA) at positions +4.5 (flpA operon) and -42.5 (flpB operon), suggesting that the respective operons might be negatively and positively autoregulated. The incomplete open reading frames (orfWA/B) located upstream of each operon were predicted to encode additional components of paralogous cation ATPases. No phenotypic effects were detected in flpA and flpB single mutants, but the double mutant had a lower intracellular zinc content, an increased sensitivity to hydrogen peroxide and an altered polypeptide profile (as determined by two-dimensional gel electrophoresis): formate production was not affected. It was concluded tentatively that FlpA and FlpB regulate overlapping modulons, including systems concerned with zinc uptake, in response to metal ion or oxidative stress.
Amino Acid Sequence↗