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Biomedical subjects

R Daniel

Publications and source records attributed to R Daniel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Involvement of C-Abl tyrosine kinase in lipopolysaccharide-induced macrophage activation.

LPS endotoxin-induced macrophage activation is recognized to be important in both nonspecific immunity and endotoxin-induced sepsis when excessive macrophage stimulation occurs. In this study, we showed that reduction of c-Abl in macrophages prevented LPS-induced growth arrest, nitric oxide production and TNF-alpha secretion by ANA-1 macrophages. These cells continued to grow but later underwent apoptosis. Reduction of c-Abl in these cells led to reduced c-Abl kinase activity associated with Ran, which recently has been shown to be an LPS-responsive gene product. Our data suggest that c-Abl tyrosine kinase is one of the intermediates downstream of the initial signal transduction event related to activation of macrophages by LPS.

Animals↗
PubMed1998

Treatment of acute exacerbations of chronic bronchitis: comparison of trovafloxacin and amoxicillin in a multicentre, double-blind, double-dummy study. Trovafloxacin Bronchitis Study Group.

The efficacy and safety of trovafloxacin and amoxicillin were compared in a double-blind, double-dummy multicentre trial involving 412 patients (> or = 40 years of age) with acute exacerbations of chronic bronchitis (AECBs). Patients were randomized to 5 days' oral treatment with 200 or 100 mg trovafloxacin administered once daily, or 500 mg amoxicillin given three times daily. Overall clinical efficacy at the end of therapy was similar in each treatment group, with clinical success (cure+improvement) achieved in 88% and 91% of clinically evaluable patients receiving trovafloxacin 200 mg and 100 mg, respectively, and in 89% of amoxicillin-treated patients. Corresponding rates at follow-up were 77%, 85% and 79%, respectively. Similar responses were noted at the end of treatment and end of study in the intent-to-treat patients. Although all three treatments produced similar bacteriological efficacy, there was a trend towards higher eradication rates for Haemophilus influenzae among patients (both clinically evaluable and intent-to-treat populations) treated with trovafloxacin 200 mg compared with those treated with amoxicillin. Both drugs were well tolerated, with treatment-related adverse events, of which headache and gastrointestinal disturbances were the most common, occurring in 12% and 6% of patients in the trovafloxacin 200 mg and 100 mg groups, respectively, and in 9% of amoxicillin-treated patients.

Acute Disease↗
PubMed1998

Trovafloxacin versus high-dose amoxicillin (1 g three times daily) in the treatment of community-acquired bacterial pneumonia.

Once-daily trovafloxacin 200 mg was compared with high-dose amoxicillin, 1 g three times daily, given for 7 to 10 days. At end of treatment (day 10), the response was clinically successful (cure + improvement) in 93% of 152 clinically evaluable trovafloxacin patients and in 89% of 160 amoxicillin patients. At study end (day 35), respective rates were 91% and 81% (95% confidence interval: 1.6, 17.6; P=0.01). In evaluable patients with positive baseline radiographs, 93% of trovafloxacin and 88% of amoxicillin patients demonstrated radiological resolution at end of treatment. Streptococcus pneumoniae and Haemophilus influenzae eradication rates were comparable at end of treatment in both treatment groups, but at study end Streptococcus pneumoniae eradication rates were higher in trovafloxacin patients (100% vs 81%). At study end, all four trovafloxacin patients with baseline penicillin-resistant Streptococcus pneumoniae were clinically cured with pathogen eradication, whereas two of five amoxicillin patients with baseline penicillin-resistant Streptococcus pneumoniae were clinical failures with pathogen persistence. For patients in whom no pathogen was identified, trovafloxacin was significantly more effective at end of treatment (P=0.096) and study end (P=0.013). Treatment-related adverse events were comparable; the most common were headache, vomiting and dizziness in trovafloxacin patients, and diarrhoea. headache and abdominal pain in amoxicillin patients.

Adolescent↗
PubMed1998

RK-2: a novel rabbit kidney defensin and its implications for renal host defense.

Defensins are endogenous antimicrobial peptides. We demonstrated recently the existence of RK-1, a defensin-like peptide in rabbit kidneys. Defining the renal-defensin system is an essential step toward understanding how the kidney responds to infection. Here, using a combination of high-performance liquid chromatography, matrix-assisted laser desorption time-of-flight mass spectrometry, amino acid compositional analysis, and microsequence analysis, we show that the rabbit kidney contains a novel alpha-defensin-like peptide, RK-2. This work establishes the existence of a new subfamily of alpha-defensins in the kidney.

Amino Acid Sequence↗
PubMed1998

Detection of genital human papillomavirus and associated cytological abnormalities among college women.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is strongly implicated in the etiology of cervical neoplasia; however, the frequency, rate, and predictors of neoplastic progression are unknown. GOAL: To measure the type-specific prevalence of cervical HPV and the rate of development of cytological abnormalities among a cohort of college women and to elucidate factors associated with acquisition of HPV DNA and progression to cytological abnormalities. STUDY DESIGN: Women 18 to 40 years of age seeking routine gynecologic care at a university health center were enrolled in a cross-sectional study with prospective, longitudinal follow-up of a subset of women. Demographic and behavioral data were collected using a written questionnaire. HPV DNA was detected in cervical scrapes by polymerase chain reaction using L1 consensus primers and a generic and 25 type-specific probes, and cervical cytological abnormalities were identified by Papanicolaou's (Pap) smear. RESULTS: HPV DNA was detected in 35% of the 414 women in the cross-sectional study; 66% of infections were with intermediate or high cancer risk HPV types. Multiple lifetime sex partners was an independent predictor of prevalent infection. Longitudinal analysis of 205 women showed that detection was transient (HPV DNA absent at follow-up) in 38% of the 84 women who were HPV-positive at enrollment. Persistent detection of the same HPV type at > or = 2 visits occurred in 14% of women and was significantly more common when intermediate or high cancer risk types were present. After 16 months of observation, 9% of HPV-infected women developed low-grade squamous intraepithelial lesions (SIL) and 5% developed high-grade SIL; the risk of incident SIL was 7.8-fold higher among women who had persistent HPV detection with the same type. CONCLUSIONS: It was concluded that cervical HPV infection is highly prevalent among college women. Although most infections are caused by intermediate of high cancer risk types, few women (5%) developed high-grade SIL during 16 months of observation.

Adolescent↗
PubMed1998

Biochemistry of coenzyme B12-dependent glycerol and diol dehydratases and organization of the encoding genes.

Glycerol and diol dehydratases exhibit a subunit composition of alpha 2 beta 2 gamma 2 and contain coenzyme B12 in the base-on form. The dehydratase reaction proceeds via a radical mechanism. The dehydratases are subject to reaction inactivation by the substrate glycerol which is caused by a cessation of the catalytic cycle because coenzyme B12 is not regenerated, instead 5'-deoxyadenosine and a catalytically inactive cobalamin are formed. The genetic organization of the dehydratase genes is quite similar in all organisms. Downstream of the dehydratase genes an open reading frame encoding a polypeptide of approximately 600 amino acids was identified which is apparently involved in the reactivation of suicide-inactivated enzyme.

Amino Acid Sequence↗
PubMed1997

Mass spectrometric determination of the cleavage sites in Escherichia coli dihydroorotase induced by a cysteine-specific reagent.

Escherichia coli dihydroorotase contains six cysteines/subunit, which are potential ligands of structural and catalytic zinc metals at protein sites of the enzyme. Specific thiol reagents modify, in nondenaturing conditions only, two of these cysteines; these two residues are thought to be ligands of structural zinc. We report here on the localization of these two cysteines on the polypeptide chain through their cyanylation by 2-nitro-5-thiocyanobenzoic acid (NTCB) and the analysis by mass spectrometry of the protein adducts. This is the first study of E. coli dihydroorotase by mass spectrometry, allowing the accurate determination of the subunit molecular weight (38,695). Treatment of dihydroorotase by NTCB induced a cleavage N-terminal to the cyanylated cysteines. The resulting fragments visualized on electrophoresis gel have been N-terminal sequenced, and their masses were determined by electrospray-ionizing mass spectrometry. This allowed the identification of cysteines 221 and 265 as the two residues cyanylated by the reagent NTCB. Results from gel filtration of dihydroorotase cyanylated on the two cysteines indicate that these residues are involved in subunit interactions leading to the active dimer. Consistent with literature data, we assume that cysteine 221 and cysteine 265, along with the neighboring cysteines 263 and 268 arranged in cluster, are potential ligands of structural zinc of E. coli dihydroorotase.

Binding Sites↗
PubMed1997

Glycerol conversion to 1,3-propanediol by Clostridium pasteurianum: cloning and expression of the gene encoding 1,3-propanediol dehydrogenase.

When grown on glycerol as sole carbon and energy source, cell extracts of Clostridium pasteurianum exhibited activities of glycerol dehydrogenase, dihydroxyacetone kinase, glycerol dehydratase and 1,3-propanediol dehydrogenase. The genes encoding the latter two enzymes were cloned by colony hybridization using the dhaT gene of Citrobacter freundii as a heterologous DNA probe and expressed in Escherichia coli. The native molecular mass of 1,3-propanediol dehydrogenase (DhaT) is 440,000 Da. The dhaT gene of C. pasteurianum was subcloned and its nucleotide sequence (1158 bp) was determined. The deduced gene product (41,776 Da) revealed high similarity to DhaT of C. freundii (80.5% identity; 89.8% similarity).

Alcohol Dehydrogenase↗
PubMed1997

Why are new patients coming to the eye clinic? An analysis of the relative frequencies of ophthalmic disease amongst new patients attending hospital eye clinics in two separate locations.

We have analysed 64,417 patient-attendances by 56,409 patients to a dedicated ophthalmic new patient service to assess the demographic and epidemiological parameters of this population. Forty-three point five per cent were male and 56.5% female. Nine per cent of patients were under 16 years of age while 27.5% were over 70 years. Comparison of patients attending an outreach new patient clinic with that at the main hospital showed that a higher proportion of patients under 16 years were seen at the outreach clinic (p < 0.001), whereas the main clinic saw a higher proportion of patients in the 16-69 year age group (p < 0.001).

Adolescent↗
PubMed1997

Radiolucent pancreatic lithiasis: a precursor stage for calcified pancreatic lithiasis or a new entity?

OBJECTIVE: Radiolucent pancreatic lithiasis (RPL) has been identified as a different entity from calcified pancreatic lithiasis. The purpose of this study is to evaluate the frequency, characteristics and evolution of RPL. PATIENTS: Between 1983 and 1995, 278 consecutive patients who presented with pancreatic lithiasis were studied. Forty-four patients had RPL (15.8%): 27 had pure radiolucent stones (PRS) (group 1), 5 had pure radiolucent stones combined with evenly calcified stones (ECS) (group 2), 2 had target calculi (TC) (radiolucent core with calcified shell) (group 3), 10 had TC combined with ECS (group 4). RESULTS: Among the 27 patients with PRS, there were 19 males with a mean age of 41 years. PRS were mainly located in the head of the pancreas with a mean diameter of 5 mm (range 3-26 mm). Seven patients among 27 with PRS (26%) were less than 20 years old (juvenile form) or more than 60 years old (senile form). They were characterized by no or low alcohol consumption and a high rate of attacks of acute pancreatitis. In group 1, PRS turned to more advanced calcified stages in 6/16 of patients (37%) followed in 30 to 144 months with a prior stage of TC in 2 cases. An evolution toward more calcified stages (TC or ECS) occurred in half of the patients belonging to group 2 and 4 in 36 to 84 months. Genetic disposition and alcohol consumption could account for the evolution toward more calcified stages. A genetic factor is suggested by a rapid evolution to evenly calcified stones in two aged children 8 and 10 years and by a high frequency of familial cases in patients belonging to groups 2 and 4 (60% and 20%) as compared to group 1 with PRS (4%). Alcohol consumption could accelerate the calcifying process since patients belonging to groups 2 and 4 had a significantly higher alcohol consumption than those with PRS (group 1). CONCLUSION: RPL is a heterogeneous pancreatic disease including juvenile and senile presentation which may represent about 15% of pancreatic lithiasis. Evolution towards calcified stages (PRS then TC then ECS) occurred in 37-50% of cases and could be related to a genetic factor and increased alcohol consumption.

Adolescent↗
PubMed1997

Comparison of PCR and hybrid capture methods for detection of human papillomavirus in injection drug-using women at high risk of human immunodeficiency virus infection.

We compared Hybrid Capture, a new technique for detection of human papillomaviruses (HPV), with a PCR assay based on L1 consensus primers. By both methods, the HPV prevalence was higher in human immunodeficiency virus (HIV)-positive women than in HIV-negative women. PCR had a higher sensitivity (0.89 versus 0.48) but lower specificity (0.43 versus 0.93) for detection of Pap smear abnormalities, compared to Hybrid Capture. The higher intensity of hybridization signal by PCR was related to higher estimates of viral load by Hybrid Capture.

DNA, Viral↗
PubMed1997

Double-blind, randomized comparison of itraconazole capsules vs. placebo in the treatment of toenail onychomycosis.

Three multicenter, randomized, double-blind, placebo-controlled studies were conducted to determine whether twelve weeks of therapy with itraconazole, 200 mg, was effective in the treatment of dermatophyte infection of the toenail. Significantly more patients treated with itraconazole (110 patients) than with placebo (104 patients) achieved clinical (65 percent vs. 3 percent) and mycologic (54 percent vs. 6 percent) success. The mean percentage of affected reference nail before the initiation of therapy was 76 percent. Adverse events were comparable in the two treatment groups. These findings demonstrate that twelve weeks of continuous itraconazole, 200 mg once daily, is a highly effective, well-tolerated therapy for the management of toenail onychomycosis.

Adolescent↗
PubMed1996

Structural and functional analysis of a promoter of the human granulin/epithelin gene.

Granulins (grns) or epithelins (epis) are peptides with molecular masses of approx. 6 kDa that modulate the growth of cells. The precursor for the grns/epis, which might itself be biologically active, is a secreted glycoprotein containing multiple repeats of the grn/epi motif. Grn/epi mRNA occurs widely in vivo, particularly in tissues rich in epithelial and haematopoietic cells. To understand better the role of the gene products for grn/epi it is important to determine the patterns of grn/epi gene expression and how this is regulated. To assist in this we have obtained the 5' sequence of the human grn/epi gene, and using chimaeras of the grn/epi -5' sequence and the chloramphenicol acetyltransferase gene we have shown a strong promoter activity associated with the 5' sequence of the human grn/epi gene. We have further delineated regions of the 5' sequence that confer high-level expression on the chimaeric gene.

Animals↗
PubMed1996

Assay of Escherichia coli dihydroorotase with enantiomeric substrate: practical preparation of carbamyl L-aspartate and high-performance liquid chromatography analysis of catalysis product.

A reasonably facile and effective procedure is described for preparing the optically active substrate of dihydroorotase (EC 3.5.2.3), N-carbamyl-L-aspartate (L-CA), which is not commercially available. Compared to the previously described methods, this procedure is not plagued by side reactions, and the L-CA is obtained in a solid form as the Mg2+/K+ mixed salt. In that salt form, the L-CA can be prepared in large quantity, and it is easier to handle and stable upon storage. L-CA can be separated from aspartate and its cyclic derivatives, dihydroorotate and hydantoin, by HPLC using a strong anion-exchange column. This HPLC method, which is used to check the purity of the synthesized carbamyl aspartate, is also effective for monitoring the enzymatic reaction.

Aspartic Acid↗
PubMed1996

A cancer help centre.

The diagnosis of cancer can be shattering to all involved. The treatment of cancer is intense and often very challenging. Prevailing attitudes to cancer are sometimes fearful, negative and depressing. This combination may leave those affected by cancer shocked, disorientated and without hope. Even worse than this, on asking consultants 'What can I do to help myself?' patients are frequently told 'Absolutely nothing'--crushing in one fell swoop their remaining fighting spirit. Not so in the case of Penny Brohn, who, when faced with the diagnosis of breast cancer, travelled the world to find alternative cancer treatments, and having successfully brought her own cancer under control, dedicated her life to creating a Centre for others wishing to fight their disease.

Complementary Therapies↗
PubMed1996

Cloning, sequencing, and overexpression of the genes encoding coenzyme B12-dependent glycerol dehydratase of Citrobacter freundii.

The genes encoding coenzyme B12-dependent glycerol dehydratase of Citrobacter freundii were cloned and overexpressed in Escherichia coli. The B12-free enzyme was purified to homogeneity. It consists of three types of subunits whose N-terminal sequences are in accordance with those deduced from the open reading frames dhaB, dhaC, and dhaE, coding for subunits of 60,433 (alpha), 21,487 (beta), and 16,121 (gamma) Da, respectively. The enzyme complex has the composition alpha2beta2gamma2. Amino acid alignments with the subunits of the recently sequenced diol dehydratase of Klebsiella oxytoca (T. Tobimatsu, T. Hara, M. Sakaguchi, Y. Kishimoto, Y. Wada, M. Isoda, T. Sakai, and T. Toraya, J. Biol. Chem. 270:7142-7148, 1995) revealed identities between 51.8 and 70.9%.

Bacterial Proteins↗
PubMed1996

The ABL genes in normal and abnormal cell development.

Genetic alteration of the c-abl protooncogene has led to abnormal cellular development, primarily within the hemopoietic system. Different forms of oncogenic alteration have variations in biological strength for cellular transformation. The abnormal Abl oncoproteins are known to suppress apoptosis, which may be the basis for causing leukemia development. However, recent evidence also shows that c-abl proto-oncoprotein can inhibit apoptosis. Expression of the Abl oncoprotein in hemopoietic stem cells (HSCs) also results in alteration in the expression of certain cell surface molecules such that the interaction between HSCs and their marrow stroma microenvironment has become abnormal. The basis for the genetic alteration of the c-abl protooncogene in patients with chronic myelogenous leukemia may or may not be due to genetic imprinting.

Animals↗