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R H White

Publications and source records attributed to R H White.

At least 37 records · Page 2Linked to original sources
PubMed2000

Identification of an archaeal 2-hydroxy acid dehydrogenase catalyzing reactions involved in coenzyme biosynthesis in methanoarchaea.

Two putative malate dehydrogenase genes, MJ1425 and MJ0490, from Methanococcus jannaschii and one from Methanothermus fervidus were cloned and overexpressed in Escherichia coli, and their gene products were tested for the ability to catalyze pyridine nucleotide-dependent oxidation and reduction reactions of the following alpha-hydroxy-alpha-keto acid pairs: (S)-sulfolactic acid and sulfopyruvic acid; (S)-alpha-hydroxyglutaric acid and alpha-ketoglutaric acid; (S)-lactic acid and pyruvic acid; and 1-hydroxy-1,3,4,6-hexanetetracarboxylic acid and 1-oxo-1,3,4, 6-hexanetetracarboxylic acid. Each of these reactions is involved in the formation of coenzyme M, methanopterin, coenzyme F(420), and methanofuran, respectively. Both the MJ1425-encoded enzyme and the MJ0490-encoded enzyme were found to function to different degrees as malate dehydrogenases, reducing oxalacetate to (S)-malate using either NADH or NADPH as a reductant. Both enzymes were found to use either NADH or NADPH to reduce sulfopyruvate to (S)-sulfolactate, but the V(max)/K(m) value for the reduction of sulfopyruvate by NADH using the MJ1425-encoded enzyme was 20 times greater than any other combination of enzymes and pyridine nucleotides. Both the M. fervidus and the MJ1425-encoded enzyme catalyzed the NAD(+)-dependent oxidation of (S)-sulfolactate to sulfopyruvate. The MJ1425-encoded enzyme also catalyzed the NADH-dependent reduction of alpha-ketoglutaric acid to (S)-hydroxyglutaric acid, a component of methanopterin. Neither of the enzymes reduced pyruvate to (S)-lactate, a component of coenzyme F(420). Only the MJ1425-encoded enzyme was found to reduce 1-oxo-1,3,4,6-hexanetetracarboxylic acid, and this reduction occurred only to a small extent and produced an isomer of 1-hydroxy-1,3,4,6-hexanetetracarboxylic acid that is not involved in the biosynthesis of methanofuran c. We conclude that the MJ1425-encoded enzyme is likely to be involved in the biosynthesis of both coenzyme M and methanopterin.

Alcohol Oxidoreductases↗
PubMed2000

Identification of the gene encoding sulfopyruvate decarboxylase, an enzyme involved in biosynthesis of coenzyme M.

The products of two adjacent genes in the chromosome of Methanococcus jannaschii are similar to the amino and carboxyl halves of phosphonopyruvate decarboxylase, the enzyme that catalyzes the second step of fosfomycin biosynthesis in Streptomyces wedmorensis. These two M. jannaschii genes were recombinantly expressed in Escherichia coli, and their gene products were tested for the ability to catalyze the decarboxylation of a series of alpha-ketoacids. Both subunits are required to form an alpha(6)beta(6) dodecamer that specifically catalyzes the decarboxylation of sulfopyruvic acid to sulfoacetaldehyde. This transformation is the fourth step in the biosynthesis of coenzyme M, a crucial cofactor in methanogenesis and aliphatic alkene metabolism. The M. jannaschii sulfopyruvate decarboxylase was found to be inactivated by oxygen and reactivated by reduction with dithionite. The two subunits, designated ComD and ComE, comprise the first enzyme for the biosynthesis of coenzyme M to be described.

Amino Acid Sequence↗
PubMed2000

Identification of enzymes homologous to isocitrate dehydrogenase that are involved in coenzyme B and leucine biosynthesis in methanoarchaea.

Two putative Methanococcus jannaschii isocitrate dehydrogenase genes, MJ1596 and MJ0720, were cloned and overexpressed in Escherichia coli, and their gene products were tested for the ability to catalyze the NAD- and NADP-dependent oxidative decarboxylation of DL-threo-3-isopropylmalic acid, threo-isocitrate, erythro-isocitrate, and homologs of threo-isocitrate. Neither enzyme was found to use any of the isomers of isocitrate as a substrate. The protein product of the MJ1596 gene, designated AksF, catalyzed the NAD-dependent decarboxylation of intermediates in the biosynthesis of 7-mercaptoheptanoic acid, a moiety of methanoarchaeal coenzyme B (7-mercaptoheptanylthreonine phosphate). These intermediates included (-)-threo-isohomocitrate [(-)-threo-1-hydroxy-1,2, 4-butanetricarboxylic acid], (-)-threo-iso(homo)(2)citrate [(-)-threo-1-hydroxy-1,2,5-pentanetricarboxylic acid], and (-)-threo-iso(homo)(3)citrate [(-)-threo-1-hydroxy-1,2, 6-hexanetricarboxylic acid]. The protein product of MJ0720 was found to be alpha-isopropylmalate dehydrogenase (LeuB) and was found to catalyze the NAD-dependent decarboxylation of one isomer of DL-threo-isopropylmalate to 2-ketoisocaproate; thus, it is involved in the biosynthesis of leucine. The AksF enzyme proved to be thermostable, losing only 10% of its enzymatic activity after heating at 100 degrees C for 10 min, whereas the LeuB enzyme lost 50% of its enzymatic activity after heating at 80 degrees C for 10 min.

3-Isopropylmalate Dehydrogenase↗
PubMed2000

Optimization of inpatient warfarin therapy: impact of daily consultation by a pharmacist-managed anticoagulation service.

OBJECTIVE: To determine the effect of daily consultation by a team of hospital pharmacists on the accuracy and rapidity of optimizing warfarin therapy. DESIGN: Comparison of a historical control cohort with a prospective cohort matched for treatment indication. SETTING: A 400-bed university teaching hospital. PATIENTS: Sixty consecutive patients hospitalized in 1992 and starting warfarin for the first time, with anticoagulation therapy managed by physicians, were compared with 60 patients matched for warfarin indication hospitalized in 1995, but with anticoagulation therapy managed with pharmacy consultation. RESULTS: Pharmacist management of initial warfarin therapy resulted in a significant reduction in the length of hospitalization compared with physician dosing, from 9.5 +/- 5.6 days to 6.8 +/- 4.4 days (p = 0.009). The number of patients and patient-days with international normalized ratio (INR) values >3.5 were reduced by pharmacist dosing from 37 patients and 142 days to 16 patients and 29 days, respectively (p < 0.001). Similarly, the number of patients and patient-days with INR >6.0 were reduced from 20 patients and 50 days to two patients and six days, respectively (p < 0.001). There were six documented bleeding complications in 1992 compared with one in 1995 (p = 0.11). The mean INR at discharge was significantly lower in the pharmacy surveillance group, 2.6 +/- 0.58, compared with the physician cohort, 3.3 +/- 2.1 (p = 0.07). Readmissions after discharge due to bleeding or recurrent thrombosis were reduced from five (at 1 mo) and 10 (at 3 mo) to two and five readmissions, respectively, by pharmacist intervention (p = 0.43). The number of patients with concurrently prescribed drugs known to significantly interact with warfarin was significantly lower (6 vs. 13; p = 0.02) in the pharmacy surveillance group. CONCLUSIONS: Among patients starting warfarin for the first time, daily consultation by a pharmacist significantly decreased the length of hospital stay and the number of patients who received excessive anticoagulation therapy. These findings translate into improved quality of care and potentially significant cost savings.

Anticoagulants↗
PubMed2000

A comparison of point-of-care instruments designed for monitoring oral anticoagulation with standard laboratory methods.

Our study compared point-of-care (POC) device monitoring with traditional clinical laboratory methods device of patients on oral anticoagulant therapy. The POC devices used in the study were Coumatrak, CoaguChek, CoaguChek Plus, Thrombolytic Assessment System (TAS) PT-One, TAS PTNC, TAS PT, Hemachron Jr. Signature, ProTime Microcoagulation System, and Medtronics ACT II. The clinical laboratory method used thromboplastins with different ISI values: Innovin and Thromboplastin C Plus (TPC). All POC INRs showed strong correlation with both laboratory methods, with correlation coefficients of >0.900. All POC methods demonstrated a significant (p <0.05) difference in INR values, except the TAS PTNC and ACT II INRs (p: 0.12 and 0.71 respectively) when compared with Innovin INRs. All POC INRs were significantly different from TPC generated INRs (p <0.05). Comparisons of the POC INRs to the group mean of the POC methods, show higher correlation (R>0.93), but there were still significant (p<0.05) differences noted between the POC group INR mean and CoaguChek Plus, ACT II, TAS PT-One, TAS PTNC, and Hemachron Jr Signature INRs. These data indicate that POC INR biases exist between laboratory methods and POC devices. Until a suitable whole blood INR standardization method is available, we conclude that clinicians using point-of-care anticoagulation monitoring should be aware of differences between POC and parent laboratory values.

Administration, Oral↗
PubMed1999

Coexistence of thin membrane and alport nephropathies in families with haematuria.

The finding of familial haematuria without a history of deafness or renal impairment is often assumed to indicate a benign prognosis. However, we describe three families in whom Alport and thin basement membrane nephropathy were separately identified within the same pedigree. Our findings illustrate the importance of fully investigating families with haematuria, even if thin basement nephropathy has been diagnosed in one member.

Basement Membrane↗
PubMed1999

Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort.

PURPOSE: To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation. SUBJECTS AND METHODS: This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995. RESULTS: In 1995, 172 (4.1%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95% CI 0.2-1.0). CONCLUSIONS: Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.

Administration, Oral↗
PubMed1999

Major bleeding after hospitalization for deep-venous thrombosis.

PURPOSE: Most studies of oral anticoagulant-related bleeding have analyzed the incidence of adverse outcomes among patients with a variety of different conditions and without any comparison with a control group. We determined the incidence, time course, and risk factors associated with major bleeding after hospital discharge among patients with deep-vein thrombosis, and estimated the excess risk of bleeding associated with oral anticoagulant therapy. METHODS: A total of 22,000 adults were hospitalized in California for 3 or more days with a diagnosis of deep-venous thrombosis between January 1, 1992, and September 30, 1994. We determined the risk factors associated with readmission for bleeding. We compared the incidence of readmission for bleeding with comparison cohorts of patients with pneumonia or cellulitis who were matched for age, gender, race, and length of hospital stay. RESULTS: Of 21,250 patients with deep-venous thrombosis who were discharged without bleeding, 1.4% were readmitted for bleeding within 91 days; the rate was 2.7 times greater in the first 30 days than in the next 61 days. Risk factors for bleeding included hospitalization with gastrointestinal bleeding during the previous 18 months (relative hazard [RH] = 2.6, 95% confidence interval [CI]: 1.6 to 4.1), hospitalization with an alcohol-related diagnosis during the previous 18 months (RH = 2.6, 95% CI: 1.4 to 4.8), chronic renal disease (RH = 2.4, 95% CI: 1.4 to 4.2), female gender (RH = 1.7, 95% CI: 1.3 to 2.2), presence of a malignancy (RH = 1.6, 95% CI: 1.2 to 2.2), nonwhite race (RH = 1.6, 95% CI: 1.2 to 2.1), and age over 65 years (RH = 1.3, 95% CI: 1.0 to 1.7). Significantly more women (n = 40) had intracranial bleeding than men (n = 18, P = 0.02). In the comparison cohorts, the incidence of readmission for bleeding within 3 months of discharge was 0.7%, and the relative risk (RR) of readmission was greater in those with deep-venous thrombosis than in those with cellulitis (RR = 2.0, 95% CI: 1.6 to 2.5) or pneumonia (RR = 2.0, 95% CI: 1.7 to 2.5). CONCLUSIONS: The incidence of rehospitalization for bleeding was greatest in the first 30 days after discharge, and was approximately twice that seen in patients hospitalized for cellulitis or pneumonia. Further studies are needed to determine why women and nonwhite patients are at increased risk for anticoagulant-related bleeding.

Adult↗
PubMed1999

Identifying two ancient enzymes in Archaea using predicted secondary structure alignment.

It is now possible to compare life forms at high levels of detail and completeness due to the increasing availability of whole genomes from all three domains. However, exploration of interesting hypotheses requires the ability to recognize a correspondence between proteins that may since have diverged beyond the threshold of detection by sequence-based methods. Since protein structure is far better conserved than protein sequence, structural information can enhance detection sensitivity, and this is the basis for the field of structural genomics. Demonstrating the effectiveness of this approach, we identify two important but previously elusive Archaeal enzymes: a homolog of dihydropteroate synthase and a thymidylate synthase. The former is especially noteworthy in that no Archaeal homolog of a bacterial folate biosynthetic enzyme has been found to date. Experimental confirmation of the deduced activity of both enzymes is described. Identification of two different proteins was attempted deliberately to help allay concern that predictive success is merely a lucky accident.

Archaea↗
PubMed1999

(R)-citramalate synthase in methanogenic archaea.

The Methanococcus jannaschii gene MJ1392 was cloned, and its protein product was hyperexpressed in Escherichia coli. The resulting protein was purified and shown to catalyze the condensation of pyruvate and acetyl coenzyme A, with the formation of (R)-citramalate. Thus, this gene (cimA) encodes an (R)-citramalate synthase (CimA). This is the first identification of this enzyme, which is likely involved in the biosynthesis of isoleucine.

Acetyltransferases↗
PubMed1998

Mechanism for the enzymatic formation of 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate during the biosynthesis of methanopterin.

A central step in the biosynthesis of the modified folate methanopterin is the condensation of p-aminobenzoic acid (pAB) and 5-phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) which produce 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate (beta-RFA-P) [White, R. H. (1996) Biochemistry 35, 3447-3456]. This reaction, catalyzed by the enzyme beta-RFA-P synthase, is unique among known phosphoribosyltransferases in that a decarboxylation of one of the substrates (pAB) occurs during the reaction and a C-riboside rather than an N-riboside is the product. In this work, the reaction catalyzed by the enzyme from Methanosarcina thermophila is shown to be analogous to other phosphoribosyltransferase reactions in that pyrophosphate is released as a product of the reaction, which is dependent upon magnesium ions. The molecular weight of the enzyme was estimated to be 65 000 using gel filtration chromatography, and the pH optimum was 4.8. Kinetic analysis indicated that the reaction involved a sequential pattern of substrate binding. Benzoic acid and several para-substituted benzoic acids inhibited beta-RFA-P synthase activity, while aniline, 4-aminobenzamide, and the methyl ester of pAB did not, indicating that an ionized carboxylic group plays a role in the binding of pAB. The observation that the enzyme was not inhibited by carbonyl reagents and that 4-hydroxybenzoic acid served as an alternate substrate, producing 4-(beta-D-ribofuranosyl)hydroxybenzene 5'-phosphate as the product, indicated that pyridoxal phosphate was not directly involved in the reaction mechanism. Incubation of the enzyme with PRPP and either pAB or 4-aminothiobenzoic acid in the presence of sodium cyanoborohydride led to the decreased production of beta-RFA-P and the accumulation of a reduced form of the proposed cyclohexadienimine reaction intermediates. These compounds were characterized by their acid-catalyzed decomposition which produces beta-D-ribofuranosylbenzene 5'-phosphate. On the basis of these results, a concerted mechanism is proposed for beta-RFA-P synthase in which an SN1-like reaction produces oxonium ion character at C-1 of PRPP which undergoes an ipso electrophilic aromatic substitution reaction at the carboxylic acid-bound carbon of pAB. Decarboxylation of the resulting cyclohexadienimine intermediate leads to the formation of beta-RFA-P.

4-Aminobenzoic Acid↗
PubMed1998

Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty.

BACKGROUND: Little is known about the incidence and time course of clinical thromboembolic events after total hip or knee arthroplasty, particularly after hospital discharge. METHODS: We used a linked hospital discharge database provided by the State of California to identify cases diagnosed as having deep vein thrombosis or pulmonary embolism within 3 months of unilateral total hip or knee arthroplasty. Also, we surveyed orthopedic surgeons to estimate the frequency of postoperative thromboprophylaxis during July 1991 through June 1993. Medical charts were audited to determine the accuracy of the coded records. RESULTS: Among 19,586 primary hip and 24,059 primary knee arthroplasties, the cumulative incidence of deep vein thrombosis or pulmonary embolism within 3 months of surgery was 556 (2.8%) after hip arthroplasty and 508 (2.1%) after knee arthroplasty. The diagnosis of thromboembolism was made after hospital discharge in 76% and 47% of the total hip and total knee arthroplasty cases, respectively (P<.001), with a median time of diagnosis of 17 days and 7 days after surgery, respectively (P<.001). Questionnaire results indicated that 95% of all cases received thromboprophylaxis and that the frequency, type, and duration of thromboprophylaxis was virtually identical after hip and knee arthroplasty. CONCLUSIONS: There is a difference in the temporal patterns of clinically symptomatic thromboembolic complications after total hip and total knee arthroplasty, suggesting differences in pathogenesis or natural history. The findings suggest that to further reduce thromboembolic outcomes, earlier, more intense prophylaxis may be needed for total knee arthroplasty, and more prolonged prophylaxis may be required after total hip arthroplasty.

Aged↗
PubMed1998

Alpha-keto acid chain elongation reactions involved in the biosynthesis of coenzyme B (7-mercaptoheptanoyl threonine phosphate) in methanogenic Archaea.

The biochemistry of the 13 steps involved in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to the coenzymes coenzyme B (7-mercapto heptanoylthreonine phosphate) and biotin, has been established in Methanosarcina thermophila. These series of reactions begin with the condensation of alpha-ketoglutarate and acetylCoA to form trans-homoaconitate. The trans-homoaconitate is then hydrated and dehydrated to cis-homoaconitate with (S)-homocitrate serving as an intermediate. Rehydration of the cis-homoaconitate produces (-)-threo-isohomocitrate [(2R,3S)-1-hydroxy-1,2, 4-butanetricarboxylic acid], which undergoes a NADP+-dependent oxidative decarboxylation to produce alpha-ketoadipate. The resulting alpha-ketoadipate then undergoes two consecutive sets of alpha-ketoacid chain elongation reactions to produce alpha-ketosuberate. In each of these sets of reactions, it has been shown that the homologues of cis-homoaconitate, homocitrate, and (-)-threo-isohomocitrate serve as intermediates. The protein product of the Methanococcus jannaschii MJ0503 gene aksA (AksA) was found to catalyze the condensation of alpha-ketoglutarate and acetylCoA to form trans-homoaconitate. This gene product also catalyzed the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologues of (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2, 6-hexanetricarboxylic acid. The alpha-ketosuberate resulting from this series of reactions then undergoes a nonoxidative decarboxylation to form 7-oxoheptanoic acid, a precursor to coenzyme B, and an oxidative decarboxylation to form pimelate, the precursor to biotin. Of the 13 intermediates in this pathway, eight have not previously been reported as occurring in biological systems.

Acetyl Coenzyme A↗
PubMed1998

Length of hospital stay for treatment of deep venous thrombosis and the incidence of recurrent thromboembolism.

BACKGROUND: Current guidelines suggest that all patients with acute deep venous thrombosis should be treated with intravenous heparin for at least 5 days, overlapping with warfarin sodium for 4 to 5 days. METHODS: Using linked state of California hospital discharge records from 1991 to 1994 we identified patients with acute deep venous thrombosis without pulmonary embolism, and determined the 6-month cumulative incidence of rehospitalization for recurrent thromboembolism. Coding was validated by reviewing the charts of 218 patients matched with the statewide data from 4 local hospitals. RESULTS: A total of 36924 linked records met study criteria. In the validation group, objectively confirmed thrombosis that was treated with intravenous heparin followed by warfarin was noted in 20%, 65%, 94%, and 95% of the patients who were hospitalized for 2 or fewer days or 3, 4, or 5 or more days, respectively. Statewide, among patients hospitalized for 3, 4, 5, and 6 days, the 6-month cumulative incidence of hospitalization for recurrent thromboembolism was 5.4%, 5.1%, 5.4%, and 6.0%, respectively. Multivariate modeling of patients hospitalized for 3 to 10 days revealed that recurrent thromboembolism was associated with the length of hospitalization (odds ratio [OR], 1.06 each additional day; 95% confidence interval [CI], 1.04-1.08), presence of malignancy (OR, 1.58; 95% CI, 1.46-1.68), age (OR, 0.85 each 10 years; 95% CI, 0.84-0.86), dementia (OR, 0.38; 95% CI, 0.26-0.49), hospitalization for multiple injuries within 3 months (OR, 0.46; 95% CI, 0.32-0.60), and surgery within 3 months (OR, 0.84; 95% CI, 0.78-0.90). CONCLUSIONS: We found no evidence that a stay of 4 days for treatment of deep venous thrombosis was associated with a higher rate of recurrent thromboembolism compared with hospitalization for 5 or more days. Although the evidence was not as strong, the incidence of recurrent thromboembolism after a stay of 3 days appeared comparable with that after a stay of 5 days. These findings suggest that fewer than 5 days of intravenous heparin overlapping with warfarin may provide effective initial treatment for deep venous thrombosis among patients deemed ready for hospital discharge.

Anticoagulants↗
PubMed1998

Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California.

BACKGROUND: Few studies have compared the incidence of deep venous thrombosis among ethnic groups. OBJECTIVE: To determine the incidence of deep venous thrombosis among ethnic groups. DESIGN: Analysis of the linked California Patient Discharge Data Set from 1991 to 1994. SETTING: California. PATIENTS: 17991 patients with idiopathic deep venous thrombosis (thrombosis without cancer or hospitalization within preceding 6 months) and 5573 patients with secondary thromboembolism (thromboembolism occurring within 3 months of seven different events). MEASUREMENTS: Ethnicity was determined by using race as documented in the data set. For idiopathic deep venous thrombosis, standardized age- and sex-adjusted incidences were calculated. For secondary thromboembolism, proportional hazards modeling was done. RESULTS: The annual incidence of idiopathic deep venous thrombosis per 1000000 persons older than 18 years of age was 230 for white persons, 293 for African Americans (rate ratio, 1.27 [95% CI, 1.07 to 1.51]), 139 for Hispanic persons (rate ratio, 0.60 [CI, 0.54 to 0.67]), and 60 for Asians and Pacific Islanders (rate ratio, 0.26 [CI, 0.22 to 0.30]). Compared with white persons, Asians and Pacific Islanders who developed secondary thromboembolism had a significantly lower relative risk (range, 0.22 to 0.61) for all seven conditions analyzed. CONCLUSIONS: Compared with white persons, Asians and Pacific Islanders have a very low incidence of idiopathic deep venous thrombosis and a very low relative risk for secondary venous thromboembolism.

Adult↗
PubMed1998

Methanopterin biosynthesis: methylation of the biosynthetic intermediates.

The basic scheme for the biosynthesis of methanopterin (MPT) in Methanobacterium thermoautotrophicum strain DeltaH, and M. thermoautotrophicum strain Marburg, has been shown to be the same as that recently determined for Methanosarcina thermophila strain TM-1. This scheme has, as one of its unique steps, the condensation of 4-aminobenzoic acid with 5-phospho-alpha-d-ribosyl diphosphate (PRPP) to form 4-(beta-d-ribofuranosyl)aminobenzene 5'-phosphate (beta-RFA-P). Labeling experiments with each of these organisms have established that the sites in the overall sequence of reactions from beta-RFA-P to MPT, where the S-adenosylmethionine-dependent C-9 and C-7 methylations of the pterin-containing intermediates occur, are organism related. In this work, cell extracts of M. thermoautotrophicum strain DeltaH, and M. thermoautotrophicum strain Marburg were found to contain significant amounts of methanopterin lacking the phosphate and 2-hydroxyglutaric acid groups.

Azo Compounds↗
PubMed1998

Renal biopsy diagnosis in children presenting with haematuria.

We reviewed the clinical and renal biopsy findings in 322 children presenting during the years 1975-1996 with recurrent macro- or continuous microscopic haematuria persisting for > or =6 months, in whom non-glomerular causes were excluded. Family involvement was documented for first-degree relatives. All biopsies were examined by light microscopy, 317 by electron microscopy and 315 by immunofluorescence. Biopsies were classified as IgA nephropathy (78), Alport nephropathy (86), thin basement membrane nephropathy (TMN) (50), miscellaneous glomerulonephritis (32), hilar vasculopathy (28) and normal glomeruli (48). Although microscopic haematuria alone was more frequent in Alport nephropathy and TMN, the pattern of haematuria in individual patients did not predict histology. Of patients with familial haematuria, 79% of biopsies showed either Alport nephropathy or TMN. Hilar vasculopathy was observed both in isolation and in all abnormal histological categories.

Adolescent↗