Antibodies to Proteus in rheumatoid arthritis.
Increased levels of Proteus antibodies were found in patients with rheumatoid arthritis and coeliac disease, when compared to normal controls or patients with SLE and sarcoidosis.
Biomedical subjects
Publications and source records attributed to P Rogers.
Increased levels of Proteus antibodies were found in patients with rheumatoid arthritis and coeliac disease, when compared to normal controls or patients with SLE and sarcoidosis.
The combination of the lipophilic antifolate trimetrexate and the rescue agent leucovorin has shown promise in the treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. The pharmacokinetic behavior of trimetrexate administered either by intravenous bolus or orally was studied in six patients with acquired immunodeficiency syndrome with a reversed-phase high-pressure liquid chromatography assay. The mean clearance following bolus injection was 38 ml/min per m2, with a range of 15 to 55 ml/min per m2. The postdistributive half-life ranged from 6 to 16 h. With oral administration, the mean bioavailability was 44% (range, 19 to 67%). An oral dose of 60 mg/m2 (162 mumol/m2) resulted in concentrations in plasma that approximated those achieved with a 30-mg/m2 (81-mumol/m2) intravenous dose. The toxicity of this combination regimen was minimal. It appears that the oral route is a practical route of administration for trimetrexate in patients with acquired immunodeficiency syndrome requiring long-term outpatient treatment or prophylaxis for P. carinii pneumonia.
The coenzyme A (CoA)-linked butyraldehyde dehydrogenase (BAD) from Clostridium acetobutylicum was characterized and purified to homogeneity. The enzyme was induced over 200-fold, coincident with a shift from an acidogenic to a solventogenic fermentation, during batch culture growth. The increase in enzyme activity was found to require new protein synthesis since induction was blocked by the addition of rifampin and antibody against the purified enzyme showed the appearance of enzyme antigen beginning at the shift of the fermentation and increasing coordinately with the increase in enzyme specific activity. The CoA-linked acetaldehyde dehydrogenase was copurified with BAD during an 89-fold purification, indicating that one enzyme accounts for the synthesis of the two aldehyde intermediates for both butanol and ethanol production. Butanol dehydrogenase activity was clearly separate from the BAD enzyme activity on TEAE cellulose. A molecular weight of 115,000 was determined for the native enzyme, and the enzyme subunit had a molecular weight of 56,000 indicating that the active form is a homodimer. Kinetic constants were determined in both the forward and reverse directions. In the reverse direction both the Vmax and the apparent affinity for butyraldehyde and caproaldehyde were significantly greater than they were for acetaldehyde, while in the forward direction, the Vmax for butyryl-CoA was fivefold that for acetyl-CoA. These and other properties of BAD indicate that this enzyme is distinctly different from other reported CoA-dependent aldehyde dehydrogenases.
Forty patients with a recently healed duodenal ulcer (DU) that presented with haemorrhage were entered into a blind, randomized study of maintenance ranitidine therapy (150 mg at night) versus a placebo preparation, to determine whether prolonged ranitidine therapy could influence the natural history of the ulcer diathesis. Duodenal ulceration or duodenal cap erosions of Lanza grade 3 recurred in 24 of the 40 patients studied during the 2-year trial period but was associated with further bleeding in only 2 cases. Maintenance ranitidine therapy significantly reduced the incidence and symptoms of DU/erosion recurrence at all time intervals beyond 3 months, the maximum protective effect being observed after 12 to 15 months of treatment (incidence, p less than 0.001; symptoms, p less than 0.03). The DU/erosion recurrence rate without treatment after 2 years of successful maintenance ranitidine therapy was significantly less than for patients randomized to the placebo group at entry to the study (p less than 0.03). Two years of maintenance ranitidine therapy appear to be beneficial for patients who have a healed DU that presented with haemorrhage. This treatment, however, cannot be recommended without reservation until the implications of the associated high incidence of asymptomatic duodenal ulceration have been fully evaluated.
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Ultrasonically guided transfer of embryos was performed transabdominally in 10 patients. The uterus was punctured by a 16-gauge needle with a stylet through a full urinary bladder. When the needle tip was in the uterine cavity the stylette was removed and a transfer catheter loaded with the embryos was inserted. No complications or technical difficulties were experienced. None of the patients became pregnant.
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A randomized controlled trial comparing the use-effectiveness between gamete intrafallopian transfer (GIFT) and in vitro fertilization (IVF) and embryo transfer (ET) procedures showed no significant difference in pregnancy rates in the management of patients presenting with idiopathic or male infertility. The cost-effectiveness of GIFT appears superior to IVF and ET with laparoscopic oocyte collection, but comparable to IVF-ET with ultrasonic oocyte collection. The lack of data on the fertilizing capacity of sperm in GIFT procedures in cases of male infertility is a real disadvantage and currently precludes the management of severe male infertility with this method.
Between 1 and 4% of human oocytes fertilized in vitro are tripronuclear. It has been reported that these tripronuclear oocytes can develop to grossly normal-appearing morulae and that chromosomally, these embryos could be triploid, diploid, or severely depleted. The etiology and proportion of apparently diploid and aneuploid embryos deriving from tripronuclear human oocytes is unknown. This study provides evidence for the first time that most (18 of 29) tripronuclear human oocytes cleave directly to 3-cells at the first cleavage division. These embryos have a severely abnormal (but not triploid) chromosomal complement. Furthermore, some (4 of 29) tripronuclear human oocytes cleave to 2-cells plus an extrusion, and these embryos are diploids, whereas some (7 of 29) cleave to 2-cells, and these embryos are triploid after the first cleavage division. These findings demonstrate that most tripronuclear human oocytes have an altered cleavage pattern at the first cleavage division, that most tripronuclear human oocytes (76% in this study) do not develop into triploid embryos, and that a correlation exists between the pattern of the first cleavage division and the subsequent karyotype of these embryos. Insight into the mechanisms by which these oocytes fail to develop into triploid embryos is also provided.
Spontaneous mutants of Clostridium acetobutylicum NRRL B643 that were resistant to allyl alcohol (AA) were selected and characterized. These mutants contained 10- to 100-fold reduced activities of butanol and ethanol alcohol dehydrogenase. The AA mutants formed two groups and produced no ethanol. Type 1 AA mutants produced significant amounts of a new solvent, butyraldehyde, and contained normal levels of the coenzyme A-dependent butyraldehyde dehydrogenase (BAD). Type 2 AA mutants produced no significant butyraldehyde and lower levels of all solvents, and they contained 45- to 100-fold lower activity levels of BAD. Following ethyl methanesulfonate mutagenesis, low-acid-producing (Acid) mutants were selected and characterized as superinduced solvent producers, yielding more than 99% of theoretical glucose carbon as solvents and only small amounts of acetate and butyrate. Following ethyl methanesulfonate mutagenesis, 13 sporulation-negative (Spo) mutants were characterized; and 3 were found to produce only butyrate and acetate, a minor amount of acetone, and no alcohols. These Spo mutants contained reduced butanol dehydrogenase activity and no BAD enzyme activity. The data support the view that the type 2 AA, the Acid, and the Spo mutants somehow alter normal regulated expression of the solvent pathway in C. acetobutylicum.
The transcription and translation of operons for arginine biosynthetic enzymes after arginine removal (arginine down shift) were studied in relA and relA+ strains of Escherichia coli. After arginine down shift, derepression of synthesis of the arginine biosynthetic enzymes ornithine carbamoyltransferase (argF) and argininosuccinate lyase (argH) began at about 15 min in relA+ cells but was delayed in relA cells for more than 2 h. However, both relA+ and relA cells accumulated high levels of argCBH mRNA, as shown by dot blot hybridization, after arginine down shift. After 15 min of arginine limitation, the proportion of ribosome-bound argCBH mRNA was equivalent in both relA+ and relA cells. During the 15 min after the arginine down shift, relA+ cells produced a significant burst of argF and argH enzyme synthesis when arginine was added back to the culture, whereas relA cells did not produce this burst of enzyme synthesis. The relA cells regained the ability to produce a burst of argF and argH enzyme synthesis when alpha-methylglucose-induced glucose starvation was combined with arginine limitation. Significant guanosine 5'-diphosphate 3'-diphosphate accumulated in relA cells under this condition. Our results support the view that during periods of severe amino acid limitation guanosine 5'-diphosphate 3'-diphosphate acts in some way to ensure the translation of argCBH mRNA.
Data have been analysed for 1775 laparoscopies that were undertaken for the collection of oocytes, and for 1401 embryo transfers that were undertaken for the treatment of infertility by in-vitro fertilization, by the Monash University in-vitro fertilization unit team. The cumulative success rates with multiple attempts were analysed by life-table analysis and life-table graphs were constructed. Almost half the patients were pregnant after five laparoscopies. These findings suggest that treatment should consist of multiple laparoscopies and that improvements should be aimed at decreasing the morbidity, stress and cost of multiple attempts.
We have applied single-crystal X-ray diffraction methods to analyze the structure of [alpha(FeII-CO)beta(MnII)]2, a mixed-metal hybrid hemoglobin that crystallizes in the deoxyhemoglobin quaternary structure (the T-state) even though it is half liganded. This study, carried out at a resolution of 3.0 A, shows that (1) the Mn(II)-substituted beta subunits are structurally isomorphous with normal deoxy beta subunits, and (2) CO binding to the alpha subunits induces small, localized changes in the T-state that lack the main directional component of the corresponding larger structural changes in subunit tertiary structure that accompany complete ligand binding to all four subunits and the deoxy to oxy quaternary structure change. Specifically, in the T-state, CO binding to the alpha heme group draws the iron atom toward the heme plane, and this in turn pulls the last turn of the F helix (residues 85 through 89) closer to the heme group. The direction of these small movements is almost perpendicular to the axis of the F helix. In contrast, when the structures of fully liganded and deoxyhemoglobin are compared, extensive structural changes occur throughout the F helix and FG corner, and the main component of the atomic movements in the F helix (in addition to the smaller component toward the heme) is in a direction parallel to the heme plane and toward the alpha 1 beta 2 interface. These findings are discussed in terms of the current stereochemical theories of co-operative ligand binding and the Bohr effect.
This study examines and compares the hemodynamic and sympathoadrenal response to bicycle exercise in hypertensive subjects during two weeks' treatment with a cardio-selective (metoprolol) and nonselective (propranolol) beta-blocker. The increase in plasma norepinephrine and epinephrine concentration following exercise was augmented to a similar degree with each beta-blocker. Pre-exercise blood pressure and heart rate were similar for the two drugs. However immediately after exercise and particularly after resting for 20 min post exercise, diastolic blood pressure was lower during metoprolol treatment. Systolic blood pressure was also lower 20 min post exercise during metoprolol treatment. These observations indicate that cardio-selective beta-blockers offer advantages in blood pressure control during exercise through intact vascular beta 2-adrenoceptors opposing sympathetically mediated vasoconstriction.
A randomized control trial involving 42 superovulated in vitro fertilization (IVF) patients was carried out to investigate the effects of providing supplementary progesterone (P) around the time of laparoscopy. P was given 12 to 15 hours and 1 hour before and 24 hours after laparoscopy in one group (group B); human chorionic gonadotropin was given 12 hours before laparoscopy in another group (group C); and the remainder received no treatment in addition to normal IVF procedures (group A). There was no difference in fertilization rate, the proportion of normally developing embryos, pregnancy rate, or birth rate between the treatment groups, We conclude that in the superovulation schedule used, P supplementation around the time of laparoscopy does not affect success rate of IVF.
A study was undertaken as a controlled comparison of two different superovulation induction protocols currently in use in major Australian in vitro fertilization (IVF) clinics. Thirty patients each from the Monash University and the Royal Women's Hospital (RWH) IVF programs were stimulated for ovulation induction by the other program. Once timing for oocyte retrieval was scheduled, all care reverted to the program from which the patient first came. Results given as pregnancies per patient commencing stimulation were: RWH patients on Monash protocol, 27%; RWH control patients, 15%; Monash patients on RWH protocol, 7%; Monash control patients, 13%. In the year preceding the trial pregnancy rates were 16.9% at Monash and 10.6% at RWH. Stimulation protocols were also compared with respect to each of administration, cost, and patient stress. The results of this cross-over trial demonstrated major differences between the two ovulation induction protocols studied, although it was not possible to conclude that differences in pregnancy rate were due to stimulation alone.
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Forty-four normotensive females, who were selected on the basis of lower prevailing potassium intake, participated in a two-period crossover study to assess the effects of potassium supplementation on blood pressure. They were randomly allocated to one of two groups who took either 80 mmol/day of KCl (Slow-K, Ciba Geigy), or matching placebo, for the first of two 4-week treatment periods. The treatments were reversed during the second 4-week period. Despite significant increases in both urinary and plasma potassium no consistent fall in blood pressure was seen during 80 mmol/day potassium intake.