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Biomedical subjects

J Auer

Publications and source records attributed to J Auer.

At least 109 records · Page 6Linked to original sources

Quality of life improvements in CAPD patients treated with subcutaneously administered erythropoietin for anemia.

Twenty-two continuous ambulatory peritoneal dialysis (CAPD) patients, mean age 48 years, at 3 U.K. renal units were assessed with the Nottingham Health Profile (NHP) before and after treatment with recombinant human erythropoietin (r-HuEPO). Mean (SD) hemoglobin (Hb) at baseline was 7.5 (1.0) gm/dL and 10.8 (1.5) gm/dL at retest. There were significant improvements in energy (p less than 0.0001), social life (p less than 0.005), relationships at home (p less than 0.05) and leisure pursuits (p less than 0.05). Twelve patients, mean age 51 years, who had already completed more than 9 months on r-HuEPO treatment were reassessed to determine the changes sustained. Mean (SD) Hb at second retest was 12.8 (1.3) gm/dL. Improvement in energy continued to be significant, and emotional wellbeing showed further improvement. Problems with household tasks, which had not shown significant improvement at Test B, were now considerably reduced (p = 0.016). The study showed far-reaching benefits similar to those reported in hemodialysis patients, in a population with a higher mean age and higher potential coexisting illness or disability than most reported hemodialysis studies.

Activities of Daily Living↗

The structure of the gene for ribosomal protein L5 in the archaebacterium Sulfolobus acidocaldarius.

The gene for the ribosomal protein L5 from the archaebacterium Sulfolobus acidocaldarius has been isolated and sequenced. The gene codes for a basic protein of molecular weight 29 165 Da. This protein shows substantial similarity to the equivalent protein from other archaebacteria as well as from yeast, and considerably less similarity to the equivalent eubacterial protein. These results support the concept of the archaebacteria as a monophyletic kingdom more closely related to eukaryotes than to eubacteria.

Amino Acid Sequence↗

Presence of a gene in the archaebacterium Methanococcus vannielii homologous to secY of eubacteria.

The nucleotide sequence of a gene located at the promoter-distal side of the 'spectinomycin-operon' homologue of the archaebacterium Methanococcus vannielii was determined. Its derived amino acid sequence displayed 20% (identical positions) or 52% (including conservative exchanges) similarity, respectively, to SECY from E coli. An alignment of the Methanococcus SECY with eubacterial SECY sequences showed the existence of 10 membrane-associated primary structure domains in equivalent positions. The 5' and 3' ends of the secY transcript were mapped and the gene was expressed in the T7 promoter/polymerase system in E col. The temperature-sensitive growth of the E coli mutant IQ292 which harbours a secYts mutation could be complemented by the secY gene from Methanococcus. This indicates that a protein integral to an archaebacterial ether-lipid membrane can be inserted into a eubacterial phospholipid membrane without apparent loss of function.

Amino Acid Sequence↗

Stepwise correction of anaemia by subcutaneous administration of human recombinant erythropoietin in patients with chronic renal failure maintained by continuous ambulatory peritoneal dialysis.

Sixteen anaemic CAPD patients (Hb less than 9 g/dl) were treated with thrice-weekly subcutaneous recombinant erythropoietin, epoetin-alfa. The dose was adjusted to induce a stepwise increase in haemoglobin. Fourteen patients reached a first target haemoglobin of 11.0-11.5 g/dl and eight of these a second of 13.0-13.5 g/dl, but one could not be maintained at this level. Failure to reach or maintain the second target in nine subjects was accounted for by incomplete responses associated with infection in one, extreme shortening of red-cell survival in another, and was unexplained in one subject. These three received the maximum dose studied of 450 IU/kg per week. Six other subjects were withdrawn from the study for reasons unrelated to treatment with erythropoietin. The median dose required to maintain the haemoglobin at 11.0-11.5 g/dl was 75 IU/kg per week and at 13.0-13.5 g/dl was 150 IU/kg per week. Quality of life, assessed in 12 patients at haemoglobin 11.0-11.5 g/dl, showed significant improvement in energy, and at 13.0-13.5 g/dl improvements in sleep and emotional wellbeing became significant. Twelve subjects required either institution of, or an increase in, treatment for hypertension. The thrice-weekly subcutaneous doses of erythropoietin were well tolerated and were a convenient and effective treatment for anaemia in patients on CAPD.

Adult↗

Is the sperm bacterial ratio a determining factor in impairment of sperm motility: an in-vitro study in man with Escherichia coli.

The effects of urogenital infection on male fertility are controversial. The object of this study was to assess whether contact between E. coli, one of the bacteria encountered most frequently in semen cultures, and sperm was involved in decreasing motility of the sperm. Sperm from healthy donors were therefore incubated at two concentrations (1.10(7) and 4.10(7) ml-1) with bacteria (10(4) and 10(6) bacteria ml-1 respectively). Sperm motility was assessed as a function of time. The endotoxin effect was also evaluated. Aliquots of the sperm were used as controls. The motility of a population of 10(6) sperm ml-1 was reduced significantly more by the presence of 10(6) ml-1 E. coli than a sperm population four times more numerous. Since the endotoxin had no effect on sperm motility, it is possible this phenomenon is due to bacterial adherence to the sperm. From this study, it is therefore probable that the presence of E. coli in semen decreases sperm motility, but that this depends on the sperm:bacterial ratio ml semen-1.

Bacterial Adhesion↗

Effect of urogenital infections on sperm parameters and hypofertility in man.

Urogenital infections can notably reduce the sperm's capacity of fecundation by affecting the spermatozoa directly. The aim of this study was to compare the main parameters of the spermogram of 2 groups of hypofertile subjects, the first group presenting negative semen cultures, the second one positive semen cultures. The only significantly different parameter between these 2 groups of hypofertile patients studied was motility. This anomaly alone could explain some states of hypofertility.

Adult↗

The Oxford-Manchester study of dialysis patients. Age, risk factors and treatment method in relation to quality of life.

A retrospective study of 159 patients who started Haemodialysis (HD) or Continuous Ambulatory Peritoneal Dialysis (CAPD), between 1981 and 1984 was carried out in two UK Renal Units. An extension of the study was carried out in one unit during 1985, gathering data on 30 patients aged greater than 65. The aim was to assess whether age, medical or social risk factors, or treatment method, affected perceived quality of life. Assessment was by standardised self-report questionnaire. The overall life satisfaction, measured on Cantril's ladder scale, showed no significant difference between dialysis patients and a normal population. On a quality of life semantic differential scale CAPD patients scored significantly better than HD patients. Satisfaction with sexual relationships showed marked deterioration in all age groups, but this did not seem to affect reported satisfaction with marriage. Those aged greater than 65 scored significantly better than younger patients on dialysis stress scales, and were generally more satisfied with life. When the study population was sub-divided into four groups, by age (less than or greater than 60) and presence or absence of additional factors, were seen to be those least satisfied with life on several different assessment scales.

Age Factors↗

The quality of life of dialysis patients treated with recombinant human erythropoietin.

In June 1986, eight haemodialysis patients, seven male, one female, entered a pilot trial of recombinant human erythropoietin (EPO) at the Churchill Hospital Renal Unit. Six patients completed the Nottingham Health Profile (NHP) before starting EPO therapy, in order to assess quality of life, and were retested when haemoglobin level reached 120 g/l. A further test was given at one year. Statistically significant improvements were seen in the areas of Energy and Emotional Wellbeing. In the subsequent UK trial, involving previously transfusion dependent patients from nine centres, the pre and post treatment NHP scores of a further 18 patients have been assessed. Highly significant improvements were found in Energy, Physical Mobility (p less than 0.005) and in Emotional Wellbeing (p less than 0.002). Improvements which did not reach significance were found in the areas of Sleep, Social Isolation and Pain problems. An increase in appetite, and less sensitivity to cold were noted by over one third of patients. Problems with Employment, Looking after the Home, and Relationships were greatly reduced. We conclude that early findings show EPO treatment to improve not only the haemoglobin levels, but also the quality of life of haemodialysis patients with the anaemia of end stage renal failure.

Anemia↗

Organization and structure of the Methanococcus transcriptional unit homologous to the Escherichia coli "spectinomycin operon". Implications for the evolutionary relationship of 70 S and 80 S ribosomes.

By means of an immunological approach and a subsequent chromosome-walking strategy a chromosomal region encoding ribosomal proteins in the archaebacterium Methanococcus vannielii was cloned. The determination of the nucleotide sequence of the 7.8 x 10(3) base DNA fragment revealed the existence of 14 putative ribosomal protein genes and two unidentified open reading frames. They are organized in a transcriptional unit that is very similar to the Escherichia coli "spectinomycin operon" in respect of both gene composition and gene order. The Methanococcus transcriptional unit contains, in addition to those genes whose products have a homologue in the E. coli operon, three genes whose products share sequence similarity with eukaryotic 80 S but not with eubacterial ribosomal proteins. The Methanococcus ribosomal proteins almost exclusively exhibit a higher sequence similarity to eukaryotic 80 S ribosomal proteins than to those of eubacteria and many of them have a size intermediate between those of their eukaryotic and eubacterial homologues. These results are discussed in terms of a hypothesis that implies that the recent eubacterial ribosome developed by a "minimization" process from a more complex organelle and that the archaebacterial ribosome has maintained features of this ancestor.

Archaea↗

Gene organization and structure of two transcriptional units from Methanococcus coding for ribosomal proteins and elongation factors.

Two transcriptional units coding for ribosomal proteins and protein synthesis elongation factors in Methanococcus vannielii have been cloned and analysed in detail. They correspond to the "streptomycin operon" and "spectinomycin operon" of the Escherichia coli chromosome. The following general conclusions can be drawn from comparison of the nucleotide and the derived amino acid sequences of ribosomal proteins from Methanococcus with those from eubacteria and eukaryotes. (i) Ribosomal protein and elongation factor genes in Methanococcus are clustered in transcriptional units corresponding closely to E. coli ribosomal protein operons with respect to both gene composition and organization. (ii) These transcriptional units contain, in addition, a few open reading frames whose putative gene products share sequence similarity with eukaryotic 80S but not with eubacterial, ribosomal proteins. They may correspond to "additional" ribosomal proteins of the Methanococcus ribosome, there being no functional homologues in the eubacterial ribosome. (iii) Methanococcus ribosomal proteins and elongation factors almost exclusively exhibit a higher sequence similarity to eukaryotic 80S ribosomal proteins than to those of eubacteria. (iv) Many Methanococcus ribosomal proteins have a size intermediate between those of their eukaryotic and eubacterial homologues. These results are discussed in terms of a hypothesis which implies that the recent eubacterial ribosome developed by a "minimization" process from a more complex organelle and that the archaebacterial ribosome has maintained features of this ancestor.

Amino Acid Sequence↗

E. coli infections of the lower urinary tract and their treatment by immunomodulation or combined immunomodulation and antigen therapy.

A model of infection by E. coli 022 of the lower urinary tract in the rat is described. The infection is characterized by the presence in the urine of a large number of E. coli (10(5)-10(7) bacteria per ml). There is pus formation in the urine. A few infected rats also exhibited prostate hypertrophy and the presence of ACB could be detected in some of the latter group. Treatment of the infected rats by the C. granulosum-derived immunomodulator P40, injected intravenously either as a single dose of 1 mg per rat 1 day after infection or as 2 fractionated doses of 0.5 mg 1 day and 3 days after infection resulted in sterilization of a significant number of urines. The interest of fractionating the dose of P40 is to reduce the incidence of prostate hypertrophy formation. Comparable results were obtained when P40 was given preventively to the rats either as a single dose 7 days before infection or as 2 fractionated doses 7 days and 1 day before infection. The association of a single preventive dose of 1 mg of P40 given 7 days before infection by administering a suspension of heat-killed E. coli 022, as a specific antigen, 1 day after infection permitted the sterilization of urines in all infected rats and prostate hypertrophy formation did not occur.

Adjuvants, Immunologic↗

[Effects of vaccination in urinary infections caused by Escherichia coli in rats].

The preventive effects of the immunomodulator P40 on the experimental E. coli infection of the lower urinary tract of the rat have been reported previously. In the present paper are presented the results obtained with the aid of vaccination using the same experimental model of infection in the rat. Active specific immunization of the animals with a vaccine consisting of the same strain as that used for infecting the rats afforded significant protection toward the infection. It is concluded that such vaccines could also be used in humans, either alone or in combination with other therapies with the aim at preventing recurrencies or relapses of infections of the lower urinary tract which were resistant to antibiotherapy.

Animals↗

Complete ulnas and fibulas in a pony foal.

Complete ulnas and fibulas were found in a 10-month-old Welsh Pony examined because of severe flexural deformity, with carpal and tarsal valgus deformities, in all limbs. Presence of these normally vestigial structures is considered a form of atavism. At one week of age, periosteal transection was performed for the angular deformity, resulting in no improvement. When performing this procedure, the authors recommend transection of these vestigial structures if present.

Animals↗

The immI region of Salmonella phage P22. 1. Characterisation of the mutants P22 cir4-1, P22 cir5-1 and P22 cir6-1.

Salmonella phage mutants P22 cir4-1, P22 cir5-1 and P22 cir6-1 at 37 degrees C form more or less clear plaques. The mutants complement each other and clear mutations of the immC region (Prell et al. 1983). The mutants exhibit a strongly reduced frequency of lysogenisation, but form stable prophages. The low frequency of lysogenisation of P22 cir5-1 and of P22 cir6-1 is suppressed by an additional ant- mutation. Similarly, about 50% of turbid plaque revertants of both mutants carry ant- suppressor mutations. This suggests interference by the cir5-1 and cir6-1 mutations with the expression of gene ant. In contrast, the cir4-1 mutation seems not to interfere with ant expression, the latent periods of P22 cir4-1 and P22 cir5-1 are reduced and extended, respectively. The geneticly related Salmonella phage L carries a gene able to complement P22 cir4-1.

Genes, Viral↗

The immI region of Salmonella phage P22. 2. The influence of the cir mutations on the regulation of antirepressor synthesis.

The effects were studied of three clear plaque mutations of phage P22 (cir4-1, cir5-1 and cir6-1) on antirepressor synthesis. The mutant site cir4-1 has no influence on the expression of gene ant. The cir5-1 and cir6-1 mutations prevent the repression of early ant synthesis shortly after infection: P22 cir5-1 exhibits a strong ant-overproduction because it renders the cir5 repressor protein defective for turning off early ant expression (Harvey et al. 1981). P22 cir6-1 exhibits only a low level of constitutive ant synthesis insensitive to cir5-directed repression. Complementation experiments between P22 wild type or mutant in the cir5 or cir6 sites reveal the following phenotypes of the cir6-1 mutation: (1) The cir6-1 site behaves as a weak promotor site insensitive to cir5-directed repression of ant synthesis. (2) In the P22 cir5-1 cir6-1 double recombinant the cir6-1 site is cis dominant preventing ant overproduction as observed in simple P22 cir5-1 infections. (3) Some of the deficient phenotypes of P22 cir6-1 can be complemented by co-infecting P22 mutants carrying a cir6+ allele. These results are explained by the following model: The active cir5 repressor protein is a dimer (or oligomer) and the cir5-1 and cir6-1 mutations map in different domains influencing the repressing as well as the dimer forming activities of this protein. Which particular cir6-1 phenotype is observed depends on the experimental conditions employed, and on the promotor site (either pANT or cir6-1) from which ant expression procedes.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene Expression Regulation↗

[Effect of an immunomodulator (P40) on Escherichia coli urinary infection in the rat].

The preventive effects of various doses of the immunomodulator P40 on the experimental E. coli infection of the upper and lower urinary tract have been investigated in the rat. Under our experimental conditions, P40 only weakly influenced the bacteriological picture of the infection in rats infected by the upper route. However, the development of nephropathia might be decreased. By contrast, P40 was found to prevent the development of infection in two thirds of cases infected by the lower route. The preventive effect of P40 on infections of the lower urinary tract seems to be mostly medicated by the stimulation of phagocytosis, although both humoral and cellular immunity are likely to be involved. In contrast, the defense is most probably to be ascribed to cellular immunity in infections of the upper urinary tract. For the future, conditions will have to be specified which enable P40 to express predominantly its stimulating effect on cellular immunity. Furthermore, the choice of the minimum active dose together with its fractionated administration will prevent side-effects (prostatitis) while resulting in equally pronounced protective action. Since P40 has already successfully been used in man for the treatment of both infectious and tumoral processes, it could as well be used for the prevention of relapses in recurrent urinary infections.

Adjuvants, Immunologic↗