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Biomedical subjects

G May

Publications and source records attributed to G May.

At least 19 recordsLinked to original sources
PubMed1992

Activity of oxidative routes of metabolism of debrisoquin, mephenytoin, and dapsone is unrelated to the pathogenesis of vinyl chloride-induced disease.

The hypothesis, that cytochrome P4502D6, cytochrome P4502CMP, cytochrome P4503A4 or N-acetyl-transferase may form active intermediary metabolites that could be etiologically related to vinyl chloride-induced disease was investigated in 21 drug-free workers with previous development of vinyl chloride-induced disease and in 23 drug-free workers from the same plant who did not develop the syndrome. Each subject received simultaneous oral administration of debrisoquin (10 mg), mephenytoin (100 mg), and dapsone (100 mg). Measurement of the debrisoquin recovery ratio, the 8-hour recovery of 4-hydroxymephenytoin, and the dapsone recovery ratio in the subsequent 8-hour urine sample provided in vivo phenotypic indexes of cytochromes P4502D6, P4502CMP, and P4503A4 activity, respectively. An 8-hour blood sample was used to measure the acetylation ratio, a measure of N-acetyltransferase activity. The frequency distributions of each drug metabolizing activity were similar between groups. Within this small sample, there was no evidence to implicate cytochromes P4502D6, P4502CMP, and P4503A4 and N-acetyltransferase in the pathogenesis of vinyl chloride-induced disease.

Arylamine N-Acetyltransferase↗
PubMed1992

The association of kidney graft outcome with pretransplant serum IgG-anti-F(ab')2 gamma activity.

Pretransplant sera of 474 kidney graft recipients were tested for IgG-anti-F(ab')2 gamma activity. The patients had significantly higher IgG-anti-F(ab')2 gamma activity than healthy controls (P = 0.0004). Serum lymphocytotoxic antibodies were correlated with IgG-anti-F(ab')2 gamma (P = 0.004), whereas CMV infection and blood transfusions were not. We found a significant association between pretransplant IgG-anti-F(ab')2 gamma activity and early and 1-year kidney graft outcome. This association was pronounced in recipients with no lymphocytotoxic antibodies. Recipients with immediately functioning grafts and a creatinine < 130 mumol/L at 1 year had strikingly higher pretransplant IgG-anti-F(ab')2 gamma activity than patients with graft failure (P < 0.0001).

Antibodies, Anti-Idiotypic↗
PubMed1991

Purification and characterization of Ku-2, an octamer-binding protein related to the autoantigen Ku.

The octamer motif (ATTTGCAT) is an important regulatory element in eukaryotic gene expression. A previously unidentified protein that recognizes this motif has been isolated from the human B cell line, Daudi. The protein, which we term Ku-2, bears a close resemblance to the DNA-binding autoantigen Ku. Like Ku, it is a heterodimer with subunits of 83 and 72 kDa; antisera raised against either subunit of Ku cross-react with Ku-2. Two peptides have been sequenced and show a strong similarity to regions in the corresponding subunits of Ku. The sequences are not identical, however, suggesting that Ku-2 may be a B cell homologue of Ku. Both Ku and Ku-2 bind to the termini of DNA duplexes, but Ku-2 also binds to an internal octamer motif. It is not known whether Ku shares the latter property or whether the octamer binding is a consequence of sequence differences between the two proteins. Ku-2 does not react with antisera against the POU domain of the octamer-binding protein Oct-2, indicating that the DNA binding domains of the two proteins are dissimilar despite the ability of both to bind to the octamer motif. We discuss the evidence for the existence of a family of octamer-binding proteins related to Ku.

Amino Acid Sequence↗
PubMed1991

Molecular analysis of the Coprinus cinereus mating type A factor demonstrates an unexpectedly complex structure.

We report here the molecular cloning of the A43 mating type factor from Coprinus cinereus, a basidiomycetous fungus. Our molecular analyses revealed an unexpected source of variation in the A factor. Though genetic studies have demonstrated that A has two subunits, alpha and beta, we located three nonoverlapping fragments in the A43 region that have A factor function following DNA-mediated transformation. The three fragments demonstrate no similarity to one another as judged by restriction enzyme maps and by hybridization on Southern blots. We conclude that the A43 factor is composed of at least three subunits. When strains carrying different A factors are examined by hybridization to the cloned subunits, extensive polymorphism is seen. Both intensity of hybridization and restriction fragment lengths vary between strains. Some strains fail to show any hybridization to a probe. In contrast, other strains from widely separated geographic locations apparently share very similar subunits. From comparative restriction enzyme mapping of A43 and a mutated A43 factor, we inferred that a 12-kb deletion in the A factor was responsible for the constitutive, dominant phenotype of the mutated A factor. The results of transformation experiments support an activator model for the activity of the A factor in regulating the A pathway.

Biological Evolution↗
PubMed1991

[Risk of CMV infection and illness after kidney transplantation].

Between 1980 and 1986 465 cadaveric kidney transplants were performed at the Kidney Transplant Centre Berlin-Friedrichshain. The post-transplant risk to acquire a cytomegalovirus (CMV) infection depended on the preoperative CMV antibody status of donor and recipient, on the nettoimmunosuppression and on the recipient's age. The highest infection rate and the most serious courses showed seronegative recipients from seropositive donors. The typical time interval of clinical manifestation included the postoperative months 1-3. A significant dependence of the frequency of infection on different immunosuppressive protocols could not be proven. But there was a significant coincidence between CMV infection and rejection crises. In spite of the raised frequency of rejection crises an influence of the CMV infection on the 1-year-graft and patient survival rates could not be demonstrated. Both an early diagnosis and an adequate therapy are of particular importance.

Age Factors↗
PubMed1991

Escherichia coli XerC recombinase is required for chromosomal segregation at cell division.

XerC is a site-specific recombinase of the bacteriophage lambda integrase family that is encoded by xerC at 3700 kbp on the genetic map of Escherichia coli. The protein was originally identified through its role in converting multimers of plasmid ColE1 to monomers; only monomers are stably inherited. Here we demonstrate that XerC also has a role in the segregation of replicated chromosomes at cell division. xerC mutants form filaments with aberrant nucleotides that appear unable to partition correctly. A DNA segment (dif) from the replication terminus region of the E. coli chromosome binds XerC and acts as a substrate for XerC-mediated site-specific recombination when inserted into multicopy plasmids. This dif segment contains a region of 28 bp with sequence similarity to the crossover region of ColE1 cer. The cell division phenotype of xerC mutants is suppressed in strains deficient in homologous recombination, suggesting that the role of XerC/dif in chromosomal metabolism is to convert any chromosomal multimers (arising through homologous recombination) to monomers.

Aminopeptidases↗
PubMed1990

The osmZ (bglY) gene encodes the DNA-binding protein H-NS (H1a), a component of the Escherichia coli K12 nucleoid.

A class of trans-acting mutations, which alter the osmoregulated expression of the Escherichia coli proU operon, maps at 27 min on the chromosome in a locus we have called osmZ. Mutations in osmZ are allelic to bglY, pilG and virR, affect gene expression, increase the frequency of the site-specific DNA inversion mediating fimbrial phase variation, stimulate the formation of deletions, and influence in vivo supercoiling of reporter plasmids. We have cloned the osmZ+ gene, mapped it at 1307 kb of the E. coli restriction map, identified its gene product as a 16 kDa protein, and determined the nucleotide sequence of the osmZ+ gene. The deduced amino acid sequence for OsmZ predicts a protein of 137 amino acid residues with a calculated molecular weight of 15,530. The primary sequence of OsmZ is identical to that of H-NS (H1a), a DNA-binding protein that affects DNA topology and is known to be associated with the bacterial nucleoid. Thus, osmZ is the structural gene for the H-NS (H1a) protein. The nucleotide sequence of osmZ is almost identical to that of hns; however, hns was incorrectly located at 6.1 min on the E. coli linkage map. Increased osmZ gene dosage leads to cell filament formation, altered gene expression, and reduced frequency of fimbrial phase variation. Our results suggest that the nucleoid-associated DNA-binding protein H-NS (H1a) plays a critical role in gene expression and in determining the structure of the genetic material.

Alleles↗
PubMed1990

Effect of increased donor age on kidney transplant outcome.

Donors over the age of 50 years provided kidneys for 28 of our 226 recipients (12.4%) transplanted from January 1, 1987 to December 31, 1988. Immediate function following transplantation occurred in 36% of the kidneys from donors both over and under the age of 50. The overall 3-month graft survival rate for transplants from donors over 50 years was 89%, compared with 78% for transplants from donors under 50 years (p greater than 0.05). Thus kidneys from well-selected older donors make an important contribution to the total pool of organs available for transplantation.

Age Factors↗
PubMed1990

[Use of OKT-3 in treatment of rejection following kidney transplantation].

Application of OKT-3 as rescue therapy in steroid-resistant rejection was effective in 7 out of 9 patients early after cadaveric kidney transplantation. Under attention of instructions for use of OKT-3 the adverse first-dose reactions are rare. The problem of OKT-3 therapy is early use and its reuse.

Adult↗
PubMed1990

[Incidence and prognostic value of cytomegalovirus-specific antibodies of the IgM class in kidney transplant recipients].

In a retrospective study of 326 patients which have been received a renal allograft between 1985 and 1988 at the Berlin Kidney Transplant Centre, all recipients were divided into 3 groups according to their antibody status against cytomegalovirus (IgM+/IgG+; IgM-/IgG+; IgM-/IgG-). Frequency and severity of CMV infections in the early period after kidney transplantation have been compared. Primary infections could be observed in 51/112 (45.5%) patients (group 3), secondary infections in 60/190 (31.6%) patients (group 2). In 7.4% of all recipients (24/326) CMV-specific IgM antibodies could be found at the time of transplantation (group 1). In primary infections the patients have had a significantly higher frequency of moderate or severe CMV diseases as in secondary infections (24.4 vs. 8.3%). In group 3 this frequency was 16.7%. In conclusion, it is not necessary to select renal allograft recipients according their positive CMV-IgM-antibody status, but a close-meshed posttransplant control is indicated.

Antibodies, Viral↗
PubMed1990

[4-way immunosuppression in pre-sensitized recipients of allogenic cadaver kidney transplants].

As a result of introduction of quadruple immunosuppression using cyclosporine, antithymocyte globulin, azathioprine and prednisone in immunological high-risk patients with a presensitization greater than or equal to 80% and/or multiple grafts the rate of immediate graft function could significantly increased, the frequency of rejection and graft rupture was reduced and the patient survival rate could improved to 100%. The problem of vascular rejection should resolved by a more aggressive biopsy approach.

Antilymphocyte Serum↗
PubMed1990

[Transplantation of the kidneys of donors with cancer--personal experiences and review of the literature].

From 1980 to 1988 more than 1,549 organ donors were harvested, 125 of them (8%) died from cancer--116 brain tumors and 9 donors with extracerebral cancer. In 3 donors suffering from extracerebral cancer 5 kidneys were transplanted. All transplants functioned well without tumor signs up to 21 months after grafting. However, because of tumor recurrence in nearly 50% of the cases described in the literature generally organs from donors suffering from extracerebral cancer should not transplanted if possible.

Brain Neoplasms↗
PubMed1990

[Spontaneous kidney transplant rupture--effect of immunosuppressive therapy on incidence of rupture].

In an analysis of 302 cadaveric kidney transplantations performed from 1986 to 1988 the frequency of spontaneous kidney allograft ruptures could significantly reduced by introduction of cyclosporine therapy. Therefore, the importance of rejection in the etiology of allograft rupture is emphasized. In comparison with an earlier analysis the prognosis of rupture with respect to organ repair has been impaired (41 vs. 68%). The importance of intense and effective immunosuppressive therapy in the early period after kidney transplantation is emphasized.

Azathioprine↗