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K Heyne

Publications and source records attributed to K Heyne.

At least 19 recordsLinked to original sources
PubMed2004

Identification of a putative p53 binding sequence within the human mitochondrial genome.

A small fraction of the total cellular amount of nuclear transcription factor p53 seems to be located at and within mitochondria. Transcription factors of the steroid receptor superfamily that, like p53, lack a classical mitochondrial leader sequence are nonetheless imported into mitochondria where they regulate mtDNA transcription through binding to specific recognition sequences. Here, we examined seven candidate sequences from the human mitochondrial genome with similarity to the consensus p53 binding motif. Two imperfect half-sites at coordinate 1553 with homology to the nuclear IGF-BP3 box A binding sequence are demonstrated to confer responsivity to p53 and the p53 relatives p73alpha and beta in the context of the cell nucleus. Mitochondrial p53 may thus bind directly to mtDNA and, perhaps, be involved in the regulation of mitochondrial transcription/replication.

Base Sequence↗
PubMed2001

Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatus infection associated with age-related skewing of lyonization.

Chronic granulomatous disease (CGD) is an inherited disorder characterized by the inability of phagocytes to generate normal amounts of superoxide (O2-), leaving patients susceptible to life-threatening infections. It was previously assumed that once carriers of the X-linked form of CGD were found to have 30% or more of functionally normal neutrophils, they would be free of risk for infection because the lyonization ratio was believed to be constant. Our report strongly contradicts this assumption. A 45-year-old X-CGD carrier had approximately 40% of normal neutrophils in her peripheral blood at age 21 years. Recently, she contracted a life-threatening pulmonary infection with Aspergillus fumigatus. After recovery, the ratio of normal-to-nonfunctional neutrophils was re-evaluated. She was found to have only 6-8% of normal neutrophils, suggesting that a striking decrease in the number of normal cells over the past 25 years was the reason for an increased susceptibility to Aspergillus infection. We conclude that age-related acquired skewing of the lyonization ratio can result in an increased susceptibility to life-threatening infections in X-CGD carriers.

Aging↗
PubMed1999

A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection.

The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

Adolescent↗
PubMed1997

Microheterogeneity of serum glycoproteins and their liver precursors in patients with carbohydrate-deficient glycoprotein syndrome type I: apparent deficiencies in clusterin and serum amyloid P.

Serum and liver protein patterns were studied, respectively, in 5 patients (serum) and 1 patient (liver) with carbohydrate-deficient glycoprotein syndrome (CDGS) type I by high-resolution two-dimensional electrophoresis (2-DE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The pattern of serum glycoproteins in all 5 patients presented abnormal trains of isoforms with decreased mass (delta molecular weight 3000) and all showed a cathodal shift. Two-dimensional electrophoresis and SDS-PAGE mass analysis of transferrin, alpha1 -antitrypsin, haptoglobin beta-chain, and alpha1-acid glycoprotein after neuraminidase and N-glycosidase F treatments demonstrated that the additional trains of the isoforms found in CDGS type I contain homologous species of isoforms. Some of them still showed charge differences, and all still contained glycans except for transferrin, with some unusual nonglycosylated isoforms. In addition, deficiencies in clusterin and serum amyloid P, not described so far, have been found in all 5 patients. The two-dimensional pattern of immunodetected precursors of serum proteins in liver cells from 1 patient with CDGS showed abnormal low-mass precursors and the absence of the precursors normally found in controls. These results suggest that these abnormal precursors accumulate during the early oligosaccharide processing of the nascent protein-bound oligosaccharides and that glycoprotein precursors undergo an altered intracellular transport while the post-translational processing along the normal pathway is still apparently functioning in patients with CDGS.

Amyloid↗
PubMed1996

p53 expressions: predicting recurrence and second primary tumors in head and neck squamous cell carcinoma.

BACKGROUND: The survival rate for head and neck squamous cell carcinoma remains poor despite therapeutic advances over the last two decades. For patients with disease confined to the head and neck, there are two major and biologically distinct patterns of treatment failures after definitive therapy: recurrence of primary disease and development of second primary tumors. Understanding the biological basis of patterns of treatment failure after definitive therapy is needed to guide the development of adjuvant treatment and strategies to prevent second primary tumors. PURPOSE: To determine whether expression of the p53 protein has prognostic significance and/or is associated with patterns of treatment failure, we examined protein expression in primary tumor specimens of patients with head and neck squamous cell carcinoma. METHODS: Immunohistochemical analysis with a monoclonal antibody (DO7) specific for p53 protein was used to detect expression of the protein in formalin-fixed, paraffin-embedded tumor samples from 69 head and neck cancer patients treated with definitive local therapy (surgery and/or radiotherapy) between January 1980 and October 1983 at The University of Texas M. D. Anderson Cancer Center. We quantitated p53 protein expression and assessed its association with duration of patient survival, patterns of treatment failure (recurrence of primary tumor and development of second primary tumor), and other clinical parameters. All reported P values resulted from two-sided statistical tests. RESULTS: We found detectable levels of p53 protein expression in the tumor cell nuclei of 41 of 69 patients. Thirty-six (52%) of 69 patients whose tumors exhibited p53 protein expression in greater than or equal to 10% of the cell nuclei were grouped as p53 positive, and 33 (48%) of 69 patients whose tumors exhibited less than 10% nuclear expression were groups as p53 negative. The clinical characteristics of the patients in the p53-positive, and p53-negative groups were well balanced. Overall survival was significantly lower, and the times to tumor recurrence, to second primary tumors, and to any treatment failure were significantly shorter in the p53-positive group that in the p53-negative group (P=.0002, P=.047, P=.003, and P=.0009, respectively), mainly because the p53 positivity was associated with earlier development of tumor recurrence and second primary tumors. The rate of second primary tumor development per person per year was also significantly higher in the p53-positive group that in the p53-negative group. By use of multivariate analysis according to the Cox regression model, p53 expression status was identified as the most significant predictor of overall survival duration (P=.007), time to tumor recurrence (P=.053), time to second primary tumors (P=.035), and time to any treatment failure (P=.004). CONCLUSIONS: The expression of p53 protein in primary head and neck squamous cell carcinoma was significantly predictive of shorter survival because of its association with earlier development of both tumor recurrence and second primary tumors. Thus, p53 expression may be a valuable marker for identifying individuals at high risk of developing a recurrence of primary disease and second primary tumors who may benefit from adjuvant therapy and chemoprevention after definitive local therapy.

Adult↗
PubMed1992

[Diagnosis and nosology of glycanosis CDG ("carbohydrate deficient glycoprotein syndrome")].

BACKGROUND: The "Carbohydrate-deficient glycoprotein syndrome" is a recently discovered inborn error of complex carbohydrate metabolism. The disease involves a number of organ systems and various deficient glycoproteins. An abnormal isoform of serum transferrin is of diagnostic value. METHODS: We analysed the glycoprotein alpha-1-antitrypsin of two affected infants and their clinically healthy parents using high resolution isoelectric focusing technique. Besides normal isoforms of alpha-1-antitrypsin, we found an abnormal cathodic isoform ("CDG-alpha-1-antitrypsin") which represented almost half of the total amount of alpha-1-antitrypsin of the patients. RESULTS: This new marker-glycoprotein suggests a defect of the production of biantennary and of triantennary N-glycans during an early step of their synthesis, resulting in monoantennary N-glycans. Also this marker-glycoprotein seems to be a specific biochemical diagnostic tool for discovering glycanosis CDG (Carbohydrate-deficient glycoprotein syndrome). The mode of inheritance is probably incomplete autosomal dominant. The same genetic defect of N-glycan synthesis may be present in more than one type of the hybrid molecule glycoprotein, and was also found in transferrin, resembling a "genetic back-pack", that might explain the multitude of clinical symptoms. CONCLUSION: In view of these findings, we present novel systematics of those diseases that are due to inborn errors of N-glycan synthesis, and which we suggest to call "glycanoses".

Abnormalities, Multiple↗
PubMed1990

Variation of alpha 1-antitrypsin glycoprotein microheterogeneity in hepatic postresuscitation disease.

Microheterogeneity of the glycoprotein alpha 1-antitrypsin has been investigated sequentially by high resolution isoelectric focusing in a child with the proteinase inhibitor MS phenotype after near-drowning. A band-splitting with additional cathodal fractions exhibited migration from the most cathodic to the anodic positions of the glycoprotein isoforms in the course of post-resuscitation disease. The pattern may reflect the time- and stage-dependent hypoxic and post-hypoxic effects on hepatocellular metabolic zonation.

Humans↗
PubMed1989

Glycogen storage disease Ib: modification of alpha 1-antitrypsin glycoprotein microheterogeneity.

Upon isoelectric focusing, alpha 1-antitrypsin shows a characteristic major band pattern caused by glycoprotein isoforms with different oligosaccharide side chains. In ten apparently healthy individuals with the Pi type MM the ratio of isoforms I, II, and III was 5.2:3.9:1.0. In six patients with glycogen storage disease Ib the ratio of isoforms in the Pi type MM was 3.6:5.5:1.9 suggesting a shift from the biantennary to triantennary oligosaccharide side chains. This shift may result from the limited availability of glucose or glucose derivatives for the synthesis of N-glycosidic glycoproteins.

Adolescent↗
PubMed1989

[Early childhood oligoarthritis (antinuclear antibody positive) in alpha 1-antitrypsin deficiency of the PiIZ type].

A 15 months old girl with gonarthritis, and positive antinuclear autoantibodies was found to have a genetically determined alpha 1-antitrypsin deficiency of the rare protease inhibitory (Pi) type IZ. The possible significance of a disturbed equilibrium of cellular inflammation-promoting proteases and extracellular protease inhibition for the pathogenesis of chronic arthritis is discussed using as illustration the presented case.

Antibodies, Antinuclear↗
PubMed1988

[Double heterozygosity (transferase-/epimerase-defect) and galactosemia cataract].

The mother of a boy who suffered from classical galactosaemia (galactose-1-phosphate uridyl transferase deficiency) has unilateral cataracta. In addition the boy had a decreased activity of the UDP-galactose-4-epimerase. The latter defect could also be demonstrated in the erythrocytes from the mother and the grandmother. In contrast to the finding of cataracta in the mother the grandmother with the same type of double heterozygosity was ophthalmologically normal. The implication of partial maternal disorders of galactose metabolism will be discussed in view of their possible role for the origin of cataracta.

Carbohydrate Epimerases↗
PubMed1988

[Postinfectious thrombocytosis as an acute phase reaction: the example of Haemophilus influenzae meningitis].

The postinfectious thrombocytosis occurring in 11 children with Haemophilus influenzae meningitis and/or septicaemia shows regular progress. The rise of thrombocyte concentrations starts around the 5th day after onset of antibiotic therapy, reaches values above 500,000/microliter between the 9th and 12th day, and relapses afterwards to normal values, which are reached around the 20th day. The range of thrombocytosis is influenced by the severity and complications (subdural effusions, secondary infection) of the infection as well as by the age of the patient. An inverse course of serum concentrations of C-reactive protein and thrombocyte concentrations points to the influence of this humoral reaction on the thrombocytic acute phase reaction.

Acute-Phase Reaction↗
PubMed1987

Roberts syndrome and SC phocomelia. A single genetic entity.

A family with three siblings showing different manifestations of Roberts syndrome or SC phocomelia is described. With regard to previously published cases of familial Roberts syndrome and SC phocomelia we conclude that these two syndromes are one and the same genetic entity.

Abnormalities, Multiple↗