[The "buried-bumper" syndrome. Comment on the contribution by M. Gawenda et al].
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Enteral Nutrition↗
Biomedical subjects
A Haid
Publications and source records attributed to A Haid.
Heme binding to a conserved Cys-Pro-Val motif is crucial for the catalytic function of mitochondrial heme lyases.
Covalent attachment of heme to the apoforms of mitochondrial cytochromes c and c1 requires the activity of cytochrome c heme lyase (CCHL) and cytochrome c1 heme lyase (CC1HL), respectively. The two enzymes differ in their cytochrome specificity, but they are related in sequence, and both contain conserved Cys-Pro-Val (CPV) motifs. By using various in vitro assays we investigated whether heme can bind directly to heme lyases and whether the CPV motif may be involved in heme binding. Heme stabilized CC1HL, as a model protein, in a folded, protease-resistant conformation, stimulated the refolding of CC1HL after urea denaturation, and inhibited the import of the CC1HL precursor into mitochondria. These effects were not observed with a point mutant, CC1HLSPV, in which cysteine was replaced by serine, and with CC1HLDeltaCPV, in which the motif was deleted. These results show that heme lyases can bind heme directly, and they identify the CPV sequence as a structural element important for this interaction. The phenotype of a yeast mutant expressing CC1HLSPV is in good agreement with such a role of the CPV motif. The mutant cells accumulate the heme-free intermediate form of cytochrome c1 and display a severe deficiency in the holo form. We suggest that the CPV motif forms a crucial part of the substrate binding site for heme.
Amino Acid Sequence↗
Incidence of extramural venous invasion in colorectal carcinoma: findings with a new technique.
In reported studies of extramural venous invasion (EVI) by colorectal carcinoma (CRC) in which conventional preparations involving a sectioning plane perpendicular to the tumor were used, an incidence as high as 36% has been found for unselected surgical material from patients operated on for cure. However, with this preparation technique, not all of the veins that exit the bowel wall roughly at right angles can be examined adequately. We investigated whether preparation of the adjacent vascular connective tissue with tangential sectioning might not result in different EVI rates. A total of 100 unselected surgical specimens of the bowel bearing 103 CRCs were prepared using a previously undescribed method, and EVI was found in 54.1% of the cases considered to have been treated curatively. To assess EVI fully, a complete study of all the vessels draining the tumor would be required yet the conventional preparation technique is associated with the distinct possibility of sampling error, because only a few vessels in each block are sectioned in the longitudinal axis. This sampling error might well be the explanation for the considerably higher incidence of EVI in our cases than in the reports in the literature. In all patients with EVI, the possibility of hematogenous metastases exists, and this has a significant bearing on the question of selecting patients for adjuvant chemotherapy.
Carcinoma↗
A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
We report a constitutional point mutation of codon 278 in exon 8 of the TP53 gene that has not yet been described as a germ-line mutation. A 52-year-old female developed multiple primary malignancies (liposarcoma, breast cancer, malignant histiocytoma, occult adenocarcinoma). The mutation found in her tumour and peripheral blood lymphocyte DNA is a cytosine to thymine transition at the second position of codon 278 resulting in an amino acid exchange from proline to leucine in the DNA-binding domain. Evaluation of the patient's family revealed that both of her sons were affected by the same mutation. Although the patient's mother had died already, we were able to demonstrate by polymorphic microsatellite analysis that the defective allele originated from the maternal side. As four brothers and one sister had inherited the same allele, which however was wild type, we were able to show that the mutation must have occurred in the germ cells of the patient's mother and that it may therefore be called de novo. This explains the lack of a high cancer incidence in the family history. All tumours tested showed positive immunohistochemical staining for p53. Loss of heterozygosity was found in five of seven tumours, one showing chromosome 17 monosomy.
Alleles↗
[Preoperative axillary ultrasound in breast carcinoma: value of the method in routine clinical practice].
AIM: To evaluate the significance of routinely performed preoperative axillary sonography in breast cancer patients. METHOD: 191 patients with surgical treated breast cancer were analysed retrospectively. 74 patients of these had an axillary sonography done by 5 different examiners. RESULTS: For detecting lymph node metastases sensitivity was 68.2% in all T-stages and 50% in T1-stages with a specificity of 100%. Classification of the axillary status (positive or negative for lymph node metastases) is possible in 90.5% for all T-stages and 94.9% for T1-stages. Microscopic and small lymph node metastases are missed by ultrasound. Compared to axillary palpation, sonography is better. CONCLUSION: Preoperative axillary sonography is an useful diagnostic method even when done routinely. If further criteria are considered, axillary dissection could be avoided in some patients.
Adult↗
[Value of preoperative axilla ultrasound in breast carcinoma].
Preoperative axillary sonography is a superior method in predicting axillary lymph node status than clinical examination in patients with breast cancer. However, the results depend on the skills and care of the examiner, metastases less than 3-5 mm are hardly visible.
Axilla↗
Biogenesis of mitochondrial heme lyases in yeast. Import and folding in the intermembrane space.
Heme lyases are components of the mitochondrial intermembrane space facilitating the covalent attachment of heme to the apoforms of c-type cytochromes. The precursors of heme lyases are synthesized in the cytosol without the typical N-terminal mitochondrial targeting signal. Here, we have analyzed the mode of import and folding of the two heme lyases of the yeast Saccharomyces cerevisiae, namely of cytochrome c heme lyase and of cytochrome c1 heme lyase. For transport into mitochondria, both proteins use the general protein import machinery of the outer membrane. Import occurred independently of a membrane potential, delta psi, across the inner membrane and ATP in the matrix space, suggesting that the inner membrane is not required for transport along this direct sorting pathway. The presence of a large folded domain in heme lyases was utilized to study their folding in the intermembrane space. Formation of this domain occurred at the same rate as import, indicating that heme lyases fold either during or immediately after their transfer across the membrane. Folding was not affected by depletion of ATP and delta psi or by inhibitors of peptidylprolyl cis-trans isomerases, i.e. it does not involve homologs of known folding factors (like Hsp60 and Hsp70). The energy derived from folding cannot be regarded as a major driving force for import, since the folded domain could be imported into mitochondria with the same efficiency as the intact protein. We conclude that protein folding in the intermembrane space obeys principles different from those established for other subcellular compartments.
Adenosine Triphosphate↗
Mutation of a highly conserved base in the yeast mitochondrial 21S rRNA restricts ribosomal frameshifting.
A mutation shown to cause resistance to chloramphenicol in Saccharomyces cerevisiae was mapped to the central loop in domain V of the yeast mitochondrial 21S rRNA. The mutant 21S rRNA has a base pair exchange from U2677 (corresponding to U2504 in Escherichia coli) to C2677, which significantly reduces rightward frameshifting at a UU UUU UCC A site in a +1 U mutant. There is evidence to suggest that this reduction also applies to leftward frameshifting at the same site in a -1 U mutant. The mutation did not increase the rate of misreading of a number of mitochondrial missense, nonsense or frameshift (of both signs) mutations, and did not adversely affect the synthesis of wild-type mitochondrial gene products. It is suggested here that ribosomes bearing either the C2677 mutation or its wild-type allele may behave identically during normal decoding and only differ at sites where a ribosomal stall, by permitting non-standard decoding, differentially affects the normal interaction of tRNAs with the chloramphenicol resistant domain V. Chloramphenicol-resistant mutations mapping at two other sites in domain V are described. These mutations had no effect on frameshifting.
Amino Acid Sequence↗
Expression of the Saccharomyces cerevisiae CYT2 gene, encoding cytochrome c1 heme lyase.
In this paper we examine the expression of the Saccharomyces cerevisiae CYT2 gene, which encodes cytochrome c1 heme lyase. This enzyme is required for covalent attachment of heme to apocytochrome c1, a subunit of the mitochondrial respiratory chain. Transcription of the 1-kb CYT2 mRNA initiates at four prominent sites at a distance of 52-225 bp in front of the AUG start codon. The level of CYT2 mRNA is not influenced by the presence or absence of oxygen or of heme, but it is subject to carbon-source control. The concentration of the CYT2 mRNA is significantly reduced in glucose-grown cells as compared to cells grown under non-repressing conditions. Neither the HAPp activator proteins nor MIG1p, a repressor protein involved in glucose repression, seem to mediate this effect.
Base Sequence↗
Molecular cloning and characterization of the Saccharomyces cerevisiae CYT2 gene encoding cytochrome-c1-heme lyase.
Cytochrome c1, a subunit of the mitochondrial ubiquinol--cytochrome-c reductase, is synthesized on cytosolic ribosomes as a precursor protein of 37 kDa. Maturation to the mature 31-kDa form involves two proteolytic processing steps of the amino-terminal presequence. After removal of the amino-terminal part by the matrix-localized processing peptidase, the carboxy-terminal part of the presequence is cleaved off by an unknown intermembrane space protease. This step depends on covalent linkage of heme to the apoprotein. At least two complementation groups (I and II) can be distinguished among mutants of the yeast Saccharomyces cerevisiae, which are defective in this second proteolytic processing, i.e. they accumulate the intermediate-sized form of cytochrome c1 instead of the mature form. Recently, it was shown that complementation group II defines the structural gene for cytochrome c1 [Sadler, I., Suda, K., Schatz, G., Kaudewitz, F. & Haid, A., (1984) EMBO J. 3, 2137-2143]. We report on the molecular cloning and characterization of the CYT2 gene representing complementation group I. It maps on chromosome XI and encodes a mitochondrial protein of about 26 kDa. Extensive similarity to Neurospora crassa and S. cerevisiae cytochrome-c--heme lyase, as well as the phenotype of cyt2 mutants, strongly suggest that we have identified the gene for cytochrome-c1--heme lyase.
Amino Acid Sequence↗
Expression of yeast cytochrome c1 is controlled at the transcriptional level by glucose, oxygen and haem.
The nuclear gene for cytochrome c1 in Saccharomyces cerevisiae (CYT1) was localized on chromosome XV. Its upstream region was identified by functional complementation. Fusion to the lacZ reporter gene on a CEN plasmid allowed study of the effect of carbon sources and of specific deletion mutations on expression of the gene in yeast transformants. Detailed promoter analysis combined with expression studies in recipient strains defective in regulatory genes identified cis-acting sites and transcription factors involved in the regulated expression of the cytochrome c1 gene. These analyses showed that, in the presence of glucose, transcription of CYT1 is positively controlled by oxygen, presumably through the haem signal, and mediated by the HAP1-encoded transactivator. It is additionally regulated by the HAP2/3/4 complex which mediates gene activation mainly under glucose-free conditions. Basal transcription is, in part, effected by CPF1, a centromere and promoter-binding factor.
Base Sequence↗
[Experiences with total parathyroidectomy and autotransplantation of intraoperatively selected parathyroid tissue in reactive renal hyperparathyroidism].
Surgery is indicated in cases of therapy-resistant reactive renal hyperparathyroidism with clinical symptoms and signs. The method of choice is total parathyroidectomy, with autotransplantation of parathyroid tissue into the forearm musculature. Twenty-two patients were parathyroidectomized. In 19 cases the intraoperative selection of tissue for autotransplantation was made by means of a stereoscopic magnifying glass. With one exception, only fragments of type 1a glands and type 1a-like areas obtained from type 2 glands were transplanted. In 18 of the 22 cases parathyroid hormone levels decreased from 1131 +/- 657 preoperatively to 87 +/- 53 pg/ml postoperatively. In 4 patients with postoperative values over 200 pg/ml a transplant-related recurrence of hyperparathyroidism or a remaining 5th gland in the cervical region was suspected. In all 22 patients serum calcium, as well as alkaline phosphatase levels returned to normal and the clinical signs of hyperparathyroidism disappeared.
Adult↗
[Surgical therapy of incisional hernias].
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Cicatrix↗
[Synchronous occurrence of neoplasias of the thyroid gland and hyperthyroid nodular struma in an endemic area].
The simultaneous occurrence of hyperthyroidism and differentiated carcinoma of the thyroid gland is more frequent than previously assumed. In our endemic goiter region 16.5% of patients with thyroid carcinoma have hyperthyroidism and 1.8% of patients with hyperthyroidism have a thyroid carcinoma. The tumors are predominantly located in autonomous adenomas but are also found in cold nodules. Not only scintigraphically cold nodules but also warm and hot nodules must be suspected of malignancy. Consistent preoperative cytodiagnosis of all goiter nodules, including hot nodules, is therefore recommended. Surgical treatment of toxic multi-nodular goiters should be considered more often.
Adenoma↗
Sequencing of the nuclear gene for the yeast cytochrome c1 precursor reveals an unusually complex amino-terminal presequence.
Cytochrome c1 is a component of the mitochondrial respiratory chain in most eukaryotes. The protein is coded by nuclear DNA, synthesized as a larger precursor outside the mitochondria and then cleaved to the mature form in two successive steps during its import into the mitochondria. We have cloned the structural gene for yeast cytochrome c1 by functional complementation of a cytochrome c1-deficient yeast mutant with a yeast genomic library in the yeast-Escherichia coli 'shuttle' vector YEp 13. The complete nucleotide sequence of the gene and of its 5'- and 3'-flanking regions was determined. The deduced amino acid sequence of the yeast cytochrome c1 precursor reveals an unusually long transient amino-terminal presequence of 61 amino acids. This presequence consists of a strongly basic amino-terminal region of 35 amino acids, a central region of 19 uncharged amino acids and an acidic carboxy-terminal region of seven amino acids. This tripartite structure of the presequence resembles that of the precursor of cytochrome c peroxidase and supports a previous suggestion on the import pathways of these two precursors.
Amino Acid Sequence↗
Immunochemical identification of membrane proteins after sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
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Antigen-Antibody Complex↗
[The importance of autopsy in present-day medicine, II. Clinical autopsy].
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Austria↗
Pathways of transcript splicing in yeast mitochondria. Mutations in intervening sequences of the split gene COB reveal a requirement for intervening sequence-encoded products.
We have studied the transcript processing of the split gene COB (or BOX) in yeast mtDNA, in both wild type and cob- mutants. Using various DNA fragments specific for coding or intervening sequences of this gene, we have determined the composition of splicing intermediates by DNA/RNA hybridization. The pattern of splicing intermediates detected in wild type reveals differing rates of the five splicings resulting in an apparent pathway of processing rather than an absolute order among the five cut and splice events. Effects of mutations in four of the five sequences have been studied. All of them interfere with transcript processing. Some block the excision of the sequence mutated only, but allow other splicing events to occur essentially as in the wild type. They suggest that in these mutants any order of splicings is possible, but that some are preferred. In contrast, other mutations located in four different sequences block several splicings simultaneously and thus suggest the existence of an obligatory order of events. In order to reconcile these findings we discuss the following hypotheses. (i) Some intervening sequences in COB specify products which are involved in transcript splicing; (ii) the biosynthesis of trace amounts of these products occurs on splicing intermediates. Their formation requires a certain order of splicing events to occur on a small number of COB transcripts. (iii) If expressed and functional, the intervening sequence-encoded products, together with other components, act on the bulk of COB transcripts, resulting in the steady state pattern of splicing intermediates observed in wild type.
Base Sequence↗