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M Hahn

Publications and source records attributed to M Hahn.

At least 19 recordsLinked to original sources
PubMed1999

Local cold exposure test with a new arterial photoplethysmographic sensor in healthy controls and patients with secondary Raynaud's phenomenon.

Local cold exposure tests are used to diagnose cold-induced vasospastic disorders and to evaluate therapeutic success. We investigated the pulsatile signal detected with a newly developed arterial photoplethysmography (APPG) method and the signal change induced by local cold exposure using a temperature-controlled finger holder, comparing it with laser Doppler flux (red and green laser, rLDF and gLDF) and red blood cell velocity measured in nailfold capillaries (CBV). Ten healthy volunteers and 10 age- and sex-matched patients suffering from Raynaud's phenomenon due to systemic sclerosis were investigated using a moderate cooling temperature of 16 degrees C for 5 min. All signals were recorded simultaneously. The results show a significant reduction of CBV (P < 0.0001), rLDF (P < 0.0003), and gLDF (P = 0.0214) during cooling and characteristic changes in the APPG signal (for instance a decrease in pulse wave amplitude; P < 0.0001). Significant differences in the APPG amplitude could be detected under resting conditions; at cooling temperatures there were also significant differences in CBV and APPG. The temperature-controlled finger holder with its built-in APPG probe appears to be a useful tool for evaluating the effect of local cooling on finger skin perfusion and differentiating between healthy controls and patients with secondary Raynaud's phenomenon due to systemic sclerosis. The gLDF signal was rather weak, limiting its value in cold stress tests. The differences between controls and patients in CBV were somewhat smaller than in previous studies, suggesting the advantage of lower local cooling temperatures, e.g., 12 degrees C.

Adult↗
PubMed1999

[Preventive surgery of inherited colorectal cancer identified through molecular diagnosis].

Numerous inherited genetic changes predisposing to cancer have already been identified and the number is increasing. Accurate prediction of individual risk by means of molecular diagnosis implies clinical consequences in the treatment of cancer-predisposing syndromes. Using familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) as an example, we present here the underlying genetic changes that contribute to tumor development. These genetic alterations can be efficiently identified through molecular diagnostic techniques. Identification of the familial germline mutation permits one to distinguish mutation carriers from non-mutation carriers within affected families and results in individually tailored surveillance and prevention. Therefore, molecular diagnosis is making a contribution to the advances in preventive surgical therapy. The indications are discussed.

Colorectal Neoplasms↗
PubMed1999

Collagen type I metabolism after bone surgery.

This study follows the postoperative course of serum collagen type I metabolites in patients after uncomplicated implantation of a cemented total hip endoprothesis (TEP; n = 12, mean age: 69.3 years), a cemented hemiendoprothesis (HEP; n = 13, mean age 79.7 years), a dynamic condylar or hip screw (DCS/DHS; n = 12, mean age 75.1 years) and osteosynthetic treatment of a Weber B or C fracture (OS; n = 17, mean age 54.3 years). The course of the propeptide of human type I procollagen (PICP) as an anabolic marker as well as of I-carboxyterminal telopeptide (ICTP) as a catabolic marker of bone metabolism was characterized. Measurements were done preoperatively and weekly for 3 weeks after surgery. The concentrations of both markers increased and reached a maximum in the 2nd or 3rd week after surgery. However, the PICP values differed, depending on the kind of surgical intervention and the type of bone healing. Secondary fracture healing with formation of callus occurred in the DCS/DHS group, which developed the highest median PICP concentrations (initial 83 microg/l, second week 337 microg/l; P < 0.001). In contrast, the primary bone healing in the OS group showed increasing ICTP but unchanged PICP concentrations. Patients in the cemented TEP and HEP groups as a kind of artificial bone healing had comparable concentrations. To consider the effective metabolism of collagen type I, the PICP/ICTP ratio was calculated. Although the median PICP and ICTP concentrations of the studied groups differed, the PICP/ICTP ratios were similar. In comparison to 54 young and healthy volunteers (median PICP/ICTP ratio: 37), the ratios of the studied groups were still normal but low (median ratios: < 20). This could be an effect of decreasing collagen type I metabolism with age. Although the results are in agreement with animal studies and histomorphometric investigations, the clinical use of PICP and ICTP determination as a tool for the detection of complicated bone healing is limited by the marked interindividual variability and the uncertain bone specificity.

Aged↗
PubMed1999

A randomized trial of peroral versus transnasal unsedated endoscopy using an ultrathin videoendoscope.

BACKGROUND: Potential advantages of unsedated endoscopy include the prevention of side effects or morbidity related to the use of sedative drugs, less intensive patient monitoring, and less expense. We compared transnasal (T-EGD) with peroral (P-EGD) unsedated endoscopy by using an ultrathin video instrument with respect to patient tolerance and acceptance. METHOD: Patients were randomized to T-EGD or P-EGD. If the initial route of insertion failed, the patient was crossed over to the other route. If this also failed, the patient underwent endoscopy under conscious sedation with an ultrathin instrument. A questionnaire for tolerance was completed by the patient (a validated 0-10 scale where "0" represents none/well tolerated and "10" represents severe/poorly tolerated). RESULTS: Of 105 recruited patients, 60 consented to undergo unsedated endoscopy. There were 20 men and 11 women (mean age 45 years) in the P-EGD group and 15 men and 14 women (mean age 48 years) in the T-EGD group. Of 35 total P-EGD patients (4 were crossed over T-EGD patients), 34 (97%) completed an unsedated examination. Of 29 T-EGD patients, 25 (86%) had a complete examination. Three T-EGD examinations failed for anatomical reasons; all 3 patients when crossed over to the P-EGD route had a successful examination. One patient was unable to tolerate either route. Between the P-EGD and the T-EGD groups, pre-procedure anxiety (3.6 +/- 0.5 vs. 3.0 +/- 0.6), discomfort during insertion (2.1 +/- 0.5 vs 3.3 +/- 0.7), gagging (4.7 +/- 0.5 vs. 3.2 +/- 0. 6), and overall tolerance (2.4 +/- 0.5 vs. 3.8 +/- 0.7) were similar (p > 0.05). However, discomfort on insertion was significantly greater in the T-EGD versus the P-EGD group (4.4 +/- 0.6 vs. 2.7 +/- 0.5: p < 0. 05). Eighty-nine percent of P-EGD patients and 69% of T-EGD patients, p = 0.07, were willing to undergo unsedated endoscopy in the future. CONCLUSION: T-EGD patients experienced significantly more pain on insertion than did P-EGD patients. Otherwise, unsedated endoscopy by either the transnasal or the peroral route is generally well tolerated. In this study it was completed in 59 of 60 patients.

Adult↗
PubMed1999

Combined molecular and clinical approaches for the identification of families with familial adenomatous polyposis coli.

OBJECTIVE: Using an interdisciplinary clinical and molecular approach, the authors identified APC germline mutations in families with familial adenomatous polyposis (FAP). Correlation of mutation site with disease manifestation and the impact of molecular data on clinical proceedings were examined. SUMMARY BACKGROUND DATA: Germline mutations in the APC gene predispose to FAP. Established and proposed genotype-phenotype correlations as well as the influence of mutation site on surgical procedures have been reported. The predictive value of APC mutation analysis for disease manifestation and therapeutic decision making needs to be investigated further. METHODS: One hundred twenty-three kindreds of the local FAP registry were included in this study. CHRPE phenotype was defined as at least one large characteristic lesion or a total of four lesions in both eyes. APC mutations were identified by protein truncation test and automated DNA sequencing from patient lymphocyte DNA and RNA. RESULTS: APC germline mutations were identified in 85/123 families with FAP. They were located between codons 213 and 1581 of the APC gene and displayed distinct genotype-phenotype correlations. CHRPE status facilitated mutation analysis by discriminating regions of interest within the APC coding region. Severe manifestations of desmoids were restricted to mutations between codons 1444 through 1581. Whereas 91% (75/82) of at-risk persons were excluded as mutation carriers, APC germline mutations were detected before clinical examination in 9% (7/82) of at-risk persons. One patient agreed to endoscopy only after mutation detection. CONCLUSIONS: This study supports the feasibility of combined molecular and clinical screening of families with FAP and may provide a guideline for routine presymptomatic molecular diagnostics in a clinical laboratory.

Adenomatous Polyposis Coli↗
PubMed1999

[Predictive molecular diagnosis and preventive surgical treatment of hereditary colorectal carcinoma: a new field of interest for surgical research].

Colorectal cancer is one of the most frequent cancers in the Western hemisphere. It seems to be well established that colorectal tumors develop as a result of an accumulation of inherited and/or acquired somatic mutational events in tumor suppressor genes and oncogenes. An increasing understanding of the molecular basis of the most prevalent colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis and therapy. Therefore, strategies have been developed for predictive molecular diagnosis and preventive surgical treatment of colorectal cancer syndromes. In the future surgical research will participate in research and development in the field of molecular diagnosis of colorectal cancer and will then evaluate the clinical management concepts as a result.

Adenomatous Polyposis Coli↗
PubMed1998

Engineering of variants of the restriction endonuclease EcoRV that depend in their cleavage activity on the flexibility of sequences flanking the recognition site.

The present work describes mutants of the restriction enzyme EcoRV that discriminate very efficiently between oligodeoxynucleotide substrates with an EcoRV recognition sequence in different sequence context. All of these EcoRV variants harbor substitutions at position 226, where in the cocrystal structure of the specific EcoRV/DNA complex an arginine contacts the backbone of the DNA substrate upstream of the recognition sequence, and cleave an oligodeoxynucleotide with an EcoRV site in a nonflexible sequence context (the recognition site being flanked by runs of A and T) with much higher catalytic efficiency (kcat/Km) than an oligodeoxynucleotide with an EcoRV site in a flexible sequence context (the recognition site being flanked by runs of AT), in contrast to the wild-type enzyme, that cleaves both substrates with the same catalytic efficiency. Steady-state and single-turnover kinetics indicate that the enhanced selectivity of the mutants is due to the catalytic step of the reaction. It is possible to enhance the discriminatory power of these EcoRV variants through the choice of appropriate reaction conditions, in particular low salt concentration and low reaction temperatures. It must be emphasized that the enhanced selectivity of these EcoRV variants toward EcoRV sites in a flexible and nonflexible sequence context, respectively, is not only seen with oligodeoxynucleotides, but also with plasmid substrates.

Base Sequence↗
PubMed1998

Crystal structures and properties of de novo circularly permuted 1,3-1,4-beta-glucanases.

The 1,3-1,4-beta-glucanases from Bacillus macerans and Bacillus licheniformis, as well as related hybrid enzymes, are stable proteins comprised of one compact jellyroll domain. Their structures are studied in an effort to reveal the degree of redundancy to which the three-dimensional structure of protein domains is encoded by the amino acid sequence. For the hybrid 1,3-1,4-beta-glucanase H(A16-M), it could be shown recently that a circular permutation of the sequence giving rise to the variant cpA16M-59 is compatible with wildtype-like enzymatic activity and tertiary structure (Hahn et al., Proc. Natl. Acad. Sci. USA 91:10417-10421, 1994). Since the circular permutation yielding cpA16M-59 mimicks that found in the homologous enzyme from Fibrobacter succinogenes, the question arose whether de novo circular permutations, not guided by molecular evolution of the 1,3-1,4-beta-glucanases, could also produce proteins with native-like fold. The circularly permuted variants cpA16M-84, cpA16M-127, and cpA16M-154 were generated by PCR mutagenesis of the gene encoding H(A16-M), synthesized in Escherichia coli and shown to be active in beta-glucan hydrolysis. CpA16M-84 and cpA16M-127 were crystallized in space groups P2(1) and P1, respectively, and their crystal structures were determined at 1.80 and 2.07 A resolution. In both proteins the main parts of the beta-sheet structure remain unaffected by the circular permutation as is evident from a root-mean-square deviation of main chain atoms from the reference structure within the experimental error. The only major structural perturbation occurs near the novel chain termini in a surface loop of cpA16M-84, which becomes destabilized and rearranged. The results of this study are interpreted to show that: (1) several circular permutations in the compact jellyroll domain of the 1,3-1,4-beta-glucanases are tolerated without radical change of enzymatic activity or tertiary structure, (2) the three-dimensional structures of simple domains are encoded by the amino acid sequence with sufficient redundancy to tolerate a change in the sequential order of secondary structure elements along the sequence, and (3) the native N-terminal region is not needed to guide the folding polypeptide chain toward its native conformation.

Amino Acid Sequence↗
PubMed1998

Identification and crystallization of a protease-resistant core of calnexin that retains biological activity.

Calnexin is a molecular chaperone that facilitates folding of glycoproteins in the endoplasmic reticulum (ER). The cloned lumenal domain of canine calnexin, cnxDeltaTMC, retains its biological activity without the transmembrane and cytosolic region. For the purpose of structure determination we generated a crystallizable core by mild proteolysis and identified its termini by N-terminal sequencing and molecular mass determination. A truncated gene was cloned accordingly. Its product, cnxDeltaN25C15, was purified to apparent homogeneity and crystallized. This truncated variant remains biologically active as shown by its binding to monoglucosylated oligosaccharides and functional interaction with ERp57. A heavy atom derivative was identified.

Amino Acid Sequence↗
PubMed1998

[Color duplex ultrasound of the finger arteries. An alternative to angiography?].

By means of modern color-coded duplex sonography (CCDS) even very small vessels can be visualized. Maximum resolution nowadays is about 0.5 mm diameter of the vessel. We compared the use of CCDS and angiography in studying of acral perfusion. Besides morphologic criteria, hemodynamic criteria were recorded. Arteries in healthy fingers appear as long and straight vessels with a clearly defined border. The physiological maximal blood flow velocity exceeded 20 cm/s. CCDS revealed tortuosity of finger arteries as typical finding in thrombangiitis obliterans. Segmental stenosis can either be identified morphologically or quantified by measurement of the flow velocity with poststenotic maximal systolic velocities of less than 20 cm/s or by the acceleration of the blood flow within the stenosis, as proven by angiographic examinations. CCDS is suitable for evaluation of acral perfusion in patients suffering from secondary Raynaud's syndrome. Apart from diagnosis of disturbed acral circulation, other possible applications of CCDS are in in the surgical field, for example replantations in hand or finger surgery.

Adult↗
PubMed1998

[Quantitative morphology of vertebral body cortical bone. Building block for noninvasive calculation of fracture threshold in osteoporosis].

The vertebral bodies consist of two main structures, trabecular and cortical bone. The histological changes within the spine, especially in cortical bone, leading to osteoporotic fractures remain, however, poorly understood. Therefore, the complete front column of the spine was removed in 26 autopsy cases without skeletal diseases and in 11 cases with proven osteoporosis. A sagittal segment prepared through the center of all vertebral bodies was undecalcified embedded in plastic, ground to a 1-mm-thick block and stained using a modification of the von Kossa method. The analysis included measurement of the mean cortical thickness of both ventral and dorsal shell (from C3 to L5). The qualitative investigation of the structure of the cortical ring completed the analysis. The skeletally intact specimens had high cortical thickness values in the cervical spine (285 +/- 22 microns), a decrease in the thoracic spine (244 +/- 14 microns) and an increase in the lumbar spine (290 +/- 15 microns). The mean thickness of the ventral shell is in general higher than the thickness of the dorsal shell. The cortical thickness of the spine showed no gender-specific differences (P = n.s.). There was a slight decrease in the cortical thickness with age; however, this decrease and the correlation of cortical thickness to age was only significant below vertebral body T8 (r = 0.225 to 0.574; Pr < 0.05 to Pr < 0.005). Most interestingly, osteoporosis is characterized by a significant decrease in cortical thickness throughout the whole spine. This decrease in cortical thickness was more marked in the dorsal shell (P < 0.05) than in the ventral shell (ventral from C3 to T6 (P < 0.05) below T6 (P = n.s.). We therefore conclude that in osteoporosis, biomechanical competence is affected by both trabecular bone loss and decrease of cortical thickness. This suggests that, in addition to trabecular bone measurements, the cortical thickness is of special interest for diagnostic radiological examinations (CT) to yield clues about the risk of vertebral fractures.

Adolescent↗
PubMed1998

Molecular biology of colorectal cancer and clinical consequences for colorectal cancer syndromes.

Because of the accomplishments in biotechnical research in the past few decades our knowledge about the molecular mechanisms of carcinogenesis has grown rapidly. Colorectal cancer has been one of the most intensively investigated tumor entities, and it seems to be well established that colorectal tumor growth is associated with an accumulation of acquired somatic mutational events in tumor suppressor genes and oncogenes. Recent progress in our understanding of the molecular basis of the most prevalent colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis and therapy. Identification and characterization of the causative genes for these colorectal cancer syndromes have enabled precise presymptomatic detection of mutations in individuals who bear an a priori risk of about 50% of developing colorectal cancer. Genotype-phenotype correlations might further increase the clinical management of hereditary colorectal cancer. Even though developments in cancer research are restricted to the minority of individuals with hereditary cancer syndromes, growing knowledge about the effect of low penetrance variations in tumor suppressor genes may affect the diagnosis and therapy of sporadic colorectal cancer.

Adenomatous Polyposis Coli↗
PubMed1998

Hypertrophied cauda equina presenting as intradural mass: case report and review of literature.

BACKGROUND: Hereditary motor and sensory neuropathy types I and III usually lead to enlargement of peripheral nerves. Rarely, spinal nerve roots may also be involved, leading to radiculopathy and/or myelopathy. METHODS: This 44-year-old man with back and lower extremity radicular pain and distal lower extremity weakness and numbness was found to have a nonenhancing intradural mass that caused a nearly complete myelographic block from L1-L4. He underwent a decompressive laminectomy with intradural exploration. RESULTS: Hypertrophic but otherwise normal-looking nerve roots were observed. Subsequent electrodiagnostic testing and sural nerve biopsy confirmed that this patient had a previously unsuspected hereditary motor and sensory neuropathy (HMSN). His pain resolved, but at latest follow-up his weakness and numbness persisted. CONCLUSIONS: Nonenhancing spinal intradural mass lesions may represent enlarged nerve roots, which have a number of potential etiologies. Electrodiagnostic studies and peripheral nerve biopsy are instrumental in establishing the diagnosis of HMSN.

Adult↗
PubMed1998

Hemodynamics in nailfold capillaries of patients with systemic scleroderma: synchronous measurements of capillary blood pressure and red blood cell velocity.

There is increasing evidence that endothelial damage occurs at a very early stage during the course of systemic scleroderma. Endothelial damage is accompanied by impaired microvascular function, which has clearly failed in patients with systemic scleroderma, as evidenced by necrosis of the fingertips in severe cases. We investigated two important determinants of microvascular function, namely capillary blood pressure and capillary red blood cell velocity, simultaneously in the same capillary. In patients with systemic scleroderma and in healthy volunteers matched for age and sex, capillary blood pressure was measured by direct cannulation and capillary red blood cell velocity by video microscopy. Capillary blood pressure and capillary red blood cell velocity were significantly lower in patients (14.27 +/- 4.34 mmHg, 230 +/- 310 microm per s) than in healthy controls (19.06 +/- 3.69 mmHg, p < 0.008, and 910 +/- 240 microm per s, p < 0.003) at an ambient temperature of 22 degrees C, whereas no significant difference in skin temperature was observed (23.7 +/- 0.9 degrees C vs 24.7 +/- 1.9 degrees C) and no occlusion of finger arteries was detected. Capillary blood pressure in enlarged capillaries did not differ from that in normal-shaped capillaries in the patients (correlation of diameter and capillary blood pressure, R2 = 0.04), which was also the case with capillary red blood cell velocity (R2 = 0.13). Capillary pulse pressure amplitude and capillary red blood cell velocity showed a strong correlation (R2 = 0.81), suggesting that the pressure gradient across the capillary loop, which is the driving force for capillary red blood cell velocity, was mainly dependent on precapillary resistance. These observations reflect the inadequate microvascular function in systemic scleroderma, which may be due mainly to a pathophysiologic functional increase in precapillary resistance, even at comfortable ambient temperatures.

Adult↗
PubMed1998

The plasma membrane H(+)-ATPase from the biotrophic rust fungus Uromyces fabae: molecular characterization of the gene (PMA1) and functional expression of the enzyme in yeast.

To study the molecular basis of biotrophic nutrient uptake by plant parasitic rust fungi, the gene (Uf-PMA1) encoding the plasma membrane H(+)-ATPase from Uromyces fabae was isolated. Uf-PMA1 exists probably as a single gene. However, two nearly identical sequences were identified; the similarity apparently is due to two Uf-PMA1 alleles in the dikaryotic hyphae. Multiple Uf-PMA1 transcripts were observed during early rust development, and reduced amounts of a single Uf-PMA1 mRNA were observed in haustoria and rust-infected leaves. This is in contrast to elevated enzyme activity in haustoria compared to germinated spores (C. Struck, M. Hahn, and K. Mendgen. Fungal Genet. Biol. 20:30-35, 1996). Unexpectedly, the PMA1-encoded rust protein is more similar to H(+)-ATPases from plants (55% identity) than from ascomycetous fungi (36% identity). When the rust PMA1 cDNA was expressed in Saccharomyces cerevisiae, both the wild-type enzyme and a mutant derivative (delta 76) deleted for the 76 C-terminal amino acids were able to support growth of a yeast strain lacking its own H(+)-ATPases. Compared to the wild-type, the delta 76 mutant enzyme displayed increased affinity to ATP, a higher vanadate sensitivity, and a more alkaline pH optimum. These results indicate that the C-terminal region of the rust enzyme exhibits auto-regulatory properties.

Alleles↗
PubMed1998

Milk thistle (Silybum marianum) for the therapy of liver disease.

Silymarin, derived from the milk thistle plant, Silybum marianum, has been used for centuries as a natural remedy for diseases of the liver and biliary tract. As interest in alternative therapy has emerged in the United States, gastroenterologists have encountered increasing numbers of patients taking silymarin with little understanding of its purported properties. Silymarin and its active constituent, silybin, have been reported to work as antioxidants scavenging free radicals and inhibiting lipid peroxidation. Studies also suggest that they protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism. In this article we review silymarin's history, pharmacology, and properties, and the clinical trials pertaining to patients with acute and chronic liver disease.

Humans↗