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Biomedical subjects

M Hahn

Publications and source records attributed to M Hahn.

At least 91 records · Page 5Linked to original sources

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↗

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↗

Doublex sequencing in molecular diagnosis of hereditary diseases.

We describe doublex sequencing of human genomic PCR products using two differently labeled primers in a single reaction and analysis on two automated DNA sequencing devices. Feasibility of the methodology is demonstrated by isothermal and cycle sequencing for two different PCR products and by cycle sequencing on both strands of a single product. It was applied to analyze mutations in patient DNAs in routine sample screening. Because it has the advantage of increased throughput and cost reduction while retaining its accuracy and reading length, we found that doublex sequencing is an attractive option for molecular diagnosis of hereditary diseases. This approach would be even more beneficial if it used DNA sequencing devices with several lasers in a single instrument.

Breast Neoplasms↗

Skin thermoregulation during local cooling in healthy volunteers and patients with systemic sclerosis--synchronous assessment of capillary red blood cell velocity, laser Doppler flux and skin temperature.

BACKGROUND: Patients with Raynaud's phenomenon due to systemic sclerosis exhibit a functional microangiopathy with endothelial cell damage. The aim of this study was to assess differences in the so-called nutritive and thermoregulative skin blood flow and to obtain further information by Fourier transformation and by nonlinear analysis of laser Doppler flux (LDF) time series. PATIENTS AND METHODS: A local cold stress test was performed in 10 patients and 10 age- and sex-matched healthy controls. Significant differences were detected between nutritive blood flow in the nailfold capillaries, assessed by capillary red blood cell velocity (CBV), and thermoregulatory blood flow, which was synchronously assessed by LDF. RESULTS: CBV was reduced during cooling, the drop being significantly larger in the patients than in the controls. In contrast, there was no significant difference in the decrease of LDF during cooling. The difference between the fall in CBV values and that in LDF was significantly more pronounced in patients. Further analysis of the LDF frequency spectrum by fast Fourier transformation revealed a significantly greater decrease in amplitude at the heart frequency level in healthy volunteers. A further analysis of the LDF signal revealed significant differences at rest and after cooling in fractal dimensions, suggesting an increased complexity of LDF signals in patients. SUMMARY: The patient's increased sensitivity towards local cold cn be observed best at the capillary level. But the changes of LDF in the frequency spectrum during cooling as calculated by fast Fourier transformation revealed significant differences. In addition differences in fractal dimensions of LDF time series suggest that an analysis of nonlinear dynamics may be a promising approach.

Adult↗

Masked rotatory subluxation of the atlas associated with fracture of the clavicle: a clinical and biomechanical analysis.

We report on two children who developed a fixed rotatory subluxation of the atlantoaxial joint due to torticollis being attributed to a fractured clavicle. Appropriate treatment was delayed for weeks to months; only after the fractured clavicle had healed and the torticollis persisted was the problem identified. Persisting rotatory subluxation also predisposes to further anterior displacement of C-1 due to an increased moment arm created by the forward displacement of the center of gravity of the head. The association of atlantoaxial subluxation should always be considered in children presenting with a clavicular fracture and an acute torticollis.

Atlanto-Axial Joint↗

Primary intracerebellar osteosarcoma arising within an epidermoid cyst.

The authors report a case of a primary extraskeletal osteosarcoma arising within an epidermoid cyst in the parenchyma of the cerebellum in a 64-year-old woman. On initial presentation, the tumor involved the midline cerebellum without attachment to the surrounding dura mater or calvarium. Complete medical and radiologic evaluation failed to reveal a primary skeletal or other extraskeletal osteosarcoma. To our knowledge, this is the first reported case of a primary extraskeletal osteosarcoma within the cerebellum. Osteosarcoma as a primary brain tumor is exceedingly rare, and only three cases (all occurring within the cerebral hemispheres) have been reported previously. The histogenesis of primary sarcomas of the brain is not evident. The associated finding of an epidermoid cyst suggests the tumor originated from a teratoma.

Cerebellar Diseases↗

Multiple endocrine neoplasia type 2-associated RET proto-oncogene mutations do not contribute to the pathogenesis of sporadic parathyroid tumors.

BACKGROUND: Parathyroid disease occurs sporadically or as part of hereditary multiple endocrine neoplasia (MEN) syndrome. The aim of this study was to evaluate the possible role of the RET proto-oncogene not only in hereditary MEN 2-associated hyperparathyroidism but also in different forms of sporadic hyperparathyroidism. METHODS: We investigated 22 patients with parathyroid disease whose family history and results of laboratory and clinical examinations excluded MEN 2 syndrome. DNA extractions of histologically confirmed tumor tissue of patients with primary hyperparathyroidism (n = 18), renal hyperparathyroidism (n = 2), and parathyroid carcinoma (n = 2) were performed. Using solid phase DNA sequencing, mutation analysis of polymerase chain reaction amplified products focused on exons 10, 11, and 16 of the RET proto-oncogene. Parathyroid tissue from four patients with known MEN 2A served as positive controls. RESULTS: No mutations of the codons 609, 611, 618, 620, 634, and 918 were found in the sporadic parathyroid tumors analyzed. DNA sequencing revealed heterozygous mutations in codon 634 of the RET proto-oncogene in four parathyroid glands from four patients with MEN 2A. CONCLUSIONS: Mutations of the RET proto-oncogene contributing to MEN 2 syndromes are absent in sporadic parathyroid tumors. Our data in conjunction with the literature suggest at least three different modes of tumorigenesis in parathyroid disease.

Adenoma↗

[The Human Genome Project and its consequences for surgery].

The Human Genome Project is an international effort to discover all 80,000 genes of the human genome and to determine the complete sequence of the three billion basepairs of the human DNA. Chromosome mapping enables fragmentation of large DNA pieces, sequencing of the resulting small fragments and realignment in the order in which they originally occurred in the chromosomes. Identification of genes involved in various benign and malignant diseases will lead to the understanding of their action and will result in prevention-based medical approaches. In addition, novel therapeutic regimens will be devised based on human gene products. Decipherment of the genetic programs of embryogenesis will enable regeneration of various tissues without the formation of scars.

Animals↗

[Basic molecular biology of colon and rectal carcinoma--when differential diagnosis?].

Colorectal cancer (CRC) is one of the most common cancers in Western populations, striking both women and men at approximately equal rates. A genetic basis for the development of cancer has already been suggested by Karl Heinrich Bauer in 1928 but only since the advancement of molecular biology direct evidence has been obtained to support the notion that cancer is a genetic disease. 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 of genetic risk factors for the development of adenomas and associated carcinomas of the colon and rectum results in predictive molecular diagnosis of malignant disease and enables preventive treatment.

Adenomatous Polyposis Coli↗

The putative tumor suppressor gene FHIT at 3p14.2 is rarely affected by loss of heterozygosity in primary human brain tumors.

To elucidate the role of the recently identified FHIT gene, located at 3p14.2 in human brain tumor carcinogenesis, a total of 259 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D3S1313, D3S1234, D3S1300, and D3S1481. In primary brain tumors, LOH was detected at a frequency of 8.4% (n = 214). Low-grade gliomas exhibited insignificantly lower LOH rates in comparison to high-grade gliomas (5.3%, n = 19, versus 11.1%, n = 90). Notably, no allelic loss was observed in 12 recurrent glioblastomas analyzed in comparison to their corresponding primary tumor lesions and in two astrocytomas with progression to higher grades of malignancy. Our data indicate that allelic loss of the FHIT gene is neither a critical event in carcinogenesis of primary brain tumors nor tumor grade-associated in astrocytic tumors. In contrast, observed LOH rate for brain metastases was as high as 54.5% (n = 45), in accordance with data thus far accumulated from analyses of corresponding primary tumors.

Acid Anhydride Hydrolases↗

Multiple chemical sensitivity syndrome and porphyria. A note of caution and concern.

Growing numbers of patients suffering from many symptoms believe that they have a condition called multiple chemical sensitivity syndrome (MCSS). It has been suggested that this syndrome can be triggered by exposure to any of a large and usually incompletely defined number of natural and synthetic chemical substances. Major medical organizations, including the National Research Council and the American Medical Association, have not recognized MCSS as a clinical syndrome because of a lack of valid, well-controlled studies defining it and establishing pathogenesis or origin. Lately, some have proposed that many patients with MCSS suffer from hereditary coproporphyria. However, this purported association is based chiefly on results from a single reference laboratory of a fundamentally flawed assay for erythrocyte coproporphyrinogen oxidase. Although patients with MCSS may, at times, have modest increases in urinary coproporphyrin excretion, this is a common finding found in many asymptomatic subjects or patients with diverse other conditions (eg, diabetes mellitus, heavy alcohol use, liver disease, and many kinds of anemia). Such secondary coproporphyrinuria does not indicate the existence of coproporphyria. To our knowledge, there is no scientifically valid evidence to support an association between MCSS and coproporphyria, nor is there any unifying hypothesis for rationally linking these 2 disorders.

Adolescent↗

Comparative study of CD26 as a Th1-like and CD30 as a potential Th2-like operational marker in leprosy.

In the last years we have been able to establish CD26 as an operational marker for a human Th1-like reaction in various granulomatous diseases. Recently, CD30 was described as a marker for a Th2-type reaction, where CD30 is preferentially expressed and its soluble form released by human T cell clones producing Th2-type cytokines. To evaluate the possibility of CD30 as an eventual operational marker for a human Th2-like reaction in vivo, we performed immunohistological stainings on frozen sections of skin biopsies from patients with lepromatous and tuberculoid leprosy. A maximum of three to four CD30-positive cells was found per section, and there was no difference in the accumulation of CD30-positive cells between the tuberculoid and the lepromatous form of leprosy. With respect to CD26-positive cells, a high number was found in tuberculoid leprosy in contrast to a greatly reduced expression of CD26 in lepromatous leprosy. We conclude that, while CD26 was confirmed as an operational marker for a Th1-like reaction in leprosy, CD30 does not represent an operational Th2 marker in this disease.

Biomarkers↗

[Monocondylar fractures of the femur. Therapeutic strategy and clinical outcome].

Twenty-nine unicondylar fractures of the distal femur were treated at the Trauma Center "Bergmannsheil", University of Bochum, Germany, between 1981 and 1994. All patients sustained their injuries from severe direct trauma. There were 16 lateral condylar fractures, 7 medial condylar fractures and 6 tangential posterior ("Hoffa-type") fractures. Twenty-eight closed injuries and 1 grade IIIB open fracture injuries to the skeleton. All fractures were treated with open reduction and internal fixation with screws within 8 h of admission. Postoperative management consisted of early continuous passive motion and minimal weight-bearing for 6-8 weeks, progressing to full weight-bearing. The mean follow-up was 68 months (18-120). The therapeutic outcome (clinical result, radiographs) was rated by the Neer score. Twenty-seven patients were available for follow-up examination. Of these, 23 were rated as excellent. 3 achieved satisfactory results, and 1 had an unsatisfactory result. All patients who did not achieve an excellent outcome had had accompanying injuries. Open reduction and internal screw fixation of unicondylar femur fractures provided overall excellent long-term results. The therapeutic outcome was significantly affected by associated injuries of the skeleton.

Adolescent↗

[Possibilities and limits of functional conservative therapy of acute Achilles tendon ruptures].

According to sonographic criteria, 55 patients underwent surgical treatment with mobilisation in a lower leg plaster or conservative treatment with early mobilisation in heel pad (3 cm) shoes when an acute Achilles tendon rupture (ATR) was diagnosed. The follow-up period in 51 patients was 2.4 years (operated group = 28 patients, conservative group = 23 patients) with clinical examination and testing of isokinetic muscle strength in knee joint flexion. After surgical treatment, minor wound infections occurred in 10.6%. Reruptures occurred in 13% of the conservative group. Following conservative treatment, the rate of stress-related achillodynia was significantly higher (P = 0.019). In the operated group mean isokinetic muscle strength was 13.7% lower than in the uninvolved leg and decreased significantly with non-operative treatment to 75.3% (P = 0.012). We recommend surgical treatment of acute ATR. The indications for conservative treatment depend on the extent of the rupture (measured by ultrasound in the equinus position), the desired level of daily activity and the patient's degree of compliance.

Achilles Tendon↗

[Vascular sports in ambulatory therapy of venous circulatory disorders of the legs. Diagnostic, therapeutic and prognostic aspects].

In 33 patients with chronic venous incompetence (CVI) caused by primary varicoses or postthrombotic syndrome stage I-III (according to Widmer) the therapeutic benefit of 6 months of medically supervised physical exercise training was documented. During the training penud there was an improvement in subjective complains such as pain and tendency for edema in the legs. Mobility in the upper ankle joint was improved asuss as venous drainage function. Clinical benefit was achieved in the reduction of ulcer size; 7 of the 10 ulcers completely healed. Medically supervised physical exercise training and optimized compression therapy are basic therapeutic approaches in conservative treatment in chronic venous insufficiency. Costs are covered by the patient's health insurance company in Germany, as long as the exercise training is medically supervised.

Adult↗

[Dynamic in vivo skin pressure measurement in quality control of compression stockings].

The well-documented positive effect of compression stocking therapy on the venous macro- and microhemodynamics of the legs can only be attained if the stockings fit well. In order to determine the effective pressure exerted by compression stockings, we usually deleted in US journals. One can get this out of journal and author's address have developed a new measuring method based on piezoresistant microprobes and a microprocessor unit. With our 2-mm-thick, 5-mm diameter probe, the pressure between the compression stocking and skin can be measured at any location desired. A temporal resolution of 50 Hz makes it possible to carry out dynamic measurements while the patient is walking or performing exercises on tiptoes. Here we present 4 typical cases out of a total of over 80 which we have evaluated. We have decided empirically that the pressure exerted by a class-2 compression stocking on the skin at the height of the ankles (b-position) should not exceed 70 mm Hg while resting and a peak of 110 mm Hg while exercising on tiptoes. At the middle of the calf (c-position) these values should not exceed 60 mm Hg at rest and 80 mm Hg on tiptoes. The pressure should decrease from the distal to proximal direction in order to produce a drainage gradient. We have found empirically that a pressure gradient of 30-40% from the b to the c measurement is favorable. Too high a proximal pressure or too high a pressure on a part of the lower leg causes pain and swelling. Too low a pressure, on the other hand, does not produce the desired vascular effect and alleviation of symptoms. Although dynamic pressure measurements take about 20-30 minutes per leg, they markedly improve patient compliance with compression therapy.

Adult↗

[Treatment of venous ulcers with low frequency pulsed current (Dermapulse): effects on cutaneous microcirculation].

Chronic venous insufficiency (CVI) is characterised by stage-dependent microangiopathy. With increasing severity there is a decrease in the number of skin capillaries and the oxygen partial pressure. The cutaneous vascular reserve, which is measured by laser-doppler fluxmetry, is reduced. Cutaneous microangiopathy is one of the main causes of the trophic disturbances associated with CVI. Low frequency pulsed current improves cutaneous microcirculation and thus nutrition as well as accelerating the formation of granulation tissue. In a open prospective pilot study, 15 patients suffering from CVI with persistent leg ulcers were treated with low frequency pulsed current (Dermapulse), which is thought to improve particularly the tissue microcirculation. The average age of the patients was 70.3 years and the average duration of ulceration was 79.1 months. The patients were treated over a period of 38 days. With this treatment, 2 ulcers healed completely and 13 showed a reduction of size of on average 63%. Capillary density increased by 43.5%, while transcutaneous oxygen partial pressure increased by 82.4%. Electrostimulation is a treatment with few or no side effects.

Aged↗