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Biomedical subjects

M Hahn

Publications and source records attributed to M Hahn.

At least 19 recordsLinked to original sources

A 3-year cohort study on short-term effects of air pollution in Germany. 1. Influences of medication and season.

A 3-year cohort study which started in September 1987 investigates the effect of air pollution in adult patients with chronic obstructive airway disease. Of 108 patients recruited during the pilot phase in 1987 only eight patients had left the study prematurely. The most important components of the study are the daily peakflow measurements and a diary on medication and symptoms. In a preliminary analysis the influence of medication and season has been analyzed for the period September 1988 to June 1989 for 53 patients. In general, the reactions to seasonal changes were small. However, a significant decrease in peak-flow values by about 5% was found for the months of May and June compared to December for patients with chronic bronchitis, emphysema and asthma.

Aged

Cloning of the rat gene encoding choline acetyltransferase, a cholinergic neuron-specific marker.

The neurotransmitter acetylcholine is synthesized by choline acetyltransferase (ChAT; EC 2.3.1.6). Since the expression of ChAT in the nervous system is restricted to cholinergic neurons, it serves as a specific marker for these neurons. In Alzheimer disease, ChAT activity is markedly reduced in the affected brain areas. Nerve growth factor can increase the ChAT activity of brain cholinergic neurons in vitro and in vivo. We have cloned the rat ChAT gene and identified one 5' noncoding exon and 14 exons that account for the entire coding sequence. The exon organization is compared with the protein domains conserved during evolution. These exons are distributed over at least 64 kilobases in the rat genome; the largest intron is at least 14 kilobases long. Within a 0.7-kilobase region immediately upstream of the confirmed sequence of the noncoding exon, TATA-like elements and numerous potential binding sites for transcription factors are found, including AP-1, Sp1, octamer-binding factor(s), CTF/NF-1, and the nuclear oncoprotein Myb.

Amino Acid Sequence

C-C-A-G-G-C-m5C-T-G-G. Helical fine structure, hydration, and comparison with C-C-A-G-G-C-C-T-G-G.

The self-complementary DNA duplex C-C-A-G-G-C-m5C-T-G-G has been refined against 1.75-A x-ray diffraction data to an R value of 17.4%. In the crystal of space group P6, 10-base pair DNA fragments with characteristic sequence-related fine structure stack end to end to form long antiparallel B-type double helices. As shown by a structure analysis at lower resolution (Heinemann, U., and Alings, C. (1991) EMBO J. 10, 35-43), the overall geometry of C-C-A-G-G-C-m5C-T-G-G is similar to that of the unmethylated analog C-C-A-G-G-C-C-T-G-G despite a different crystal environment. The present high resolution structure analysis permits a detailed comparison of the two duplexes and their hydration spheres. Helical parameters are significantly correlated between both molecules, with the exception of the base pair propeller. Sugar pucker and backbone torsion angles alpha, gamma, delta, and chi show similar mean values, but their individual values deviate significantly between duplexes. In contrast, torsion angles beta, epsilon, and zeta change along the strands of both duplexes in much the same way. The effect of single-site methylation on DNA conformation appears to be small and limited to the base pairs directly involved. Methylation tends to push base pairs toward the minor groove of the helix. A regular minor groove hydration pattern involves dual hydrogen bonding of water molecules to O-4' and base atoms of C-C-A-G-G-C-m5C-T-G-G.

Base Sequence

Enzyme and immunohistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: a new embedding method for routine application.

A simplified method of low temperature methyl and butyl methacrylate embedding (up -20 degrees to -15 degrees C) is demonstrated using a proper redox system of benzoyl peroxide and aromatic amine. This method combines the morphological superiority of plastic-embedded bone tissue and bone marrow sections with the advantages of specific enzyme histochemical and immunochemical markers. The method permits good preservation of morphological details, the survival of antigenic determinants and the retention of enzyme activities. The specimens were fixed in 1.6% formaldehyde and 5% sucrose in 0.02 M phosphate buffer at pH 7.4, washed in 0.02 M phosphate buffer and 5% sucrose, dehydrated with acetone and impregnated with monomers of embedding medium. All these steps were carried out at +4 degrees C. The method presented is especially suitable for enzyme histological and immunohistological diagnosis of primary and secondary bone tumours, soft tissue tumours, as well as myelo- and lymphoproliferative disorders of bone marrow biopsies. Examples are demonstrated with mono- and polyclonal antibodies and reaction products of hydrolytic enzymes.

Biopsy

Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture.

The stability of trabecular bone depends not only on the amount of bone tissue, but also on the three-dimensional orientation and connectedness of trabeculae, which is summarized as trabecular microarchitecture. In previous studies we could demonstrate that in three-dimensional bone tissue the relation of trabecular plates to rods is reflected in the ratio of concave to convex surfaces of the bone pattern in two-dimensional bone sections. For the quantification of the connectedness of these bone patterns we developed a new histomorphometric parameter called Trabecular Bone Pattern factor (TBPf). The basic idea is that the connectedness of structures can be described by the relation of convex to concave surfaces. A lot of concave surfaces represent a well connected spongy lattice, whereas a lot of convex surfaces indicate a badly connected trabecular lattice in two-dimensional sections. By means of an automatic image analysis system we measure trabecular bone area (A1) and perimeter (P1). A second measurement of these two parameters (now A2 and P2) is done after a simulated dilatation of trabeculae on the screen. This dilatation results in a characteristic change of bone area and perimeter depending on the relation of convex to concave surfaces. TBPf is defined as a quotient of the difference of the first and the second measurement: TBPf = (P1 - P2)/(A1 - A2). First measurements of TBPf in 192 iliac crest bone biopsies of autopsy cases show that there is not only age-related loss of bone volume, but also a decrease of trabecular connectedness. By means of TBPf we can demonstrate a significant difference in the age-related loss of trabecular connectivity between male and female individuals.

Autoanalysis

[Histologic reactions of the bone-implant zone and cortical bone area after long-term hip replacement].

29 femora with cemented hip endoprostheses and 17 age related controls were analyzed regarding different histological criteria. All specimens were processed to undecalcified ultra thin grindings and in addition a few to surface stained block-grindings. The reactions at the bone implant interface in cases without loosening of the implant are: accumulation of macrophages and multinucleated giant cells, fibrous tissue membranes with a mean thickness of 103 microns and mineralization defects near the cement. The mean rate of direct bone/bone-cement contact is 2.7% of the whole cement surface. The phenomenons at the interface were explained as being the result of micromovement and resulting from wear and tear. The cortical bone demonstrates a remarkable loss of bone (up to 60% after 12 years) following an increase of osteoclastic resorption with no change of osteoblast activity. The localization of the bone loss indicates a relation to the new load situation after implantation.

Aged

[Transitory AV block as a cardiac manifestation of Lyme disease].

After one day of dizziness a 28-year-old man experienced a syncope on getting up. ECG revealed a 3 degrees atrioventricular (AV) block unresponsive to drug treatment. A temporary pacemaker was implanted. Erythema migrans 4 weeks before admission suggested Lyme carditis, and the diagnosis was confirmed serologically (ELISA increased polyvalently, IgM antibody titre 1:64, IgG antibody titre 1:512). On antibiotic treatment with amoxicillin (1 g three times daily) and prednisolone (initially 80 mg daily, with gradual dose reduction) the sinuatrial block regressed within 10 days. Holter monitoring still demonstrated occasional sinoatrial conduction disturbances for some days, until sinus rhythm was permanently re-established. This case illustrates that transitory AV block can be the sole manifestation of sporadic Lyme disease in Europe and should therefore be included in the differential diagnosis of any acute cardiac disease.

Adult

Genomic organization of the rat aromatic L-amino acid decarboxylase (AADC) locus: partial analysis reveals divergence from the Drosophila dopa decarboxylase (DDC) gene structure.

Aromatic L-amino acid decarboxylase (AADC) is responsible for the conversion of L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan to dopamine and serotonin, respectively, which are important neurotransmitters. We characterized genomic clones derived from the rat AADC locus by Southern blot and nucleotide sequencing analyses to explore the exonal organization of the gene. Our results suggest that the rat AADC gene is relatively large, containing at least 12 exons and spanning at least 40 kb in the rat genome. In this study, nine exons corresponding to 71% of the published cDNA sequence were identified, the smallest of which was as short as 20 base pairs (bp). In the Drosophila dopa decarboxylase (DDC) gene, the sequences homologous to these nine exons are all present in the fourth exon. This implies that either multiple intron sequences have been added to the vertebrate AADC gene or alternatively, deleted from the invertebrate gene after the divergence of vertebrates and invertebrates during evolution.

Animals

Undecalcified preparation of bone tissue: report of technical experience and development of new methods.

For reliable quantitative and qualitative analysis of bone specimens undecalcified preparation is essential. The "conventional" technique for this purpose is embedding in methylmethacrylate. Larger bone specimens, highly sclerotic specimens, cortical bone or bone implants consisting of metals or ceramics require modifications of this technique or completely new methods. We report our experience with the undecalcified preparation of 47,700 bone specimens. New techniques such as the cutting of large area sections up to a size of 5 x 6 cm and grinding procedures for completely artefact-free preparation which are applied in special cases are also described. A new technique of combined two- and three-dimensional analysis of bone specimens is presented. In our experience these methods are fundamental for morphological investigation of bone.

Bone and Bones

Chronic orchialgia in the pain prone patient: the clinical perspective.

Chronic pain syndromes are well known to the medical community. The incidence of chronic pain syndromes and cost of evaluating these patients are rapidly increasing. Chronic testicular pain is a fairly common manifestation of a chronic pain syndrome. Retrospectively, we reviewed the records of 48 patients with chronic testicular or scrotal pain (greater than 6 months) evaluated at our institution during the last 7 years. These patients had multiple diagnostic and interventional procedures with few positive findings. There was little improvement in these patients after multiple surgical procedures. Based on the paucity of objective clinical findings a carefully directed diagnostic evaluation for orchialgia is outlined. The treatment of these patients is best managed by a multidisciplinary approach involving the urologist and a pain clinic environment. We believe that extensive diagnostic testing is not indicated in the absence of clinical findings and may serve to worsen the condition or lead to iatrogenic injury. Surgical intervention should be limited to cases when a clear indication is present.

Adult

Indwelling epidural catheters for pain control in gynecologic cancer patients.

Seven patients with severe pain caused by an advanced, incurable gynecologic malignancy were treated with an indwelling epidural catheter connected to an implantable subcutaneous port through which morphine was infused. There were few major complications associated with insertion or maintenance of the system. The average usage was 60 days, although the system functioned continuously for 6 months in one patient. Pain distribution in these women ranged from the upper abdomen to the lower extremities. All patients, including one with liver metastases, reported good to excellent pain control with the epidural narcotics. Two subjects with upper abdominal pain occasionally required supplemental oral oxycodone, but the other five patients had adequate pain relief with the epidural system alone. The indwelling epidural system provides excellent analgesia for patients with advanced, incurable gynecologic cancer.

Adult

Multiple hormone actions: the rises in cAMP and Ca++ in MDCK-cells treated with glucagon and prostaglandin E1 are independent processes.

Glucagon and prostaglandin E1 stimulate adenylate cyclase in Madin-Darby canine kidney cells with an approximate EC50 of 3*10(-8) and 1*10(-7) M respectively. The rise in cAMP is accompanied by a transient rise in intracellular Ca++ measured with the fluorescent calcium indicator Indo-1. A comparable increase in intracellular Ca2+ without a rise in cAMP occurs with the cholinergic agonist carbamylcholine. Stimulation of adenylate cyclase by the beta-adrenergic agonist isoproterenol or directly by forskolin has no effect on intracellular Ca++. By all criteria studied the rise in intracellular Ca++ and the increase in cAMP are independent from each other.

1-Methyl-3-isobutylxanthine

Nitrogen partial pressures in man after decompression from simulated scuba dives.

In five subjects arterial and central venous nitrogen partial pressures (PN2) were measured after decompression from a chamber dive following a decompression schedule for scuba diving. The simulated dives consisted of exposure at rest to air at 6 bar for 30 min. corresponding to a depth of 50 m. Afterwards the subjects were decompressed with decompression stops at 2.5, 2.2, 1.9, 1.6 and 1.3 bar with a total decompression time of 73 min. Immediately after decompression and every 40 min. until the 240th min. arterial and central venous blood samples were analyzed for PN2 using a manometric Van Slyke apparatus. Venous PN2 remained elevated until 160 min. after decompression indicating still incomplete nitrogen wash-out at least two hours after decompression had been accomplished. Bubble formation is discussed as a cause for prolonged nitrogen elimination. Our data confirm that nitrogen elimination is prolonged after decompression from simulated dives at rest.

Arteries

[Ensuring ureter viability: experimental study].

1. In experiments on dogs we observed that the remaining of the peripelvic and periureteral tissue in taking from the kidney is not decisive for the blood supply of the ureter. That these findings are important also for the clinic is confirmed by the following fact: in order to draw the ureter through the natireflux tunnel, 2-4 cm of the periureteral tissue must be removed. However, we never observed a necrosis restricted to this place. 2. In all experiments the blood supply of the upper half of the donor ureters was confirmed without any mistake. Therefore we recommend to shorten the ureter to this length for the UNC. 3. The preservation by means of hypothermy or permanent machine perfusion has no negative effect on the blood supply of the ureter.

Animals