Search PubMed⌕ Search

Biomedical subjects

M Richter

Publications and source records attributed to M Richter.

At least 199 records · Page 11Linked to original sources

Activation and labelling of the purified skeletal muscle ryanodine receptor by an oxidized ATP analogue.

We have tested the periodate-oxidized ATP analogue 2',3'-dialdehyde adenosine triphosphate (oATP) as a ligand for the skeletal muscle ryanodine receptor/Ca(2+)-release channel. Ca2+ efflux from passively loaded heavy sarcoplasmic reticulum vesicles of skeletal muscle is biphasic. oATP stimulates the initial phase of Ca2+ release in a concentration-dependent manner (EC50 160 microM), and the efflux proceeds with a half-time in the range 100-200 ms. This oATP-modulated initial rapid Ca2+ release was specifically inhibited by millimolar concentrations of Mg2+ and micromolar concentrations of Ruthenium Red, indicating that the effect of oATP was mediated via the ryanodine receptor. The purified Ca(2+)-release channel was incorporated into planar lipid bilayers, and single-channel recordings were carried out to verify a direct interaction of oATP with the ryanodine receptor. Addition of oATP to the cytoplasmic side activated the channel with an EC50 of 76 microM, which is roughly 30-fold higher than the apparent affinity of ATP. The oATP-induced increase in the open probability of the ryanodine receptor displays a steep concentration-response curve with a Hill coefficient of approximately 2, which suggests a co-operativity of the ATP binding sites in the tetrameric protein. oATP binds to the ryanodine receptor in a quasi-irreversible manner via Schiff base formation between the aldehyde groups of oATP and amino groups in the nucleotide binding pocket. This allows for the covalent specific incorporation of [alpha-32P]oATP by borhydride reduction. A typical adenine nucleotide binding site cannot be identified in the primary sequence of the ryanodine receptor. Our results demonstrate that oATP can be used to probe the structure and function of the nucleotide binding pocket of the ryanodine receptor and presumably of other ATP-regulated ion channels.

Adenosine Triphosphate↗

Parathyroidectomy in primary hyperparathyroidism: preoperative localization and routine biopsy of unaltered glands are not necessary.

BACKGROUND: An assessment was made of operative risk and outcome after parathyroidectomy for primary hyperparathyroidism. METHODS: A retrospective study was conducted in a single center university hospital in Switzerland. The 173 patients (130 women and 43 men) ranged from 17 to 89 years of age (mean, 62.0 years). No routine preoperative localization methods were used for primary neck exploration. Parathyroidectomy was performed under general anesthesia. No routine use was made of intraoperative biopsy of glands whose macroscopic appearance was normal. The 173 patients underwent 179 operations (170 primary and 9 secondary interventions). Resection of a single gland was performed in 127 cases (73.4%) and of two glands in 36 cases (20.8%). Subtotal parathyroidectomy (3 1/2 glands) was performed in 10 cases (5.8%). RESULTS: Of 170 patients with primary intervention, 164 (96.5%) were normocalcemic after operation. Six of 170 patients (3.5%) underwent early reexploration. Three additional patients underwent late secondary procedures. These nine secondary operations were successful in seven patients (78%). At follow-up (mean, 24.7 months after operation) normocalcemia was noted in 163 of 171 patients (95.3%). Persistent and recurrent hyperparathyroidism occurred in 1.2% and 3.5% of patients, respectively. Permanent postoperative hypoparathyroidism was noted in 4% (six of seven patients underwent a subtotal parathyroidectomy for multiglandular hyperplasia). Operative morbidity and mortality were 2.3% and 0.6%, respectively. CONCLUSIONS: Our surgical strategy for treatment of primary hyperparathyroidism has proved to be safe with a favorable outcome in more than 95% of patients. This was possible without the routine use of preoperative localization studies and intraoperative biopsy of macroscopically normal glands. Routine biopsy of normal-appearing glands seems to be unnecessary and may increase the risk of hypoparathyroidism.

Adolescent↗

The role of proctolin in the antenna-heart beat acceleration of Periplaneta americana (L.).

So-called accessorial pulsatile circulatory organs in insects have developed during evolutionary reduction of the vascular system. As such a peripheral organ, the antenna-heart supplies the antennae with haemolymph. In the antenna-heart, the beat rhythm is generated by a myogenic automatism and is controlled neuronally. The electrical stimulation of the antenna-heart nerve produces an immediate heart beat inhibition brought about by octopamine release. Following this heart inhibition, an accelerating effect can be observed, which is based on a peptidergic mechanism. Proctolin-like material was found in both the dilator muscle and the antenna-heart nerve by means of immunocytochemistry. After HPLC-separation of antenna-heart tissue, proctolin was identified by sequencing the bioactive material and subsequent mass spectrometry. Proctolin proved to be extraordinarily effective producing stimulation of the antenna-heart beat rate up to 450%. The threshold concentration is 10(-10) mol.1(-1) and the value of the dissociation constant was fixed to KO = 1.3 x 10(-8) mol.1(-1). The chrono-trophic effect is caused by an increase in the steepness of the rising phase of pacemaker activity. The enhancement of the membrane resistance Rinput indicates a reduction of K(+)-conductance by proctolin. The PI-second messenger system is involved as well. Proctolin was identified and isolated from a real target organ. This fact and the physiological results furnished proof of peptidergic transmitter function of proctolin in the antenna-heart.

Animals↗

Molecular simulation of 8-styrylxanthines.

Regarding theophylline as representative xanthine derivative, it was shown that the net charges of various semiempirical quantum chemistry methods are transferable by scaling. PM3 should be preferred for calculation of xanthine derivatives. Molecular modelling indicated that there is a conformational similarity of the lead structure of xanthine and adenosine derivatives. The substituents bound to the C8 of xanthine and to the C2 of adenosine derivatives are involved in the discrimination into adenosine A2 antagonists and agonists. The A2 affinity of xanthines is mainly determined by the type of N7 substitution (hydrogen/methyl), the lipophilic substituent constant related to the C8 substituents, and the dipole moment of the molecules. To simulate chemically the A1 affinity, a further term (lowest unoccupied molecular orbital energy) must be added. In addition, hydrogen-bonding forces were hypothesized using a newly synthesized 3,6-diaminocarbazole derivative as synthetic adenosine pseudoreceptor.

Adenosine↗

[The functional evaluation of orthodontically aligned impacted canines].

The purpose of this study was to examine functional occlusion of impacted maxillary canines which had been moved orthodontically into the line of occlusion. Examinations were performed on both patients and on an articulator, which was adapted to correspond to the axiographical findings. Functional contacts on the working side during lateral movement of the mandible were found in all orthodontically aligned impacted canines. Half the aligned teeth were involved in canine guidance, half in group function. Balancing side interferences were detected in 22% of the cases. The result of this study revealed a nearly identical function in the aligned canines when compared with the spontaneously erupted canines on the other side of the same maxilla. This became apparent during lateral excursion of the mandible. The angle of mesiodistal inclination of the tooth central axis with an occlusal plane was 84 degrees for aligned and 82 degrees on average for the spontaneously erupted canines.

Adolescent↗

[Lipofibroma of the median nerve. Clinical report of two cases].

The following article presents two new cases of a lipofibroma of the median nerve. This formation is a very rare benign tumor of peripheral nerve tissue. Up to now 30 cases have been reported in the literature and are reviewed in this article and are compared with the two cases reported. Besides the operative treatment, which made the neuropathological diagnosis possible, preoperative diagnosis has been extended by MNT-scans of the involved parts of the nerve. The noninfiltrating character of the tumor could be well recognized on these scans. The signal quality and the anatomical proximity to the median nerve made the diagnosis of a lipofibroma likely. By the postoperative histological reviews the diagnosis was confirmed in classic manner. The immunological marking of the S-100 protein showed a remarkable reduction of this protein in these peripheral nerve tumors. The two cases reported by us recapitulate the clinical history typically and describe symptoms and our treatment for the lipofibroma of the median nerve.

Biomarkers, Tumor↗

Sequence heterogeneity of the eae gene and detection of verotoxin-producing Escherichia coli using serotype-specific primers.

The distribution of the Escherichia coli attaching and effacing (eae) gene in strains of verotoxin-producing E. coli (VTEC) isolated from cattle and humans was studied. The majority of strains isolated from humans with bloody diarrhoea or HUS and cattle with severe diarrhoea were eae positive (82 and 83% respectively). In contrast, 59% of VTEC isolated from asymptomatic cattle were eae negative and of the remaining 41% that were eae positive, the majority were serotype O157. H7. The nucleotide sequence of the 3' end of the eae gene of enteropathogenic E. coli (EPEC) of serotype O55. H7 was found to be almost identical to that of serotype O157. H7. Specific primers are described which detect the eae sequences of VTEC serotypes O157. H7, O157. H-, and EPEC serotypes O55. H7 and O55. H-. The nucleotide sequence of the 3' end of the eae gene of serotype O111. H8 differed significantly from that of O157. H7. Primers were developed to specifically identify the eae sequences of VTEC serotypes O111. H- and O111. H8. We conclude that whereas the majority of VTEC associated with disease in cattle and humans possess the eae gene, the gene itself may not be necessary to produce haemorrhagic colitis and HUS. Sequence heterogeneity in the 3' end of eae alleles of VTEC permits specific identification of subsets of these organisms.

Adhesins, Bacterial↗

Single and multiple strain colonization in patients with Helicobacter pylori-associated gastritis: detection by macrorestriction DNA analysis.

Helicobacter pylori isolates from 18 patients were examined by macrorestriction DNA analysis to determine whether > or = 2 strains can coexist in the human stomach. Four biopsy samples from different sites in each patient's stomach were cultured, and 12-14 clones of H. pylori per patient were analyzed. DNA of 15 of the 18 isolates was digestible: 12 by NotI and 3 by NruI. Within 14 of these digestible isolates, the patterns of all clones were identical. The isolate of 1 patient showed two digestion patterns, a finding that was confirmed by arbitrary primer polymerase chain reaction. The typeable isolates of all patients, except 2 who underwent gastroscopy on the same day, differed markedly from each other. These results indicate a noticeable discrepancy between the pronounced interpatient heterogeneity and the rare intrapatient variation of H. pylori.

Base Sequence↗

Correction of mandibular dentoalveolar retrusion by segmental mandibular surgery.

Mandibular dentoalveolar retrusion is a common problem that often can be related to missing or extracted teeth in the mandibular arch. The correction of this type of malformation through surgical mandibular advancement to eliminate the large overjet significantly increases the chin prominence, resulting in a poor facial appearance. With the use of a combined orthodontic and surgical treatment that includes segmental osteotomies of the anterior part of the mandible, this negative effect can be avoided and arch length can be restored. This procedure was carried out in three patients aged 26 to 33 years. The bony spaces created distal to the anterior segment were filled with iliac bone grafts. At the end of the orthodontic treatment, the missing premolars were replaced with conventional fixed dentures, bonded prostheses, or implants.

Adult↗

[Historical development of the treatment of fractures of the middle third of the face involving occlusion].

In the past decade principles of diagnosis and treatment of complex facial fractures have evolved dramatically. External appliances fixed to a headcap and semi-rigid immobilisation by wire suspensions which impose long term intermaxillary immobilisation have little by little disappeared. Conservative and often delayed fracture management has led to a more surgical and early approach in order to avoid difficult and often frustrating reoperations. The basic principles of fracture treatment are always based on re-establishing the occlusion to assume good function. The improvement in esthetic results are now derived from a better understanding of facial skeleton biomechanics, wide exposure of bony fragments and use of anatomic rigid internal fixation. Consequently, the duration of hospitalisation and job absence have been considerably reduced. This article reviews the historical steps from antiquity to present day, which mark the evolution of middle third fracture treatment.

Facial Bones↗

Similarity of primary radical pair recombination in photosystem II and bacterial reaction centers.

We report temperature and magnetic field dependent measurements of the recombination dynamics of the radical pair P680+Pheo- in D1D2cytb559 reaction centers of photosystem II and compare the results to those obtained in bacterial reaction centers. In photosystem II the rate of recombination to the groundstate is found to be slower than in the bacterial reaction centers by a factor of at least 50. This difference arises from the different redox potentials of the pigments of plant and bacterial reaction centers. In contrast, the rate of recombination to the triplet state is similar in all reaction centers, indicating a similar electronic coupling which allows us to conclude upon the structural similarity.

Chlorophyll↗

[Staging laparoscopy in Hodgkin's disease. A valid alternative to staging laparotomy].

A 30-year-old man with Hodgkin's disease, stage IA, had received radiotherapy to the supradiaphragmatic lymph nodes two years ago. During follow-up observations the patient felt well, but sonography revealed three tumours in the spleen. The erythrocyte sedimentation rate was found to be raised to 50/75 mm. Therefore, splenectomy and staging of the other parts of the abdomen for histological clarification and deciding on further therapeutic action were indicated. Thus splenectomy with bilateral liver wedge resections were performed laparoscopically, together with excision of mesenteric, paraaortic and para-iliac lymph nodes. The patient was discharged home on the 4th postoperative day. Histological examination revealed stage IIIE Hodgkin's disease. This case demonstrates that in favourable conditions staging laparoscopy can obtain the same information as conventional staging laparotomy, but it is much better tolerated by the patient.

Adult↗

Interferon-alpha and interleukin-2 in the treatment of metastatic melanoma. Comparison of two phase II trials.

BACKGROUND: Interferon-alpha (IFN alpha) and interleukin-2 (IL-2) are active agents against malignant melanoma. There is, however, no consensus on the optimal dosing schedule of both drugs. This is a report of two sequential immunotherapy trials in patients with metastatic melanoma using two different IL-2 dosing schedules. METHODS: Schedule A consists of IFN alpha, 10 million U/m2/day subcutaneously for 5 days, followed by continuous intravenous infusion of IL-2, 1 mg/m2/24 hours for 5 days. Schedule B consists of the same dose of IFN alpha, but a modified regimen of IL-2. To improve the induction of high-affinity IL-2 receptors, the initial IL-2 dose was increased (1 mg/m2/6 hours, followed by 1 mg/m2/12 hours, and 1 mg/m2/24 hours). To reduce toxicity, the dose was reduced thereafter to 0.25 mg/m2/24 hours for the following 3 days. Both regimens were repeated after 4 weeks. RESULTS: 27 patients were treated with schedule A with a response rate of 18% (1 complete response [CR], 4 partial responses [PR]), 95% confidence interval, 6-36%. The response rate in 27 patients treated with schedule B was 41% (3 CR, 8 PR), 95% confidence interval, 22-61%. Severe, often dose-limiting toxicity was associated with IL-2 in schedule A, particularly hypotension and fluid retention. Toxicity was reduced significantly in schedule B. Maximal serum levels of soluble CD25 were 17,022 +/- 13,070 U/ml in schedule A, and 31,148 +/- 4227 U/ml in schedule B (P < or = 0.01). Serum levels of TNF alpha were significantly lower in schedule B than in schedule A, as were the side effects. CONCLUSIONS: Toxicity of IL-2 is reduced by modifying the schedule of administration, which also enhances the immunologic response and appears to increase the response rate.

Adult↗