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R Maier

Publications and source records attributed to R Maier.

At least 19 recordsLinked to original sources

Sequence constraints and recognition by CTL of an HLA-B27-restricted HIV-1 gag epitope.

Previous studies on the variation of an immunodominant HLA-B27-restricted HIV-1 gag p24 epitope (KRWIIL GLNK, amino acids 263-272) have demonstrated the persistence of variants recognized by CTL. Sequence comparisons of HIV isolates showed that this region is relatively conserved and as a consequence might restrict antigenic variation. To evaluate the possibility of HIV-1 to yield infectious mutants of this epitope that lack the ability to bind to HLA-B27 or escape HLA-B27-restricted CTL recognition, single-point mutations were constructed in the infectious molecular clone of HIV-1 Lai. Changes of arginine 264, the anchor amino acid for HLA-B27, to lysine or glycine resulted in infectious HIV-1 variants. The respective synthetic peptides showed reduced ability to sensitize target cells for CTL recognition and a corresponding loss of binding affinity to HLA-B27. In contrast, mutation of glycine 269 to lysine or glutamate abrogated HIV-1 infectivity. The corresponding peptides were able to bind to HLA-B27 but were not recognized by CTL. These data show that HIV-1 tolerates some genetic variation of the HLA-B27-restricted CTL epitope in gag p24 and that single-point mutations can alter quantitatively the immunologic properties. Further, it demonstrates that the mere nonrecognition of peptides derived from quasispecies analysis of small regions might simply correspond to nonviable virus variants and cannot be taken as evidence for CTL escape mutants. Together with the previously published data on the persistence of CTL epitopes, these results suggest that CTL do not play a major role in driving HIV-1 evolution in vivo.

Amino Acid Sequence

Tyrosine kinases are involved with the expression of inducible nitric oxide synthase in human articular chondrocytes.

The present study characterizes mechanisms involved with the induction of nitric oxide (NO) production, nitric oxide synthase (NOS) enzymatic activity and mRNA expression in human articular chondrocytes. Activation of chondrocytes with lipopolysaccharide (LPS) or IL-1 resulted in time- and dose-dependent increases in iNOS mRNA followed by increased NOS enzymatic activity and NO release. The protein tyrosine kinase (PTK) inhibitors herbimycin A or genistein reduced IL-1 or LPS-induced NO release and NOS enzymatic activity. This was associated with inhibition of iNOS mRNA expression as determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. In contrast, inhibitors of protein kinase C (PKC) or protein kinase A (PKA) did not affect these responses. These results were confirmed in experiments with second messenger agonists where neither activation of PKC, nor increases in cyclic adenosine monophosphate (cAMP) or increased intracellular calcium levels were associated with the induction of iNOS mRNA or NO release. These results suggest that PKC, PKA and calcium-dependent signals are not required or sufficient for the stimulation of NO production. However, NO production is dependent on tyrosine kinases due to their role in the expression of iNOS mRNA.

Amino Acid Oxidoreductases

[Clinical experiences and results of high-dosage methylprednisolone therapy in spinal cord trauma 1991 to 1993].

Studies in animals and especially the NASCIS II study illustrated the neuroprotective effects of methylprednisolone, but they are disputed. At the University Clinic of Traumatology, Vienna, 31 patients with spinal cord injuries were given methylprednisolone as a bolus of 30 mg/kg body weight followed by a maintenance dose of 5.4 mg/kg body weight/h for another 23 hours. Twenty-seven patients were stabilised within 8 hours, 2 patients were not operated on, because of their low prognosis. Two patients could be treated conservatively, because the spinal fractures were supposed to be stabile. Then follow-up studies of these patients were between 1 and 3.2 years. All patients (100%) with incomplete neurologic deficits (n = 18) showed a significant recovery and even 3 patients (23.1%) with primarily a complete tetraplegia (n = 13) showed a nearly entire recovery. Compared to these results we look back at 113 patients with complete and incomplete neurologic deficits who were treated at the I. University Clinic of Traumatology, Vienna, and would have got methylprednisolone following our current management procedures.

Adolescent

Stereoselective increase of plasma concentrations of the enantiomers of propranolol and atenolol during exercise.

OBJECTIVE: In vitro studies have shown that, like catecholamines, both propranolol and atenolol are taken up by and released from adrenergic cells. We performed this study to investigate whether this may also play a role in humans and whether stereoselective aspects are important. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study of two groups of 12 healthy volunteers. Subjects received single oral doses of 80 mg (R,S)-, 40 mg (R)-, and 40 mg (S)-propranolol; 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol; and placebo at intervals of 1 week. Exercise was performed at 4 and 9 hours after drug intake, and blood samples were taken before and at the end of each exercise period. The plasma concentrations of the (R)- and (S)-enantiomers of propranolol and atenolol, as well as those of epinephrine and norepinephrine, were determined by HPLC. RESULTS: Effects of exercise on the plasma levels of the enantiomers of propranolol and atenolol were similar. When the optically pure enantiomers were administered, exercise caused a marked and significant increase of the plasma concentrations of the (S)- but not of the (R)-enantiomers. When the drugs were administered in the racemic form, the plasma levels of both the (R)- and (S)-enantiomers were elevated to the same extent. The increase of norepinephrine levels during exercise was more pronounced than that of epinephrine and paralleled that of the (S)-enantiomers of the beta-blockers. CONCLUSION: Bearing the in vitro data in mind, we conclude that (S)-propranolol and (S)-atenolol are taken up into and released from adrenergic cells together with norepinephrine during exercise. The reason why the plasma concentrations of (R)-propranolol and (R)-atenolol are increased only during exercise in the presence of the corresponding (S)-enantiomers remains to be determined.

Administration, Oral

Aggressive fluid resuscitation and broad spectrum antibiotics decrease mortality from typhoid ileal perforation.

One of the most severe complications of typhoid enteritis is perforation of ileal ulcerations. The typically high mortality rates from these perforations are in part due to extremely limited supportive care in hospitals in typhoid endemic areas. In the setting of a rural African hospital, this study demonstrated a decrease in overall mortality rate from 40% with one layer closure and chloramphenicol alone to 19% with two-layer closure and chloramphenicol, gentamicin and metronidazole. This was primarily due to a decrease in late (> 24 h) mortality. There was also a decrease in overall mortality rate from 43% with < 10 ml/kg of intraoperative fluid administration to 14% with > 10 ml/kg. This was primarily due to a decrease in early (< 24 h) mortality. Even within the constraints of the rural developing world, more aggressive initial fluid resuscitation can decrease early mortality, while broader spectrum antibiotics and two-layer closure can decrease late mortality from typhoid ileal perforation.

Adolescent

Cytokine regulation of chondrocyte functions.

Regulation of chondrocyte secretory functions and proliferation by cytokines and growth factors is central to cartilage development and maintenance of homeostasis in the mature organism. Depending on the type of extracellular stimulus, chondrocytes can be induced to enter a catabolic matrix degrading or anabolic matrix forming functional program. Interleukin I and transforming growth factor beta are the prototypic stimuli for the catabolic and anabolic program, respectively. Insight into the regulation of chondrocytes by cytokines and growth factors provides the basis for improved concepts of osteoarthritis pathogenesis and new perspectives for therapeutic interventions.

Cartilage

Inducible nitric oxide synthase from human articular chondrocytes: cDNA cloning and analysis of mRNA expression.

Human articular chondrocytes can be induced by IL-1 beta, TNF-alpha or LPS to release high levels of nitric oxide. Using degenerate PCR primers based on homologous regions from previously cloned NOS enzymes, a 1.9 kb cDNA fragment was amplified from IL-1 beta stimulated but not from resting chondrocytes. Screening of a lambda gt11 cDNA library, which was prepared from RNA of IL-1 beta activated chondrocytes, resulted in the isolation of the complete cDNA, encoding a protein of 1153 amino acids. Comparison of the cDNA sequence identified human chondrocyte iNOS to be almost identical to the sequence recently reported for the hepatocyte enzyme, differing in 12 amino acids. Northern blot analysis revealed, that stimulated chondrocytes express a single 4.5 kb iNOS mRNA species. IL-1 beta induction of iNOS mRNA was detectable by 6 h and continued to be elevated throughout a 72 h culture period. Screening of a human bone cDNA library identified this inducible NOS to be also expressed by bone cells.

Amino Acid Oxidoreductases

Comparison of the costs of acute treatment for gunshot and stab wounds: further evidence of the need for firearms control.

Gun control is proposed primarily to decrease the incidence of injury and death from gunshot wounds (GSWs). We hypothesize that decreasing the number of GSWs will also produce significant economic savings, even if personal violence were to continue at the same rate, maintaining the same overall incidence of penetrating trauma. We analyzed charges and reimbursements for the treatment for all patients with GSWs (n = 1116) and stab wounds (SWs) (n = 1529) admitted to a level I trauma center from 1986 through 1992. Mean and median charges were higher for GSWs ($14,541; $7,541) than for SWs ($6,446; $4,249) (p < 0.05). There was a 12% per year increase in the annual number of GSWs (p = 0.001), leading to a disproportionate increase in the annual total charges for GSWs (p = 0.013), compared with SWs. Public expenditures, including bad debt and government reimbursement, increased for GSWs (p = 0.019) but not SWs. Thus, if all patients with GSWs instead suffered SWs, there would be an annual savings of $1,290,000 overall and of $981,000 of public funds from this institution alone. Treatment costs for GSWs are higher than those for SWs and are rising more rapidly, with an increasing amount of public funds going to meet these costs. Considerable savings to society would accrue from any effort that decreased firearm injuries, even if the same level of violence persisted using other weapons.

Cost of Illness

[Treatment of spinal injuries].

The treatment of spinal column injuries relies on the well founded knowledge in functional spinal anatomy. An exact diagnosis is based on a thorough clinical and neurological examination. X-rays, CT-scan and eventually an MRI examination. A fracture classification is imperative for further conservative and operative treatment. Fractures and fracture dislocations of the thoracic and lumbar spine are generally classified in groupings based on the three column theory of Dennis. The whiplash injury is the most common soft tissue injury of the cervical spine. The initial therapy of this trauma intends to achieve a fast reduction of pain and inflammatory tissue reactions. Of all fractures regarding the human beings the spinal column is affected in about one percent. The most common fracture localisation is the thoraco-lumbar spine. Fractures of the atlas (Jefferson fracture) and odontoid fractures type Anderson I and Anderson III are usually treated by a halo west for 8-12 weeks. Odontoid fractures type Anderson II are stabilised by screw fixation. Fractures below C 2 require an operative stabilisation in most cases. Ventral, dorsal and combined ventral-dorsal spondylodeses are performed. Fractures of the thoracic and lumbar spine are treated conservatively in about 80-90% of our cases. Fractures of the upper thoracic spine usually require no external fixation, functional treatment is possible. Fractures below Th 11 are treated by reduction and casting for 12 weeks. Within the last 15 years the operative treatment of these fractures continually increased. Dorsal stabilisation with pedicle implants prevailed in the last years. The aftercare of spinal trauma patients consists in an intensive physical therapy for at least three months.

Diagnostic Imaging

[Imaging in struma diagnosis].

Since Cassen and Taylor and Stewart introduced 131iodine scans of the thyroid, these have become an integral part of the routine diagnostic procedures for thyroid disease. Today 131I is no longer used due to its excessive radioactivity; 123iodine or 99mtechnetium are now preferred. Pitfalls in the use of 99mTc are that in some thyroid disorders, such as certain forms of thyroid carcinomas and chronic thyroiditis, a normal iodine trapping (but not organification) may occur. This mechanism can lead to false conclusions. Sonography in the imaging of organ boundaries has been used in Germany for 15 years to an increasing extent. To date following correlations between thyroid disorders and sonographic features have been found: In 80% of patients with Graves' disease the thyroid tissue is characterized by low echogenicity. In over 95% of patients with chronic thyroiditis, combined with hypothyroidism, the same has been observed. Subacute or granulomatous thyroiditis is characterized by regions of low echogenicity, corresponding to areas of inflammation. Thyroid carcinomas have appeared up to now as nodules of low echogenicity. However, the use of high frequency ultrasound imaging has complicated the situation. Nevertheless, nodules of low echogenicity show a higher rate of malignancy than nodules of higher echogenicity.

Diagnosis, Differential

TSG-6: a TNF-, IL-1-, and LPS-inducible secreted glycoprotein associated with arthritis.

TSG-6 (TNF-stimulated gene 6) was originally discovered by differential screening of a cDNA library prepared from TNF-stimulated human diploid FS-4 fibroblasts. We show that the 35-kDa protein encoded by TSG-6 was undetectable in the medium of untreated FS-4 cultures, whereas its production reached approximately 1400 and 700 ng/10(6) cells after 24-h treatment with IL-1 or TNF, respectively. Stimulation of TSG-6 protein and mRNA levels was also demonstrated in normal human mononuclear cells by treatment with TNF and, especially, by LPS. In view of the inducibility of TSG-6 by inflammatory cytokines and its earlier demonstrated affinity for hyaluronan, we examined the presence of TSG-6 protein in the synovial fluids from patients with various forms of arthritis. TSG-6 protein was undetectable in the joint fluids of persons with no known history of arthritis, but high levels of TSG-6 oere demonstrated in the synovial fluids of a majority of arthritis patients. TSG-6 protein was also detected in the sera of some of the arthritis patients, albeit at concentrations that were less than in the joint fluids. To investigate the source of TSG-6 in the synovial fluids, we examined the production of TSG-6 protein in cultures of synovial cells. Synoviocytes from rheumatoid arthritis patients produced TSG-6 protein constitutively, and this production was increased by treatment with TNF or IL-1, but not with TGF-beta. Steady-state levels of TSG-6 mRNA were also increased in synoviocytes after treatment with TNF or IL-1. The presence of high levels of TSG-6 protein in the synovial fluids of arthritis patients and its inducibility by inflammatory cytokines in fibroblasts, mononuclear cells, synoviocytes, and chondrocytes suggest a role for TSG-6 in arthritis and inflammation.

Adolescent

Interleukin-11, an inducible cytokine in human articular chondrocytes and synoviocytes, stimulates the production of the tissue inhibitor of metalloproteinases.

This study on the regulation of interleukin (IL)-11 expression in human connective tissue cells shows that IL-11 expression is not restricted to cells of hematopoietic origin but can also be induced in articular chondrocytes and synoviocytes. IL-11 mRNA was induced in chondrocytes in response to transforming growth factor (TGF)-beta 1 and IL-1 beta. Stimulation with IL-6 or growth factors, such as basic fibroblast growth factor, leukemia inhibitory factor, and platelet-derived growth factor-AA, had only weak or no detectable effects. Activation of protein kinase C by phorbol esters and inhibition of protein synthesis by cyclohexamide increased IL-11 transcripts, whereas calcium ionophore A23817 or dibutyryl cyclic AMP had no effect. Immunoprecipitations revealed the synthesis of IL-11 protein in response to TGF-beta 1, IL-1 beta, as well as phorbol 12-myristate 13-acetate, and a synergistic action of TGF-beta 1 and IL-1 beta was observed. Similar findings on IL-11 expression were made in synoviocytes. Analysis of effects on cell function showed that IL-11 stimulated the production of the tissue inhibitor of metalloproteinases in chondrocytes and synoviocytes but did not affect chondrocyte proliferation or increase stromelysin activity. These results suggest that IL-11 does not contribute to connective tissue degradation but conversely induces protective effects in joint tissue.

Cartilage, Articular

Titanium Riechert head ring for MR stereotaxy. Technical note.

Magnetic Resonance has become the preferred neuro-imaging modality. To fully take advantage of the high anatomical resolution the Riechert stereotactic system was adapted for use in Magnetic Resonance Stereotaxy. The head ring which until recently was made of an aluminum alloy has been replaced by an unsegmented head ring of pure titanium without changing the dimensions and fixation mode. No significant misregistration due to eddy currents has been noticed. Minor distortion induced by the titanium head ring can be corrected mathematically. Thus the geometric information is limited only by the pixel resolution of the MR image.

Artifacts

Diastolic zero-flow in the umbilical artery in twin pregnancies.

Clinical arterial blood flow measurements in single pregnancies can not be precisely estimated yet. ARED (absent or reverse end diastolic) flow of the umbilical artery (UA) commonly indicates a symptom of fetal jeopardy. The interpretation of blood flow measurement in twin pregnancies is still controversial. On one hand, no differences in a single pregnancies are found, and on the other hand, increased resistance indices have been reported. In the feto-fetal transfusion syndrome mostly there are normal blood flow measurements. When pathological blood flow occurs, usually it affects the donor. By means of 4 case reports with ARED flow, the value of the investigation method in management of twin pregnancies is demonstrated. Three out of four fetuses with an ARED flow in the UA have died. Case fetus with a normal flow velocimetry survived. Even feto-fetal transfusion syndrome may cause pathological blood flow curves. In fetuses with ARED-flow in the UA fetal hypoxia and acidosis are to be expected. A careful evaluation of the cardiotocogram is indicated with a viable fetus. A possible fetal disturbance may be seen early in blood flow curves and may help provide better obstetrical management.

Adult

[Treatment procedure in humeral shaft fractures with primary or secondary radial nerve damage].

We give an account of 28 patients with fractured humerus diaphysis, suffering from primary and seven patients suffering from secondary lesion of the radialis nerve, all treated by operation. In each case the radialis nerve was exposed and the fracture was treated by fixation with compression plates. In case of primary lesions of the radialis nerve, we found intraoperative damages by traction (six times), contusions (seven times), intraneural hämatomas (six times) and for one time perforation of the nerve by bones. The rest of this group (eight times) did not show any pathological finding. Those patients with secondary lesion of the radialis nerve showed damages by traction (three times) and in two cases the nerve was walled up by callus or connective tissue. Two times we could not find any pathological alteration of the nerve. 23 (six) out of 28 (seven) patients with primary (secondary) lesion of the radialis nerve could be followed up. On this occasion we stated complete neurological restitution 20 times (four times) and incomplete restitution three times (two times). The great number of pathological findings, which necessitate operative treatment, the short duration of remission and the high rate of restitution confirm us to leave the way of conservative treatment in cases of primary or secondary lesion of the radialis nerve and the indication of acute operation is given.

Adolescent

Long-term variability of heart rate increases with successful closure of patent ductus arteriosus in preterm infants.

Long-term variability (LTV) of heart rate was calculated continuously by a microprocessor in 25 preterm infants undergoing indomethacin treatment for closure of patent ductus arteriosus (PDA), in 24 preterm infants without signs of PDA, and in 10 neonates treated with prostaglandin E1 for cyanotic heart malformation. In infants with patent ductus arteriosus, LTV was lower than in controls. Following indomethacin, LTV increased most markedly (from 1.5 to 3.2; p less than 0.01) in infants with improved ventilation. The increase was less marked (from 1.8 to 2.5; p less than 0.05) in infants whose degree of respiratory failure did not change. LTV remained largely unchanged in infants who deteriorated. In 9 out of the 10 neonates treated with prostaglandin E1, LTV increased. We conclude that LTV corresponds to brain stem oxygenation and may be a useful tool to monitor treatment of PDA.

Alprostadil

[Evaluation of central speech disorders using objective criteria: a psychophysiologic contribution to the discussion of the neural plasticity hypothesis].

Examinations of aphasic patients by using cognitive tasks were based on the hypothesis that semantically evoked potentials correlate to the processing of information in the different speech processing of information in the different speech processing areas. It was found that patients with Broca aphasia generated synchronization potentials in the Wernicke area in contrast to Wernicke patients. We suppose a correlation between the timing in sensorial speech processing areas and the generation of synchronization potentials.

Aphasia, Broca