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Biomedical subjects

J Pahnke

Publications and source records attributed to J Pahnke.

At least 19 recordsLinked to original sources
PubMed2004

Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease.

BACKGROUND: Transcranial ultrasound may be used to detect increased iron levels of the substantia nigra (SN) in patients with Parkinson disease (PD) and in control subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron metabolism have been linked to basal ganglia disorders. One of these is ceruloplasmin (Cp), which is vitally involved in iron transport across the cell membrane. METHODS: One hundred seventy-six patients with PD according to the UK Brain Bank criteria and 180 ethnically matched control subjects, who were previously examined for SN iron signal changes by transcranial ultrasound, were examined for mutations in the Cp gene using denaturing high-performance liquid chromatography and subsequent sequencing for verification of unequivocal signals. Immunohistochemistry of PD midbrains was performed to examine the presence of Cp in Lewy bodies. RESULTS: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E) was significantly associated with PD and the ultrasound marker for increased SN iron levels. Moreover, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients and control subjects. Immunohistochemistry demonstrated that Cp co-localizes with Lewy bodies in PD. CONCLUSIONS: Detection of sequence variations in a single Parkinson disease (PD) patient or associated with the ultrasound marker for increased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunoreactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis of PD. Further functional analyses are warranted to investigate whether these variations are causally linked to the complex pathogenesis of PD in a subset of cases.

Aged↗
PubMed2004

Expression of stromelysin-1 (MMP-3), gelatinase B (MMP-9), and plasminogen activator system during fetal calvarial development.

AIMS: To investigate whether degrading proteases can be found in patent calvarial sutures. Sutural growth and fusion means replacement of the sutural connective tissue, rich in fibronectin and collagen type V, by expanding calvarial bone. Proliferation of one tissue into the border area of another implies the presence of enzymes able to degrade extracellular matrix (ECM). An important family of proteases is the matrix metalloproteinases (MMPs), as is the plasminogen/plasmin system. METHODS AND RESULTS: Expression of two MMPs with substrate specifity for fibronectin and collagen type V and of the plasminogen activator system was studied by immunohistochemistry in samples of human fetal calvariae (age range weeks 19-35 of gestation). In all cases, intense staining for MMPs, urokinase, and urokinase receptor was found in the sutural connective tissue and along the outer and inner borders of calvarial bone. CONCLUSIONS: Our findings suggest that degradation of sutural connective tissue takes place during sutural growth. This might facilitate proliferation of calvarial bone. Recently, it was shown that an important regulatory mechanism of sutural growth is apoptosis of osteoblasts in the osteogenic front. Intact fibronectin is known to prevent apoptosis of proliferating osteoblasts while fibronectin degradation induces their apoptosis.

Extracellular Matrix↗
PubMed2002

Cerebral beta-amyloid deposition is augmented by the -491AA promoter polymorphism in non-demented elderly individuals bearing the apolipoprotein E epsilon4 allele.

The apolipoprotein E epsilon4 allele (APOE, gene; apoE, protein) is widely accepted as a risk factor for Alzheimer's disease (AD). Our previous studies found that APOEepsilon4 promotes AD pathogenesis by fostering the early deposition of the amyloidogenic peptide Abeta in the aging brain. Recent reports suggest that polymorphisms in the upstream promoter region of APOE differentially affect the production of apoE and also may have an important influence on the probability of developing AD. In this study, we asked whether APOE promoter -491 (A/T) variants interact with APOE polymorphisms to modulate the degree of beta-amyloid- and tau-related pathology in the medial temporal lobe of the non-demented elderly. Our results confirm that APOEepsilon4 is associated with increased formation of senile plaques, cerebrovascular amyloid, and neurofibrillary tangles in the medial temporal lobe. We also found that homozygosity for A at position -491 of the APOE promoter (-491AA) correlates with increased Abeta17-24 and Abeta42 deposition in APOEepsilon4-positive cases, but not in cases lacking the epsilon4 allele. In comparison, Abeta burden is significantly less in epsilon4 carriers with the -491AT and -491TT promoter allelotypes. There was no effect of -491 polymorphisms on Abeta40 deposition (which is relatively sparse in the non-demented elderly), on the number of activated microglia, or on the amount of neurofibrillary tangles. We conclude that the amyloidogenic effects of apoE4 are exacerbated by polymorphisms in the APOE promoter that enhance apoE production.

Aged↗
PubMed2002

Immunolocalization of urokinase and its receptor in prematurely fused cranial sutures of infants.

In cranial sutural samples derived from five children with premature cranial suture fusion we have performed immunostaining for the urokinase plasminogen activator (uPA) and urokinase receptor (uPAR). We have found a strong reactivity for cell- or matrix-bound uPA and uPAR in the sutural connective tissue and associated with the osteoblasts and osteocytes lining the calvarial bone. The sutural tissue itself showed a banding with different intensity of urokinase and uPAR staining concerning connective tissue. It is proposed that the components of the plasminogen activating system are involved in tissue turnover of sutural tissue and in sutural growth.

Connective Tissue↗
PubMed2000

Treatment with nimodipine or mannitol reduces programmed cell death and infarct size following focal cerebral ischemia.

The present study was conducted to evaluate the effects of nimodipine and mannitol on infarct size and on the amount of apoptosis after transient focal cerebral ischemia. Focal cerebral ischemia was induced in male Sprague-Dawley rats (weight 300-380 g) by transient occlusion of the right middle cerebral artery (MCAO) using an intraluminal thread model. All animals underwent ischemia for 2 h, followed by 24 h of reperfusion. Group I (n=16) was untreated. Group II (n=16) received 15% mannitol (1 g/kg as bolus) and group III (n=9) received 15 microg/kg/h nimodipine intravenously beginning 15 min prior to MCAO. Twenty-four hours after reperfusion, the brain was taken and sectioned in coronal slices. The slices were stained with H&E and with the transferase dUTP nick-end labeling (TUNEL) technique. Histopathological analysis revealed a significant (P<0.05) decrease in infarct size in the striatum with both drugs: mannitol (group II) 25.4+/-5.9% and nimodipine (group III) 21.5+/-11.0% versus control (group I) 34.9+/-7.0% and in the cortex 2.7+/-2.0% (group II) and 6.3+/-2.4% (group III) versus control 14.4+/-9.0% (group I). The number of apoptotic cells was statistically lower in the therapy groups (group III 9.6, group II 25.8) versus control (group I 57.9) (Mann-Whitney-Wilcoxon U-test Z>1.96, P<0.05). This study indicates that mannitol and nimodipine provide neuroprotection by preventing both the necrotic and apoptotic components of cell death after transient focal cerebral ischemia and may be effective as neuroprotective drugs for cerebrovascular surgery.

Animals↗
PubMed2000

Apolipoprotein E4 promotes the early deposition of Abeta42 and then Abeta40 in the elderly.

The apolipoprotein Eepsilon4 allele (ApoEepsilon4) is associated with a selective increase in deposition of the 40-amino acid form of the beta-amyloid peptide (Abeta40) in endstage Alzheimer's disease. To determine how apoE genotype affects the early events in beta-amyloid pathogenesis, we analyzed the medial temporal lobes of 244 elderly persons who were not clinically demented using antibodies selective for the C termini of Abeta40 and Abeta42. We found that: (1) the number of both Abeta42- and Abeta40-positive senile plaques increase with age; (2) Abeta42 appears at younger ages, and in more amyloid deposits, than does Abeta40 in all ApoE groups; (3) when compared at similar ages, older persons with ApoEepsilon4 are more likely to have Abeta42- and Abeta40-immunoreactive deposits than are persons without ApoEepsilon4; (4) Abeta40-containing plaques arise at least a decade later than do Abeta42 plaques, and are seldom found in the medial temporal lobe of older persons lacking ApoEepsilon4; and (5) in the absence of overt Alzheimer's disease, cerebral amyloid angiopathy is rare in the elderly, but in our sample was significantly augmented in ApoEepsilon4 homozygotes. We conclude that ApoEepsilon4 hastens the onset of Abeta42 deposition in the senescent brain, which in turn fosters the earlier evolution of fibrillar, Abeta40-positive plaques, thereby increasing the risk of Alzheimer's disease.

Age Factors↗
PubMed2000

Systematics in lymphatic tumor spread of carcinomas of the upper aerodigestive tract--a clinical study based on embryologic data.

BACKGROUND: The aim of this study was to assess the incidence and pattern of cervical lymph node (LN) metastases in carcinomas of the upper aerodigestive tract in relation to primary tumor (PT) invasion of the equivalents of pharyngeal arches (PhA) and occipital and cervical somites (OCS) in adults. METHODS: The pretherapeutic computed tomography scans and clinical findings in 729 patients with histologically proven carcinoma of the upper aerodigestive tract (112 nasopharyngeal, 289 oropharyngeal, 252 laryngo-hypopharyngeal, and 76 oral cavity carcinomas, with LN involvement in 70% of the total) were analyzed in relation to PT invasion of equivalents of PhA and OCS. Tumors were recorded according to the infiltration of these equivalents. The metastatic involvement of the different cervical LN groups was analyzed and correlated to the pattern of PT invasion of equivalents of PhA and OCS by the chi-square test. RESULTS: The findings show that the pattern of cervical LN involvement depends on the location and extension of the PT and its invasion of equivalents of the PhA and OCS. Jugular LN metastases were found in tumors invading the equivalents of PhA 2-6. Submandibular LN metastases were evident in tumors invading tissues arising from the first PhA and the tongue. Retropharyngeal, spinal accessory and transversa colli LN metastases were found in tumors invading tissues arising from OCS. The frequency of LN metastases in the different LN chains decreased in the cranio-caudal direction. Each neck hemisphere showed separate lymphatic drainage. CONCLUSIONS: Analysis of PT extension in relation to PhA and OCS equivalents allows patterns of LN involvement to be predicted.

Adult↗
PubMed2000

[MR tomography study of the development of the sphenoid sinus].

BACKGROUND: Aim of this study was to evaluate the postnatal growth pattern of the sphenoid sinus. PATIENTS: 83 cerebral MRI examinations of infants and children aged 5 months to 14 years were retrospectively reviewed for pneumatization and growth of sphenoid sinus. RESULTS: A continuous increase of pneumatization and growth of the sphenoid sinus was demonstrated between infancy and adolescence including considerable individual variations. Even in children less than two years old remarkable spatial extends of this sinus could be found in some cases. CONCLUSION: Diagnosis of an acute or chronical sinusitis in pediatric patients should alert the clinician to the possibility of a sphenoidal participation.

Adolescent↗
PubMed1999

[Long-term breathing via tracheostoma].

PATIENTS AND METHODS: From 1988 to 2/1997 we had introduced intermittent positive pressure ventilation (IPPV) in 298 patients. In most cases non-invasive nasal mask ventilation was possible, in 21 patients (7%) a tracheostoma was necessary. These 21 patients were analysed retrospectively due to age, sex, diagnose, ventilation mode, course of illness, home care and costs. RESULTS: We had 13 male and 8 female patients, aged 49 years on average (min. 2, max. 84). 90% had neuromuscular diseases especially muscle dystrophies. Ventilation therapy was performed volume controlled with the cannula unblocked during daytime and blocked at night. Eighteen patients had industrial cannulas (72% Shiley, 28% Rüsch), 3 patients used silver cannulas. Daily ventilation amounted 24 hours in 7 patients, 6 to 14 hours in 14 patients. During the observed time 7 patients remained in stable health situation, in 9 patients the underlying disease was progressive and 5 of them died. IPPV was performed 50.7 months on an average, in living patients 68.8 months, in died 7.6 months. Fifteen patients lived at home, 5 were cared in nursing home, 1 patient stayed in hospital. Outside the hospital the bigger part of costs was paid by sick funds and care funds, the smaller part by social welfare offices. Often costs were divided. Total costs for caring about 24 hours ventilated patient at home amounted up to 21,000 German marks each month.

Adolescent↗
PubMed1998

Gene structure, expression in Escherichia coli and biochemical properties of the NAD+ -dependent glyceraldehyde-3-phosphate dehydrogenase from Pinus sylvestris chloroplasts.

Photosynthetic eukaryotes typically possess two distinct glyceraldehyde-3-phosphate dehydrogenases, an NAD+ -specific enzyme in the cytosol (GapC: EC 1.2.1.12) and an NADP+ -dependent enzyme in the chloroplast (GapAB: EC 1.2.1.13). The gymnosperm Pinus sylvestris is an exception in that it is known to express a gene encoding a transit peptide-bearing GapC-like subunit that is imported into chloroplasts (GapCp), but the enzymatic properties of this novel GAPDH have not been described from any source. We have expressed the mature GapCp unit from Pinus in Escherichia coli and have characterized the active enzyme. GapCp has a specific activity of 89 units per milligram and is strictly NAD+ -dependent, showing no detectable activity with NADP+. Values of the apparent Km for NAD+ and glyceraldehyde-3-phosphate were determined as 62 and 344 microM, respectively. The Pinus GapCpl gene possesses 12 introns, two in the region encoding the transit peptide and ten in the region encoding the mature subunit, all of which are found at positions strictly conserved across genes for higher plant GapC. A cDNA encoding a homologue of GapCp was isolated from the heterosporous fern Marsilea quadrifolia, indicating that NAD+ -dependent chloroplast GAPDH also occurs in other higher plants.

Amino Acid Sequence↗
PubMed1997

[Noninvasive ventilation in acute respiratory insufficiency].

BACKGROUND AND AIM: Noninvasive positive pressure ventilation (NPPV) via face mask offers in comparison to endotracheal intubation in treating patients with acute respiratory failure (ARF) advantages like allowing swallowing and coughing. We report our experiences and try to verify the indications and the efficacy of NPPV. PATIENTS AND METHODS: In the period of January 1991 until August 1996 109 patients (30 female, 79 male, mean age 61 +/- 12 years) received mechanical ventilation with NPPV representing 25% of all MVs in this term. As baseline capillary blood gases (CBG) were found: pH: 7.30 +/- 0, 10; pCO2: 64 +/- 19; pO2: 60 +/- 19 (all patients received supplemental oxygen). Success of NPPV was determined by an improvement of the baseline CBG. RESULTS: NPPV was successful in 77 (71%) patients. Considering the kind of respiratory insufficiency the patient population was divided into 4 groups 1. acute hypoxemic respiratory failure, 2. acute hypercapnic ventilatory failure, 3. acute decompensation of chronic respiratory insufficiency (CRI) and 4. combined failure. Considering these subgroups we obtained the best results in the group of patients with hypercapnic disturbances. In patients with hypoxemic RF we observed a success of NPPV if the improvement of CBG occurred in the early stage (< or = 12 hours) of NPPV. CONCLUSION: Our data indicate that application of NPPV is an effective and safe alternative to endotracheal intubation in many patients with hypercapnic ventilatory failure. NPPV is also successful in patients with hypoxemic RF with a milder course.

Acute Disease↗
PubMed1997

[Patient-related rejection of nasal IPPV therapy. Patients, reasons, follow-up].

PATIENTS: We retrospectively analysed the course of 33 patients who had rejected nasal IPPV-therapy (1988 to February 1996). RESULTS: The death-rate was higher (48%) compared to nasal IPPV patients in the same time (18%). The patients were divided in 3 main diagnostic groups (COPD, restrictive thoracic wall, neuromuscle disease). We observed the highest death-rate in COPD patients (66%) and the lowest death-rate in the group with scoliosis or chest wall disease (23%). This is the same result tendencially as in patients with nasal IPPV (mortality-rate COPD 66%, restrictive chest wall 6%).

Adult↗
PubMed1997

Floral homeotic genes were recruited from homologous MADS-box genes preexisting in the common ancestor of ferns and seed plants.

Flowers sensu lato are short, specialized axes bearing closely aggregated sporophylls. They are typical for seed plants (spermatophytes) and are prominent in flowering plants sensu stricto (angiosperms), where they often comprise an attractive perianth. There is evidence that spermatophytes evolved from gymnosperm-like plants with a fern-like mode of reproduction called progymnosperms. It seems plausible, therefore, that the stamens/carpels and pollen sacs/nucelli of spermatophytes are homologous to fern sporophylls and sporangia, respectively. However, the exact mode and molecular basis of early seed and flower evolution is not yet known. Comparing flower developmental control genes to their homologs from lower plants that do not flower may help to clarify the issue. We have isolated and characterized MADS-box genes expressed in gametophytes and sporophytes of the fern Ceratopteris. The data indicate that at least two different MADS-box genes homologous to floral homeotic genes existed in the last common ancestor of contemporary vascular plants, some descendants of which underwent multiple duplications and diversifications and were recruited into novel developmental networks during the evolution of floral organs.

Amino Acid Sequence↗
PubMed1996

[Noninvasive intermittent ventilation. A prospective data collection in patients with hypoventilation syndrome].

INTRODUCTION: Noninvasive intermittent ventilation is usually performed in patients with severe ventilatory pump disorder. From 1988 to 3/1995 we treated 163 patients with the aim of home mechanical ventilation (HMV). PATIENTS AND RESULTS: In March 1993 115 of these 163 patients practiced HMV, 22 had already died and 26 had rejected or broken off ventilation therapy. The 115 patients were classified in three main diagnostic groups: Scoliosis or chest wall disease (n = 76), COPD (n = 11) and neuromuscular disease (n = 28). The mean pCO2 at rest of all patients before ventilation therapy was 56 (+/- 12) Torr and fell to 46 (+/- 5) Torr in the course of therapy. The maximum statical inspiration pressure PImax rose from average 3, 8 (+/- 2, 3) to 4, 9 (+/- 2, 0) kPa. There was a probability of surviving two years after onset of ventilation therapy of 85% in the scoliosis group, of 60% in the neuromuscular group and of 30% in the COPD group. CONCLUSIONS: According to results of others home ventilation therapy was very successful in patients with chest wall disease. In some patients with neuromuscular disorder quality of life could be improved and life prolonged. Only half of the COPD patients could be treated successfully, whereas the other half had no benefit from noninvasive ventilation therapy.

Adolescent↗