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Biomedical subjects

K Körner

Publications and source records attributed to K Körner.

At least 19 recordsLinked to original sources
PubMed1998

Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-L-arginine induces cortical spreading ischemia when K+ is increased in the subarachnoid space.

We investigated the combined effect of increased brain topical K+ concentration and reduction of the nitric oxide (NO.) level caused by nitric oxide scavenging or nitric oxide synthase (NOS) inhibition on regional cerebral blood flow and subarachnoid direct current (DC) potential. Using thiopental-anesthetized male Wistar rats with a closed cranial window preparation, brain topical superfusion of a combination of the NO. scavenger hemoglobin (Hb; 2 mmol/L) and increased K+ concentration in the artificial cerebrospinal fluid ([K+]ACSF) at 35 mmol/L led to sudden spontaneous transient ischemic events with a decrease of CBF to 14+/-7% (n=4) compared with the baseline (100%). The ischemic events lasted for 53+/-17 minutes and were associated with a negative subarachnoid DC shift of -7.3+/-0.6 mV of 49+/-12 minutes' duration. The combination of the NOS inhibitor N-nitro-L-arginine (L-NA, 1 mmol/L) with [K+]ACSF at 35 mmol/L caused similar spontaneous transient ischemic events in 13 rats. When cortical spreading depression was induced by KCl at a 5-mm distance, a typical cortical spreading hyperemia (CSH) and negative DC shift were measured at the closed cranial window during brain topical superfusion with either physiologic artificial CSF (n=5), or artificial CSF containing increased [K+]ACSF at 20 mmol/L (n=4), [K+]ACSF at 3 mmol/L combined with L-NA (n=10), [K+]ACSF at 10 mmol/L combined with L-NA (five of six animals) or [K+]ACSF at 3 mmol/L combined with Hb (three of four animals). Cortical spreading depression induced longlasting transient ischemia instead of CSH, when brain was superfused with either [K+]ACSF at 20 mmol/L combined with Hb (CBF decrease to 20+/-20% duration 25+/-21 minutes, n=4), or [K+]ACSF at 20 mmol/L combined with L-NA (n=19). Transient ischemia induced by NOS inhibition and [K],ACSF at 20 mmol/L propagated at a speed of 3.4+/-0.6 mm/min, indicating cortical spreading ischemia (CSI). Although CSH did not change oxygen free radical production, as measured on-line by in vivo lucigenin-enhanced chemiluminescence, CSI resulted in the typical radical production pattern of ischemia and reperfusion suggestive of brain damage (n=4). Nimodipine (2 microg/kg body weight/min intravenously) transformed CSI back to CSH (n=4). Vehicle had no effect on CSI (n=4). Our data suggest that the combination of decreased NO. levels and increased subarachnoid K+ levels induces spreading depression with acute ischemic CBF response. Thus, a disturbed coupling of metabolism and CBF can cause ischemia. We speculate that CSI may be related to delayed ischemic deficits after subarachnoid hemorrhage, a clinical condition in which the release of Hb and K+ from erythrocytes creates a microenvironment similar to the one investigated here.

Animals↗
PubMed1997

CDF-1, a novel E2F-unrelated factor, interacts with cell cycle-regulated repressor elements in multiple promoters.

The cdc25C , cdc2 and cyclin A promoters are controlled by transcriptional repression through two contiguous protein binding sites, termed the CDE and CHR. In the present study we have identified a factor, CDF-1, which interacts with the cdc25C CDE-CHR module. CDF-1 binds to the CDE in the major groove and to the CHR in the minor grove in a cooperative fashion in vitro , in a manner similar to that seen by genomic footprinting. In agreement with in vivo binding data and its putative function as a periodic repressor, DNA binding by CDF-1 in nuclear extracts is down-regulated during cell cycle progression. CDF-1 also binds avidly to the CDE-CHR modules of the cdc2 and cyclin A promoters, but not to the E2F site in the B- myb promoter. Conversely, E2F complexes do not recognize the cdc25C CDE-CHR and CDF-1 is immunologically unrelated to all known E2F and DP family members. This indicates that E2F- and CDF-mediated repression is controlled by different factors acting at different stages during the cell cycle. While E2F-mediated repression seems to be associated with genes that are up-regulated early (around mid G1), such as B- myb , CDE-CHR-controlled genes, such as cdc25C , cdc2 and cyclin A , become derepressed later. Finally, the fractionation of native nuclear extracts on glycerol gradients leads to separation of CDF-1 from both E2F complexes and pocket proteins of the pRb family. This emphasizes the conclusion that CDF-1 is not an E2F family member and points to profound differences in the cell cycle regulation of CDF-1 and E2F.

3T3 Cells↗
PubMed1997

Characterization of the TATA-less core promoter of the cell cycle-regulated cdc25C gene.

The TATA- and Inr-less promoter of the human cdc25C gene is regulated during the cell cycle through binding of a repressor to two contiguous promoter-proximal elements, the CDE and CHR. In this study we have characterized in detail the region of the cdc25C promoter immediately downstream of these elements. Several lines of evidence suggest that this region of approximately 60 bp acts as the core promoter. This sequence: (i) harbors most of the transcription initiation sites; (ii) possesses basal promoter activity in vivo ; (iii) shows no stable protein binding in vivo as indicated by genomic dimethyl sulfate and phenanthroline copper footprinting; (iv) contains single-stranded regions in vivo as shown by potassium permanganate footprinting; (v) is hypersensitive to DNase I cleavage in permeabilized cells. Mutational analysis of the core promoter revealed the presence of three sites which play a role in transcription. Two of these sites were found to represent low affinity binding sites for transcription factors of the Sp1 family. Mutation of these sites led to decreased levels of transcription, while their alteration to canonical Sp1 sites impaired cell cycle regulation. Thus the transient interaction of Sp1 with the core promoter appears to be necessary for maximal transcription without perturbing cell cycle regulation.

Binding Sites↗
PubMed1995

Nitric oxide modulates the CBF response to increased extracellular potassium.

The response of the regional cerebral blood flow (rCBF) to brain topical superfusion of 20 mM K+ was characterized in a closed cranial window preparation in barbiturate anesthetized and ventilated rats: Increasing K+ in the artificial cerebrospinal fluid (ACSF) induced a rCBF elevation (measured by laser-Doppler flowmetry) of +85 +/- 37% above baseline (n = 19). This elevation was stable for > 3 h with continuous superfusion of increased K+ (n = 5) and partially reversible to a level of +18 +/- 19% above baseline when returning to a physiological K+ concentration. Nitric oxide synthase (NOS) inhibition by brain topical superfusion with N omega-nitro-L-arginine (L-NA) revealed (a) Addition of L-NA to high-potassium ACSF reduced the rCBF increase from +94 +/- 36% to +21 +/- 18% (p < or = 0.01, n = 7). (b) When L-NA was superfused for 60 min before increasing K+, rCBF decreased to -17 +/- 7% below baseline. Subsequent coapplication of L-NA and increased K+ induced only an elevation of +7 +/- 4% above baseline (n = 4). (c) When the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was added during NOS inhibition to restore basal tissue NO levels, the resultant level of rCBF was +28 +/- 54% above baseline. Subsequent increase of K+ in the presence of NOS inhibition and SNAP elevated rCBF to +137 +/- 89% above baseline (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Effect of preparation and preservation modality on thrombocyte quality].

In patients with acute leukemia, chemotherapy leads to subsequent aplasia-associated thrombocytopenia requiring the substitution of platelets to avoid and treat bleeding complications. A multitude of tests to assess the quality of platelet concentrates is available to date. In this study, we investigated the quality of platelet concentrates prepared by two different methods, preparation from platelet-rich plasma versus preparation from buffy coat, and stored under varying conditions, namely horizontal versus vertical rotation, by measuring the binding rate of corresponding antibodies to platelet membrane glycoproteins GPIb, GPIIb-IIIa, GPIa-IIa and GPIV using flow cytometry. Expression of platelet surface antigens was well maintained during platelet preparation and storage for 7 days. Preparation and storage modalities showed no significant effect on the expression of membrane glycoproteins. These results indicate that platelet function as represented by antibody binding is well maintained during platelet preparation and storage leading to sufficient hemostasis following transfusion.

Acute Disease↗
PubMed1990

Electroresection with a new endotracheally applicable resectoscope.

Besides dilatation, cryotherapy, laser and surgical resection, the technique of endoscopic, endotracheal electroresection provides an alternative in the treatment of endotracheal stenoses. The instrument is similar to the resectoscope used in urology, but additionally equipped with a longer action range and respiration facility. It is insulated at the tip of the shaft. The electroresectoscope was employed on 64 occasions at our institution in three indications: endotracheal diseases, granulomas following tracheostomy; and short subglottic membrane stenoses, partly secondary to long-term intubation. Indications, advantages and drawbacks of the method are discussed.

Anastomosis, Surgical↗
PubMed1989

Transient functional obstruction of the colon in neonates: examination of its development by manometry and biopsies.

Between 1975 and 1983, 17 neonates with transient functional obstruction of the colon were studied in our surgical department. Five could be successfully treated conservatively with enemas. In the remaining 12 cases colostomy was necessary. In three cases colostomy was performed too late and the patients died. In the other nine cases rectal biopsies and anorectal manometries were performed repeatedly. In spite of clear radiological signs of colonic obstruction such as in Hirschsprung's disease in each case, and identical clinical signs, true aganglionosis could be excluded. Rectoanal manometry 4 months after colostomy showed that the situation had normalized in five cases, but was still pathological in four cases, as in aganglionosis. Of the rectal biopsies, five showed signs of immaturity of ganglionic cells and three were normal. Rectoanal manometry 12-24 months later showed normal reaction in all cases, and of the five cases with immaturity of the ganglionic cells at 4 months one was still pathologic at 12-24 months. In eight of 12 cases the colostomy was closed without relapse of the obstruction, even on long-term follow up. Aganglionosis of the ultrashort type was excluded. In cases of severe transient functional obstruction of the colon in neonates, in which colostomy is necessary, rectoanal manometry and rectal biopsies should be performed as early as possible. Rectoanal manometry, at least, should be done before closure of the colostomy to avoid relapse of the obstruction from closing it to early: the functional disturbance may persist for several months. The term "small left colon syndrome" should be abandoned in favor of "transient functional obstruction,", as the latter describes the clinical condition far better.

Biopsy↗
PubMed1989

[Study of the prevalence of sleep apnea syndrome in patients with chronic diseases of the respiratory organs using pulse oximetry and polysomnography].

In the literature, depending upon the group of subjects investigated and the diagnostic criteria applied, the prevalence of the sleep apnea syndrome (SAS) is reported to be between 1 and 10%. In the present study, 220 nonselected male patients (age range: 45.1 +/- 11.4 years, Brocca index 109.0 +/- 18.0%, 147 cases of chronic bronchitis, 65 of bronchial asthma, 8 with other diseases of the airways, 44.1% obstructive ventilation disturbances, 41.8% smokers) were investigated. As a screening method, nocturnal monitoring of oxygen saturation with the aid of a digital pulse oximeter (Draeger) was carried out. On average, 65.4 +/- 136.5 cases of desaturation to less than 90% SaO2/8 hours sleep were observed. In 48 patients with a Brocca index of more than 120%, desaturations at 156.1 +/- 244.5 were significantly more frequent than in 172 patients with a low relative weight (40.2 +/- 67.0, p less than 0.0001). Forty-eight patients (21.8%) revealed more than 80 episodes of SaO2 drops per night. Twenty-two patients were submitted to polysomnographic investigation. In 13 patients--6% of the overall group--who had more than 100 episodes of apnea/hypopnea (AHI 47.2 +/- 30.1), a sleep apnea syndrome was demonstrated.

Adult↗
PubMed1983

[Electroencephalographic and computer tomography findings in vascular epilepsy of ischemic origin].

143 patients with vascular epilepsy have been investigated, in whom generalised seizures were predominant (67%). 5% of the patients were younger than 30 years and 20% were between 30 and 50 years old. Pathological CT findings were seen in 78%. Focal lesions were most common particularly in patients with partial epileptic seizures as compared with those which had generalised seizures (p less than 0.05). In the EEG focal changes also dominated, but there was no significant difference in their occurrence with regard to patients with generalised or partial seizures. Epileptic potentials were observed in 17% of the patients with the emphasis on those with generalised epilepsies (p less than 0.05). Comparing EEG and CT in 69% of the patients concomitant pathological findings could be found. In patients with partial seizures there was a particularly good correlation between the focal changes in the EEG and lesions in the CT.

Adult↗