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Biomedical subjects

J Kohl

Publications and source records attributed to J Kohl.

At least 19 recordsLinked to original sources
PubMed2006

Independent wheat B and G genome origins in outcrossing Aegilops progenitor haplotypes.

The origin of modern wheats involved alloploidization among related genomes. To determine if Aegilops speltoides was the donor of the B and G genomes in AABB and AAGG tetraploids, we used a 3-tiered approach. Using 70 amplified fragment length polymorphism (AFLP) loci, we sampled molecular diversity among 480 wheat lines from their natural habitats encompassing all S genome Aegilops, the putative progenitors of wheat B and G genomes. Fifty-nine Aegilops representatives for S genome diversity were compared at 375 AFLP loci with diploid, tetraploid, and 11 nulli-tetrasomic Triticum aestivum wheat lines. B genome-specific markers allowed pinning the origin of the B genome to S chromosomes of A. speltoides, while excluding other lineages. The outbreeding nature of A. speltoides influences its molecular diversity and bears upon inferences of B and G genome origins. Haplotypes at nuclear and chloroplast loci ACC1, G6PDH, GPT, PGK1, Q, VRN1, and ndhF for approximately 70 Aegilops and Triticum lines (0.73 Mb sequenced) reveal both B and G genomes of polyploid wheats as unique samples of A. speltoides haplotype diversity. These have been sequestered by the AABB Triticum dicoccoides and AAGG Triticum araraticum lineages during their independent origins.

Crosses, Genetic↗
PubMed2005

[Reproduction after breast cancer: what advice do we have for our patients?].

Nowadays women delay their childbirth to the 30ies. Therefore, more breast cancer patients haven't completed their family planning and want to get children after the diagnosis of breast cancer. Because of anthracycline and cyclophosphamide containing polychemotherapies for the adjvuant treatment of breast cancer, about 50 % of the patients will be ammenorrhoic after finishing treatment. So far there are no valid treatment options for preserving ovarian function after chemotherapy. There is no increased risk for relapse if a breast cancer patient becomes pregnant. However, the timing of the pregnancy has not yet been fixed. It depends on the prognosis, the age, the personal situation and personal preferences.

Antineoplastic Agents↗
PubMed2005

The use of an open-freezing system with self-seeding for cryopreservation of mouse ovarian tissue.

Chemoradiotherapy in young women with cancer has substantially improved life expectancy in these patients, but these treatments often cause infertility. One method of preserving fertility is to cryopreserve ovarian tissue. In this study, an automatic open-vessel freezing system with self-seeding was tested for cryopreservation of murine ovarian tissue; the mouse is a species widely used in human and veterinary medical research. The freezing system concerned, is used for cryopreservation of oocytes and embryos in Europe. Twenty severe combined immunodeficiency (SCID) mice were ovariectomized. The ovarian tissue was either directly transplanted heterotopically into the neck muscle (group 1, n = 6) or cryopreserved after equilibration with 1.5 M dimethylsulphoxide and propanediol. After thawing, the tissue was transplanted in SCID mice (group 2, n = 6). Before and after thawing, a part of the ovarian tissue was examined with the LIVE/DEAD fluorescent viability staining. The count of follicles revealed intact (fresh 24.1%/thawed 21.7%), impaired (fresh 35.1%/thawed 35.4%), and dead follicles (fresh 40.8%/thawed 42.9%). The healthy follicular loss because of the cryopreservation was 10.0%. All recipient mice were killed after 3 weeks. Transplanted ovarian tissue was found macroscopically in all mice. Histological examination showed several growing follicles in all developmental phases in both groups of SCID mice [group 1 (fresh grafts): 315 +/- 76.3 (mean +/- SD); group 2 (cryopreserved grafts): 237 +/- 63.4]. These results demonstrate that the use of an open-freezing system allows the survival of cryopreserved mouse ovarian tissue.

Animals↗
PubMed2004

Predictive value of impaired uterine transport function assessed by negative hysterosalpingoscintigraphy (HSSG).

BACKGROUND: Hysterosalpingoscintigraphy (HSSG) has given insight into the dynamics of rapid sperm transport inside the female genital tract. RESULTS: While there is an increase of an ipsilateral transport on the side bearing the dominant follicle in 70% of the subjects in the periovulatory phase, 15% of the patients do not demonstrate transport to the fallopian tubes (negative HSSG). In these patients the pregnancy rate achieved spontaneously or by intrauterine insemination is significantly reduced compared to the patients who showed an intact transport mechanism confirmed by positive HSSG. On the other hand, by means of assisted reproductive techniques (ART), pregnancy rates were higher in the group of patients showing negative HSSG (P < 0.0005). CONCLUSIONS: Our data clearly indicate that HSSG is a helpful method to evaluate the integrity of the utero-tubal transport mechanism. As pregnancy rates remain low in patients with negative HSSG, this result should be considered as an indication for IVF-treatment even in patients with patent fallopian tubes and normozoospermia of the partner.

Fallopian Tube Patency Tests↗
PubMed2001

Ultrastructural and histological effects of exposure to CEES or heat in a human epidermal model.

Ultrastructural and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) studies were conducted to compare mechanisms of 2-chloroethyl ethyl sulfide (CEES) and heat-induced injury to EpiDerm. Twenty-two hours after 2-h exposure to the monofunctional alkylating agent CEES, budding of cytoplasm, clumping of nuclear chromatin, disintegration of nuclear membranes and cytoplasmic structures, and cytoplasmic vacuolization were detected, especially in the basal cells near the pseudobasement membrane. TUNEL techniques revealed DNA fragmentation distinct from that normally associated with terminal keratinocyte differentiation. Similar evaluations 22.5 h after 90 min exposure of EpiDerm to elevated temperature (45 degrees C) produced a different pattern of cell damage. Swelling of intercellular spaces, extensive cytoplasmic vacuolization, disruption of normal nuclear shape, reduced cell membrane integrity, and release of cellular material in the basal region characterized heat injury. Heat did not alter the DNA fragmentation normally associated with keratinocyte maturation. These data suggest that CEES elicited an apoptotic mechanism of cell death with features of terminal differentiation such as nuclear membrane disintegration and loss of cytoplasmic structures. Heat, alternatively, produced changes more typical of oncotic necrosis.

Apoptosis↗
PubMed2000

Freezing of human ovarian tissue--not the oocytes but the granulosa is the problem.

The freezing of human ovarian tissue may be the key for restoring fertility after systemic therapy of cancer. In contrast to others we investigated the survival rate of whole follicles, and had a special look at the granulosa cells. Ovarian tissue was collected laparoscopically (n = 10) and divided into equal parts for freezing (n = 1570) or as control (n = 1660). The cryopreservation was done slowly, or as a ultrarapid freezing. After thawing the number of follicles, oocytes and granulosa cells surviving was counted and corrected for equal volumina of the samples. While 84.5% of the oocytes survived freezing, only 40.4% of the follicles were intact after thawing. The data show that the procedure damaged follicles, which mainly affected the granulosa cells. As the intactness of follicles may play a critical role for the maturation of the oocytes after thawing the protocols should be optimised to meet the needs of oocytes and granulosa cells.

Adult↗
PubMed2000

Effects of CEES on inflammatory mediators, heat shock protein 70A, histology and ultrastructure in two skin models.

Chemical warfare threats require the development of diverse models for the assessment of countermeasures. Human skin products, Skin2 (differentiating keratinocytes on a fibroblast-collagen matrix) and EpiDerm (differentiating keratinocytes) were exposed (2 h) to the sulfur mustard 2-chloroethyl ethyl sulfide (CEES, 1-2 mg l(-1) min(-1)) in humidified air or to humidified air alone. Tissues were evaluated histologically, ultrastructurally and for viability 22 h later; media and tissues were also analyzed for inflammatory mediators. Histology showed that CEES induced the separation of dermal and epidermal regions in Skin2 with severe damage to basal keratinocytes. Histology and electron microscopy of both products revealed condensation of nuclear chromatin, retraction of spinous processes, collapse of the tonofibrillar network and cytoplasmic vacuolization and blebbing in those cells with loss of pseudobasement membrane integrity. Exposure of Skin2 to CEES increased extracellular interleukin-1alpha (IL-1alpha), prostaglandin-E2 (PGE2) and especially IL-1 receptor antagonist (IL-1Ra) release (56,334 vs 84,614 pg ml(-1)), but decreased interleukin-6 (IL-6, 4,755 vs 351 pg ml(-1)). Exposure of EpiDerm to CEES led to unaffected extracellular and reduced intracelluar IL-1alpha (371 vs 92 pg ml(-1)). Extracellular IL-1Ra greatly increased (2,375 vs 24,875 pg ml(-1)), whereas cellular levels decreased (16,5425 vs 96,625 pg ml(-1)). Extracellular (224 vs 68 pg ml(-1)) and intracellular (485 vs 233 pg ml(-1)) soluble interleukin-1 receptor H (sIL-1RII) decreased. Prostanglandin E2 increased (1,835 vs 2,582 pg ml(-1)), whereas heat shock protein 70A (Hsp70A) remained statistically unchanged (57,000 vs 96,000 pg ml(-1)). Failure to obtain a heat shock response to CEES may contribute to the susceptibility of tissue to the alkylating agent. Consistent and marked responses of cellular and extracellular IL-1Ra to CEES suggest a potential for use as a tissue status marker and primary antiinflammatory regulator in skin.

Biomarkers↗
PubMed2000

Coordination-related changes in the rhythms of breathing and walking in humans.

Coordination of the respiratory rhythm with the rhythm of limb movements has often been observed during rhythmical exercise (e.g. in locomotion). It is usually associated with changes in the respiratory time course, but not in the locomotor rhythm. Therefore, we hypothesised that in walking, the extent of coordination-related changes (CRC) in respiratory parameters would increase with closer coordination. With respect to the controversially discussed question of a possible energetic advantage due to coordination, we devoted particular interest to the CRC in oxygen uptake (VO2). In addition, we investigated the incidence and the extent of CRC in the stepping rhythm. We examined 18 volunteers walking on a treadmill at three different workload levels, which were adjusted by altering either the velocity or slope of the treadmill. Each walking test was carried out twice, once with spontaneous breathing and once with breathing paced by a step-related acoustic signal to enhance the coordination between breathing and walking. No correlation was found between the CRC in the analysed parameters and the degree of coordination. However, the extent of CRC of ventilation and VO2 decreased with increasing workload. With the transition to coordination, increases and decreases of VO2 occurred about equally often. From this we conclude that energetic economisation in walking, as reflected by a reduction in VO2, is rather a side-effect of coordination, and is probably due to a more precise regulation of the breathing pattern. The economisation was more pronounced at higher work loads than at lower work loads. Our results revealed that coordination is also associated with changes in the stepping rate, which occurred more frequently when the variability of breathing was restricted by acoustic pacing of the breathing rhythm. This finding suggests that the choice of walking rhythm is not completely free, but can be influenced by the breathing rhythm. CRC in the walking rhythm might contribute to the avoidance of excessive CRC in the respiratory time course, which would entail an inefficient breathing pattern and thus, an energetic disadvantage.

Acoustic Stimulation↗
PubMed2000

Effects of hypobaric hypoxia on vascular endothelial growth factor and the acute phase response in subjects who are susceptible to high-altitude pulmonary oedema.

In order to investigate whether vascular endothelial growth factor (VEGF) and inflammatory pathways are activated during acute hypobaric hypoxia in subjects who are susceptible to high-altitude pulmonary oedema (HAPE-S), seven HAPE-S and five control subjects were exposed to simulated altitude corresponding to 4000 m in a hypobaric chamber for 1 day. Peripheral venous blood was taken at 450 m (Zürich level) and at 4000 m, and levels of erythropoietin (EPO), VEGF, interleukin-6 (IL-6) and the acute-phase proteins complement C3 (C3), alpha1-antitrypsin (alpha1AT), transferrin (Tf) and C-reactive protein (CRP) were measured. Peripheral arterial oxygen saturation (SaO2) was recorded. Chest radiography was performed before and immediately after the experiment. EPO increased during altitude exposure, correlating with SaO2, in both groups (r = -0.86, P < 0.001). Venous serum VEGF did not show any elevation despite a marked decrease in SaO2 in the HAPE-S subjects [mean (SD) HAPE-S: 69.6 (9.1)%; controls: 78.7 (5.2)%]. C3 and alpha1AT levels increased in HAPE-S during hypobaric hypoxia [from 0.94 (0.11) g/l to 1.07 (0.13) g/l, and from 1.16 (0.08) g/l to 1.49 (0.27) g/l, respectively; P < 0.05], but remained within the clinical reference ranges. No significant elevations of IL-6, Tf or CRP were observed in either group. The post-exposure chest radiography revealed no signs of oedema. We conclude that VEGF is not up-regulated in HAPE-S and thus does not seem to increase critically pulmonary vascular permeability during the 1st day at high altitude. Furthermore, our data provide evidence against a clinically relevant inflammation in the initial phase of exposure to hypoxia in HAPE-S, although C3 and alpha1AT are mildly induced.

Acute-Phase Proteins↗
PubMed2000

Il-1-related cytokine responses of nonimmune skin cells subjected to CEES exposure with and without potential vesicant antagonists.

Sulfur mustard provokes an acute inflammatory response in skin. To determine if keratinocytes regulate this response and whether three potential vesicant antagonists can counteract adverse changes, specimens of EpiDerm (MatTek Corp., Ashland, MA), a human skin model of differentiating keratinocytes, were exposed 2 h to humidified air with or without 2-chloroethyl ethyl sulfide (CEES, 1.72-1.73 mg/L/min) with or without 10 mM niacinamide, a poly (ADP-ribose) polymerase (PARP) inhibitor, 25 microM CGS9343B (calmodulin antagonist), or 8.4 mM leupeptin (cysteine protease inhibitor). After a 22-h incubation, levels of interleukin-1 alpha (IL-1alpha), its receptor antagonist (IL-1Ra), soluble type II receptor (sIL-1RII) and prostaglandin-E(2) (PGE(2)) were determined. Methylthiazole tetrazolium (MTT) viability tests and histological observations were also conducted. PGE(2) levels were abundant but unaffected by CEES regardless of antagonist presence. Total amounts (media plus lysate) of IL-1alpha, IL-1Ra, and sIL-1RII were reduced with CEES irrespective of antagonist. CEES promoted the release of IL-1Ra. Exposure of EpiDerm to CEES in the presence of the vesicant antagonists did not improve viability or counteract histological damage. We conclude CEES depresses total IL-1alpha and related cytokines, does not affect PGE(2) release, and adverse changes associated with CEES-exposed EpiDerm are not ameliorated by these particular antagonists. Dramatically increased (5- to 10-fold) release of IL-1Ra may provide a useful marker for cytotoxicity. The high level of IL-1Ra and increased release with injury suggest a primary function in down-regulating IL-1 inflammatory responses in skin.

Benzimidazoles↗
PubMed1999

Artificial human skin: cytokine, prostaglandin, Hsp70 and histological responses to heat exposure.

Artificial human skin, Skin2 (keratinocytes and fibroblasts) and EpiDerm (keratinocytes), was used to determine heat-induced release/accumulation of mediators of injury and repair. Skin2 was exposed to 37 or 41-45 degrees C for 90 min, followed by 37 degrees C for 22.5 h. Media were analyzed for interleukin-1alpha (IL-1alpha), prostaglandin-E2 (PGE2), thromboxane-B2 (TxB2) and nuclear matrix apparatus protein (NMAP, viability). Specimens were taken for microscopy. Media and lysates from Skin2 and EpiDerm (37 and 45 degrees C) were analyzed for IL-1alpha, its soluble receptor (sIL-1RII), receptor antagonist (IL-1Ra), interleukin-6 (IL-6) and heat shock protein-70A (lysates only). Significant release of IL-1alpha and PGE2 was detected only above 43 degrees C, where viability deteriorated and histological damage (especially to keratinocytes) was observed. With both skin products, sIL-1RII release was heat-depressed. IL-1alpha and IL-1Ra were elevated in media and IL-1Ra appeared to lower the bioactivity of IL-1alpha. Heat depressed IL-6 release from Skin2 fibroblasts. IL-6 production and release were negligible with EpiDerm. Heat increased Hsp-70A in both products. We conclude keratinocytes and fibroblasts are not primary cytokine and prostaglandin sources in heatstroke (< 44 degrees C) but could be in evaporative cooling failure, focal hot spots, or systemic responses. Levels of IL-1Ra, PGE2 and Hsp70A may be important markers of cell status.

Antigens, Nuclear↗
PubMed1997

Volume changes in the forearm and lower limbs during 2 h of acute hypobaric hypoxia in nonacclimatized subjects.

To investigate the role of fluid shifts during the short-term adjustment to acute hypobaric hypoxia (AHH), the changes in lower limb (LV) and forearm volumes (FV) were measured using a strain-gauge plethysmograph technique in ten healthy volunteers exposed to different altitudes (450 m, 2500 m, 3500 m, 4500 m) in a hypobaric chamber. Arterial blood pressure, heart rate, arterial oxygen saturation (SaO2), endtidal gases, minute ventilation and urine flow were also determined. A control experiment was performed with an analogous protocol under normobaric normoxic conditions. The results showed mean decreases both in LV and FV of 0.52 (SD 0.39) ml x 100 ml(-1) and -0.65 (SD 0.32) ml x 100 ml(-1), respectively, in the hypoxia experiments [controls: LV 0.28 (SD 0.37), FV 0.41 (SD 0.47) ml x 100 ml(-1)]. Descent to normoxia resulted in further small but not significant decreases in mean LV [-0.02 (SD 0.11) ml x 100 ml(-1)], whereas mean FV tended to increase slightly [ + 0.02 (SD 0.14) ml x 100 ml(-1)]; in the control experiments mean LV and FV decreased continuously during the corresponding times [-0.19 (SD 0.31), -0.18 (SD 0.10) ml x 100 ml(-1) , respectively]. During the whole AHH, mean urine flow increased significantly from 0.84 (SD 0.41) ml x min(-1) to 3.29 (SD 1.43) ml x min(-1) in contrast to the control conditions. We concluded that peripheral fluid volume shifts form a part of the hypoxia-induced acute cardiovascular changes at high altitude. In contrast to the often reported formation of peripheral oedema after prolonged exposure to hypobaric hypoxia, the results provided no evidence for the development of peripheral oedema during acute induction to high altitude. However, the marked increase in interindividual variance in SaO2 and urine flow points to the appearance of the first differences in the short-term adjustment even after 2 h of acute hypobaric hypoxia.

Adult↗
PubMed1997

Effect of exercise-induced hyperventilation on airway resistance and cycling endurance.

The purpose of the present study was to investigate the effect of exercise induced hyperventilation and hypocapnia on airway resistance (Raw), and to try to answer the question whether a reduction of Raw is a mechanism contributing to the increase of endurance time associated with a reduction of exercise induced hyperventilation as for example has been observed after respiratory training. Eight healthy volunteers of both sexes participated in the study. Cycling endurance tests (CET) at 223 (SD 47) W, i.e. at 74 (SD 5)% of the subject's peak exercise intensity, breathing endurance tests and body plethysmograph measurements of pre- and postexercise Raw were carried out before and after a 4-week period of respiratory training. In one of the two CET before the respiratory training CO2 was added to the inspired air to keep its end-tidal concentration at 5.4% to avoid hyperventilatory hypocapnia (CO2-test); the other test was the control. The pre-exercise values of specific expiratory Raw were 8.1 (SD 2.8), 6.8 (SD 2.6) and 8.0 (SD 2.1) cm H2O.s and the postexercise values were 8.5 (SD 2.6), 7.4 (SD 1.9) and 8.0 (SD 2.7) cm H2O.s for control CET, CO2-CET and CET after respiratory training, respectively, all differences between these tests being nonsignificant. The respiratory training significantly increased the respiratory endurance time during breathing of 70% of maximal voluntary ventilation from 5.8 (SD 2.9) min to 26.7 (SD 12.5) min. Mean values of the cycling endurance time (tcend) were 22.7 (SD 6.5) min in the control, 19.4 (SD 5.4) min in the CO2-test and 18.4 (SD 6.0) min after respiratory training. Mean values of ventilation (VE) during the last 3 min of CET were 123 (SD 35.8) l.min-1 in the control, 133.5 (SD 35.1) l.min-1 in the CO2-test and 130.9 (SD 29.1) l.min-1 after respiratory training. In fact, six subjects ventilated more and cycled for a shorter time, whereas two subjects ventilated less and cycled for a longer time after the respiratory training than in the control CET. In general, the subjects cycled longer the lower the VE, if all three CET are compared. It is concluded that Raw measured immediately after exercise is independent of exercise-induced hyperventilation and hypocapnia and is probably not involved in limiting tcend, and that tcend at a given exercise intensity is shorter when VE is higher, no matter whether the higher VE occurs before or after respiratory training or after CO2 inhalation.

Adult↗
PubMed1996

Analysis of coordination between breathing and walking rhythms in humans.

We investigated the coordination between breathing and walking in humans to elucidate whether the coordination degree depends more on metabolic load or on breathing or stride frequencies and whether coordination causes energetic economization expressed by reduction of oxygen uptake (VO2). Eighteen healthy volunteers walked on a treadmill at three load levels realized by different velocities and slopes. We analyzed the time intervals between step onset and the onset of inspiration or expiration related to stride duration (relative phase, phi) and computed the relative-phase histogram to assess the degree of coordination. The degree of coordination between breathing and stepping enhanced with increasing walking speed. Increased work load achieved by slope at constant walking speed improved coordination only slightly. No significant VO2 reduction due to coordination was found. VO2 was more strongly related to ventilation variations occurring during coordination. Also the sympathetic tone reflected by the spectral power of heart rate variability was not reduced during coordination. We conclude that during walking the coordination degree increases with increasing stride frequency and that coordination does not necessarily cause energetic economization.

Adult↗
PubMed1995

Heterogeneous activity of pulmonary vagal receptors during high-frequency oscillation ventilation.

The purpose of the study was to examine the response of vagal pulmonary slowly adapting stretch receptors (SAR) to high-frequency oscillation ventilation (HFO) in rabbits by analyzing the afferent activity recorded in vagal single-fiber preparations. The vagal afferent activity was recorded during short runs of HFO with a stroke volume of 2-3 ml/kg applied at oscillation frequencies (fosc) of 5, 10, 15, 20, and 25 Hz and each frequency at three levels of mean airway pressure (P(aw)), namely, 1, 3, and 8 cm H2O. The receptor discharge rates during HFO were compared with those during quiet spontaneous breathing as well as during static lung inflations and deflations. The majority of SAR was stimulated by HFO, however, the SAR discharge patterns during HFO were less homogeneous than during static lung inflations. The heterogeneity of SAR responses to HFO became pronounced with increasing P(aw) and fosc. From the results, we conclude that HFO elicits heterogeneous discharge patterns of SAR, but the previously reported heterogeneity of responses of rapidly adapting receptors was even greater. This heterogeneity of vagal activity is probably the result of heterogeneous mechanical conditions within the lungs during HFO and may, in turn, give rise to the various types of respiratory reflex responses to HFO.

Afferent Pathways↗
PubMed1995

Running training and co-ordination between breathing and running rhythms during aerobic and anaerobic conditions in humans.

The study was carried out on ten triathletes, six sprinters and ten subjects not trained in running (controls) to assess the effects of training history on the co-ordination between breathing and running rhythms during running on a treadmill. Three exercise intensities were used: 50%, 80% and 110% of the subject's anaerobic threshold (AT). All three intensities were performed twice: once with spontaneous breathing and once with breathing intentionally co-ordinated to the running rhythm. Heart rate, respiratory parameters and leg movements were continuously recorded. Blood lactate concentrations were measured discontinuously. The degree of co-ordination between running and breathing was quantified as the percentage of inspirations and/or expirations starting during the same phase of step. The results showed that the degree of both spontaneous and intended co-ordination at aerobic exercise intensities was in all three groups the same and increased in all groups with increasing intensity from 50% to 80% of AT; further increase of intensity to 110% of AT was associated with a significant decrease of co-ordination in controls and sprinters, whereas triathletes were able to maintain the same high degree of co-ordination as at 80% of AT. It was concluded that running training of either type at aerobic work loads had no effect on the co-ordination between running and breathing rhythms. At anaerobic intensities, however, the degree of co-ordination between running and breathing rhythms was higher in the endurance trained athletes than in the sprinters or in the untrained subjects. The degree of co-ordination increased with increasing regularity of breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗