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Biomedical subjects

S Kunkel

Publications and source records attributed to S Kunkel.

At least 37 records · Page 2Linked to original sources

Modulation of leucocyte adhesion molecules, a T-cell chemotaxin (IL-8) and a regulatory cytokine (TNF-alpha) in allergic contact dermatitis (rhus dermatitis).

To understand the molecular events which are important in leucocyte trafficking in cutaneous inflammation, poison ivy/oak extract was applied topically to the skin, and the simultaneous assessment of a variety of clinical and immunopathological parameters performed. The clinical response of subjects was divided into three main groups: I, 2-24h after application, before the onset of erythema; II, 48 h-1 week after application during maximal clinical changes; III, 2-3 weeks after application when the inflammation had subsided. Six different biopsies per subject were evaluated over the study period and the density of dermal cellular infiltrate, and the distribution of intercellular adhesion molecule-1, (ICAM-1), endothelial leucocyte adhesion molecule-1, (ELAM-1), vascular cell adhesion molecule-1, (VCAM-1), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha), determined. Eight hours after exposure, before lymphocytes and monocytes had entered the dermal interstitium or epidermis, the keratinocytes expressed TNF-alpha and ICAM-1, whilst the endothelial cells expressed ELAM-1, VCAM-1 and ICAM-1. Group II biopsies revealed increasing keratinocyte expression of TNF-alpha and ICAM-1 with the appearance of IL-8, which correlated with the onset of epidermal T-cell trafficking. The endothelium was strongly positive for ELAM-1 and VCAM-1, but there was no influx of neutrophils. Group III biopsies showed a decrease in the expression of ICAM-1, VCAM-1 and ELAM-1 by both keratinocytes and endothelium with a reduction in epidermal/dermal inflammation, although the endothelial cell staining of VCAM-1 and ELAM-1 did not completely disappear. These results suggest that on exposure to poison ivy/oak, keratinocytes rapidly produce TNF-alpha which leads to an early autoinduction of ICAM-1, and later IL-8. There is also a paracrinemediated induction and augmentation of underlying endothelial cell ELAM-1, VCAM-1 and ICAM-1.

Adult↗

[The GnRH-TRH double stimulation test before and following surgical removal of uterine leiomyoma].

In seven patients with uterine leiomyomatosis investigated the function of hypothalamic-pituitary-ovarian axis has been with a GnRH-TRH-double stimulation test. The basal levels of estradiol, progesterone, LH, FSH and PRL as well as the pituitary reaction after the stimulation were determined. Three patients had a tendency to a basal hypergonadotropinemia and four patients to hypoprolactinemia. The pituitary reaction following the stimulation does not show any connection between leiomyoma and secretion pattern of the hypothalamic-pituitary-ovarian axis.

Adult↗

[Spermatocyte antibodies in serum and follicular fluid of IVF and GIFT patients].

With a new SPAK-ELISA test system (Seratec GmbH) we determined sperm antibodies in sera of 60 IVF, 11 GIFT patients and their husbands. We evaluated sperm antibodies in sera of 12 IVF (20.0%), 3 GIFT (27%) and 3 males with normozoospermia parameters (4.2%). Compared to seronegative patients either the number of oocytes and their quality as the fertilization- and embryo transfer rate during the IVF/GIFT procedure were not affected. No intact pregnancy occurred in cases of sperm antibodies in sera. In 16.6% of all seropositive IVF patients the detection of sperm antibodies in the follicular fluids correspond to sera. We recommend to remove autologous serum for the oocyte culture in cases of sperm antibodies in serum of IVF patients.

Antibodies↗

[Heterologous and homologous radioimmunoassays for human prolactin. 1. Development and critical evaluation of the method].

Based on the production of a high specific antibody against ovine prolactin a heterologous prolactin RIA (self proposed method) is introduced. From this work both a homologous and a heterologous system have been developed and used for the PRL-RIA kit production. Substances necessary for setting up the kits, their investigations and applications are described. Statistical considerations about precision, sensitivity, specificity and accuracy show the validity of these heterologous PRL-systems.

Female↗

Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B.

The latent period of AIDS is influenced by factors which activate human immunodeficiency virus (HIV) replication in different cell types. Although monocytic cells may provide a reservoir for virus production in vivo, their regulation of HIV transcription has not been defined. We now report that HIV gene expression in the monocyte lineage is regulated by NF-kappa B, the same transcription factor known to stimulate the HIV enhancer in activated T cells; however, control of NF-kappa B and HIV in monocytes differs from that observed in T cells. NF-kappa B-binding activity appears during the transition from promonocyte to monocyte in U937 cells induced to differentiate in vitro and is present constitutively in mature monocytes and macrophages. In a chronically infected promonocytic cell, U1, differentiation is associated with HIV-1 replication as well as NF-kappa B binding activity. These findings suggest that NF-kappa B binding activity is developmentally regulated in the monocyte lineage, and that it provides one signal for HIV activation in these cells.

Cell Differentiation↗

Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B.

Binding of peptide hormones to surface membrane receptors leads to the transcription of specific genes within relevant target cells. How these signals are transduced to alter gene expression is largely unknown, but this mechanism probably involves a sequence of enzymatic steps that activate factors in the nucleus that modulate transcription. We now demonstrate that two different peptide hormones, or cytokines, stimulate the human immunodeficiency virus enhancer, and this effect is mediated by nuclear factor (NF) kappa B (nuclear factor that binds the kappa immunoglobulin light chain gene enhancer). These cytokines, tumor necrosis factor alpha and interleukin 1, act on multiple cell types and represent the only naturally occurring activators of this transcription factor among eight cytokines examined. Although NF-kappa B binding can be stimulated by phorbol 12-myristate 13-acetate, tumor necrosis factor alpha acts through an independent mechanism, inducing NF-kappa B binding in HT-2 cells, which did not show increased binding in response to phorbol 12-myristate 13-acetate, and causing superinduction in Jurkat T-lymphoma cells. Tumor necrosis factor alpha is also a more selective activator of T cells than phorbol 12-myristate 13-acetate, having no effect on lymphokine production in EL-4 cells at the same time it induces NF-kappa B. These findings suggest that human immunodeficiency virus gene expression can be induced in T cells without activating lymphokine secretion and that the role of these cytokines in the activation of latent human immunodeficiency virus infection deserves further clinical evaluation. Finally, this link between binding at the surface membrane and stimulation of a specific transcription factor should help define intermediates for these cytokine activation pathways.

Cell Line↗

[Hormone profile and follicle development in ovarian stimulation treatment for in vitro fertilization. II. Prolactin, estradiol and progesterone profile].

144 patients were treated by 5 different stimulation protocols in the IVF-program of the University Women's Hospital Rostock (Clomiphene/hCG, Clomiphene/Anthrogon/hCG, Pergonal/hCG, Anthrogon/hCG, Folistiman/hCG). Estradiol-17 beta and progesterone were determined during the follicular phase of 172 cycles by RIA. The results were compared between the treatment groups by means of Student's t-test or Mann-Whitney's nonparametric test. Additionally, in 37 cycles prolactin was determined. The levels of estradiol-17 beta in all treated groups were higher as compared with spontaneous cycles. Between the groups statistically significant differences were found in start and velocity of E2-rise, in the average level of E2, and in the level of preovulatory peaks. The latent phase of stimulation was significantly longer in patients treated with pergonal than in Anthrogon treated patients. Moreover, in the Anthrogon group the rate of "high responder" was higher. On average, in patients with a very fast growth rate of estradiol-17 beta (greater than 1.9 nmol/l) during the late follicular phase the percentage of less mature oocytes was increased after follicular puncture. The levels of progesterone started to rise in all groups between day-2 and -1 (day 0: day of LH-peak). On day 0, patients with Pergonal and Anthrogon had the significantly highest level. Levels above the 1s-range occurred in 12 patients during the follicular phase. This elevation of progesterone took place in 3 patients without any rise of basal LH-levels. 80.4% of 37 patients investigated were found to have prolactin levels above 500 mE/l during the late follicular phase. This transient hyperprolactinemia correlated with the rise of estradiol levels and continued during the early and mid luteal phase. Hence preventive administration of bromocryptine appears to be advisable in cycles stimulated with gonadotropins.

Chorionic Gonadotropin↗

[The hormonal micromilieu and oocyte status in the stimulated in vitro fertilization cycle].

FSH, LH, PRL, estradiol-17 beta and progesterone were determined in 651 follicular fluids of 173 patients treated by ovarian stimulation for IVF. The stimulation was performed according to 5 different schemes: clomiphene/HCG, HMG (Pergonal)/HCG, HPG (Anthrogon)/HCG, clomiphene/HPG/HCG, Folistiman (heterologeous pituitary gonadotropin)/HCG. The mean levels of hormones of all follicles of each stimulation scheme were determined and differences between the groups were estimated by Student's t-test and the x-square-test. Additionally, in a hierarchy of follicles made depending on the follicular fluid volume the hormonal levels were compared between different rank numbers of one stimulation group and between different groups of stimulation. The maturation of oocytes judged by a maturation index and their ability for cleavage in culture after insemination was investigated in relation to the hormonal content of the follicular fluid. Stimulation by gonadotropins (Pergonal, Anthrogon, Folistiman) led to an decreased mean level of follicular steroids. This was related to an increased part of follicles poor in steroids after stimulation by gonadotropins. Within the follicular population follicles stimulated by clomiphene/HCG had a reduction of the levels of estradiol in higher rank numbers, but there were no clear evidences for such a reduction in the other stimulated groups. In all stimulation groups a significant reduction of progesterone levels was observed in higher rank numbers of follicles. Oocytes with a high maturation index mainly derived from follicles rich in progesterone. After insemination, development of oocytes in culture was compatible even with very high or low levels of hormones. There was no relation of the levels in FSH and LH to cumulus expansion and levels of estradiol of the follicular fluid. There was also no clear correlation between the levels of prolactin in follicular fluid and the cleavage rate.

Estradiol↗

[Loss of bone substance in long-term dialysis--the value of serochemical parameters].

During long-term hemodialysis therapy a loss of bone substance--an osteopenia--may occur. The diagnosis is possible by bone biopsy. We have analyzed the bone metabolism-associated serochemical parameters in patients suffering from osteopenia in comparison with patients with normal bone volume. 21 patients were analyzed: 14 females, 7 males, duration of dialysis 44 +/- 29.9 months, age 47.3 +/- 12.5 years. The serum values of calcium, anorganic phosphate, alkaline phosphatase, pH and c-terminal parathormone are determined. The histological bone examination according to the Delling classification did show following distribution: Type I--0, type II--10, type III--10 (without renal osteopenia--1). A quarter of the patients did show a reduction of the bone mass. The parathormone value was significantly reduced in these patients in comparison with patients without osteopenia. No significant changes could observed in the comparison of alkaline phosphatase, serum calcium, anorganic phosphate and pH value. Our results show that in patients with osteopenia the serum parathormone level is reduced relatively.

Adult↗

Coincidence of gonadal dysgenesis and hyperprolactinemia.

It is reported about 4 female patients aged from 3 to 31 years (average age 18 years) with gonadal dysgenesis and hyperprolactinemia. Beside one all these females were not treated with synthetic sexual steroids. In 3 of the 4 patients both hyperprolactinemic and hypergonadotropic serum levels were observed. In one case the gonadotropic serum levels were normal. A stimulation test with GnRH-TRH or arginine-GnRH-TRH, respectively, was performed. In patients with gonadal dysgenesis a change on the area of hypothalamo-hypophyseal axis is supposed to cause the hyperprolactinemia.

Adolescent↗

[Pregnancy following gamete intra-fallopian transfer (GIFT)].

In the present paper we will report on a pregnancy following a Gamete Intra Fallopian Transfer (GIFT). This is a 26 years old female, treated in our sterility dispensaire for a secondary sterility since 1982. All basic hormone levels were normal. The andrological examination of her husband showed an oligozoospermia stage 2. A following hormone treatment was unsuccessful. Stimulation, monitoring and laparoscopy are demonstrated.

Adult↗

[Pregnancy tests].

An overview is given about the development of immunological pregnancy tests in urine. As a result both the new knowledge of hCG biochemistry and the production of monoclonal antibodies a number of various tests were developed. Both work consuming and sensitivity are used for estimation of pregnancy tests.

Antibodies, Monoclonal↗

[GnRH-TRH stimulation tests in patients with mastopathy].

20 eumenorrhoic patients with clinical manifest mastopathie and biphasic basal body temperature curve were investigated with GnRH-TRH stimulation tests. The tests were carried out in the early/middle follicular phase (13 patients, 3rd to 8th day) of cycle and in the corpus luteum phase (7 patients, 20th to 24th day) of cycle. Compared with the normal level our results showed a significant increase of the basic prolactin secretion. In response to the TRH stimulation 3 females had an excessive PRL answer. There were no deviations of other evaluated hormonal parameters from the normal range of healthy females.

Adolescent↗

[Basal and gonadotropin releasing hormone-stimulated gonadotropin secretion in patients with chronic uremia].

In 11 patients with chronic uremia both the basal and stimulated levels of LH and FSH in serum were determined by RIA. After renal transplantation the investigations were repeated in 2 cases. The basal levels of LH were unphysiologically increased whereas FSH was found in the normal range. The stimulation of LH by GnRH was adequate in 6 patients and in 5 there was no response. As a result of renal transplantation there was a drop of LH in serum. It is supposed that the unphysiological increase of LH in patients with chronic uremia is the cause for the disturbances of the menstrual cycle.

Adult↗

[Basal and TRH stimulated TSH secretion and determination of total thyroxine (T4). Thyroxine-binding capacity and free thyroxine index (FT4-I) in patients with chronic uremia].

In 11 patients with chronic uremia both the basal and TRH stimulated TSH levels and T4, TBC and FT4-I were determined. The investigations were repeated in 2 cases after renal transplantation. TSH and T4 in serum were determined by RIA, TBC by radio reagent assay. FT4-I was calculated. In 8 patients the basal TSH levels were in the normo- and in 3 in the hypothyreotropic range. In 9 patients the response to TRH was adequate. There were deviations from the physiological range in 7 patients for T4 and in 6 for FT4-I.

Adult↗

[Basal and stimulated secretion of prolactin and growth hormone in patients with chronic uremia].

In 11 patients with chronic uremia both the basal and the stimulated levels of PRL and HGH were determined by RIA. The investigations were repeated in 2 patients after renal transplantation. The basal PRL levels were as well hyper- and normoprolactinemic as hypoprolactinemic. Also the PRL response did not show any uniform tendency to the TRH stimulation. After renal transplantation in 1 patient there was a decrease of the hyperprolactinemic serum levels into the normoprolactinemic range whereas the response was not influenced to TRH. Both the basal and the stimulated levels of HGH were in the physiological range. The response of HGH to the stimulation is explained as the so-called paradox TRH effect underlined by missing of the stimulation after renal transplantation.

Adult↗

[Effect of sulprostone on prolactin, HPL, HCG, progesterone and estradiol serum level in abortion induction in the first trimester in primigravidae].

The influence of the i.m. application of Sulproston for induction of abortion was examined on the serum levels of PRL, HCG, HPL, estradiol and progesterone in 8 primigravidae during the first trimenon. The hormones were determined by RIA. There was a drop of HCG, HPL, estradiol and progesterone beginning 4 to 16 hours after the first application of Sulproston. PRL was not influenced.

Abortifacient Agents↗