Biomedical subjects

F Kiesewetter

Publications and source records attributed to F Kiesewetter.

At least 19 recordsLinked to original sources

PubMed2006

Successful uterus cryopreservation in an animal model.

Cryopreservation of whole organs would not only be advantageous for experimental biology but also for transplantation surgery. The objective of this study was to evaluate the feasibility of cryopreserving swine uterus as an experimental model of cryopreservation affecting a whole visceral muscle organ. Organs were frozen slowly (0.2 degrees C/min) after arterial perfusion with 10% dimethyl sulfoxide solution for 10 min and equilibration in this solution for 30 min. Viability of the organs was tested by biochemical parameters, LIVE/DEAD fluorescent staining and capability for contraction in a perfusion system. Ten fresh and ten cryopreserved uteri showed living cells in the LIVE/DEAD assay, and were viable for at least 7 h as shown by their ability to produce rhythmic contractions after oxytocin administration. This is the first report known to us on successful cryopreservation of a whole swine uterus to demonstrate that perfusion with a cryoprotectant and slow freezing provides a promising method for cryopreserving whole organs, and may encourage further studies with other cryoprotective agents and freezing protocols as well as other organs.

Animals↗

PubMed2006

Psoriasis confined strictly to vitiligo areas--a Koebner-like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.

Adult↗

PubMed2005

DNA-flow cytometry of 207 pituitary adenomas: ploidy, proliferation, and prognosis.

The principal factors involved in pituitary adenoma formation are unknown. DNA-flow cytometry is a useful study providing an estimation of a tumor proliferative rate. In this study, DNA-flow cytometry was performed to evaluate its capability to both assess prognosis and predict recurrence. Two hundred and seven fresh pituitary adenoma specimens were assessed by flow cytometry. Pre-operative endocrine function, previous medical treatment, radiographic appearance, surgical findings and immunohistochemistry were recorded for each patient. Patient outcomes were assessed at a mean follow-up of 5.3 +/- 3.1 yr. Endocrinologically inactive pituitary adenomas were predominantly euploids (50.8%). The highest proliferation rates occurred in Nelson's syndrome and the lowest in Cushing's disease. A significant difference in proliferation was observed with prolactinomas and acromegaly when a medical treatment was performed before primary surgery. Massive histological invasiveness was directly associated with a significant increase in proliferation rate. Radiotherapy did not affect the recurrence rate (4.4%) statistically. In conclusion, DNA-flow cytometry was found to be useful for determining ploidy and obtaining an overview of cell cycle status. It was helpful in identifying patients requiring closer follow-up, such as those with invasive adenomas and Nelson's syndrome. No single parameter revealed by DNA-flow cytometry could predict tumor prognosis or recurrence in the follow-up of 7.5 +/- 1.3 yr.

Adenoma↗

PubMed2005

Individual assessment of sperm morphology of single spermatozoa used for intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is an integral part of assisted reproduction. Although many papers have shown that global sperm count, sperm motility and sperm morphology of the ejaculate play no role in the fertilization rate after ICSI, embryologists who carry out ICSI, try to use the 'best looking' spermatozoa. The aim of the study was to investigate whether those spermatozoa with the best morphology really achieve the highest fertilization rate. In the present study, a total of 798 spermatozoa used for ICSI were documented by high-resolution photo. After ICSI the oocytes were cultured in single droplets and the formation of pronuclei was assessed 16 h later. The spermatozoa (all normal according to WHO criteria) were classified into four groups of different morphology. Group 1: normal head shape (approximately 5 microm diameter), group 2: like group 1, but with 15-20% smaller diameter, group 3: like group 1, but with 15-20% larger diameter, and group 4: like group 1, but with slight mid-piece cytoplasmic irregularities. Using the Pearson chi-square test, no significant difference in terms of fertilization was found among the different groups, showing that marginal sperm differences do not alter the fertilization process in ICSI.

Humans↗

PubMed2003

Leptin concentrations in semen are correlated with serum leptin and elevated in hypergonadotrophic hypogonadism.

Leptin seems to play a role in both food intake and energy balance as well as in the regulation of reproductive features. In order to investigate the regulation of testicular functions by leptin we analysed leptin concentrations in the semen of men with different andrological diseases. It was demonstrated that semen leptin concentrations were inversely correlated with serum testosterone levels and directly with serum leptin concentrations. Furthermore, semen leptin concentrations display only a fraction of serum leptin levels. Semen leptin levels of patients with azoospermia due to hypergonadotrophic hypogonadism, associated with increased follicle-stimulating hormone levels and of high-grade oligozoospermia, were significantly elevated (1.19 +/- 0.46 and 1.09 +/- 0.54 microg l(-1), respectively), while semen levels of leptin in patients with obstructive azoospermia (0.54 +/- 0.41 microg l(-1)) and low-grade oligozoospermia (0.54 +/- 0.34 microg ml(-1)) were comparable with those of normozoospermic men (0.21 +/- 0.21 microg l(-1)). Our data suggest that dysfunction of testicular epithelia as found in hypergonadotrophic hypogonadism and high-grade oligozoospermia with decreased testosterone levels causes elevated spermal leptin concentrations. However, the correlation of semen with serum leptin concentrations indicates that leptin is not actively transported but rather leaks through the blood-testis barrier.

Adult↗

PubMed2001

[Skin manifestations of Erdheim-Chester disease. Case report and review of the literature].

A 46 year old woman suffering from Erdheim-Chester disease is reported for the first time in the German dermatologic literature. She showed periorbital xanthelasmas and indurated erythemas on both flanks. Histologically the skin manifestations were also a sign of the basic disease which had spread to various organs. Small granulomas with foam cells, macrophages and few giant cells were found in the corium. Immunohistochemistry demonstrated positive reactions to protein S-100 and alpha-1-Antichymotrypsin, while CD 1 a-antigen and PNA were negative. Further localizations of Erdheim-Chester disease were found in the femurs, tibiae and mandibula as well as in the right breast, retroorbital region and abdominal aorta. Infiltration of the retroperitoneal cavity led to urinary retention and nephrectomy. With systemic corticosteroid therapy, the skin lesions on the flanks regressed but recurred after discontinuance of the drug. Erdheim-Chester disease is now classified as part of the histiocytoses which is confirmed by our immunohistochemical findings. The histiocytes are probably not identical with Langerhans cells. The diagnosis is usually made by the radiologist on the basis of typical osteosclerotic symmetrical lesions of the long bones, histologically representing lipoid granulomas. Common non-osseous manifestations of the disease are in the retroperitoneal region, orbita and intracranially (partially associated with diabetes insipidus) which are often fatal. On the skin, xanthelasma and xanthoma are present in 1/6 of the cases; in some patients yellow-brown papular and widespread infiltrated lesions have been described. As regards to therapy corticosteroids chemotherapy, radiation and immunomodulating agents as well as surgery have been used with limited success.

Diagnosis, Differential↗

PubMed2001

Neuropathy is a major contributing factor to diabetic erectile dysfunction.

Erectile dysfunction (ED) in diabetes is multifactorial. So far, the impact of neuropathy has not been well determined. This study was performed to assess the frequency of abnormal neurophysiological tests in patients with ED due to diabetes compared to patients with ED due to nondiabetic neuropathies in order to estimate the contribution of neuropathy in diabetic ED. Forty-nine men with ED were studied. We classified ED as 'diabetic', 'neuropathic' or 'ED of other origin'. 26.6% of the men fulfilled the criteria of diabetic ED, 42.9% had neuropathic ED. In every patient history taking, a questionnaire focusing on autonomic symptoms other than ED, clinical examination, nerve conduction studies (NCS), sphincter ani electromyography (EMG), heart rate variability testing (HRV) and quantitative sensory testing (QST) was performed. Vascular function was assessed by the intracavernosal prostaglandin E1 (PGE1) injection test. The frequency of abnormal results in diabetic and neuropathic patients was compared. Vascular function was abnormal in only one patient with diabetic ED and three patients with neuropathic ED. Both groups had similar frequencies of autonomic symptoms other than ED (64% in diabetic vs. 64% in neuropathic patients), abnormal EMG (33% vs. 40%) and abnormal QST (vibratory perception 83% vs. 84%, cold perception 9% vs. 19%, warm perception 42% vs. 43%). Abnormal clinical findings (50% vs. 33%), NCS (75% vs. 50%) and HRV (39% vs. 25%) were slightly, but not significantly more frequent in men with diabetic ED than neuropathic ED. The tests indicating neuropathy showed abnormalities in men with diabetic ED as frequently as in men with neuropathic ED. Some tests even suggested neuropathy more often in diabetic than in neuropathic ED. The findings support the hypothesis that neuropathy contributes significantly to the pathophysiology of ED in diabetes mellitus.

Adult↗

PubMed1999

Deletion monitoring in skin tumors by interphase-FISH using band-specific DNA probes.

Thin sections from archival paraffin blocks of various skin tumors (26 melanomas, 15 squamous cell carcinomas, 5 keratoacanthomas, 5 basal cell carcinomas) were subjected to interphase-FISH (I-FISH) with DNA probes which are specific for chromosomal regions often involved in deletions in human cancer. These were probes for chromosome 3p21, the p53 gene on chromosome 17p13, and, in a few selected cases, a probe for chromosome 9p21. It was demonstrated that deletions of these regions could be reliably detected and related to tumor type and histology, i.e. grading. The most common deletion was that of 3p21 which was found in all studied squamous cell carcinomas (SCC) of low differentiation, in 60% of the Bowen carcinomas, in 70% of the metastatic melanomas less than 1.5 mm thick, and in over 55% of those which thickness over 2 mm. In contrast, FISH-detected p53 deletion was a rare finding in the investigated tumors. However, this gene was even found in an increased copy number in 60% of the poorly differentiated SCCs (grade 4) and in 50% of the non-metastatic melanomas less than 1.5 mm thick. Deletion of 9p21 was detected in 13 of the 14 tumors on which pertinent examinations could be performed. I-FISH was shown to be a reliable technique for the rapid detection of chromosome band specific deletions in archival material of human skin tumors.

Adult↗

PubMed1999

Differentiation between Spitz nevi and malignant melanomas by interphase fluorescence in situ hybridization.

Spitz nevi are benign melanocytic neoplasias which have distinct pathological features that make the pathological differential diagnosis from malignant melanomas extremely difficult. The Spitz nevi may be misdiagnosed as malignant melanoma and vice versa. Therefore, interphase fluorescence in situ hybridization (I-FISH) was used for a possible discrimination between Spitz nevi and malignant melanomas on the basis of numerical aberrations of the chromosome complement in interphase nuclei of thin sections. Previous studies had shown changes in malignant melanomas which were not found at the same level in normal tissue or benign tumors. Thin sections of archival paraffin material from 42 Spitz nevi with different histological type and grade of anomaly were subjected to FISH-analyses using commercially available biotinylated and/or digoxigenated alphoid DNA probes of chromosomes 1, 6, 7, 9, 17 and 18, which were applied in combinations in a two- or three-color-FISH. Unaffected epithelial areas from the same sections served as. The obtained data were compared with those collected previously from thin sections of malignant melanomas prepared in the same way. Due to the sometimes limited nevus area investigated, the number of evaluable nuclei was lower than expected from previous experiences with malignant melanomas. Therefore, only 20 nevi could be reliably evaluated. The comparison of the group of Spitz nevi with the group of controls did not show any significant difference regarding chromosomes 1, 6, 7, 9 and 17 (Wilcoxon test). The method used to detect chromosomal loss or gain in the individual Spitz nevi demonstrated only two nevi (one of the spindle cell type with a low to middle grade of anomaly, the other of the epitheloid cell type with a middle grade of anomaly) with a gain of chromosome 7 and chromosome 17, respectively. So, with respect to the histological type and grade of anomaly, no numerical aberrations could be detected in Spitz nevi. The comparison of the group of Spitz nevi with subgroups of malignant melanomas (metastatic, non-metastatic, melanomas with a thickness <1.5 mm and melanomas with a thickness >2. 0 mm) and with the whole group of malignant melanomas showed significant differences concerning chromosome 9 (Mann-Whitney U test), signal indices, which were higher in the melanomas than in the Spitz nevi. Regarding chromosomes 6, 7 and 17 no significant differences could be shown, although a trend of gain in melanomas and of loss in Spitz nevi was observed of these chromosomes.

Adolescent↗

PubMed1998

Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome: clinical and neuropathological observations in a 33-year-old man.

The syndrome of ichthyosis follicularis, alopecia, and photophobia (IFAP) is an uncommon neuroichthyosis described in only 10 males so far. We report on a man with congenital ichthyosis and alopecia with apparently normal development in early infancy. Photophobia and generalized myoclonicastatic seizures began during or after the first year of age and were associated with progressive impairment of motor skills and mental abilities. He died at 33 years of age. Neuropathological findings showed an unusual deformation of the temporal lobes and olivocerebellar atrophy. Cytogenetic and molecular studies did not uncover deletions in either Xp22.2 to 3 or in Xq27.3 to qter.

Abnormalities, Multiple↗

PubMed1998

[Lupus erythematosus/lichen ruber planus overlap syndrome. 5 cases in a patient sample of the Erlangen University Dermatology Clinic (1894-1995)].

The simultaneous occurrence of lupus erythematosus (LE)- and lichen ruber (LP)-like symptoms is called LE/LP-overlap syndrome (LE/LP-OS). It is defined by concomitant clinical, histologic and immunhistologic features of both diseases. To date, 47 cases of this rare dermatosis have been reported with marked differences in the skin lesions: They are either of intermediate appearance between LE and LP (type I = intermediate type), or show a coexistence of LE- and LP-specific lesions (type II = polar type). To determine the frequency and characteristics of the LE/LP-OS we reviewed our LE-patients from 1984-1995. 5 cases were diagnosed. The frequency of LE/LP-OS in our patients is higher than generally assumed. Due to its variable clinical, histological and immunhistological appearance and the lack of unequivocal pathognomonic signs, this overlap-dermatosis may be underdiagnosed. Since therapeutic consequences result from the diagnosis, criteria are suggested to facilitate the recognition of the LE/LP-OS.

Adult↗

PubMed1998

DAZ (Deleted in AZoospermia) genes encode proteins located in human late spermatids and in sperm tails.

We analysed the location of proteins encoded by the DAZ (Deleted in AZoospermia) genes in human testis tissue and in mature spermatozoa. The DAZ genes are known to be expressed exclusively in the human male germ line, and are candidate genes for the expression of the azoospermia factor AZFc mapped recently to distal Yq11. They encode testis-specific RNA binding proteins, the function of which is not yet known. Immunostaining experiments with antibodies prepared for the specific peptide domain encoded by the DAZ2 transcript (formerly SPGY1) revealed the presence of DAZ proteins in the innermost layer of the male germ cell epithelium and in the tails of spermatozoa. This suggests a function for DAZ proteins in the RNA metabolism of late spermatids, presumably in the storage or transport of testis-specific mRNA, the translation of which is repressed until the formation of mature spermatozoa. Deletion of DAZ genes is supposed not to interfere with human sperm maturation but to result in a gradual reduction of mature spermatozoa.

Amino Acid Sequence↗

PubMed1997

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm.

The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNA-binding proteins (RBM and DAZ/SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.

Adult↗

PubMed1997

[Metageria--clinical manifestations of a premature aging syndrome].

A 19-year old caucasian patient suffered from ulceration and scaring of his fingers since age two. During childhood, fibrosing contractures on the phalanges developed. Since puberty, his eunuch-like stature, bird-like face and exophthalmos had become under obvious. His hair was extraordinarily fine; his pubic hair rare. Radiological examination revealed ankylosis and osteoporosis of the phalanges and carpals. Angiography showed occlusion of multiple digital and interdigital arteries. Furthermore, a bilateral posterior cataract, restrictive respiratory disease, impaired glucose tolerance, hyperuricemia, proteinuria and primary hypogonadism were diagnosed. These findings are characteristic for the premature aging syndromes. The cardial symptoms of tall stature, bird-like face, pseudoexophthalmos, skleroderma-like and poikiloderma-like cutaneous lesions, scarce hair growth, early diabetes mellitus and arteriosclerosis led to the diagnosis of metageria.

Adult↗

PubMed1997

Hydroxyurea for treatment of unresectable and recurrent meningiomas. II. Decrease in the size of meningiomas in patients treated with hydroxyurea.

In this paper the authors present the first evidence that meningiomas respond to treatment with hydroxyurea. Hydroxyurea was administered as an adjunct chemotherapeutic treatment in patients with recurrent and unresectable meningiomas. Hydroxyurea was used because experimental data demonstrated that it inhibits growth of cultured human meningioma cells and meningioma transplants in nude mice by inducing apoptosis. The authors therefore treated four selected patients with hydroxyurea. All patients had undergone multiple gross resections and all except one received radiotherapy. Three patients with recurrent Grade I meningiomas assessed according to World Health Organization (WHO) guidelines received hydroxyurea because of an increased tumor growth rate, documented by magnetic resonance (MR) imaging, within a 6- or 12-month interval. A fourth patient with a malignant meningioma (WHO Grade III) began a course of treatment with hydroxyurea immediately after his sixth palliative operation without waiting for another relapse to be demonstrated on MR imaging. Because of their location and invasive growth behavior none of the meningiomas could have been removed completely by surgical intervention. All patients received hydroxyurea at a dosage level of 1000 to 1500 mg/day (approximately 20 mg/kg/day). In a man with a large sphenoid wing meningioma invading the right cavernous sinus and the temporal base, the intracranial tumor mass was reduced by 60% during 6 months of treatment. A woman with a large ball-shaped meningioma of the right sphenoid wing invading the cavernous sinus exhibited a 74% decrease of the initial tumor volume in 10 months of treatment with oral hydroxyurea. Serial MR images obtained monthly revealed that the process of size reduction was continuous and proportionate. The shrinkage of the tumor was accompanied by a complete remission of symptomatic trigeminal neuralgia after 2 months and by improved abducent paresis after 5 months. The third patient had a slowly growing meningioma that exhibited a 15% reduction in mass when reassessed after 5 months of hydroxyurea treatment. The fourth patient with the malignant meningioma in the left cerebellopontine angle has had no recurrence for 24 months. Long-term treatment with hydroxyurea may result in full remission of tumors in meningioma patients. The preliminary data indicate that hydroxyurea provides true medical treatment in patients with unresectable and recurrent meningiomas, replacing palliative surgery and radiotherapy in the management of this disease.

Adult↗

PubMed1997

Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway.

Meningiomas, which invade intracranial bone structures and the adjacent connective tissue, are frequently unresectable because of their aggressive and recalcitrant growth behavior. They have a high recurrence rate, and in approximately 10% of these tumors there is an increased risk of malignancy. Significant morbidity and mortality rates associated with recurrent meningiomas demand nonsurgical approaches. To date, adjuvant hormonal treatment has not proven beneficial. The anticancer drug hydroxyurea was therefore tested for its potential use in the treatment of meningiomas. Early-passaged cell cultures were established from 20 different meningiomas. The addition of 5 x 10(-4) and 10(-3) M hydroxyurea over a period of 5 to 9 days resulted in a remarkable decrease in cell proliferation and even blocked tumor cell growth when compared with untreated cells. A significant arrest of meningioma cell growth in the S phase of the cell cycle was revealed on DNA flow cytometry. Electron micrographs of hydroxyurea-treated tumor cells showed ultrastructural features consistent with apoptosis, and light microscopy demonstrated DNA fragmentation by in situ DNA strand break labeling. Short-term treatment of meningioma cell cultures with hydroxyurea for 24 to 48 hours resulted in discrete oligonucleosomal fragments (DNA ladder), another characteristic sign of apoptosis. In addition to the in vitro studies, tissue from five different meningiomas was transplanted into nude mice followed by treatment with 0.5 mg/g body weight hydroxyurea over 15 days. In situ DNA strand break labeling demonstrated DNA fragmentation in distinct regions with different tumor cell densities in all hydroxyurea-treated meningioma transplants. These data provide evidence that hydroxyurea is a powerful inhibitor of meningioma cell growth, most likely by causing apoptosis in the tumor cells. Thus, hydroxyurea may be a suitable chemotherapeutic agent for the long-term treatment of unresectable or semi- to malignant meningiomas, or for preventing recurrent growth of meningiomas after resection.

Animals↗

PubMed1996

Proliferation parameters for pituitary adenomas.

In this review, the value of assessing proliferation parameters in surgically resected pituitary tumour tissue is analyzed. Histological examination of basal dura biopsies identifies invasive growth even when intraoperatively not apparent to the surgeon. Determination of DNA-polymerase activity, Ki-67 immunohistochemistry and DNA-flow-cytometry shows a clear difference in the proliferative potential of enclosed and invasive pituitary adenomas. Among the various endocrinologically differentiated groups ACTH-secreting adenomas associated with Nelson's syndrome and thyrotropinomas were the most rapidly proliferating. At present, however, our results reveal that the prognosis of an individual patient cannot be reliably predicted on the basis of such studies.

Adenoma↗

PubMed1996

[High frequency color coded duplex ultrasound of small finger arteries--new diagnostic possibilities? A noninvasive method for visualizing digital circulation].

Small vessels with luminal diameters of 0.2-2.0 mm have not been studied with routine ultrasound diagnostic procedures. Modern color Doppler imaging technology, however, should allow visualization of the blood flow even in such small vessels. The present study was therefore aimed at demonstrating the possibilities of examining small arteries in the fingertips of healthy volunteers with color Doppler imaging. The question was whether or not a standardized visualization was possible. We found that small arteries and their blood flow could be demonstrated in all (n = 10) healthy subjects. Furthermore, we demonstrated pathologic findings in the fingertip arteries of a patient with thrombangitis obliterans as an example of the diagnostic value of these new procedures.

Adolescent↗