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Biomedical subjects

J Kunze

Publications and source records attributed to J Kunze.

At least 37 records · Page 2Linked to original sources
PubMed1999

Ellis-van Creveld syndrome: examination at 15 weeks' gestation.

In 1940, Ellis and van Creveld defined a syndrome they referred to as chondro-ectodermal dysplasia. This autosomal recessive condition, now usually referred to as Ellis-van Creveld syndrome (EVC), comprises bilateral postaxial polydactyly, a chondrodysplasia, characterized by shortness of limbs, and ectodermal dysplasia. Congenital heart defects are also common. There are many reports in medical literature describing affected newborns and even, older children. Here, we report the clinical, radiological and histological findings in a 15-week-old affected fetus. The diagnosis of Ellis-van Creveld syndrome in this fetus is based on a positive family history (an affected sib) and shortness of long bones as well as hexadactyly diagnosed by prenatal ultrasonography. On post-mortem examination, bilateral postaxial hexadactyly and symmetrical shortness of the long bones was noted. Histologically, there was too short a zone of cartilagineous columns in the metaphyses, a reduced number of chondrocytes and an irregularly structured spongiosa within the ossification zone. In addition, the fetus was found to have an atrio-ventricular canal. This heart defect is presumably rare in this syndrome. Other characteristic features such as small and dysplastic nails, sparse hair and abnormalities of the teeth were, of course, not yet present in this early developmental stage. In addition to EVC, the fetus had a 47,XXY chromosome constitution.

Adult↗
PubMed1998

Unilateral terminal aphalangia in father and daughter--exogenous or genetic cause?

Published cases of familial unilateral terminal transverse defects are scarce. We report on a morphologically similar defect of the hand in a father and his daughter. The hand anomaly is similar in both, but on the opposite side. Thalidomide was taken in the sensitive period of the pregnancy by the father's mother. To our knowledge this is the second description of unilateral terminal aphalangia in successive generations. In order to evaluate the possible genetic basis we analyze epidemiological studies in respect to the recurrence risk of cases with isolated limb reduction defects. We compare reports of familial occurrence concerning the degree of relationship as well as the pattern of malformation. The latter seems to be an important aspect from an evolutionary and a developmental viewpoint. For our observation an autosomal dominant transmission is the most likely although multifactorial determination cannot be excluded.

Adult↗
PubMed1998

Superior hydrodynamics of a modified cavopulmonary connection for the Norwood operation.

BACKGROUND: In the Fontan circulation, energy consumption at the cavopulmonary connection is crucial. Our hypothesis was that a modification of the standard Norwood variant of cavopulmonary connection with an extended anastomosis would improve hydrodynamics. METHODS: The in vitro hydrodynamics of two different Perspex glass models resembling the Norwood variant of cavopulmonary connection (model I) and the modification (model II) were analyzed in a mock circulation at nonpulsatile flows of 2 to 5 L/min to simulate rest and exercise. The pulmonary flow split was varied to imitate varying lung resistances. Inferior-to-superior caval flow ratio and size of models were increased to simulate growth. RESULTS: The pulmonary flow was preferentially directed to the left lung in model I and was better balanced in model II. Power losses increased exponentially with total flow in both models and were markedly higher in model I. These differences were attenuated in the larger models. Anastomotic turbulences were larger in model I. Power losses in both models were relatively insensitive to changes in pulmonary flow split. CONCLUSIONS: The proposed modification of the Norwood variant of cavopulmonary connection seems to be hydrodynamically advantageous and warrants further evaluation.

Anastomosis, Surgical↗
PubMed1998

Diffuse mesangial sclerosis: association with unreported congenital anomalies and placental enlargement.

A case of diffuse mesangial sclerosis (DMS) associated with a number of undescribed congenital anomalies is reported. The occurrence of additional anomalies, especially ocular anomalies, is a common finding in DMS. However, neither megalocornea, Dandy-Walker malformation, postaxial hexadactyly, rocker-bottom feet, nor atrial septal defect, as observed in our patient, has been reported previously in association with DMS. This case might be considered an atypical manifestation of the Galloway-Mowat syndrome. In contrast to most cases of DMS, the patient revealed intrauterine proteinuria as the placenta was enlarged to 31% of birth weight. This case demonstrates that the large placenta, >25% of birth weight, is not only pathognomonic of the congenital nephrotic syndrome of the Finnish type but can also occur in DMS.

Abnormalities, Multiple↗
PubMed1998

Intracellular pharmacokinetics of anthracyclines in human leukemia cells: correlation of DNA-binding with apoptotic cell death.

Anthracyclines are major components of the most therapeutical strategies in hematological oncology. These drugs are not directly cytotoxic but induce apoptosis. Due to their lipophilicity, anthracyclines are rapidly distributed in myeloid and lymphatic leukemia cells. Within 20 min after treatment, daunorubicin and idarubicin are found to intercalate into DNA. Shortly after treatment, DNA damage occurs and increases within 3 hours. Apoptosis can be monitored 12-24 hours after treatment, at this timepoint the majority of DNA strand breaks have already been repaired. A statistically highly significant linear correlation could be established between the DNA binding rate of anthracyclines and the resulting cell death. This indicates that DNA binding is a prerequisite for the induction of apoptosis. With respect to cellular resistance mechanisms, 2 different pharmacodynamic phases can be distinguished: intracellular distribution and cellular reaction. The endpoint of the "distribution phase" is marked by the DNA intercalation of the anthracyclines. Cellular resistance mechanisms which decrease the DNA binding include membrane transport mechanisms and vesicular trapping of the drugs. The "reaction phase" might be disturbed by complex antiapoptotic mechanisms. The assessment of DNA binding in malignant cells during or shortly after treatment with anthracyclines might be a useful tool to distinguish cellular resistance mechanisms.

Antibiotics, Antineoplastic↗
PubMed1997

Prenatal diagnosis of a Currarino triad.

Prenatal diagnosis of the Currarino triad by means of obstetrical ultrasonography is described. Three related cases are presented. A literature review regarding the therapeutic, ultrasound-guided approach are discussed. The Currarino triad is a genetically transmitted syndrome consisting of an anorectal malformation, a sacral boney defect and a presacral mass. Prenatal diagnosis aids the early recognition and surgical management of persistent spinal-rectal fistulas, thus potentially avoiding life-threatening bacterial meningitis. Copyright 1997 Elsevier Science Ireland Ltd.

Journal Article↗
PubMed1997

Extreme microcephaly, severe growth and mental retardation, flexion contractures, and ichthyotic skin in two brothers: a new syndrome or mild form of Neu-Laxova syndrome?

Two brothers with congenital microcephaly, growth and mental retardation, flexion contractures, dorsal edema of hands and feet, and ichthyotic skin changes are described. Mild manifestations of Neu-Laxova syndrome have to be considered but long survival and only mild intrauterine growth retardation not described in this syndrome may be evidence of a different condition.

Contracture↗
PubMed1996

Phenotypic differences in Angelman syndrome patients: imprinting mutations show less frequently microcephaly and hypopigmentation than deletions.

Angelman syndrome (AS) is a relatively frequent disorder of psychomotor development caused by loss of function of a gene from chromosome 15q11-q13, a region subject to genomic imprinting. The AS gene(s) is exclusively expressed from the maternal chromosome. Several kinds of mutations have been found to cause AS. More than half of the cases exhibit a deletion of the maternal 15q11-q13 region. Recently, we and others described a new mutation type, the imprinting mutation, characterised by normal, biparental inheritance but aberrant methylation patterns of the entire chromosomal region. In AS, a paternal imprint is found on the maternal chromosome probably leading to functional inactivation of the AS gene(s). We have now compared the phenotype of 9 AS patients with imprinting mutation to that of nine age-matched ones with a maternally derived deletion. Both groups were evaluated for 19 common AS symptoms. All patients, independently of their molecular findings, showed classical AS symptoms such s mental retardation, delayed motor development, and absent speech. In contrast, for two signs, hypopigmentation and microcephaly, a different distribution among both groups was observed. Only one of nine AS patients with an imprinting mutation, but seven of nine in the deletion control group showed either symptom. Our results suggest that imprinting mutations, in contrast to deletions, cause only incomplete loss of gene function or that maternally derived deletions affect also genes not subject to genomic imprinting. We conclude that AS is caused by loss of function of a major gene that is imprinted but that there are also other genes that contribute to the phenotype when in hemizygous condition.

Albinism, Oculocutaneous↗
PubMed1996

A new observation of two cases of acrofacial dysostosis type Genée-Wiedemann in a family--remarks on the mode of inheritance: report on two sibs.

We report on a Yugoslavian sibpair with postaxial acrofacial dysostosis type Genée-Wiedemann with some novel signs which broaden the spectrum of this syndrome. The manifestations of the present cases are compared with those of the previously described patients. Life expectancy, change of symptoms over time, and the mode of inheritance are discussed.

Abnormalities, Multiple↗
PubMed1996

Computer assisted diagnosis of malformation syndromes: an evaluation of three databases (LDDB, POSSUM, and SYNDROC).

Computer programs which can be used as an aid to diagnose multiple congenital anomaly syndromes have been used for many years, but up to now they have been evaluated very rarely. The diagnostic abilities of three of these systems [LDDB (London Dysmorphology Database), POSSUM (Pictures of Standard Syndromes and Undiagnosed Malformations), and SYNDROC] were analyzed. All three programs are based on an algorithm which defines a diagnosis by a set of phenotypic components all having the same weight (descriptive algorithm). A second algorithm is applied by SYNDROC to rank competing diagnoses in order of probability. This pseudo-Bayesian algorithm provides a coefficient of certitude (CC). For a test the clinical findings of 102 patients who had received a firm diagnosis were used. Two search strategies were tried: "novice's strategy" with all findings taken for a search and "expert's strategy" with a selected set of anomalies. Only those diagnoses that were suggested with the 1st rank, defined as the highest degree of agreement, or the highest CC were studied. The greatest resemblance between suggestions of the databases and the clinical diagnosis was obtained with the expert strategy. The highest number of matches were produced by SYNDROC (80 with expert strategy) and the lowest by POSSUM (54 with novice strategy). The overall agreement between the databases is about 40% for the 1st rank. This number reflects that different authors use different pivotal signs for the description of a syndrome. With the pseudo-Bayesian algorithm 59 cases obtained the highest CC value. Great difficulties exist with the subjective estimates for the calculation of these values; the absolute CC values seem to be meaningless. A small number of unusual cases with special combinations of anomalies provide serious problems for correct diagnosis.

Abnormalities, Multiple↗
PubMed1996

[HPV-5 typing with nested PCR and sequencing in epidermodysplasia verruciformis].

We report a case of epidermodysplasia verruciformis (EV) with typical cutaneous manifestations in light-exposed areas. The diagnostic criteria were the characteristic macular lesions, the virus transformed keratinocytes on histological examination and the detection of human papillomavirus (HPV) DNA by a nested-PCR approach for EV-associated types. In this case we found HPV-type 5, the most common type of HPV in EV, directly by sequencing and sequence analysis.

Adult↗
PubMed1996

[Cutaneous malacoplakia in a patient with psoriasis vulgaris].

A 58 year old patient suffering from psoriasis vulgaris had typical erythematous, scaly plaques for 20 years. In addition, an erosive, therapy-resistant plaque was found in the perianal region. A biopsy was taken to exclude malignancy; it showed intracytoplasmic Michaelis-Gutmann-bodies as a marker for malakoplakia, which rarely occurs in the skin. In further electron microscopic investigation, intracytoplasmatic bacteria could be demonstrated. An underlying malignancy or chronic renal insufficiency with immunosuppression were not found in this patient; both are often associated with malakoplakia.

Anal Canal↗
PubMed1996

Autosomal dominant hypertension and brachydactyly in a Turkish kindred resembles essential hypertension.

We examined a Turkish kindred with a unique form of autosomal dominant hypertension that cosegregates 100% with brachydactyly and maps to chromosome 12p. Affected adults were 10 to 15 cm shorter than unaffected people; however, their body mass index (27 kg/m2) was not different. Blood pressure increased steeply with age in the affected people so that by age 40 years, they had a mean blood pressure of 140 mm Hg, compared with 92 mm Hg in unaffected individuals. Complete clinical, roentgenographic, and laboratory evaluation was performed in 6 subjects, including 24-hour blood pressure measurements and humoral determinations before and after volume expansion with 2 L normal saline over 4 hours followed by volume contraction on the following day with a 20-mmol sodium diet and 40 mg furosemide at 8 AM, noon, and 4 PM. Two affected men aged 46 and 31 years; 3 affected women aged 40, 31, and 30 years; and 1 unaffected man aged 29 years were studied. Systolic pressures ranged from 170 to 250 mm Hg, and diastolic pressures ranged from 100 to 150 mm Hg in affected people; the unaffected man had a blood pressure of 120/70 mm Hg. Thyroid, adrenal, and renal functions were normal; electrolyte and acid-base statuses were normal. Calcium and phosphate homeostasis was normal. Day-night circadian blood pressure rhythm was preserved. The subjects were not salt sensitive; renin, aldosterone, and catecholamine values reacted appropriately to volume expansion and contraction. Affected people had mild cardiac hypertrophy and increased radial artery wall thickness. Fibroblasts from affected people grew more rapidly in culture than from unaffected people. We conclude that this novel form of inherited hypertension resembles essential hypertension.

Adult↗
PubMed1996

The knowledge base of bee navigation

Navigation in honeybees is discussed against the background of the types of memories employed in the navigational task. Two questions are addressed. Do bees have goal-specific expectations, and when are novel routes travelled? Expectations are deduced from (1) context stimuli as determinants for local cue memories, (2) landmark-dependent path integration, (3) sequential learning of landmarks, and (4) motivation- and context-dependent memory retrieval. Novel routes are travelled under two conditions: (1) goal-cue-based piloting and (2) integration of simultaneously activated vector memories. Our data do not support the conclusion that memory integration in bees is organised by a cognitive map. The assumption of purely separate memories that are only retrieved according to the chain of events during navigational performance also appears to be inadequate. We favour the view that multiple memories are integrated using external and internal sources of information. Such configural memories lead to both specific expectations and novel routes.

Journal Article↗
PubMed1996

Topoisomerase II activities in AML blasts and their correlation with cellular sensitivity to anthracyclines and epipodophyllotoxines.

We have developed a method to quantify topoisomerase (topo) II activities in partially purified nuclear extracts from human leukemia cells. By virtue of their different pH optima in the reaction buffer, two different topo II activities were found with activity optima at pH 7.9 and at pH 8.9 under high stringency conditions. The activities could be identified as topo II beta activity (pH 7.9) and topo II alpha activity (pH 8.9) by their different sensitivities to topo II alpha inhibitors, dephosphorylation experiments and immunoprecipitation with polyclonal antibodies. Seventy-two bone marrow or blood samples from patients with acute myeloid leukemias have been examined and their in vitro sensitivities to anthracyclines and epipodophyllotoxines correlated to the activities of topo II alpha and topo II beta. Although the topo II alpha activity could be directly inhibited by incubation of the cells with the mentioned drugs, no correlation between the topo II alpha activity and the sensitivity of the cells could be found. In contrast, the topo II beta activity which was not substantially inhibited by the drugs inversely correlated with the sensitivity of the cells. These findings were statistically significant for idarubicin (P=0.017) and daunorubicin (P=0.006). Vice versa, resistant cells (IC90 > median) had a higher topo II beta activity. Clinical relevance might be indicated by the finding that cells from patients that relapsed after initial treatment with anthracyclin-containing regiments had a significantly higher topo II alpha/beta activity ratio (P=0.0276). Obviously, the sensitivity of AML cells is substantially influenced by the activity of the resistant topo II (topo II beta) which gives evidence that the remaining topo II activity after treatment helps the cell to survive the DNA repair phase.

Antibiotics, Antineoplastic↗
PubMed1996

Topoisomerase II activities in AML and their correlation with cellular sensitivity to anthracyclines and epipodophyllotoxines.

We have developed a method to quantify topoisomerase (topo) II activities in partially purified nuclear extracts from human leukemia cells. By virtue of their different pH optima in the reaction buffer, two different topo II activities were found with activity optima at pH 7.9 and at pH 8.9 under high stringency conditions. The activities could be identified as topo II beta activity (pH 7.9) and topo II alpha activity (pH 8.9) by their different sensitivities to topo II alpha inhibitors, dephosphorylation experiments and immunoprecipitation with polyclonal antibodies. Seventy-two bone marrow or blood samples from patients with acute myeloid leukemias have been examined and their in vitro sensitivities to anthracyclines and epipodophyllotoxines correlated to the activities of topo II alpha and topo II beta. Although the topo II alpha activity could be directly inhibited by incubation of the cells with the mentioned drugs, no correlation between the topo II alpha activity and the sensitivity of the cells could be found. In contrast, the topo II beta activity which was not substantially inhibited by the drugs inversely correlated with the sensitivity of the cells. These findings were statistically significant for idarubicin (P= 0.017) and daunorubicin (P = 0.006). Vice versa, resistant cells (IC50 > median) had a higher topo II beta activity. Clinical relevance might be indicated by the finding that cells from patients that relapsed after initial treatment with anthracyclin-containing regiments had a significantly higher topo II alpha/beta activity ratio (P=0.0276). Obviously, the sensitivity of AML cells is substantially influenced by the activity of the resistant topo II (topo II beta) which gives evidence that the remaining topo II activity after treatment helps the cell to survive the DNA repair phase.

Antibiotics, Antineoplastic↗