Biomedical subjects

J Pohlenz

Publications and source records attributed to J Pohlenz.

At least 55 records · Page 3Linked to original sources

PubMed1997

Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH.

Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We now report the occurrence of RTSH in 3 unrelated families. Contrary to previous reports, the inheritance of RTSH in 2 of the families was dominant rather than recessive and was not associated with abnormalities in the TSHR gene. Abnormalities in the TSHR gene were excluded by sequencing all coding sequences, exon/intron junctions, and the promoter region of the gene. Furthermore, the involvement of the TSHR in the manifestation of the RTSH phenotype was excluded in 2 families by linkage analysis using intragenic polymorphic markers. We excluded defects in the TSH beta-subunit by sequencing its gene and by showing that the circulating TSH in affected subjects from all families had normal bioactivity. Also, no abnormalities were found in the Gs alpha gene of one family analyzed by GC-clamped denaturing gradient gel electrophoresis. This study shows that RTSH may be a manifestation of several different genetic defects that requires the exploration of other candidate genes involved in the TSH-TSHR-Gs alpha cascade and genes participating in its regulation.

Adult↗

PubMed1997

Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity.

Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness to thyroid hormone caused by mutations in the thyroid hormone receptor beta (TRbeta) gene. Mutant TRbetas exhibit variable degrees of impaired T3 binding resulting in reduced T3-mediated function. The dominant mode of inheritance is attributed to the ability of mutant TRbetas to interfere with the function of the wild-type (WT) TR, a phenomenon known as dominant negative effect (DNE). We recently identified two families with RTH having mutations in amino acid 243 (R243Q and R243W) in whom the mechanism of RTH appears to be distinct from that of other natural TRbeta mutations. These mutations, which are located in the hinge domain of the TRbeta, do not significantly alter the binding affinity for T3, measured in vitro. The present study was undertaken to characterize the properties of these mutant TRbetas to understand the molecular basis of the RTH phenotype. Two other mutant TRbeta producing RTH with mild (320H) and severe (345R) impairment of T3 binding were studied in parallel. The results demonstrate that TRbetas 243Q and 243W could be translocated into the nucleus where they exerted normal ligand-independent repression of positively regulated thyroid hormone response elements. Yet, the addition of 10 nmol/L T3 failed to normalize the transactivation (16-13% of WT) and revert the DNE exerted by the two TRbeta mutants. In contrast, at this T3 concentration, the transactivation function of 320H was significantly higher (50% of WT), and the DNE was completely abolished, in keeping with the mild clinical form of RTH. Formation of 243Q and 243W homodimers on thyroid hormone response elements could not be as readily prevented by T3 as those formed by the WT and 320H TRbetas. These results suggest that the substitution of R243 in TRbeta produces RTH by increasing the propensity for the formation of tightly bound homodimers or by reduction of the receptor affinity for T3 only after it binds to DNA.

Animals↗

PubMed1996

New point mutation (R243W) in the hormone binding domain of the c-erbA beta 1 gene in a family with generalized resistance to thyroid hormone.

Two years after the first mutation on exon 7 in the carboxy-terminal part of the hinge domain (D) was reported (Behr and Loos 1992), we have identified the second mutation on exon 7 in patients with GRTH. Interestingly, our mutation it is not located in the two previously described "hot spot regions", but instead very close to the hinge domain (D) of the receptor protein that is essential for the function of the hormone binding domain (E) (Lin et al., 1991). Confirming the observation that the majority of single base substitutions causing human genetic diseases or DNA polymorphisms follow the hot spot mutation rule of CG to TG and CG to CA transition (Barker et al., 1984), an additional CpG dinucleotide transition has been identified.

Adult↗

PubMed1996

An improved DNA test for bovine leucocyte adhesion deficiency.

A modified DNA test, based on the polymerase chain reaction, was developed for the monogenic recessive disease bovine leucocyte adhesion deficiency (BLAD). The test was improved by the selection of new primers which facilitated the interpretation of the results. An easily scorable banding pattern makes the test useful in cattle breeding schemes and for clinical diagnosis. A total of 2381 samples was analysed over a period of three years. The carrier rate among young bulls at artificial insemination (AI) stations decreased from 11.6 per cent in 1993 to 9.9 per cent in the first five months of 1995. Continuous screening of young bulls before entering AI is still recommended unless both parents are proven to be genetically free of BLAD. The carrier rate among clinically suspect animals was not increased, and carriers are therefore not expected to be immunodeficient. Despite all efforts to eradicate the disease, calves with BLAD were still observed in 1995.

Animals↗

PubMed1996

Treatment of pituitary resistance to thyroid hormone (PRTH) in an 8-year-old boy.

We report on an 8-year-old boy with pituitary resistance to thyroid hormone (PRTH) having a cysteine for arginine substitution at codon 320 in the TR-beta gene who was presented because of thyrotoxicosis. Due to its suppressive effect on the pituitary thyrotropin secretion, treatment with D-thyroxine (D-T4) was started. After a few days, clinical euthyroidism was achieved but thyroid stimulating hormone secretion was not suppressed. Symptoms of thyrotoxicosis relapsed when therapy was interrupted so that therapy with D-T4 was reinstituted and continued to date. Symptoms did not recur, and the psychomotor development proceeded normally. D-T4 should therefore be considered in the treatment of thyrotoxicosis in PRTH.

Amino Acid Sequence↗

PubMed1996

Renal coccidiosis with cystic tubular dilatation in four bats.

Renal coccidiosis was diagnosed in four bats of different species (Pipistrellus pipistrellus, Myotis mystacinus, M. nattereri, and Nyctalus noctula). Multiple white and partly indented foci up to 2 mm in diameter were visible on the renal surface. Histologically, the foci appeared as cystic dilated tubules with proliferated epithelium. Asexual and sexual coccidian stages were seen in the epithelial cells, and the extremely distended tubular lumina were filled with schizonts, free zoites, microgamonts, macrogamonts, and unsporulated oocysts. Because the majority of the renal tissue appeared uninvolved in the disease process at the gross and histologic levels and there was no evidence for uremia in other organs, renal function was probably not impaired. Precise classification of the coccidia was impossible because no sporulated oocysts were available. The parasite morphology and the hitherto unreported cystic dilatation of infected tubules containing all developmental stages differ from renal coccidioses reported previously and therefore suggest an undescribed coccidian species.

Animals↗

PubMed1995

Effect of oestrogen/gestagen replacement therapy on liver enzymes in patients with Ullrich-Turner syndrome.

The absence of breast development and the prevention of osteoporosis in Ullrich-Turner syndrome (UTS) require oestrogen/gestagen substitution therapy. In 8 out of 35 (23%) patients with UTS treated with conjugated equine oestrogens and cyclically with norethisterone acetate, the serum liver enzymes increased to conspicuous levels (AST 35; 20-73 U/l, ALT 92; 37-141 U/l, GGT 77; 25-227 U/l, [median; min-max]). These findings were compared with those in 41 tall girls who received a six-fold larger dose of conjugated equine oestrogens for the reduction of final height. None of these 41 girls showed abnormal serum liver enzyme levels. The conspicuous rise in serum liver enzyme levels occurred in the majority of the UTS patients before norethistherone acetate was added to the oestrogen replacement therapy. No essential morphological equivalent was found in liver sonography and biopsy studies. During the follow up the elevated serum liver enzyme levels showed reversibility when medication was temporarily discontinued and either a slow decrease or a steady state after therapy was continued. CONCLUSION. Patients with UTS on oral oestrogen replacement therapy are more susceptible to develop increased serum liver enzyme levels as compared with eukaryotic females treated with the same oestrogen preparation for other disorders. As the underlying pathomechanism is unknown and adverse long-term effects cannot be ruled out, avoiding the portal vein and using the transdermal application of oestrogen may represent a viable solution to the problem.

Adolescent↗

PubMed1995

Pathomorphological and immunohistological findings in cattle experimentally infected with rinderpest virus isolates of different pathogenicity.

Experimental infection of nine cattle with seven rinderpest virus strains of different pathogenicity resulted in significant variations of clinical signs, morphological lesions and distribution of viral antigen in tissues. The severity of clinical disease was correlated with the extent of tissue alterations and the amount of immunohistologically detectable viral antigen. Both mild and virulent strains of rinderpest share essentially the same tissue tropisms in vivo, i.e. epithelio- and lympho-tropism. However, rinderpest virus isolates of higher pathogenicity showed a more rapid and wider distribution with more extensive lesions than milder strains, which probably accounts for the higher mortality.

Animals↗

PubMed1995

Studies of the detection of Listeria monocytogenes by culture and PCR in cerebrospinal fluid samples from ruminants with listeric encephalitis.

A total of 14 cerebrospinal fluid (CSF) samples from ruminants clinically suspected of suffering from listeric encephalitis were examined by polymerase chain reaction (PCR) for the detection of Listeria monocytogenes (L. m.). Of these samples, 11 were examined bacteriologically. Although the clinical diagnosis was confirmed in eight of 11 ruminants by histological and/or bacteriological examination of the brains, L. m. was only detected in one of the CSF samples using PCR, and in none by culture. The PCR-positive CSF sample was obtained from a sheep which had been treated with antibiotics prior to CSF sampling. From these findings, it was concluded that L. m. only occasionally gains access to the meningoventricular system in the course of listeric encephalitis of ruminants and that a reliable aetiological in vivo diagnosis of listeric encephalitis generally cannot be based on the detection of L. m. in the CSF of affected ruminants.

Animals↗

PubMed1995

Phenotypic variability in patients with generalised resistance to thyroid hormone.

Genetic linkage of generalised resistance to thyroid hormone (GRTH) to the human thyroid receptor beta 1 gene has been identified. To date 38 different mutations in several kindreds have been documented. We report on a family with GRTH displaying an adenine for guanine substitution at nucleotide 1234 resulting in a threonine for alanine substitution at codon 317 of exon 9. This mutation has been described for different phenotypes, suggesting that the heterogeneity in GRTH may be the result of multiple genetic factors.

Adult↗

PubMed1995

[The hemorrhagic form of acute bovine virus diarrhea: literature review and case report].

Infection of cattle with certain strains of BVD-virus causes a severe thrombocytopenia. The most obvious clinical and pathological lesions are multiple hemorrhages. Until now, problems with the Hemorrhagic syndrome have been reported predominantly from veal calf operations in the U.S.A. This publication presents first a literature review about the Hemorrhagic syndrome. The current data are based upon retrospective studies of field cases and experimental infections. Afterwards clinical, pathological and virological findings from three herds of veal calves in Germany are reported in which hemorrhagic diathesis was observed in calves and BVD-virus was isolated from tissues of diseased calves. The findings in these herds closely resemble the ones described in the literature for the Hemorrhagic syndrome. Therefore, infection with BVD-virus should be considered as differential diagnoses in Germany too, when hemorrhagic diathesis is observed in cattle.

Animals↗

PubMed1994

[The differentiation between premature thelarche and pubertas praecox on the basis of clinical, hormonal and radiological findings].

In a retrospective study of 39 girls (aged 10 months to 7 10/12 years) with premature breast development criteria for distinguishing between premature thelarche and precocious puberty were analysed. Serum estradiol levels and bone age were determined and a test with luteinizing hormone-releasing hormone (LHRH) performed (inclusion criteria). On the basis of the LHRH test and bone age, premature thelarche was diagnosed in 29 patients and precocious puberty in ten: while those with premature thelarche had a follicle-stimulating hormone (FSH) pattern of rise, in those with precocious puberty the rise in gonadotropin was of the LH type. The LH/FSH ratio 30 min after stimulation was < 1 (median 0.15 [0.03-0.34] in patients with premature thelarche, but > 1 (median 2.1 [1.34-5.67] in those with precocious puberty. Bone age was accelerated by at least 18 months in those with precocious puberty, but it corresponded to their chronological age or was only slightly accelerated in those with premature thelarche. These data thus indicate that premature thelarche and central precocious puberty can be reliably distinguished by the LHRH test and bone age.

Age Determination by Skeleton↗

PubMed1994

Bovine spongiform encephalopathy in Germany.

Bovine spongiform encephalopathy (BSE) has been described as an epidemic central nervous disorder in cattle from the United Kingdom. The disease is thought to have emerged by an interspecies transmission of the scrapie agent of sheep to cattle, after feeding scrapie-contaminated meat and bone meal (MBM). The disease has caused substantial economic losses for the British cattle industry. Because of strict veterinary regulations for the import of adult British cattle by the European Union and for MBM by most of the member states the spread of BSE to continental Europe could be efficiently controlled, and only few cases have been described outside the UK. Here we report the first German case of BSE diagnosed in a Scottish Highland cow. The affected cow was imported into Germany before the import ban for cattle from the UK was implemented. BSE was confirmed by histopathology, immunohistochemistry, animal experiments, immunoblotting and by electron microscopic detection of scrapie-associated fibrils (SAFs).

Animals↗

PubMed1994

[Bovine leukocyte adhesion deficiency: clinical picture and differential diagnosis].

The pathological clinical and laboratory findings obtained in 50 calves and young cattle affected with Bovine Leukocyte Adhesion Deficiency are compared with those found in 114 calves and young cattle showing marked neutrophil leukocytosis of other origin (age: < 2 years; leukocyte count: > 30,000 per microl; percentage of lymphocytes: < 55%).

Animals↗

PubMed1993

Distribution of cytopathogenic and noncytopathogenic bovine virus diarrhea virus in tissues from a calf with experimentally induced mucosal disease using antigenic and genetic markers.

A comparative analysis of the distribution of cytopathogenic (cp) and noncytopathogenic (ncp) bovine virus diarrhea disease (BVD) virus in tissues from a calf with experimentally induced mucosal disease was performed using immunohistology and polymerase chain reaction after reverse transcription (RT-PCR) of viral RNA. For immunohistology, an antigenic marker on the superinfecting cp BVD virus defined by a monoclonal antibody (mab) was used, and overall presence of antigen was assessed with a pestivirus specific mab. The primers selected for RT-PCR detected the genomic insertion in the p125 region of the superinfecting cp BVD virus. Both methods gave consistent results.

Animals↗

PubMed1993

Intestinal lesions in experimental phocine distemper: light microscopy, immunohistochemistry and electron microscopy.

The involvement of the intestinal mucosa and of the gut-associated lymphoid tissue in phocine distemper was studied in six severely diseased harbour seals 11 to 16 days after experimental infection. Five seals exhibited a mild or moderate enteritis in the small or large intestine. In all the seals, a moderate to severe depletion of submucosal lymphoid follicles was found. Likewise, antigen of phocine distemper virus (PDV) was demonstrated immunohistochemically in the intestinal wall of all the seals. Most antigen was found in the submucosal lymphoid follicles, followed by the crypt epithelium and follicle-associated epithelium (FAE). Ultrastructurally, intracytoplasmic tubular structures were detected in the FAE and interpreted as morbilliviral nucleocapsids. The results indicate a direct cytopathogenic effect of PDV on intestinal lymphoid and epithelial cells and suggest an important role of the intestinal tract in phocine distemper and, by analogy, in other morbillivirus infections as a regular site of virus replication, virus shedding and immunosuppression.

Animals↗

PubMed1993

Uterine and placental alterations in pregnant sows associated with the porcine epidemic abortion and respiratory syndrome (PEARS).

In the winter of 1990/91 a new, economically devastating disease occurred in european pig breeding herds, characterized by late-term abortion, stillbirth and a high morbidity and mortality of suckling piglets. Because of the clinical picture the disease was named porcine epidemic and respiratory syndrome (PEARS). In this study investigations were carried out in tissues of uterus and placentae of late gestational sows (107 to 112 days of gestation) in three different groups of animals: group I = control animals (n = 2) group II = naturally infected sows (n = 12) from farms, where PEARS recently had been introduced; group III = sows (n = 2), experimentally inoculated with placental homogenates from animals of group II. Both in naturally infected as well as in experimentally infected sows a multifocal, lymphohistiocytic vasculitis and perivascular cell infiltration was observed in the endometrium and maternal part of the placenta, but not in the fetal one. In the fetomaternal unit there were multifocal microseparations of the epithelial layers present. Transmission electron microscopically spherical or oval virus-like particles of 45 to 75 mm in diameter were frequently found on the surface of endothelial cells of blood vessels in the maternal placenta, in a few cases in the intercellular channel system between uterine epithelial cells or on endothelial cells of capillaries in the fetal placenta. Serological results indicate, that an infection with Lelystad virus had occurred in naturally and experimentally infected sows and that transplacental infection was present.

Abortion, Veterinary↗

PubMed1993

Prolonged persistence of cytopathogenic bovine viral diarrhea virus (BVDV) in a persistently viremic cattle.

A bull persistently viremic with noncytopathogenic (ncp) BVDV was inoculated with the cytopathic (cp) BVDV strain TGAC, which had been found to be antigenically different from the endogenous ncpBVDV (ncpW8). Neutralizing antibodies against strains NADL and TGAC were detectable 12 days and four weeks post infection, respectively. The animal developed fever and diarrhea 15 weeks post infection. On days 3 and 8 after onset of diarrhea a cpBVDV (cpX) was isolated from feces. Antigenic analysis using monoclonal antibodies (MoAbs) showed that cpX and the endogenous ncpBVDV (ncpW8) had identical reactivity patterns except for one epitope that was neither expressed on TGAC nor on ncpW8. Using polymerase chain reaction analysis it was shown that both TGAC and cpX contained a p8 phi gene duplication combined with genomic insertions of identical size. Restriction enzyme analysis of the TGAC and cpX amplicons using four enzymes showed an identical cleavage pattern, except for HaeIII digestion where an additional fragment was observed with cpX. These results suggest that cpBVDV strain TGAC persisted in the viremic animal and apparently caused disease after 15 weeks.

Animals↗