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Biomedical subjects

B Lorenz

Publications and source records attributed to B Lorenz.

At least 19 recordsLinked to original sources
PubMed2006

Genotype-phenotype correlation and longitudinal course in ten families with Best vitelliform macular dystrophy.

AIM: Longitudinal course and genotype-phenotype correlation in patients and carriers with heterozygous mutations in hBEST1 (bestrophin). METHODS: Thirteen patients and seven possible carriers were characterised by mutation analysis with SSCPA and direct sequencing, clinical examination and fundus autofluorescence (AF). Electrophysiology (EOG and mfERG) and optical coherence tomography (OCT) were additionally performed whenever possible. RESULTS: We identified seven different heterozygous mutations in ten unrelated families with Best disease. I296del was the most frequent mutation. Five of nine individuals with I295del and two of three with N99K were asymptomatic carriers. One patient with I295del mutation had funduscopically unilateral Best disease. In three children (all with I295del), EOG initially showed a clearly present light peak that deteriorated during 5 years of follow-up in two of them. Increased AF corresponded well to funduscopically visible lesions. During 3-6 years of follow-up, the lesion area did not change significantly, but there were obvious changes in the inner structure of the lesion. CONCLUSION: In the present series I295del, the most frequent mutation in our study, and N99K showed reduced penetrance. EOG was normal in young patients even if prime signs were visible. The lesion area did not depend on the mutation and did not correlate with VA. Lower VA was associated with a more irregular AF pattern due to scarring or haemorrhage. Our results indicate a disease causing effect that is cumulative over time.

Adolescent↗
PubMed2005

Novel cellular phenotypes and subcellular sites for androgen action in the forebrain.

Historically, morphological studies of the distribution of androgen receptors in the brain led to conclusions that the major regional targets of androgen action are involved in reproduction, that the primary cellular targets are neurons, and that functional androgen receptors are exclusively nuclear, consistent with the classical view of steroid receptors as ligand-dependent transcription factors. In this review, we discuss three separate but interrelated recent studies highlighting observations made with newer methodologies while assessing the regional, cellular or subcellular distribution of androgen receptors containing cells in the forebrain. Regional studies demonstrated that the largest forebrain target for androgen action in terms of the number of androgen receptor expressing cells is the cerebral cortex, rather than the main hypothalamic and limbic centers for reproductive function. Cellular studies to determine the phenotype of androgen receptor expressing cells confirmed that most of these cells are neurons but also revealed that small subpopulations are astrocytes. The expression of androgen receptors in astrocytes is both region and age dependent. In contrast, reactive astrocytes in the lesioned adult rat brain do not express androgen receptors whereas reactive microglia do. Finally, androgen receptor immunoreactive axons were identified in the cerebral cortex of the rat and human. These observations do not overturn classical views of the cellular and subcellular locus of steroid action in the nervous system, but rather broaden our view of the potential direct impact of gonadal steroid hormones on cellular function and emphasize the regional and developmental specificity of these effects on the nervous system.

Androgens↗
PubMed2005

[Best's disease. Overview of pathology and its causes].

Best's disease is a hereditary affection with reduced penetrance and juvenile onset. The fundus may be unremarkable or present various stages up to scarring of the macula. Histopathology of advanced stages discloses deposits of lipofuscin on Bruch's membrane, the innermost layer of which is the basal membrane of the retinal pigment epithelium (RPE). The deposits correlate with lipofuscin and melanofuscin granulae in the RPE. Photoreceptors correlating with the lesions have lost their outer segments and the RPE as well as the photoreceptors appear edematous. Loss of photoreceptor function does not necessarily follow progression of fundus appearance. Loss of function usually correlates with a reduced Arden ratio of the electro-oculogram even in the absence of funduscopic changes.Best's disease is caused by mutations in VMD2 (hBEST1). Bestrophin, the gene product of hBEST1, is a regulatory part of a Ca(2+) channel or a Ca(2+)-dependent Cl(-)channel. In this paper the relevant data on clinical and genetic pathology are summarized and evaluated.

Bestrophins↗
PubMed2004

Field-induced reentrant novel phase and a ferroelectric-magnetic order coupling in HoMnO3.

A reentrant novel phase is observed in the hexagonal ferroelectric HoMnO3 in the presence of magnetic fields in the temperature range defined by a plateau of the dielectric constant anomaly. The plateau evolves with fields from a narrow dielectric peak at the Mn-spin rotation transition at 32.8 K in zero field. The anomaly appears both as a function of temperature and as a function of magnetic field without detectable hysteresis. This is attributed to the indirect coupling between the ferroelectric (FE) and antiferromagnetic (AFM) orders, arising from an FE-AFM domain wall effect.

Journal Article↗
PubMed2004

[Clinical and molecular genetic findings in isolated sporadic Duane syndrome].

BACKGROUND: Duane retraction syndrome (DURS) accounts for 1 - 4 % of all cases of strabismus. Approximately 90 % of the cases are sporadic with a preponderance for females and the left eye. Many associated ocular and systemic findings have been described. Recently, mutations of SALL4 have been found in patients with autosomal-dominantly inherited Okihiro syndrome (DURS associated with forearm malformations). The aim of this study was the clinical examination of patients with isolated sporadic DURS and the molecular genetic analysis of SALL4 in these patients. SUBJECTS AND METHODS: Twenty-five patients with non-familial DURS (aged 1 - 75 years, 16 female, 9male) were examined clinically and were interviewed concerning associated pathologies. DNA was prepared from peripheral lymphocytes, and the complete coding region of SALL4 was sequenced. RESULTS: In 18 patients DURS affected the left eye, in four the right eye, and was bilateral in three patients. One patient had fused vertebrae, one had a cone-rod-dystrophy. No hearing impairments or malformation of the upper limbs were observed. No mutation in the coding region of SALL4 could be detected. DISCUSSION: Associated conditions in DURS patients most commonly involve the ear, the spinal column, the kidneys and the heart and the upper limbs. No mutations in SALL4 could be detected in patients with isolated sporadic DURS as opposed to findings in familial Okihiro syndrome. However, Okihiro syndrome shows marked intra- and interfamilial variability, suggesting that in rare cases of isolated DURS a causative SALL4 mutation may be found.

Duane Retraction Syndrome↗
PubMed2003

Causes of blindness at the "Wiyata Guna" School for the Blind, Indonesia.

AIM: To determine the anatomical site and patterns of cause of blindness in one of the biggest schools for the blind in Indonesia with a view to determining potentially preventable and treatable causes. METHODS: 165 students in one school for the blind in Bandung, Indonesia, were examined clinically and data reported using the WHO/PBL childhood blindness assessment form. RESULTS: Most of the students (96.4%) were blind (BL); 3% were severely visually impaired (SVI). The major causes of SVI/BL in this study were: (1) corneal staphyloma, corneal scar, and phthisis bulbi (mainly attributed to infection) in 29.7%; (2) retinal dystrophies (mainly Leber congenital amaurosis, early onset retinitis pigmentosa) in 20.6%; (3) congenital and familial cataract (13.3%); (4) microphthalmus, anophthalmus (10.9%). The whole globe was the major anatomical site of visual loss (32.7%), followed by the retina (26.0%), cornea (17.6%), lens (13.3%), optic nerve (6.1%), and uvea (4.3%). CONCLUSIONS: This is a small study in a selected population and the results should be interpreted with caution. This blind school study, adopting the WHO/PBL eye form for data analysing, is the first reported for Indonesia. Hereditary disease and infective causes of blindness are the predominant causes of blindness, accounting for 42.4% and 29.7%, respectively. This pattern of causes is a mixed pattern which lies in an intermediate position between the patterns seen in developing countries and those seen in developed countries. The importance both of preventive public health strategies and of specialist paediatric ophthalmic and optical services in the management of childhood blindness in Indonesia are therefore strongly suggested to cover the problems that exist.

Blindness↗
PubMed2002

[Results of surgical management of abducens paralysis].

BACKGROUND: The pre- and postsurgical results after mono- and bilateral transposition surgery for abducens nerve palsy are reported. PATIENTS AND METHODS: In 13 eyes from 11 patients with 6th nerve paralysis, transposition surgery modified after Kaufmann was performed after a median duration of 13 months (range 6-28 months). The actual angle of strabismus, the capability of abduction and the field of binocular single vision with the tangent screen according to Harms were measured prior to surgery, immediately after surgery (1-3 weeks) and in the later postsurgical period (9-12 months). RESULTS: Of the patients 7 achieved fusion with binocular single vision, 5 of these patients had to accept an ocular torticollis of 10 degrees (range 5-15 degrees) and 4 patients had a tendency to exclusion. Of the 11 patients, 9 were treated successfully with one single surgical procedure 2 of which had bilateral abducens nerve palsy and 2 patients needed 2 further operations. The median preoperative convergent angle in the primary position was reduced from 28 degrees (range 16 degrees-60 degrees) to a median angle of 0 degree, sometimes only latent (range D 7 degrees-C 4 degrees) in the late postoperative period. The median postoperative abduction over the midline was 10 degrees (range 3 degrees-25 degrees). CONCLUSIONS: Bilateral 6th nerve paralysis was treated effectively with simultaneous transposition surgery in both eyes. In most cases an additional weakening of the medial rectus muscle was not necessary. An initial overcorrection with exotropia in the early postoperative period is desired and is a predictive factor for a good late postoperative result.

Abducens Nerve Diseases↗
PubMed2002

Atypical expression of cleidocranial dysplasia: clinical and molecular-genetic analysis.

Cleidocranial dysplasia (CCD) and the Rubinstein-Taybi syndrome (RTS) are two rare congenital syndromes that have many clinical signs in common. We present an 18-year-old-patient with untypical CCD expression who was misdiagnosed with RTS at the age of 2 years. An extensive craniofacial examination was carried out with respect to morphological and dental aspects. The molecular-genetic analysis of two underlying genes (CBFA1 and CBP) for CCD and RTS was performed using SSCP, direct sequencing and FISH. While the clinical examination showed uncharacteristic CCD symptoms with some findings common for RTS, the molecular-genetic analysis revealed a missense mutation in the CBFA1 gene, which is considered to be the etiological factor for CCD. Our findings with this patient presented clear evidence for the wide morphologic variety that can be related to a certain gene such as CBFA1. The diagnosis of rare diseases is currently based on the clinical phenomenology of small groups or single cases. The use of molecular-genetic biology extends the horizon of diagnostic and scientific possibilities. In this patient, it allowed us to compare the clinically diagnosis to molecular-genetic data. We conclude that molecular-genetic analysis may be a helpful tool in the differential diagnosis of many congenital diseases such as CCD and RTS.

Adolescent↗
PubMed2002

A randomized, controlled study of the safety and efficacy of topical corticosteroid treatments of sunburn in healthy volunteers.

Topical glucocorticosteroids are frequently used for the treatment of sunburn despite the scarcity of randomized, double-blind controlled trials to support this indication. This randomized, intra-individually controlled trial compared the efficacy and safety of two topical glucocorticosteroids, 0.1% methylprednisolone aceponate milk (MPA) and 0.1% hydrocortisone 17-butyrate emulsion (HCB), for treatment of sunburn in 24 healthy volunteers of skin type III. After irradiation of the skin by simulated sunlight, treatments were blinded and randomly allocated to 36 cm2 test areas on both sides of the spine. Volunteers were treated twice daily for 7 days and assessed daily with 1-day follow-up. The untreated area was not blinded. Primary efficacy measures were sum score and sunburn reaction based on erythema, oedema, burning and itching. Secondary efficacy measures were physician's global assessment, individual signs/symptoms, colorimetry, dermatological improvement, and time to healing. Intra-individual comparisons were made. Differences in sum score were apparent on days 3-4 and significant on days 4-5 for corticosteroids compared with nontreatment. Treated areas had significantly lower sunburn reaction than untreated areas (P = 0.1% and P = 0.5% for MPA and HCB, respectively). Differences between treatments were not significant. Secondary efficacy measures were in line with these findings. None of the three adverse events reported were considered to be related to treatment. We conclude that MPA and HCB are safe and effective in the treatment of sunburn.

Administration, Topical↗
PubMed2002

[Interdisciplinary endoscopic outpatient management of connatal dacryocystoceles].

Dacryocystocele may represent a rare type of connatal stenosis of the lacrimal duct. If conservative measures fail and in case of secondary inflammation, probing or regular surgery is usually recommended. We report on 15 neonates suffering from 18 connatal dacryocystoceles which were presented to the clinic of ophthalmology at the 16th (6 - 44) day of life. There was a definite female preponderance (65 %). Conservative treatment (external massage, at times i. v. antibiotic therapy) had proven to be ineffective. The neonates were subjected to outpatient nasal endoscopy and the ballooning cyst of the inferior nasal meatus was managed by endoscopic marsupialization in 14 cases applying local anesthesia. Two nasal cysts had to be operated on in general anesthesia due to obstructing local anatomy which obviated endoscopical microsurgery. Three additional dacryocystoceles have been detected incidentally in 2 neonates being subjected to surgery in general anesthesia for choanal atresia and lacrimal probing respectively. The corresponding dacryocystoceles were managed by concomitant endonasal microsurgery. We advocate interdisciplinary (ophthalmological and rhinological) outpatient examination in all neonates with suspected dacryocystoceles. Diagnosis is based on palpation, probing and nasal endoscopy applying local anesthesia together with mucosal decongestion. Microsurgical marsupialization immediately follows and will lead to persisting relief of symptoms.

Ambulatory Surgical Procedures↗
PubMed2001

Mutation spectrum and splicing variants in the OPA1 gene.

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy that features low visual acuity leading in many cases to legal blindness. We have recently shown, with others, that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein, underlie the dominant form of optic atrophy. Here we report that OPA1 has eight mRNA isoforms as a result of the alternative splicing of exon 4 and two novel exons named 4b and 5b. In addition, we screened a cohort of 19 unrelated patients with dominant optic atrophy by direct sequencing of the 30 OPA1 exons (including exons 4b and 5b) and found mutations in 17 (89%) of them of which 8 were novel. A majority of these mutations were truncative (65%) and located in exons 8 to 28, but a number of them were amino acid changes predominantly found in the GTPase domain (exons 8 to 15). We hypothesize that at least two modifications of OPA1 may lead to dominant optic atrophy, that is alteration in GTPase activity and loss of the last seven C-terminal amino acids that putatively interact with other proteins.

Alternative Splicing↗
PubMed2001

CNGA3 mutations in hereditary cone photoreceptor disorders.

We recently showed that mutations in the CNGA3 gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.

Amino Acid Sequence↗
PubMed2001

Mammalian intestinal alkaline phosphatase acts as highly active exopolyphosphatase.

Recent results revealed that inorganic polyphosphates (polyP), being energy-rich linear polymers of orthophosphate residues known from bacteria and yeast, also exist in higher eukaryotes. However, the enzymatic basis of their metabolism especially in mammalian cells is still uncertain. Here we demonstrate for the first time that alkaline phosphatase from calf intestine (CIAP) is able to cleave polyP molecules up to a chain length of about 800. The enzyme acts as an exopolyphosphatase degrading polyP in a processive manner. The pH optimum is in the alkaline range. Divalent cations are not required for catalytic activity but inhibit the degradation of polyP. The rate of hydrolysis of short-chain polyP by CIAP is comparable to that of the standard alkaline phosphatase (AP) substrate p-nitrophenyl phosphate. The specific activity of the enzyme decreases with increasing chain length of the polymer both in the alkaline and in the neutral pH range. The K(m) of the enzyme also decreases with increasing chain length. The mammalian tissue non-specific isoform of AP was not able to hydrolyze polyP under the conditions applied while the placental-type AP and the bacterial (Escherichia coli) AP displayed polyP-degrading activity.

Acid Anhydride Hydrolases↗
PubMed2001

Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America.

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.

Albinism, Ocular↗