Characteristic clinical features of idiopathic neuralgic amyotrophy in childhood.
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Adenovirus Infections, Human↗
Biomedical subjects
J Gärtner
Publications and source records attributed to J Gärtner.
Retrobulbar abscess in a neonate.
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Abscess↗
Genomic organization and characterization of human PEX2 encoding a 35-kDa peroxisomal membrane protein.
Peroxins are proteins involved in peroxisome biogenesis and are encoded by PEX genes. The human PEX2 gene encodes a 35-kDa peroxisomal integral membrane protein which is a member of the zinc finger protein family. Mutations in the PEX2 gene are the primary defect in a subset of patients with Zellweger syndrome and related peroxisome biogenesis disorders. The role of zinc finger proteins in peroxisome assembly and function is poorly understood. Here we report the cloning and characterisation of the human PEX2 structural gene. PEX2 was assigned to human chromosome 8q13-q21 and its murine homologue to mouse chromosome 3. The gene is approximately 17.5 kb in length, and contains four exons. The entire coding sequence is included in one exon, exon 4. The 5'-flanking region has features of housekeeping genes (GC enrichment, two Sp1 sites) and tissue-specific, inducible genes (two CCAAT boxes). In more than 1.5 kb of 5'-flanking sequences we did not identify consensus peroxisomal proliferator responsive elements (PPRE).
Animals↗
The human PEX3 gene encoding a peroxisomal assembly protein: genomic organization, positional mapping, and mutation analysis in candidate phenotypes.
In yeasts, the peroxin Pex3p was identified as a peroxisomal integral membrane protein that presumably plays a role in the early steps of peroxisomal assembly. In humans, defects of peroxins cause peroxisomal biogenesis disorders such as Zellweger syndrome. We previously reported data on the human PEX3 cDNA and its protein, which in addition to the peroxisomal targeting sequence contains a putative endoplasmic reticulum targeting signal. Here we report the genomic organization, sequencing of the putative promoter region, chromosomal localization, and physical mapping of the human PEX3 gene. The gene is composed of 12 exons and 11 introns spanning a region of approximately 40 kb. The highly conserved putative promoter region is very GC rich, lacks typical TATA and CCAAT boxes, and contains potential Sp1, AP1, and AP2 binding sites. The gene was localized to chromosome 6q23-24 and D6S279 was identified to be the closest positional marker. As yeast mutants deficient in PEX3 have been shown to lack peroxisomes as well as any peroxisomal remnant structures, human PEX3 is a candidate gene for peroxisomal assembly disorders. Mutation analysis of the human PEX3 gene was therefore performed in fibroblasts from patients suffering from peroxisome biogenesis disorders. Complementation groups 1, 4, 7, 8, and 9 according to the numbering system of Kennedy Krieger Institute were analyzed but no difference to the wild-type sequence was detected. PEX3 mutations were therefore excluded as the molecular basis of the peroxisomal defect in these complementation groups.
ATP-Binding Cassette Transporters↗
Organelle disease: peroxisomal disorders.
UNLABELLED: Peroxisomes are virtually ubiquitous organelles involved in numerous catabolic and anabolic pathways. Interest in peroxisomes stems from an expanding group of genetic diseases in which there is either deficiency of a specific peroxisomal function (single protein defects) or failure to assemble the organelle resulting in defects of multiple peroxisome functions (peroxisome biogenesis disorders). The paradigm for the former is X-linked adrenoleukodystrophy caused by mutations in the adrenoleukodystrophy gene and, for the latter, Zellweger syndrome caused by mutations in peroxin genes. CONCLUSION: The identification and functional characterisation of the peroxisomal disease genes is proceeding at rapid pace helped immeasurably by work in various yeast model systems. The ultimate goal is to elucidate how the encoded proteins produce normal appearing and functioning peroxisomes. The achievement of this goal will lead to a better understanding of peroxisomal disorders, their pathogenesis and treatment.
Adrenoleukodystrophy↗
Disorders related to peroxisomal membranes.
The peroxisome is a ubiquitous, subcellular organelle participating in a diverse array of metabolic pathways. The peroxisomal membrane and its components play a key role in organelle assembly and functions. Disorders related to peroxisomal membranes are the peroxisome biogenesis disorders and X-linked adrenoleukodystrophy. Identification and functional characterization of these disease genes is proceeding at rapid pace helped immeasurably by work in various yeast model systems. The ultimate goal is to elucidate how the encoded proteins interact to produce apparently normal and functioning peroxisomes. The achievement of this goal will lead to a better understanding of disease pathogenesis and hopefully open therapeutic options.
Adrenoleukodystrophy↗
Multiple symmetric lipomatosis: an unusual cause of childhood obesity and mental retardation.
Multiple symmetric lipomatosis (MSL), also known as Launois-Bensaude syndrome or Madelung's disease, is a rare disorder predominantly seen in middle-aged male patients. The disorder is characterized by large subcutaneous fat masses distributed around the neck, shoulders, and other parts of the trunk, often associated with nervous system abnormalities. A close relationship to alcoholism, metabolic disturbances and malignant tumours has been observed. Until now, MSL has only been described in adults. We report on the first two children, a 9-year-old girl and a 13-year-old boy, with the characteristic clinical findings of MSL. The girl presented with severe obesity, developmental delay, mild mental retardation, peripheral neuropathy, and latent hypothyroidism. In addition, she had elevated lactate concentrations in blood and cerebral spinal fluid suggesting mitochondrial dysfunction. Biochemical analyses of muscle showed a respiratory chain complex II deficiency. The boy suffered from severe obesity, mild mental retardation and insulin resistant diabetes mellitus. In both children, analyses of the mitochondrial genome did not reveal major deletions nor the MERRF 8344 point mutation. MSL seems to be a new neurometabolic disorder with heterogeneous clinical expression whose pathogenesis is still unknown.
Adolescent↗
Hugo Wolfgang Moser--an excellent "science dealer".
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Adrenoleukodystrophy↗
Mutations in PEX1 in peroxisome biogenesis disorders: G843D and a mild clinical phenotype.
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ATPases Associated with Diverse Cellular Activitie↗
Outpatient coronary angiography with 4 French catheters.
The early 4 French (Fr), pre-formed, Judkins coronary catheters had unsatisfactory maneuverability due to reduced torque stability. Technical innovations have led to improved 4 Fr catheters. This prospective study evaluates the safety and feasibility of the 4 Fr Quick Care Infinity catheter (Cordis, Miami, Florida). Within a series of 2,366 patients investigated for suspected coronary artery disease, 302 were selected for outpatient treatment according to the guidelines for outpatient catheterization. Fluoroscopy time was 2.8 +/- 2.5 minutes. It was not necessary to change to larger catheters in any patient. After sheath removal, hemostasis was achieved within 14 +/- 8 minutes. Strict bed rest lasted 181 +/- 65 minutes; patients were discharged 303 +/- 76 minutes after arterial puncture. Sixteen of the 302 patients (5.3%; 95% confidence interval (CI): 3.1-7.9%) changed to inpatient treatment for reasons unrelated to the arterial access. Eight patients (2.6%; CI: 1.1-5.1%) required one night of hospitalization for control of hematoma. The following morning, vessel murmur, pain, and large hematoma (more than 10 cm diameter) occurred in 1 (0.3%), 6 (2.0%), and 6 (2.0%) patients, respectively. This necessitated hospital admission in 2 patients (0.7%; CI: 0.0-2.3%) for up to 2 days. Major entry site complications requiring blood transfusion or surgery did not occur (CI: 0.0-0.3%). It was concluded that outpatient catheterization for coronary artery disease using the new 4 French catheters is feasible and can be rapidly and safely performed in a selected patient population.
Adult↗
Megalencephaly, mega corpus callosum, and complete lack of motor development: a previously undescribed syndrome.
We report on 3 sporadic cases of in utero onset megalencephaly. Children were born to healthy nonconsanguineous parents after uneventful pregnancies. Head circumferences were just above the 97th centile at birth in 2 patients, 2 cm above the 97th centile in 1 patient, and subsequently increased to 4.5-6.5 cm above the 97th centile at age 5 years. All patients completely lacked motor and speech development and showed very little intellectual progress. There was a distinctive facial aspect with frontal bossing, low nose bridge, and large eyes, but no cutaneous abnormalities and no signs of other organ involvement. Magnetic resonance imaging showed bilateral megalencephaly with a broad corpus callosum, enlarged white matter, and focally thick gray matter, resulting in pachygyric appearance of the cortex. Opercularization was incomplete, and the Sylvian fissures were wide. Somatosensory evoked potentials in 1 patient showed normal latencies of cervical and contracortical potentials but bilaterally increased cortical amplitudes. To the best of our knowledge, no similar case observations have been recorded previously.
Agenesis of Corpus Callosum↗
Genomic organization of the 70-kDa peroxisomal membrane protein gene (PXMP1).
The 70-kDa peroxisomal membrane protein (PMP70) is a member of a family of half-ATP-binding cassette (ABC) transporter proteins located in the human peroxisomal membrane. Other members include the PMP70-related peroxisomal membrane protein, the adrenoleukodystrophy protein (ALDP), and the adrenoleukodystrophy-related protein. The functions of ABC transporters in the peroxisomal membrane are poorly understood. Evidence from yeast and human mutants suggests that they are involved in the peroxisomal import of fatty acids and/or fatty acyl-CoAs into the organelle. We report the cloning and characterization of the human PMP70 structural gene (gene symbol: PXMP1) localized on human chromosome 1p21-p22. PXMP1 is approximately 65 kb in length, contains 23 exons, and is quite different in structure from the gene (ALD) that encodes the related protein, ALDP. We also analyzed the 5' flanking region of the human PXMP1 gene and the corresponding region of murine Pxmp-1. Both promoters have features of housekeeping genes, including a high GC content and multiple consensus Sp1 binding sequences. In more than 3 kb of Pxmp-1 5' flanking sequence we did not identify a consensus peroxisomal proliferator responsive element.
ATP-Binding Cassette Transporters↗
Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70.
The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa peroxisomal integral membrane protein. In humans, PEX2 mutations are responsible for complementation group 10 of the human peroxisome biogenesis disorders (PBD), a genetically heterogeneous group of lethal, autosomal recessive diseases including the Zellweger syndrome and related phenotypes. To develop additional cellular models for Zellweger syndrome, we produced a series of new mutant CHO cell clones in the same complementation group as Z78/C (Z2, Z7, Z22, and Z105). As expected, expression of human PEX2 restores peroxisomal biogenesis in all of these clones. Surprisingly, expression of the human 70 kDa peroxisomal membrane protein (PMP70) also restores peroxisome biogenesis in these same CHO cell clones. We confirmed this effect of PMP70 expression on peroxisome biogenesis by determining the subcellular latency of catalase, the immunohistochemical localization of catalase and the beta-oxidation of very long chain fatty acids (VLCFA). By contrast, expression of a mutant allele of PMP70 identified in a patient with Zellweger syndrome did not restore peroxisome biogenesis in the PEX2-deficient CHO cell clones. Our results indicate that overexpression of PMP70 suppresses the phenotype of PEX2 gene mutations. These observations suggest a functional interaction between PEX2 and PMP70 in the peroxisome membrane.
ATP-Binding Cassette Transporters↗
Clinical and genetic aspects of X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (ALD), a leukodystrophy characterized by abnormal accumulation of saturated very long chain fatty acids in brain white matter and adrenal cortex, is the most common inherited peroxisomal disorder. The biochemical defect is localized to the level of lignoceroyl-CoA synthesis, a step in the peroxisomal beta-oxidation of very long chain fatty acids. The responsible gene encodes a peroxisomal integral membrane protein of as yet unknown function which is a member of the ATP-binding cassette transporter protein superfamily. The patient gene mutations are heterogeneously distributed over the functional protein domains with a tendency to clustering in the nucleotide-binding fold. The mechanisms by which these mutations cause a loss of protein function is unknown. Diagnosis of patients and carriers, including prenatal testing, is mainly based on the clinical picture, the demonstration of increased levels of saturated very long chain fatty acids in tissues and body fluids as well as on DNA mutation analyses. There are at least six distinct clinical phenotypes ranging from the severe childhood cerebral form to asymptomatic persons. The various phenotypes commonly occur within the same kindred. Modifying genes and/or environmental factors may contribute to this phenomenon. At present, there is no proven therapy for the prevention or cure of the neurological disabilities. Several approaches are under investigation including diets, immunosuppression, bone marrow transplantation and gene therapy.
Adolescent↗
Paraneoplastic limbic encephalitis in two teenage girls.
Paraneoplastic neurological disorders represent remote effects of cancer without invasion of tumor cells into the nervous system. Limbic encephalitis is a distinct entity mostly associated with small-cell carcinoma of the lung. We present the cases of two teenage girls who were admitted with clinical symptoms typical for limbic encephalitis. In the course of the disease, they exhibited characteristic evolutionary changes of brain MRI abnormalities. Onset of neurological symptoms and type of underlying neoplasia were different in both patients. In one girl the initial workup led to the diagnosis of nodular sclerosing Hodgkin disease which so far had not caused any symptoms besides the described neurological abnormalities. A diagnostic brain biopsy showed inflammatory changes and excluded invasion of malignant cells into the central nervous system. The other patient had been diagnosed with a small cell carcinoma of the ovary several months before neurological and brain MRI abnormalities were observed. This is the first report in which clinical picture, evolution of MRI abnormalities, and--in one case--characteristic neuropathological changes are suggestive of paraneoplastic limbic encephalitis in two adolescent girls.
Adolescent↗
A new leukoencephalopathy with bilateral anterior temporal lobe cysts.
We describe an identical syndrome of cystic leukoencephalopathy in three Turkish children, including two siblings. The neurological findings were noted within the first months of life and include severe intellectual impairment, motor retardation, and spasticity. Magnetic resonance imaging of the brain showed extensive cysts within the anterior temporal lobes, ventricular enlargement and white matter disease. The signal intensities of the cysts' content were identical to those of the cerebrospinal fluid. The patients' screening for known inborn errors of metabolism, especially those characterised by white matter involvement, did not reveal any abnormality. The clinical picture and the magnetic resonance imaging characteristics are unique diagnostic features of a new disease entity so far not described in the literature.
Child↗
[Is the implantation of a second intraocular lens prior to the removal of the first implants remaining in the vitreous cavity incorrect medical treatment?].
BACKGROUND: The implantation of an intraocular lens into the capsular bag is a common procedure in modern cataract surgery. In case of a break of the posterior capsule it is possible to implant the intraocular lens by rhexis-, ciliary sulcus- or pars-plana-fixation. The following case is in so far remarkable, as a second intraocular lens has been implanted while a dislocated intraocular lens was still in the vitreous cavity. PATIENT: We report on a 70-year-old patient who underwent cataract surgery. After a break in the posterior capsule the intraocular lens dislocated into the vitreous cavity. A second intraocular lens has been implanted in the ciliary sulcus. 41 days after cataract surgery the dislocated intraocular lens has been removed by pars-plana-vitrectomy without any problems. CONCLUSION: Intraocular lens implantation in the ciliary sulcus is not proved to be a hindrance with regard to the transcleral removal of a posteriorly dislocated intraocular lens, following the principles of intraocular foreign body surgery.
Aged↗
The significance of rota representation in the design of rotas.
Shift scheduling is based on some representation of shift schedules. The number of different representations currently used is high, and one might expect small practical differences between these representations. However, an analysis of several prominent representations revealed strong differences regarding possible outcomes of the scheduling process and the effort needed for their assessment. Limitations of some representations do not only concern specific rota design issues, such as different staffing levels or different workhours, but also rather simple and straightforward rotas. Furthermore, there is no single representation that is strictly and unequivocally better than the others. Most representations simplify the development of some rotas, while they make it very difficult or even impossible to develop others. Therefore, both designers and the computer systems used for design should use and support several representations and therefore allow smooth transitions between them. In addition knowledge about rota construction techniques should be maintained, as it may ease assessment dramatically.
Computer Simulation↗