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B Korf

Publications and source records attributed to B Korf.

35 records · Page 2Linked to original sources
PubMed1992

Immunocytochemical demonstration of interphotoreceptor retinoid-binding protein in cerebellar medulloblastoma.

Previously, immunoreactive rod-opsin and S-antigen (arrestin), two highly characteristic markers of retinal photoreceptors and pinealocytes, were shown to be present in certain medulloblastoma cells. It, thus, has been suggested that such cells differentiate along the photoreceptor lineage. This is corroborated in the present immunocytochemical investigation using antibodies against another photoreceptor-cell marker, the interphotoreceptor retinoid-binding protein (IRBP). As shown in preparations of human retina and pineal organ, IRBP can be successfully demonstrated in formalin-fixed and paraffin-embedded tissue: the IRBP immunoreaction is located to the outer and inner segments of retinal photoreceptor cells and to perikarya of certain pinealocytes. Examination of formalin-fixed, paraffin-embedded biopsy specimens of 66 cerebellar medullo-blastomas revealed varying numbers of IRBP-immuno-reactive tumor cells in 19 cases that were formerly shown to contain rod-opsin and S-antigen immunoreaction. IRBP-immunoreactive tumor cells were also found in a retinoblastoma and a pineocytoma, but not in neuroblastoma, ganglioneuroblastoma, glioblastoma, oligodendroglioma and astrocytoma. The results indicate: (1) cerebellar medulloblastomas are heterogeneous in their differentiation potential; (2) one type of medulloblastoma displays photoreceptor characteristics; (3) this type appears to be closely related to retinoblastoma and pineal cell tumors; and (4) all three types of tumors may display additional common features to be explored in future studies.

Antigens↗
PubMed1992

A syndrome of autosomal dominant alternating hemiplegia: clinical presentation mimicking intractable epilepsy; chromosomal studies; and physiologic investigations.

We report the familial occurrence and apparent autosomal dominant inheritance of alternating hemiplegia of childhood. The proband, a 9-year-old boy, presented with developmental retardation, rare tonic-clonic seizures, and frequent episodes of flaccid alternating hemiplegia that had been presumed to represent postictal paralysis. The hemiplegia spells, which started in his first year, did not respond to multiple antiepileptics. Between attacks, there was choreoathetosis and dystonic posturing. Father, brother, paternal uncle, and paternal grandmother had similar histories of alternating hemiplegia. Investigations included negative CT, metabolic, and coagulation studies. EEG and SPECT 99mTc exametazime scanning failed to reveal any significant slowing or any major changes in cortical perfusion during hemiplegia as compared with nonhemiplegic periods. The karyotype revealed a balanced reciprocal translocation, 46,XY,t(3;9)(p26;q34) in the patient, in all the affected living relatives, and in one apparently unaffected sibling. The asymptomatic mother had a normal karyotype. Analysis of DNA markers was consistent with the karyotype results. Both affected siblings were treated with and responded to flunarizine therapy, with a greater than 70% decrease in attack frequency. Documented flunarizine trough serum concentrations were 28.9 ng/ml in the proband and 6.6 ng/ml in his brother.

Adult↗
PubMed1991

Stage IV neuroblastoma in infants. Long-term survival.

Before the advent of multiagent chemotherapy, the prognosis for patients with Stage IV neuroblastoma of all ages was dismal. More recently, marked improvement in infants with Stage IV neuroblastoma has been reported. Twenty-four infants with Stage IV neuroblastoma have been treated at the Dana-Farber Cancer Institute/The Children's Hospital, and the Joint Center For Radiation Therapy, Boston, Massachusetts, between 1970 and 1988. Twenty-three of these patients were treated with multiagent chemotherapy and one with a single drug. In the initial report, ten of 11 patients were alive without evidence of disease after intensive therapy. In this report the authors update their initial series of patients and include 13 additional patients who subsequently presented to our institutions with Stage IV neuroblastoma younger than 1 year of age. The 5-year actuarial event-free survival for the 24 patients is 75%. No patient without bone metastases died from neuroblastoma, and 12 of 16 patients with bone metastases remained disease free. These results confirm that infants with Stage IV neuroblastoma have a very good prognosis when treated with intensive multiagent chemotherapy.

Adrenal Gland Neoplasms↗
PubMed1991

Consistent cytogenetic aberrations in hepatoblastoma: a common pathway of genetic alterations in embryonal liver and skeletal muscle malignancies?

Cytogenetic analyses of four consecutive hepatoblastomas revealed near-diploid stemline karyotypes with relatively simple chromosome aberrations. Cytogenetic abnormalities shared by each tumor included trisomy for all of part of chromosome 2 and trisomy for chromosome 20. In two cases, partial trisomy for chromosome 2 resulted from direct duplication of long arm material with the shortest region of overlap being 2q23-2q35. In one tumor, each metaphase also contained a variable number of double minute chromosomes found not to derive from NMYC amplification. Interestingly, trisomy for 2q and trisomy 20 are also characteristic events in pediatric embryonal rhabdomyosarcomas. Furthermore, others have reported loss of heterozygosity for the short arm of chromosome 11 in both hepatoblastoma and childhood embryonal rhabdomyosarcoma, and both these malignant diseases are associated with Beckwith-Wiedemann syndrome. These cytogenetic and molecular findings suggest a parallel pathway of genetic steps in the initiation and/or progression of tumors of embryonal liver and skeletal muscle.

Carcinoma, Hepatocellular↗
PubMed1990

Genetic linkage of the human apolipoprotein AI-CIII-AIV gene cluster and the neural cell adhesion molecule (NCAM) gene.

The genes encoding apolipoproteins AI, CIII, and AIV, three plasma proteins involved in lipid metabolism, are clustered within a 15-kb DNA segment (apoAI-CIII-AIV gene cluster) located on human chromosome 11 at band q23. The gene encoding the neural cell adhesion molecule (NCAM), a cell surface glycoprotein involved in cell-cell recognition during morphogenesis, is also located on chromosome 11, band q23. In this report, 12 previously described restriction fragment length polymorphisms (RFLPs) in the apoAI-CIII-AIV gene cluster were tested for cosegregation with a newly identified BamHI RFLP in the NCAM gene using 13 families. The results show that the apoAI-CIII-AIV gene cluster and the NCAM gene loci are linked with a maximum lod score of 15.9 at a recombination fraction of 0.028. In addition, an approach for the most efficient use of the apoAI-CIII-AIV gene cluster polymorphisms, based on the evaluation of their individual and cumulative heterozygosities, is presented.

Apolipoprotein A-I↗
PubMed1990

Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2-13.3 (SMA 5q).

We made phenotypic analysis of 14 families with spinal muscular atrophy (SMA) linking to chromosome 5q11.2-13.3 (SMA 5q), and 2 that may not map to this locus, to assess clinical symptoms among SMA families known to result from mutation at the identical gene/locus. Although the current number of families is still small, the correlation of clinical phenotype and molecular genotype supports 2 observations. First, SMA mutations at the 5q locus present with a broad continuum of clinical abnormalities, and 2nd, the single clearly unlinked family presents with an unusual phenotype characterized by relatively late onset and early death. Thus, there are as yet no unambiguous cases of typical SMA families that are clearly unlinked to the locus at 5q-ie, no clear cases of nonallelic heterogeneity. Analysis of SMA 5q families supports the view that, with certain exceptions, there is little phenotypic intrafamilial variability. When families were ranked by severity of disease there was a strong correlation with age of onset. Onset within the 1st few months was associated with early death, but not in all cases. With rare exception, onset after 1 year of age was associated with less severe disease and greater longevity.

Chromosome Mapping↗
PubMed1989

Ontogenetic development of S-antigen- and rod-opsin immunoreactions in retinal and pineal photoreceptors of Xenopus laevis in relation to the onset of melatonin-dependent color-change mechanisms.

In Xenopus laevis Daud., the ontogenetic occurrence of two photoreceptor-specific proteins, S-antigen and rod-opsin, was investigated and correlated to the maturation of the neurohormonal effector system involved in melatonin-dependent color-change mechanisms. Tadpoles ranging from stage 12 to 57 (Nieuwkoop and Faber 1956) were fixed in Zamboni's or Bouin's solution. Frozen or paraffin sections of either total heads or dissected brains and eyes were prepared and treated with highly specific antisera against S-antigen and rod-opsin. In the retina, immunoreactive S-antigen and rod-opsin were first demonstrated in a few centrally located photoreceptors at stage 37/38. Photoreceptors of the peripheral (iridical) portions of the retina gradually became immunoreactive during further development. As in the retina, the first S-antigen-immunoreactive photoreceptors in the pineal complex appeared at stage 37/38. At this and all later stages investigated rod-opsin immunoreactivity was restricted to a few dot-like structures resembling developing pineal outer and inner segments. In most animals rod-opsin immunoreactivity was completely absent from the pineal complex. The analysis of retinal proteins with the immunoblotting technique (Western blot) revealed that the S-antigen antibody bound to a 48-kDa protein and the rod-opsin antibody to a 38-kDa protein. The body lightening reaction was determined with the aid of the melanophore index in larvae fixed in light or darkness, respectively. Aggregation of melanophore melanosomes in darkness (the melatonin-dependent primary chromatic response) first occurred at stage 37/38 when melanophores started to differentiate and became pigmented. These results indicate that in Xenopus laevis (i) the molecular mechanisms of photoreception develop simultaneously in retina and pineal complex; (ii) most pineal photoreceptors differ from retinal rods in that they contain immunoreactive S-antigen but essentially no immunoreactive rod-opsin; and (iii) the differentiation of phototransduction processes coincides with the onset of melatonin-dependent photoneuroendocrine regulation of color-change mechanisms.

Animals↗
PubMed1987

Rapid cloning of multiple amplified nucleotide sequences from human neuroblastoma cell lines by phenol emulsion competitive DNA reassociation.

A protocol for the rapid cloning of many DNA fragments from an amplified genomic region is described. The procedure is based on a modification of the phenol-emulsion reassociation technique (PERT) previously used to clone DNA fragments missing from a chromosomal deletion [Kunkel et al., Proc. Natl. Acad. Sci. USA 82 (1985) 4778-4782]. The procedure was used to construct recombinant libraries in the plasmid pBR322 which were highly enriched for amplified sequences from two neuroblastoma cell lines, CHP-126 and IMR-32. Many new amplified DNA fragments were isolated from these libraries, indicating that the PERT methodology should be of general use in isolating amplified DNA from other cell lines and tumors.

Base Sequence↗
PubMed1986

Bilateral lucency of the globus pallidus complicating methylmalonic acidemia.

A child was seen because of encephalopathy and metabolic ketoacidosis at 19 months. She was found to have a cobalamin-responsive form of methylmalonic acidemia of the cbl A complementation group. However, after treatment with cyanocobalamin and a protein-restricted diet, with recovery from the encephalopathy, she was found to have a tremor and bilateral dystonic posturing in association with lucencies in the globus pallidi shown by computed tomographic scan.

Brain Diseases↗
PubMed1986

Amplification and rearrangement of DNA sequences from the chromosomal region 2p24 in human neuroblastomas.

Seven DNA fragments which map to or very near human chromosome band 2p24 are shown to be differentially amplified in DNA from specific subsets of an enlarged series of human neuroblastoma cell lines and primary neuroblastomas. Of these DNA fragments, the probe NB-19-21 for the oncogene N-myc is the most frequently amplified, with a second expressed sequence (pG21) amplified in 9 of those 11 cell lines and 16 of those 25 tumors exhibiting amplification of N-myc. The remaining probes are in turn each amplified in progressively smaller, nested subsets of the cell lines and tumors in which both N-myc and pG21 are amplified. These data permit construction of models for the organization of a "neuroblastoma amplicon," i.e., an originally amplified DNA domain, with N-myc positioned most central and the other DNA fragments increasingly peripheral; comparable models result for the cell lines and the tumors. Five of the seven probes examined detect novel DNA fragments in these specimens, reinforcing previous observations that extensive DNA rearrangement can occur during DNA amplification in neuroblastoma cell lines and in primary neuroblastomas. Such rearrangements could contribute significantly to the evolution of the neuroblastoma amplicon in different specimens to progressively smaller units, preserving, in the limit, amplification of N-myc.

Base Sequence↗
PubMed1985

Differential amplification, assembly, and relocation of multiple DNA sequences in human neuroblastomas and neuroblastoma cell lines.

DNA amplification, manifested by homogeneously staining regions in chromosomes and by extrachromosomal, double minute bodies, is characteristic of many neuroblastoma cell lines. Sequences recruited from a specific domain on the short arm of chromosome 2 (2p) are amplified in advanced-stage primary neuroblastomas, whereas sequences from distinctly different regions of 2p are amplified in the neuroblastoma cell line IMR-32. Five different DNA segments, which include the oncogene N-myc, three other fragments derived from the homogeneously staining region of the neuroblastoma cell line IMR-32, and a fifth fragment, derived from the neuroblastoma cell line NB-9, showed differential and variable amplification in 24 advanced-stage neuroblastoma tumors out of 112 tested specimens. All five fragments were mapped within the chromosomal region 2p23-2p25 by three different approaches. However, eight other fragments cloned from the homogeneously staining region of IMR-32 cells, which were not amplified in the tumor tissues examined, were mapped to two more proximal domains of 2p, thousands of kilobases apart from each other and from the chromosomal domain that is amplified in the tumors. These results establish the amplification, to different degrees, of a variable-sized segment of one domain near the terminus of 2p in advanced neuroblastomas. These tumors might ultimately be distinguished according to the pattern of amplification of DNA segments within this domain. The data presented also indicate the existence of a new and complex amplification mechanism in at least one neuroblastoma cell line (IMR-32), which involves not only relocation of DNA from specific genomic domains but also the formation of novel units by splicing together very distant DNA segments.

Base Sequence↗
PubMedDate not supplied

Prediction of dystrophin phenotype by DNA analysis in Duchenne/Becker muscular dystrophy.

Allele-specific molecular diagnosis of Duchenne and Becker muscular dystrophies (DMD and BMD) has been largely dependent upon muscle biopsy for dystrophin protein assay. We performed lymphocyte DNA mutation analysis by polymerase chain reaction on 14 boys presenting with a clinical picture compatible with DMD or BMD. DNA analysis revealed that 12 of 14 boys had a deletion of the dystrophin gene, thus establishing the diagnosis of DMD/BMD. Furthermore, genotypes for 9 of 12 deletion patients permitted prediction of the specific allelic disorder (i.e., DMD or BMD). Subsequent dystrophin testing confirmed all of the DNA-based diagnoses. We propose that DNA mutation analysis be included in the initial evaluation of patients suspected of having DMD/BMD, thus potentially eliminating the need for muscle biopsy in the majority of patients.

Biopsy↗
PubMedDate not supplied

Establishing priorities in neurofibromatosis research: a workshop summary.

Progress in understanding the biology of the neurofibromatoses (NF1 and NF2) offers hope for the development of new, effective methods of treatment. In May 2000, the National Institute of Neurological Disorders and Stroke (NINDS) hosted a workshop that included leading researchers and clinicians from the NF community. The goal of the meeting was to assess current knowledge and identify priorities for future research. Needs identified included the development of better animal models, further study of the function of the NF1 and NF2 genes, and investigation of the role of modifier genes. The participants agreed that it will also be important to define further the natural history of NF1 and NF2 and to develop an infrastructure to support clinical trials. They also discussed the possible creation of research consortia and NF centers to promote the integration of basic and clinical research.

Animals↗
PubMedDate not supplied

Growth type of plexiform neurofibromas in NF1 determined on magnetic resonance images.

This article describes some types of growth in plexiform neurofibroma (PNF) on magnetic resonance images (MRI). This tumor is almost exclusively associated with NF1. On MRI, the tumor is depicted as a hyperintensive area on T2-weighted images. We distinguished 3 patterns of tumor growth: first, the superficial and non-invasive tumors, that are restricted to the cutis and subcutis, only eventually having outgrowth to the muscles beneath and are slow growing. Second, the displacing PNF that develop in deeper layers of the skin or within the body. They can grow to a large extent but do not invade adjacent muscles or skin. Thirdly, the invasive type with no visible margins that cannot be resected without adjacent structures or organs. A combination of these tumors can sometimes be noted, e.g. a displacing tumorous nerve developing in a large lumpy, non-invasive PNF. These categories might be used as a current guideline for medical advice, surgical treatment planning and medication trials.

Cell Division↗