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P Greenstein

Publications and source records attributed to P Greenstein.

7 recordsLinked to original sources
PubMed2000

Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA.

OBJECTIVE: To elucidate the molecular basis of a mitochondrial myopathy associated with recurrent myoglobinuria and cytochrome c oxidase (COX) deficiency in muscle. BACKGROUND: Recurrent myoglobinuria is typically seen in patients with inborn errors of carbohydrate or lipid metabolism, the main sources of energy for muscle contraction. Relatively little attention has been directed to defects of the mitochondrial respiratory chain in patients with otherwise unexplained recurrent myoglobinuria. METHODS: Having documented COX deficiency histochemically and biochemically in the muscle biopsy from a patient with exercise-induced recurrent myoglobinuria, the authors sequenced the three mitochondrial DNA (mtDNA)-encoded COX genes, and performed restriction fragment length polymorphism analysis and single-fiber PCR. RESULTS: The authors identified a nonsense mutation (G5920A) in the COX I gene in muscle mtDNA. The mutation was heteroplasmic and abundantly present in COX-negative fibers, but less abundant or absent in COX-positive fibers; it was not found in blood or fibroblasts from the patient or in blood samples from the patient's asymptomatic mother and sister. CONCLUSIONS: The G5920A mutation caused COX deficiency in muscle, explaining the exercise intolerance and the low muscle capacity for oxidative phosphorylation documented by cycle ergometry. The sporadic occurrence of this mutation in muscle alone suggests that it arose de novo in myogenic stem cells after germ-layer differentiation. Mutations in mtDNA-encoded COX genes should be considered in patients with recurrent myoglobinuria.

Adult↗
PubMed1997

Congenital myotonic dystrophy pathology and somatic mosaicism.

We present the pathology and molecular genetic analysis of an infant with congenital myotonic dystrophy. The proband/infant, born at 35 weeks' gestational age to a mother with myotonic dystrophy and 750 CTG repeats, was markedly hypotonic and had severe cardiomyopathy. She died after 16 days of life. At autopsy, skeletal and heart muscles were immature and had a decrease in contractile elements. DNA CTG trinucleotide repeat analysis of the proband demonstrated 2,480 repeats in blood and a slightly greater number of repeats in skeletal muscles, viscera, and gray matter. Corresponding to the clinical course and pathology, cardiac tissues displayed somatic mosaicism, with repeats ranging from 2,760 to 3,220.

Adult↗
PubMed1995

Patterning activities of vertebrate hedgehog proteins in the developing eye and brain.

BACKGROUND: The hedgehog (hh) family of secreted signaling proteins is responsible for developmental patterning in a variety of systems, including the neural tube, limbs and somites. Within the neural tube, at the level of the spinal cord, products of the vertebrate gene sonic hedgehog (shh) are proposed to function as a ventral patterning influence, with the capability of inducing floor plate and motor neurons. RESULTS: We report the isolation of tiggy-winkle hedgehog (twhh), a novel member of the zebrafish hh gene family. Both twhh and shh are expressed in the ventral midline of the embryonic zebrafish neural tube and brain, but twhh expression becomes limited to the neural tube, whereas shh is also expressed in the notochord. Both genes are expressed in the developing brain, in domains that include a discrete region in the floor of the diencephalon, located between the sites of the future optic stalks. Using pax-2 and pax-6 as markers of proximo-distal fate within the developing eye, we found that ectopic expression of either hh gene promoted proximal fates and suppressed distal fates. In contrast, proximal fates were lost in cyclops mutant embryos, which lack twhh- and shh-expressing forebrain cells. Both twhh and shh proteins undergo autoproteolytic processing in vivo; a fragment corresponding to the amino-terminal cleavage product was sufficient to carry out all signaling activities associated with twhh in eye and brain development. CONCLUSIONS: These findings suggest that secreted signals encoded by members of the hedgehog gene family, emanating from the ventral midline of the neural tube, not only play important roles in dorso-ventral patterning of the brain but also appear to constitute an early patterning activity along the proximo-distal axis of the developing eyes.

Amino Acid Sequence↗
PubMed1995

Zebrafish wnt8 and wnt8b share a common activity but are involved in distinct developmental pathways.

The specification of the vertebrate body plan is dependent on numerous signaling molecules, including members of the Wnt family. We have identified two zebrafish wnt8 paralogs related to Xwnt-8B and Xwnt-8, respectively. A RT-PCR assay demonstrated that wnt8 is expressed maternally, with transcripts detected throughout embryogenesis, whereas wnt8b transcripts were first detected during late gastrulation. The wnt8 transcripts at 50% epiboly are spatially restricted to those cells at the blastoderm margin, overlying gsc-expressing cells in the axial hypoblast. During late gastrulation, wnt8 was no longer detected in the marginal cells at the dorsal midline and by mid-segmentation, transcripts were found in the presumptive tail bud. In contrast, wnt8b expression is spatially restricted to prospective neuroepithelium, and later to neural-specific structures. Overexpression of both wnts results in two major phenotypes: radialized embryos and embryos with anterior defects. These phenotypes were preceded by significant changes in the spatial expression patterns of gsc and ntl transcripts, reminiscent of activities of Xwnt-8 in Xenopus, and consistent with a role for wnt8 in the specification or patterning of mesoderm.

Amino Acid Sequence↗
PubMed1993

Asymmetric catalepsy after right hemisphere stroke.

We describe the appearance of left hemineglect and striking cataleptic posturing, more prominent in left-sided extremities, in a patient without psychiatric illness. Neuroimaging demonstrated a large posterior right hemisphere infarct involving the parietal, occipital, and temporal lobes, the insula, and caudate. Additional movement abnormalities that comprise the full catatonia syndrome were absent, including stereotypy, mannerisms, ambitendency, automatic obedience, mutism, negativism, and echopraxia. Catatonia has been reported to be produced by lesions of diverse etiology affecting the frontal lobe, limbic system, diencephalon, or basal ganglia. In these cases, catalepsy has been manifest only rarely, and motor signs that are present are generally bilateral. This case demonstrates that asymmetric catalepsy can be produced by right hemisphere stroke, and provides partial support for earlier clinical literature relating catalepsy and the parietal lobe.

Aged↗
PubMed1982

Functional contouring of the palatal vault for improving speech with complete dentures.

A method for functionally modifying the contour of the palatal vault of maxillary complete dentures was described. This can be achieved at the trial stage of the denture construction and incorporated in the finished denture. Alternatively, the procedure can be accomplished at the time of insertion and the palatal vault modified with self-polymerizing acrylic resin. The immediate speech achieved by the modification is much more normal and eliminates the waiting and training period after denture insertion. Because the modification of the palatal vault is achieved by the functional contact of the tongue during articulation, the tongue does not have to adapt to the presence of the denture in order to achieve "normal speech." One of the advantages of the method is the ease with which it can be performed in a clinical setting and the minimal requirement of any extra material or equipment. Moreover, no special skills are needed to achieve successful results, which can be exceptionally gratifying.

Aged↗