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Biomedical subjects

L Li

Publications and source records attributed to L Li.

At least 1,675 records · Page 93Linked to original sources
PubMed1994

[Comparative study of 201Tl-scintigraphic image and endomyocardial biopsy findings in patients with dilated cardiomyopathy].

201Tl-SPECT image was compared with the findings of endomyocardial biopsy in patients with dilated cardiomyopathies (DCM), and diagnostic value of 201Tl patchy pattern image for fibrosis with DCM was evaluated. Serial 22 patients diagnosed as DCM with endomyocardial biopsy findings were selected for this study (age: 50 +/- 17 y.o., Male/Female = 17/5). Patchy pattern of 201Tl-SPECT image was visually classified to 4 stage according to the severity of inhomogeneous defect, and pathologic findings of fibrosis was also classified into 4 according to the severity of fibrosis (0: none, 1: mild, 2: moderate, 3: severe). Ejection fraction calculated from left ventriculography and end-diastolic dimension by echocardiography were also compared with 201Tl-SPECT image. Out of 22 patients, 21 patients (95%) showed fibrosis, and 18 patients (82%) showed patchy pattern with 201Tl-SPECT. Severity of patchy pattern was not in good relation to that of fibrosis (r = 0.374). 201Tl image was not related to the function nor dimension. Four autopsy studies revealed a good relation of macroscopic severity, spatial distribution of fibrosis and inhomogeneous 201Tl-defect pattern before death. Patchy pattern of 201Tl-SPECT image will show the myocardial fibrosis in patients with DCM, and is independent of the function. 201Tl-SPECT may show more clinically useful findings of spatial distribution and severity of fibrosis with focal myocardial biopsy.

Adolescent↗
PubMed1994

Genomic loci of human mitogen-activated protein kinases.

Mitogen-activated protein (MAP) kinases [also known as Erks] have been established to function as important mediators of signal transduction by growth factor receptors. Several components of the MAP kinase signal transduction pathway have been demonstrated to be oncogenically activated in malignant tumors. These include growth factor receptors, the GTP-binding protein Ras, and the protein kinase Raf. The genes that encode MAP kinases therefore represent potential targets of carcinogenic insults. Here, we report the genomic loci of three MAP kinase genes are widely distributed within the human genome: p41mapk (Erk2) at 22q11.2; p44mapk (Erk1) at 16p11.2; and p63mapk (Erk3-related) at 18q12-21.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1993

Myelin protein zero gene mutated in Charcot-Marie-tooth type 1B patients.

Autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at theta = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes > 50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.

Animals↗
PubMed1993

Synaptic and photoreceptor components in retinal pigment epithelial cell transplanted retinas of Royal College of Surgeons dystrophic rats.

Plexiform layer synaptic and photoreceptor cell components were investigated in retinas of Royal College of Surgeons (RCS) dystrophic rats transplanted with normal retinal pigment epithelial (RPE) cells by immunocytochemistry using previously characterized monoclonal antibodies. In retinas of normal adult rats and RPE-cell transplanted retinas of 4 month-old RCS rats, HNK-1, a marker for a carbohydrate of the neural cell adhesion molecule (N-CAM), was detected immunocytochemically in the inner and outer plexiform layers and ganglion cell bodies and their axons. HNK-1 was also detected in the inner plexiform layer of nontreated retinas of 4 month-old RCS rats, but was reduced to scattered patches in the outer plexiform layer. In addition, immunoreactivity for the SVP-38 antibody recognizing synaptophysin was found in both plexiform layers of normal adult rat retinas and RPE-transplanted retinas of 4 month-old RCS rats. Furthermore, photoreceptor cell bodies and their inner and outer segments were immunostained for the opsin monoclonal antibody RET-P1 in retinas of normal adult rats and RPE-cell transplanted retinas of 4 month-old RCS rats. However, in nontreated retinas of 4-month-old RCS rats, only immunostained debris material was detected. These results strongly suggest that normal RPE transplants not only rescue photoreceptor cells in RCS rats, but also maintain an essential functional capacity, in this case, synaptic components in the plexiform layers.

Animals↗
PubMed1993

C-terminal deletion mutants of the FokI restriction endonuclease.

We have constructed two C-terminal deletion mutants of the FokI restriction endonuclease by using the polymerase-chain-reaction technique and expressed them in Escherichia coli. The two mutant proteins (MP) of 41 and 30 kDa, were purified to homogeneity and their DNA-binding properties were characterized. The 41-kDa MP specifically binds the DNA sequence, 5'-GGATG/3'-CCTAC, like the wild-type (wt) FokI, but does not cleave DNA. The 30-kDa MP does not bind DNA. The affinity of the 41-kDa MP for the DNA substrate is comparable to that of wt FokI. The 41-kDa MP interacts with its substrate like the wt FokI, as revealed by hydroxyl radical footprinting experiments. In the presence of a DNA substrate, the 41-kDa MP is cleaved by trypsin into a 30-kDa N-terminal fragment and an 11-kDa C-terminal fragment. Addition of the HPLC-purified 11-kDa C-terminal fragment to the 30-kDa MP restores its sequence-specific DNA-binding property. These results confirm that the N-terminal 41-kDa fragment of the FokI ENase constitutes the DNA recognition domain of the ENase.

Amino Acid Sequence↗
PubMed1993

Prenatal diagnosis of Charcot-Marie-Tooth disease type 1A by multicolor in situ hybridization.

Genetic heterogeneity within the most common genetic neuropathy, Charcot-Marie-Tooth disease (CMT) results in about 70% slow nerve conduction CMT1 and 30% normal nerve conduction CMT2. Autosomal dominant CMT1A on chromosome 17p11.2 represents about 70% of CMT1 cases and about 50% of all CMT cases. Three different size CMT1A duplications with variable flanking breakpoints were characterized by multicolor in situ hybridization and confirmed by pulsed field gel electrophoresis and quantitative polymerase chain reaction (PCR) amplification. These different size duplications result in the same CMT1A phenotype confirming that trisomy of a normal gene region results in CMT1A. The smallest duplication does not include the 409 locus used previously to screen for CMT1A duplications. Direct analysis of interphase nuclei from fetuses and at-risk patients by multicolor in situ hybridization to a commonly duplicated CMT1A probe is informative more often than polymorphic PCR analysis, faster than pulsed field gel electrophoresis (PFGE), and faster, more informative, and more reliable than restriction enzyme analysis. CMT1B restriction enzyme analysis of CMT pedigrees without CMT1A is expected to diagnose another 8% of at-risk CMT1 patients (total: 78%).

Amniocentesis↗
PubMed1993

Blastic phase chronic myeloid leukemia with a four-break rearrangement: t(11;9)(9;22)(q23;p22q34;q11).

Chromosome analysis of bone marrow (BM) aspirate from a 36-year-old man with chronic myeloid leukemia (CML) in blastic phase (BP) showed a four-break rearrangement t(11;9)(9;22)(q23; p22q34;q11), which can be considered a t(9;22)(q34;q11) and a secondary t(9;11)(p22;q23). It is not surprising that additional chromosome abnormalities occur in patients with Ph-positive CML in BP, but it is of interest that t(9;11)(p22;q23), characteristic of acute myeloid leukemia French-American-British (FAB) type M5 (ANLL-M5) was observed. The possible meaning of this additional change in BP of CML is discussed.

Adult↗
PubMed1993

Regulation of rat 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Role of the NH2-terminal region.

The role of the NH2-terminal region of the liver and skeletal muscle 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases was investigated, as well that of a mutant of the liver isoform lacking the first 22 amino acids, by the overexpression of these enzymes in Escherichia coli and the comparison of their kinetic properties. The muscle isoform and the deletion mutant had Km values for fructose 6-phosphate which were 50- and 20-fold higher, respectively, than that of the liver isoform, and the bisphosphatase maximal velocity of the liver deletion mutant was 4-fold higher than that of the native liver isoform. Phosphorylation of the liver isoform increased bisphosphatase activity by 2-3-fold and the Km for fructose 6-phosphate of the 6-phosphofructo-2-kinase by 10-15-fold, but these kinetic effects were greatly diminished for the deletion mutant despite equivalent phosphorylation by cAMP-dependent protein kinase. Arg-173 of the skeletal muscle isoform was found to be functionally equivalent to the residue corresponding to the essential fructose 6-phosphate binding residue of the liver kinase domain, Arg-195. The results suggest that 1) the NH2-terminal regions of the liver and skeletal muscle isoforms are important determinants of fructose 6-phosphate affinity, and 2) the initial 22 amino acids of the liver isoform exert an inhibitory influence on the bisphosphatase and mediate, at least in part, the response of both activities of the enzyme to cAMP-dependent phosphorylation.

Amino Acid Sequence↗
PubMed1993

Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion.

Our previous studies have shown that nitric oxide synthase (NOS) can be induced in motoneurons after spinal root avulsion lesion and the lesion-induced NOS is coincident with the death of the injured neurons. The present study examined whether the death of injured motoneurons can be prevented by inhibition of NOS. Nitroarginine, a specific inhibitor of NOS, was injected into adult rats which underwent spinal root avulsion. At a dose of 50 mg/kg/day, nitroarginine significantly inhibited the activity of lesion-induced NOS and significantly reduced the death of motoneurons due to spinal root avulsion. Results of the present study indicate that NO, produced by lesion-induced NOS, may be involved in and responsible for the neuronal death after traumatic injury.

Amino Acid Oxidoreductases↗
PubMed1993

Expression of human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Escherichia coli. Role of N-2 proline in degradation of the protein.

Human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is 96% identical to the rat and bovine liver enzymes, and all of the critical catalytic and substrate binding residues in both the kinase and bisphosphatase domains are conserved in the three enzymes. However, in contrast to rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, which is readily expressed in an Escherichia coli T-7 RNA polymerase-based expression system, the human liver bifunctional enzyme could not be expressed in this system. Western blot and slot blot analysis revealed that although both the bifunctional enzyme protein and its mRNA were rapidly induced by the addition of isopropyl-1-thio-beta-D-galactopyranoside, the protein underwent rapid degradation. Deletion of the N-2 proline residue or its mutation to arginine, the corresponding residue in the rat liver enzyme, revealed that this proline residue was responsible for its rapid degradation. The Pro-2-->Arg mutant could be expressed with a high yield (20 mg/liter) in E. coli. The results support the hypothesis that a proline residue at N-2 facilitates bifunctional enzyme degradation in E. coli. The E. coli expressed mutant form was purified to homogeneity by phosphocellulose chromatography, and its kinetic properties were compared with those of the rat liver enzyme. The kinetic properties of the two enzymes were identical except for the presence of substrate (fructose 6-phosphate) inhibition of the human liver enzyme but not of the rat liver enzyme. The ability to express and purify large amounts of human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase will permit structure/function and x-ray crystal structure studies of the enzyme and ultimately its targeting for drug therapy.

Amino Acid Sequence↗
PubMed1993

Alteration of the cleavage distance of Fok I restriction endonuclease by insertion mutagenesis.

Fok I restriction endonuclease recognizes the nonpalindromic pentadeoxyribonucleotide 5'-GGATG-3'.5'-CATCC-3' in duplex DNA and cleaves 9 and 13 nucleotides away from the recognition site. Recently, we reported the presence of two distinct and separable protein domains within this enzyme--one for the sequence-specific recognition and the other for endonuclease activity. Here, we report the construction of two insertion mutants of Fok I endonuclease. The mutant enzymes were purified, and their cleavage properties were characterized. The mutants have the same DNA sequence specificity as the wild-type enzyme. However, compared with the wild-type enzyme, they cleave one nucleotide further away from the recognition site on both strands of the DNA substrates. Thus, it is possible to alter the cleavage distance of Fok I by protein engineering.

Amino Acid Sequence↗
PubMed1993

Ultrastructural evidence for hair cell regeneration in the mammalian inner ear.

It has long been thought that hair cell loss from the inner ears of mammals is irreversible. This report presents scanning electron micrographs and thin sections of the utricles from the inner ears of guinea pigs that show that, after hair cell loss caused by treatment with the aminoglycoside gentamicin, hair cells reappeared. Four weeks after the end of treatment, a large number of cells with immature hair bundles in multiple stages of development could be identified in the utricle. Thin sections showed that lost type 1 hair cells were replaced by cells with a morphology similar to that of type 2 hair cells. These results indicate an unexpected capacity for hair cell regeneration in vivo in the mature mammalian inner ear.

Animals↗