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Biomedical subjects

A M Wang

Publications and source records attributed to A M Wang.

At least 55 records · Page 3Linked to original sources
PubMed1991

Lysosomal alpha-N-acetylgalactosaminidase deficiency, the enzymatic defect in angiokeratoma corporis diffusum with glycopeptiduria.

Recently a novel case of angiokeratoma corporis diffusum with glycoaminoaciduria was described in a 46-yr-old Japanese woman. Known causes of the cutaneous manifestation were eliminated by enzyme analyses, and further characterization of the accumulated urinary O-linked sialopeptides revealed identity to those excreted by patients with an infantile neuroaxonal dystrophy due to lysosomal alpha-N-acetylgalactosaminidase deficiency. Investigation of the alpha-N-acetylgalactosaminidase activity and protein in the proband revealed less than 2% of normal activity and the absence of detectable immunoreactive enzyme protein, findings comparable to those in the patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. In addition, the proband's unaffected offspring had half-normal levels of alpha-N-acetylgalactosaminidase activity, consistent with this enzymatic deficiency being the primary metabolic defect in this autosomal recessive trait. Ultrastructural examination of skin and blood cells from the adult proband revealed the presence of prominent lysosomal inclusions containing diffuse amorphous and filamentous material. In contrast, these morphologic findings were not observed in the nonneural tissues from patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. These studies document the occurrence of two forms of alpha-N-acetylgalactosaminidase deficiency and sialopeptiduria, a severe infantile-onset form of neuroaxonal dystrophy without angiokeratoma or visceral lysosomal inclusions and an adult-onset form characterized by angiokeratoma, extensive lysosomal accumulation of sialoglycopeptides and the absence of detectable neurologic involvement.

Fabry Disease↗
PubMed1990

Human alpha-N-acetylgalactosaminidase-molecular cloning, nucleotide sequence, and expression of a full-length cDNA. Homology with human alpha-galactosidase A suggests evolution from a common ancestral gene.

Human alpha-N-acetylgalactosaminidase (alpha-GalNAc, E.C. 3.2.1.49), the lysosomal glycohydrolase that cleaves alpha-N-acetylgalactosaminyl moieties from glycoconjugates, is encoded by a gene localized to chromosome 22q13----qter. The deficient activity of alpha-GalNAc is the enzymatic defect in Schindler disease, an inherited neuroaxonal dystrophy. To isolate a full-length cDNA, the enzyme from human lung was purified to homogeneity, 129 non-overlapping amino acids were determined by microsequencing the N terminus and seven tryptic peptides, and four synthetic oligonucleotide mixtures were used to screen a human fibroblast cDNA library. A full-length cDNA, pAGB-3, isolated from a placental lambda gt11 cDNA library, had a 2158-base pair (bp) insert with an open reading frame which predicted an amino acid sequence that was colinear with all 129 microsequenced residues of the purified enzyme. The pAGB-3 insert had a 344-bp 5'-untranslated region, a 1236-bp open reading frame encoding 411 amino acids, a 514-bp 3'-untranslated region, and a 64-bp poly(A) tract. A signal peptide sequence of 17 amino acids as well as six N-glycosylation sites were predicted. The pAGB-3 cDNA was subcloned into the p91023(B) mammalian expression vector and human alpha-GalNAc activity was transiently expressed in COS-1 cells, demonstrating the functional integrity of the full-length cDNA. Northern hybridization analysis of mRNA revealed two transcripts of about 3.6 and 2.2 kilobases (kb), and primer extension studies indicated a cap site at nucleotide -347 for the 2.2-kb transcript. The 3.6-kb cDNA (pAGB-35) was isolated; the 3598-bp pAGB-35 insert was identical to that of the 2.2-kb insert but had additional 5'- and 3'-untranslated sequences including a second downstream polyadenylation signal at nucleotide 3100-3105. Isolation of a genomic clone, gAGB-1, and sequencing the 2048-bp region including pAGB-3 revealed a 1754-bp intron between codons 319 and 320, which also was the site of a 70-bp insertion and a45-bp deletion in other cDNA clones. Notably, the alpha-GalNAc cDNA had remarkable amino acid homology with the human alpha-galactosidase A (alpha-Gal A) cDNA suggesting the evolutionary relatedness of these genes. The alpha-GalNAc cDNA had 46.9-64.7% amino acid identity in sequences (codons 1-319) corresponding to alpha-Gal A exons 1 through 6, while the comparable exon 7 sequence (pAGB-3 codons 320-411) had only 15.8% homology with numerous gaps.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

Cloning, sequence analysis, and expression of the bacteriophage T4 cd gene.

The cd gene of bacteriophage T4, which encodes the enzyme deoxycytidylate deaminase, was isolated as a 1.9-kilobase DNA fragment and completely sequenced. The deduced amino acid sequence was found to be 193 residues long compared with 188 for the corresponding enzyme from bacteriophage T2. There were nine amino acid differences between the two enzymes in addition to a 5-residue insert near the carboxyl terminus of the T4 deaminase which was not present in the T2 deaminase. The cd-containing fragment also contained all of gene 31 (Nivinskas, R., and Black, L. W. (1988) Gene (Amst.) 73, 251-257) and thus precisely locates the two genes relative to one another within the T4 phage genomic map. Attempts to place the cd gene within a high expression vector have not been successful so far due to possible toxic effects of the gene product. However, placement of the gene within pUC18 resulted in a degree of expression which is about 10-20 times that found in T4-infected Escherichia coli. The enzyme was purified to homogeneity and found to possess properties similar to T2 phage deoxycytidylate deaminase.

Amino Acid Sequence↗
PubMed1990

Hepatic scintigraphic changes associated with gestational trophoblastic disease.

We reviewed the results of radionuclide liver imaging in 70 patients newly referred for evaluation and treatment of persistent gestational trophoblastic tumors. Some 58 patients (83%) had abnormal liver scans but no focal defects and no discernible hepatic malignancy. These diffusely abnormal scans may reflect chemotherapeutic and/or hormonal effects on the liver and should not be interpreted as indicative of metastases.

Female↗
PubMed1990

Schindler disease: an inherited neuroaxonal dystrophy due to alpha-N-acetylgalactosaminidase deficiency.

The clinical, pathological and biochemical features of a neuroaxonal dystrophy resulting from the deficient activity of lysosomal alpha-N-acetylgalactosaminidase are described. This neurodegenerative disorder was recognized in two brothers who had the typical clinical manifestations and neuropathological lesions observed in patients with Seitelberger disease, the infantile form of neuroaxonal dystrophy. Axonal 'spheroids' were observed histologically in the grey matter, and ultrastructural examination revealed the characteristic formations in dystrophic axons in the myenteric plexus and neocortex. Using a newly synthesized fluorogenic substrate, 4-methylumbelliferyl-alpha-N-acetylgalactosaminide, the markedly deficient activity of alpha-N-acetylgalactosaminidase was demonstrated in the affected brothers while their consanguineous parents had intermediate activities, consistent with the autosomal recessive transmission of this disease. No detectable alpha-N-acetylgalactosaminidase was seen in immunoblots using monospecific rabbit antihuman alpha-N-acetylgalactosaminidase antibodies. Abnormally increased amounts of urinary glycopeptides were observed by high resolution thin layer chromatography. Analytical studies identified four of the accumulating urinary compounds, the blood group A trisaccharide GalNAc alpha 1----3(Fuc alpha 1----2)Gal and three O-linked glycopeptides, GalNAc alpha 1----O-serine and -threonine, NeuNAc alpha 2----3Gal beta 1----3(NeuNAc alpha 2----6)GalNAc alpha 1----O-serine and -threonine, and NeuNAc alpha 2----3Gal beta 1----4GlcNAc beta 1----6(NeuNAc alpha 2----3Gal beta 1----3)GalNAc alpha 1----O-serine and -threonine. Of eight unrelated patients diagnosed as having infantile neuroaxonal dystrophy by pathological studies, none had deficient alpha-N-acetylgalactosaminidase activity, emphasizing the biochemical heterogeneity underlying this diagnostic entity. These findings document the first delineation of a metabolic defect in an inherited neuroaxonal dystrophy and suggest that the axonal pathology in this disorder, and perhaps in the other neuroaxonal dystrophies, results from abnormal glycoprotein metabolism involving O-linked glycopeptides.

Axons↗
PubMed1990

Characterization of the restriction site of a prokaryotic intron-encoded endonuclease.

The 1016-base-pair (bp) intron in the T4 bacteriophage thymidylate synthase gene (td) contains a 735-bp open reading frame that encodes a protein product with endonucleolytic activity. The endonuclease shows specificity for the intronless form of the td gene. Highly purified endonuclease cleaves the DNA of the intronless form of the td gene in vitro at 24 bp upstream of the exon 1-exon 2 junction, generating a 2-base staggered cut with 3'-hydroxyl overhangs. Although the endonuclease cleaves in exon 1, it requires some exon 2 sequence for recognition. The maximum recognition sequence lies in an 87-bp stretch, from 52 bp upstream to 35 bp downstream of the cleavage site, ending at 11 bp into exon 2. The td intron endonuclease appears involved in the conversion of the intronless form of td to intron-containing td gene in the T-even phages. A role for intron mobility is discussed.

Base Sequence↗
PubMed1990

Association of vertebral end plate fracture with pediatric lumbar intervertebral disk herniation: value of CT and MR imaging.

A retrospective review of the radiologic findings in 31 patients less than 21 years old who underwent laminotomy for lumbar disk herniation revealed six cases of associated avulsion fracture of the vertebral end plate, a prevalence of 19%. All fractures were found in the 14-17-year-old subgroup (six of 19), a prevalence of 32%. In four patients, plain radiographs did not reveal the fracture. Computed tomographic (CT) findings were diagnostic in all six cases. Magnetic resonance (MR) images, obtained in three patients, demonstrated the avulsed cortical fragment and what are assumed to be the attached Sharpey fibers. On sagittal MR images, these structures had a configuration with the appearance of a "Y" or "7". Four of these six patients underwent bilateral laminotomies. The need for more extensive surgical resection may not be apparent at plain radiography or myelography but can be predicted with CT and MR imaging.

Adolescent↗
PubMed1990

Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy.

Schindler disease is a recently recognized infantile neuroaxonal dystrophy resulting from the deficient activity of the lysosomal hydrolase, alpha-N-acetylgalctosaminidase (alpha-GalNAc). The recent isolation and expression of the full-length cDNA encoding alpha-GalNAc facilitated the identification of the molecular lesions in the affected brothers from family D, the first cases described with this autosomal recessive disease. Southern and Northern hybridization analyses of DNA and RNA from the affected homozygotes revealed a grossly normal alpha-GalNAc gene structure and normal transcript sizes and amounts. Therefore, the alpha-GalNAc transcript from an affected homozygote was reverse-transcribed, amplified by the polymerase chain reaction (PCR), and sequenced. A single G to A transition at nucleotide 973 was detected in multiple subclones containing the PCR products. This point mutation resulted in a glutamic acid to lysine substitution in residue 325 (E325K) of the alpha-GalNAc polypeptide. The base substitution was confirmed by dot blot hybridization analyses of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. Furthermore, transient expression of an alpha-GalNAc construct containing the E325K mutation resulted in the expression of an immunoreactive polypeptide which had no detectable alpha-GalNAc activity.

Base Sequence↗
PubMed1989

Quantitation of mRNA by the polymerase chain reaction.

A method for the quantitation of specific mRNA species by the polymerase chain reaction (PCR) has been developed by using a synthetic RNA as an internal standard. The specific target mRNA and the internal standard are coamplified in one reaction in which the same primers are used. The amount of mRNA is then quantitated by extrapolating against the standard curve generated with the internal standard. The synthetic internal standard RNA consists of a linear array of the sequences of upstream primers of multiple target genes followed by the complementary sequences to their downstream primers in the same order. This quantitative PCR method provides a rapid and reliable way to quantify the amount of a specific mRNA in a sample of less than 0.1 ng of total RNA. In addition, the same internal standard RNA is used, with appropriate primer pairs, to quantitate multiple different mRNA species.

Arteriosclerosis↗
PubMed1989

Internal carotid artery stenosis: accuracy and reproducibility of color-Doppler-assisted duplex imaging.

The accuracy, rapidity, and reproducibility of color-Doppler-assisted duplex sonography in the diagnosis of significant internal carotid artery stenosis were prospectively evaluated. Only the point of maximal color shift on the color map was used for spectral analysis. When compared with angiography in 60 carotid bifurcations, a measured peak systolic velocity above 1.25 m/sec was 87% accurate in the detection of significant internal carotid artery stenoses greater than 50%. Determination of maximal internal carotid artery velocity was 40% faster with color-Doppler-assisted duplex sonography than with nonassisted duplex ultrasound. The correlation coefficient for interobserver agreement was .90. It increased to .97 when cases of extensive (greater than 1 cm) acoustic shadowing (7% of bifurcations) were excluded. The authors conclude that the color flow map is an accurate and reproducible means of depicting the point of maximal stenosis within the internal carotid artery.

Aged↗
PubMed1989

[The ratios and kinds of clinical bacteria isolated in Taiwan's large-size hospitals].

The prevalence of clinical bacteria, as isolated from Linko Chang-Gung Memorial Hospital (2,300 beds) in the period January 1985 to December 1986 and from Taipei Veterans General Hospital (2,300 beds) during the period January 1986 to December 1986, was analyzed with the following findings: (i) The isolation ratio of anaerobic and aerobic or facultative bactria during the period of investigation were 7.8% (5,513/70,799) and 92.2% (65,286/70,799), respectively. (ii) Of the total aerobic or facultative isolates from the two hospitals, 32.9% (21,510/65,286) were Gram positive cocci and bacilli, 67.1% (43,776/65,286) were Gram negative cocci and bacilli. (iii) Of these Gram-negative bacilli, 65.2% (28,490/43,675) were Enterobacteriaceae were Enterobacteriaceae and glucose fermentative Gram negative bacilli, 32.0% (13,984/43,675) were glucose nonfermentative Gram negative bacilli, and 2.7% (1,200/43,675) were fastidious Gram negative bacilli. (iv) The more common species among the members of Enterobacteriaceae were Escherichia coli 35.7% (10,163/28,490), and Klebsiella pneumoniae 18.2% (5,186/28,490). The other common species included Enterobacter cloacae, Proteus mirabilis, Serratia marcescens, Morganella morganii, Citrobacter freundii and Proteus vulgaris. The frequencies of Salmonella species and Shigella species in these two large hospitals were up to 1.6% (456/28,490) and 0.5% (149/28,490), respectively. The most common isolate among other glucose fermentative Gram negative bacilli was Aeromonas hydrophila 3.0% (843/28,490). The finding of 0.1% (11/28,490) Vibrio alginolyticus was considered as clinically significant in Taiwan. (v) Of these glucose nonfermentative Gram negative bacilli, 69.4% (9,704/13,984) were Pseudomonas aeruginosa, 18.9% (2,637/13,984) Acinetobacter species, 10.8% (1,516/13,984) Pseudomonas species. (vi) The most common bacteria among fastidious Gram negative bacilli was Haemophilus influenzae, 96.2% (1,154/1,200). (vii) Of these Gram negative cocci, 59.4% (60/101) was Neisseria gonorrhoeae and 6.9% (7/101) N. meningitidis. (viii) The more common isolates of Gram positive bacilli included Bacillus species and Corynebacterium species (diphtheroids). (ix) Of these Gram positive cocci, the isolation rates of Staphylococcus species and Streptococcus species were 54.6% (10,838/19,827) and 45.4% (9,002/19,847), respectively. The most common isolate among Gram positive cocci was Staphylococcus aureus, 30.2% (5,994/19,847); the next, enterococcus, 24.9% (4,936/19,847); then S. epidermidis, 22.2% (4,390/19,847). The less common isolates were Streptococcus pyogenes 1.1% (212/19,847) and S. pneumoniae, 1.7% (329/19,847).(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗
PubMed1989

[Cervicofacial actinomycosis: report of a case].

Actinomycotic infection involving the head and neck is not commonly diagnosed and is often a diagnostic enigma to the otolaryngologist. The reasons for this are due to the infrequency of this disease itself, the current general lack of familiarity with this disease and the pronounced sensitivity of actinomyces organisms to most of the common antibiotics in current use. The case reported here is fairly typical of cervicofacial actinomycosis. A 26-year-old man suffering from trismus and a noncharacteristic mass over the right parotidomasseteric region for one month after a lower molar tooth was extracted presented at our hospital. There were many yellowish gritty "sulfur granules" found within the pus when surgical drainage was made. Immediate Gram stain examination of these granules showed numerous filamentous Gram-positive bacilli, some of which showed true branching. Bacterial culture grew only an anaerobic organism which was identified as Actinomyces israelii by biochemical tests. This patient improved after further treatment with intensive intravenous penicillin injections for ten days and prolonged oral tetracycline treatment for two months. We suggest that increased alertness of clinicians and microbiologists to the presence of anaerobic organisms as the cause of cervicofacial infections could result in an earlier and more frequent diagnosis of actinomycosis.

Actinomyces↗
PubMed1988

Cavernous hemangioma of the thoracic spinal cord.

A 25-year-old woman presented with a four-year history of progressive right-lower-extremity weakness and atrophy and a left hemisensory deficit was found. Metrizamide-enhanced spinal CT scan showed an intramedullary lesion at the level of T1-T2; this had expanded the cord in fusiform fashion but showed no evidence of a cystic component. Surgical resection was performed and the pathological diagnosis was cavernous hemangioma. Two and one-half years later, her left hemisensory deficit was worsening and a spinal MRI showed high signal intensity mass in the region of the previous surgery consistent with chronic hematoma which was re-evacuated with some improvement in the patient's neurological condition.

Adult↗
PubMed1988

What is expected of CT in the evaluation of stroke?

This study was based on 5042 cranial CT examinations in a 2-year period. 19.8% of all cranial CT scans were performed for confirmation or evaluation of clinically suspected stroke. 87% of the clinical diagnoses of stroke were confirmed by CT scan. Intracranial hemorrhage made up a small percentage in this study. The establishment of this diagnosis was a valuable service in the patients' management. Brain tumor may rarely present clinical symptoms mimicking stroke and may have a normal CT initially.

Cerebral Hemorrhage↗