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Biomedical subjects

L Ho

Publications and source records attributed to L Ho.

At least 37 records · Page 2Linked to original sources
PubMed1996

Strength of porcelain fused to titanium beams.

The purposes of this study were to measure strengths of layered porcelain fused to titanium beams, determine failure modes, and investigate the porcelain-titanium interface. A three-point flexural test and formulas derived especially for this purpose were used. The strength of layered porcelain-ceramic beams was limited by the cohesive tensile or compressive strengths of the porcelain, not by the porcelain-titanium interfacial bond, namely, the porcelain failure occurred at lower loads than did failure of the porcelain-titanium interface. The porcelain-titanium bond strength was at least 26 MPa. Scanning electron microscopy and energy-dispersive x-ray spectroscopy demonstrated that the bond was limited by delamination of a thin titanium-titanium oxide interface. Theoretic curves that describe effects of relative layer and total thickness on the force-bearing capacity of model beams were plotted. These curves indicated that porcelain-titanium prostheses should be made as thick as is practical, but the relative thickness of the porcelain and titanium layers would be less important.

Analysis of Variance↗
PubMed1996

Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.

Hermansky-Pudlak syndrome (HPS) is an often-fatal autosomal recessive disease in which albinism, bleeding, and lysosomal storage result from defects of diverse cytoplasmic organelles: melanosomes, platelet dense bodies, and lysosomes. HPS is the most common single-gene disorder in Puerto Rico, with an incidence of 1 in 1,800. We have identified the HPS gene by positional cloning, and found homozygous frameshifts in this gene in Puerto Rican, Swiss, Irish and Japanese HPS patients. The HPS polypeptide is a novel transmembrane protein that is likely to be a component of multiple cytoplasmic organelles and that is apparently crucial for their normal development and function. The different clinical phenotypes associated with the different HPS frameshifts we observed suggests that differentially truncated HPS polypeptides may have somewhat different consequences for subcellular function.

Albinism, Oculocutaneous↗
PubMed1996

High levels of circulating beta-amyloid peptide do not cause cerebral beta-amyloidosis in transgenic mice.

We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human beta-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick beta-actin promoter. There were exceptionally high levels of beta-amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral beta-amyloidosis despite extremely high levels of circulating beta-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of beta-amyloid precursor protein may play a predominant role in cerebral beta-amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.

Amyloid beta-Peptides↗
PubMed1995

Human papillomavirus testing in primary cervical screening.

Several studies have examined the role of tests for human papillomavirus (HPV) in screening for cervical cancer but as yet the relevance is unclear. We looked at HPV testing for types 16, 18, 31, and 33 on material taken at the time of a cervical smear in 2009 eligible women having routine screening. Women with any degree of dyskaryosis or high levels of one of these HPV types were referred for colposcopy. 44% of the cervical intraepithelial neoplasia (CIN) lesions of grade 2/3 detected had negative cytology and were found only by HPV testing. A further 22% of the CIN 2/3 lesions were positive for HPV but showed only borderline or mild cytological changes. The positive predictive value of HPV testing was 42%, which was similar to that for moderate dyskaryosis. HPV types 16 and 31 were more sensitive and specific for CIN 2/3 than were types 18 or 33. However, 25% of the CIN 2/3 lesions were not detected by these four HPV tests. We suggest that HPV testing could usefully augment but not replace conventional cytology. These results should stimulate a much larger randomised trial to assess the impact of these improved CIN 2/3 detection rates on the subsequent incidence of invasive cancer.

Adult↗
PubMed1995

Amyloid beta protein (A beta) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43).

Biochemical and immunocytochemical analyses were performed to evaluate the composition of the amyloid beta protein (A beta) deposited in the brains of patients with Alzheimer's disease (AD). To quantitate all A beta s present, cerebral cortex was homogenized in 70% formic acid, and the supernatant was analyzed by sandwich enzyme-linked immunoabsorbent assays specific for various forms of A beta. In 9 of 27 AD brains examined, there was minimal congophilic angiopathy and virtually all A beta (96%) ended at A beta 42(43). The other 18 AD brains contained increasing amounts of A beta ending at A beta 40. From this set, 6 brains with substantial congophilic angiopathy were separately analyzed. In these brains, the amount of A beta ending at A beta 42(43) was much the same as in brains with minimal congophilic angiopathy, but a large amount of A beta ending at A beta 40 (76% of total A beta) was also present. Immunocytochemical analysis with monoclonal antibodies selective for A beta s ending at A beta 42(43) or A beta 40 confirmed that, in brains with minimal congophilic angiopathy, virtually all A beta is A beta ending at A beta 42(43) and showed that this A beta is deposited in senile plaques of all types. In the remaining AD brains, A beta 42(43) was deposited in a similar fashion in plaques, but, in addition, widely varying amounts of A beta ending at A beta 40 were deposited, primarily in blood vessel walls, where some A beta ending at A beta 42(43) was also present. These observations indicate that A beta s ending at A beta 42(43), which are a minor component of the A beta in human cerebrospinal fluid and plasma, are critically important in AD where they deposit selectively in plaques of all kinds.

Alzheimer Disease↗
PubMed1995

Tetraploids of the lung fluke Paragonimus westermani found in China.

Two groups of Paragonimus westermani (Tematoda: Platyhelminthes) exist in nature: diploids and triploids. Generally, these two groups live allopatrically, but in Kuandian, Liaoning Province, in the Republic of China, they live sympatrically. In our Chinese experiment on Paragonimus we used metacercariae of P. westermani, which we collected in Kuandian, Xigutai, and performed a cytological analysis. The results were as follows: (1) the P. westermani in Xigutai lived sympatrically as diploids and triploids; (2) all of the small metacercariae were diploids; (3) the large metacercariae were in large proportion triploids; (4) we found one tetraploid specimen in both the medium and the large metacercariae--this was the first time tetraploid lung flukes were discovered; (5) the somatic chromosomes of the tetraploids were different in numbers (4n = 44), but we could not find any difference in the karyotype of haploid sets and that of the diploids and the triploids; (6) unlike the triploids, during their meiosis the tetraploids produced a chromosome pairing, and we found a tendency of the large chromosomes to become quadrivalent; and (7) also unlike the triploids, a great number of spermatids were found in the tetraploid testes. Because of these findings, we can consider tetraploids to be autotetraploids, and these are probably produced by the fertilization of diploids and triploids. We also think that the gametes of tetraploids have a fertilization capability.

Animals↗
PubMed1995

Variation of human papillomavirus type 6 (HPV-6) and HPV-11 genomes sampled throughout the world.

We examined the genomic diversity of human papillomavirus type 6 (HPV-6) and HPV-11 isolates from different parts of the world by comparing the nucleotide sequences of part of the long control region of three reference clones and 62 HPV-6 and 40 HPV-11 isolates from Africa, Europe, Asia, and North and South America. The genomic sequence of the HPV-6b reference type had to be amended by inclusion of a 94-bp segment, which is also present with minor differences in HPV-6a. Aside from two small inserts typical of all variants related to HPV-6a and three inserts found in HPV-11 variants, no major alterations to the size of the long control regions of these viruses were observed. This corrects the previous impression that these two HPV types are highly polymorphic. Altogether, 19 HPV-6 and 10 HPV-11 variant genomes could be distinguished, and most of the differences were due to point substitutions. The variants of either type were continuously connected in phylogenetic trees rather than clustered separately into subtype groups. Thirteen mutations, namely, the two HPV-6a inserts and 11 substitutions in HPV-6 or HPV-11 variants, reduced the dissimilarity between the types, but they bridged only a small fraction of the genetic distance between the two types. Genomes more obviously intermediate between HPV-6 and HPV-11 were not found and probably do not exist any more. A single HPV-11 variant was found in Africa, but otherwise, no significant correlations of HPV-6 or HPV-11 variants with geography or ethnicity of the patient cohort were found. Functional analysis of diverse enhancer variants showed activities that differed two-to threefold, and it must be considered that transcriptional differences may alter the biology or pathology of these viruses. Similar variants were found in lesions from anatomically different sites and in both benign and malignant lesions.

Base Sequence↗
PubMed1995

PDGF signalling is required for gastrulation of Xenopus laevis.

During Xenopus gastrulation, platelet-derived growth factor (PDGF) receptor-alpha is expressed in involuting marginal zone cells which migrate over ectodermal cells expressing PDGF-A. To investigate the role of PDGF signalling during this process, we have generated a novel point mutant of PDGF receptor-alpha analogous to the W37 mutation of c-kit. This molecule is a specific, potent, dominant inhibitor of PDGF signalling in vivo. Injection of RNA encoding this protein into Xenopus embryos prevents closure of the blastopore, leads to abnormal gastrulation and a loss of anterior structures. Convergent extension is not inhibited in these embryos, but rather, involuting mesodermal cells fail to adhere to the overlying ectoderm. PDGF may therefore be required for mesodermal cell-substratum interaction.

Animals↗
PubMed1995

Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism.

Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF). We describe the analysis of 26 unrelated patients with piebaldism-like hypopigmentation--17 typical patients, 5 with atypical clinical features or family histories, and 4 with other disorders that involve white spotting. We identified novel pathologic mutations or deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of the atypical patients. Overall, we have identified pathologic KIT gene mutations in 21 (75%) of 28 unrelated patients with typical piebaldism we have studied. Of the patients without apparent KIT mutations, none have apparent abnormalities of the gene encoding SLF itself (MGF), and genetic linkage analyses in two of these families are suggestive of linkage of the piebald phenotype to KIT. Thus, most patients with typical piebaldism appear to have abnormalities of the KIT gene.

Adolescent↗
PubMed1995

Association between HLA DQB1 * 03 and cervical intra-epithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) and cervical cancer have been shown to be strongly associated with infection by human papillomavirus (HPV). However, other factors may be contributory in the progression from normal epithelium to CIN and cervical cancer, since not all women with HPV infection develop disease. Recently, it was demonstrated that there is a high risk for cervical cancer and CIN in women with HLA DQB1 * 03 (RR = 7.1, p < 0.0009) (1). Subsequent reports have been conflicting, due to sample size, genetic heterogeneity and differences in the techniques employed for the detection of HLA DQB1 * 03. MATERIALS AND METHODS: DNA from cervical smears of 178 women with CIN and 420 controls with normal cervical cytology was analyzed by polymerase chain reaction (PCR) with type-specific primers for HPV 16, 18, 31, and 33. The DNA from test and control samples were also analyzed by a novel PCR technique, which mutates the first base of codon 40 (DQ alleles) from T to G to create an artificial restriction site for an enzyme Mlu I that distinguish DQB1 * 03 from other alleles and are confirmed by digestion of amplified DNA with Mlu I. Further analysis of individual DQB1 * 03 alleles was performed using PCR and allele-specific primers. RESULTS: One hundred forty-four (34%) out of 420 controls (all HPV 16, 18, 31, or 33 negative and normal cytology), 37/66 (56%) of CIN I and 72/112 (64%) of CIN III were positive for DQB1 * 03 (trend test, p < 0.001, chi 2 = 37.3). A significant association was observed between DQB1 * 03 and CIN (odds ratio 3.03; 95% CI 2.11-3.45). Of women with CIN, 131/178 (73.5%) had HPV (types 16, 18, 31, or 33) infection. There was a significant association between DQB1 * 03 and presence of HPV (odds ratio 3.43; 95% CI 2.25-5.10). Homozygosity for DQB1 * 03 was more strongly associated with CIN than heterozygosity (odds ratios 4.0 and 2.63, respectively); and for the presence of HPV (odds ratio 4.47; 95% CI 2.58-7.77). HLA DQB1 * 0301 was the most strongly associated allele with CIN and HPV (odds ratios 2.53 and 2.63, respectively). CONCLUSIONS: HLA DQB1 * 03 is associated significantly with CIN and may be permissive for HPV infection. Further analysis of class II HLA typing in CIN is necessary to evaluate this association.

Base Sequence↗
PubMed1995

Unusual manifestations of Mycoplasma pneumoniae infection in children.

Mycoplasma pneumoniae infection is no longer a benign condition it was originally thought to be. Many extrapulmonary manifestations affecting major organ systems like the central nervous system, cardiovascular system, haematological system, gastrointestinal system, musculoskeletal system and renal system have been described. Early recognition of these manifestations is often difficult and serological diagnosis may not be helpful. Three patients with large pleural effusions, encephalitis, hemiplegia, hepatitis, autoimmune haemolytic anaemia and renal failure are discussed to highlight the many varied presentations associated with this infection.

Child↗
PubMed1994

Lack of efficacy of single-dose prednisolone in moderately severe asthma.

OBJECTIVE: To assess the effectiveness of single-dose prednisolone in reducing the length of illness and hospital stay in children admitted with moderately severe asthma. DESIGN: A randomised, double-blind, controlled trial of a single dose of prednisolone in 64 children presenting with an acute attack of asthma with arterial oxygen saturation less than 93%. RESULTS: No significant differences in the rate of recovery of oxygen saturation, lung function measurements or duration of hospital stay were found. CONCLUSIONS: This study failed to confirm the benefit of a single dose of prednisolone in the management of children with acute severe asthma.

Acute Disease↗
PubMed1994

Detection of DNA and E7 transcripts of human papillomavirus types 16, 18, 31 and 33, TGF beta and GM-CSF transcripts in cervical cancers and precancers.

The association of human papillomavirus (HPV) with a high proportion of cervical cancers should allow the efficiency of cytological screening methods to be improved. We report here that quantitative detection of HPV types 16, 18, 31 and 33 DNA and the corresponding E7 transcripts by polymerase chain reaction (PCR) may be of value in identifying precancers and cancers. In clinical specimens with major cervical lesions, the level of E7 transcription does not appear to be related to concomitant transcription of either transformation growth factor-beta (TGF beta) or granulocyte-macrophage colony stimulating factor (GM-CSF) genes.

Base Sequence↗
PubMed1994

Localization of PDGF A and PDGFR alpha mRNA in Xenopus embryos suggests signalling from neural ectoderm and pharyngeal endoderm to neural crest cells.

In situ hybridization analysis of Xenopus laevis embryos reveals that mRNA encoding the platelet-derived growth factor alpha receptor (PDGFR alpha) is expressed in cephalic neural crest masses prior to migration from the future neural tube and during their migration into the visceral arches. The analysis of fluorescently labeled neural crest tissue transplanted to unlabeled host embryos demonstrates that neural crest cells are the only detectable source of PDGFR alpha mRNA within visceral arches. Transcripts encoding PDGF A are present in neural ectoderm, otic vesicle and pharyngeal endoderm. Their location suggests that PDGF A provides a signal, first from the neural epithelium and later from the otic vesicle and pharyngeal endoderm, to cephalic neural crest cells during their migration in the arch region.

Animals↗
PubMed1994

Xenopus laevis cellular retinoic acid-binding protein: temporal and spatial expression pattern during early embryogenesis.

There is increasing evidence that retinoic acid (RA) has a role in establishing normal axial patterns during Xenopus laevis embryo-genesis. Several types of retinoid binding proteins are thought to mediate the effects of RA. We report the isolation of a cDNA, named xCRABP-b, which encodes a X. laevis cellular retinoic acid-binding protein (xCRABP). This cDNA hybridises to a transcript in gastrular stage embryos of approximately 3 kb, much larger than those CRABP transcripts expressed in mice. The expression of the xCRABP mRNA is generally restricted to tissues which are sensitive to the teratogenic effects of excess RA. It is likely, that during normal X. laevis embryogenesis, concentrations of RA in RA-responsive cells are modulated by the xCRABP gene product.

Amino Acid Sequence↗