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Biomedical subjects

L T Chow

Publications and source records attributed to L T Chow.

At least 55 records · Page 3Linked to original sources

Primary juxtacortical chondrosarcoma dedifferentiating after 20 years.

We present the clinical, radiographic and pathological features of a juxtacortical chondrosarcoma which underwent dedifferentiation to an osteosarcoma in a 47-year-old woman. The tumour, abutting the femoral diaphysis, had initially presented 20 years earlier. Local excision was performed at presentation and again 10 years later, but the tumour recurred on each occasion. Serial radiographs showed cortical saucerisation evolving to cortical buttressing and mounding. After 20 years a dramatic radiographic change heralded tumour dedifferentiation.

Chondrosarcoma↗

Isolated congenitally complete heart block attributable to combined nodoventricular and intraventricular discontinuity.

Intraventricular together with atrial-axis and nodoventricular discontinuity, in which various parts of the conduction system are replaced by fibrous or fatty tissue, constitute the three major pathological categories of isolated congenitally complete heart block. Intraventricular discontinuity is distinctly rare, with only two previous cases reported in the literature, one of which was associated with a familial history of heart block. The cardiac conduction systems of two cases of isolated congenitally complete heart block were serially sectioned and analyzed histopathologically. The findings were correlated with the clinical features, in particular, the family histories and maternal serum anti-Ro antibodies. Both cases, a 9-day-old neonate and an 8-year-old schoolgirl, showed a combination of nodoventricular and intraventricular discontinuity, with absence of the atrioventricular penetrating bundle, the entire right, and the proximal portion of the left bundle branch. The branching bundle was absent in the first case and replaced by fatty tissue in the second. In contrast to the commoner atrial-axis discontinuity in which the atrioventricular node itself is usually replaced by fibrous or fatty tissue with variable involvement distally, the sinus node, and in particular, the atrioventricular node were normal in both of our cases. There was no family history in either case, whereas tests for the maternal serum anti-Ro antibody were positive in the first but negative in the second case. Intraventricular discontinuity as a cause of isolated congenitally complete heart block is very rare. In our cases, it co-existed with nodoventricular discontinuity. It can be sporadic, familial, or associated with positive maternal serum anti-Ro antibodies.

Atrioventricular Node↗

Extra-articular pigmented villonodular synovitis of the temporomandibular joint.

Pigmented villonodular synovitis, a benign but locally destructive fibrohistiocytic proliferative lesion involving tendon sheaths, bursae and diarthrodial joints, is distinctly rare in the temporomandibular joint. We report one such case occurring in a 42-year-old housewife who presented with a progressively enlarging right zygomatic mass for six months. On exploration, an orange-brown firm mass, 5 x 3 x 2 cm, was seen adherent to the lateral aspect of the capsule of the right temporomandibular joint, and eroding into the inferior aspect of the right temporal bone and part of the mandibular condyle. The mass was completely excised. Pathological examination showed features typical of those of pigmented villonodular synovitis and the lesion was entirely extra-articular in location. The patient remained well with no evidence of local recurrence two years after operation. Review of the literature and careful analysis of the clinicopathological features showed that the vast majority of the reported cases of pigmented villonodular synovitis of the temporomandibular joint belonged to the extra-articular variant, which is associated with a more aggressive local infiltrative behaviour and higher rate of local recurrence than the localized type. The recommended treatment for this condition is therefore wide local excision, aiming to remove the lesion as completely as possible without producing severe disability for the patient.

Adult↗

Benign fibrous histiocytoma of the choroid.

Benign fibrous histiocytoma (BFH) is a common soft tissue tumour. However, its occurrence in the orbit was not well recognised in the past. It is only in recent years that this condition has become more frequently diagnosed. Now, it is believed to be the commonest mesenchymal tumour of the orbit in adults. Its occurrence in the uveal tract is, however, exceedingly rare. Only one case of presumed fibrous histiocytoma of the choroid has been reported in the literature. We report herein a case of BFH of the choroid in the left eye of a Chinese woman. The patient presented with a huge but asymptomatic raised choroidal mass. Results of choroidal biopsy showed no sign of malignancy but definitive diagnosis could not be made. Enucleation was finally performed. The diagnosis was made on detailed evaluation of the results of the immunohistochemical staining and the ultrastructural findings. The patient remained well at the latest follow-up, which was 33 months after enucleation. Although BFH of the choroid is vary rare, its benign nature and the availability of choroidal biopsy for tissue diagnosis make it important to include this as one of the differential diagnoses for amelanotic choroidal mass.

Aged↗

The structure and autonomic innervation of the vesico-ureteric junction in cases of primary ureteric reflux.

OBJECTIVE: To determine the histological structure and autonomic innervation of the vesico-ureteric junction (VUJ) in cases of primary ureteric reflux, to compare the results with those reported previously for non-refluxing VUJs and thus determine possible structural anomalies which could be responsible for vesico-ureteric reflux (VUR). MATERIALS AND METHODS: Nineteen specimens of VUJs with reflux were obtained from four males and 10 females undergoing ureteric reimplantation. Serial frozen sections were cut and stained either with Masson's trichrome or immunostained for protein gene product (PGP 9.5), a general nerve marker, dopamine beta hydroxylase (D beta H), a marker for noradrenergic nerves, or neuropeptide Y (NPY). RESULTS: Longitudinally orientated muscle bundles of narrow diameter accompanied the ureter to its termination at the ureteric orifice. Where they merged with those of the superficial trigone. In some specimens, an additional muscle component was identified, situated on the outer aspect of the ureteric muscle coat, consisting of an incomplete layer of distinctive muscle whose constituent cells formed an interlacing mesh-work. Occasionally, specimens included detrusor muscle which consisted of relatively large diameter compact bundles separated from the ureter by a connective tissue sheath. D beta H- and NPY-immunoreactive (-IR) nerves were numerous among the ureteric muscle bundles. Many NPY-IR nerves occurred within the detrusor muscle while D beta H-IR nerves were mainly perivascular. When present, the outer muscle component was richly innervated by both D beta H- and NPY-IR nerves. PGP immunoreactivity varied among regions in the same section, PGP-IR nerves frequently being less numerous than those containing D beta H or NPY. CONCLUSION: These results indicate that the morphology of the VUJ in cases of VUR is indistinguishable from the normal VUJ described previously. Furthermore, the density and distribution of D beta H- and NPY-IR nerves is identical to that in controls. However, the antigenicity of PGP in the reflux specimens appears to be masked in some regions by an unknown factor.

Autonomic Nervous System↗

Postmortem changes in the immunohistochemical demonstration of nerves in human ventricular myocardium.

In order to delineate the effects of death on the immunofluorescence of autonomic nerves supplying the human ventricular myocardium, we studied percutaneous myocardial samples obtained postmortem from 5 individuals within 3 h of death. Subsequent samples were obtained daily from the same individuals up to a total of 5-11 d. The antibodies employed included those against protein gene product 9.5 to demonstrate nervous tissue, dopamine beta-hydroxylase and tyrosine hydroxylase to reveal catecholaminergic neural tissue and neuropeptide Y. An indirect immunofluorescence technique using the avidin-biotin method was employed. The density of myocardial protein gene product 9.5 immunoreactive nerves declined on the 7th day, and became markedly diminished by the 11th day. Immunoreactive dopamine beta-hydroxylase nerves decreased on the 5th day, and were difficult to identify by the 9th day. The density of tyrosine hydroxylase and neuropeptide Y containing nerves rapidly diminished on the 3rd and 4th days, and became undetectable by the 7th and 8th days, respectively. The present results indicate that, depending on the type of antibodies used, immunohistochemical techniques can be used on human hearts obtained up to within 6 d of death to study cardiac innervation.

Aged↗

Viral E6-E7 transcription in the basal layer of organotypic cultures without apparent p21cip1 protein precedes immortalization of human papillomavirus type 16- and 18-transfected human keratinocytes.

Organotypic cultures of human keratinocytes provide a useful model system to study human papillomavirus (HPV)-host cell interactions. In this study, we analyzed organotypic cultures of two HPV type 16 (HPV16) (FK16A and FK16B)- and two HPV18 (FK18A and FK18B)-transfected keratinocyte cell lines through the process of immortalization in vitro. For FK16A and FK18B cells, passages of both mortal cells in their extended life span and subsequent immortal stages were studied. Mortal cells of FK16A and FK18B showed a morphology reminiscent of mild to moderate dysplasia, whereas in their immortal descendants, severely dysplastic features were observed. Immortal FK18A cells were mildly to moderately dysplastic, while FK16B cells were severely dysplastic. The increasing degrees of dysplasia were associated with a decreasing expression of differentiation markers cytokeratin 10 and profilaggrin. All raft cultures expressed E6-E7 mRNAs in the basal layer, while the amount of viral transcripts in the suprabasal cells was in general proportional to the degree of dysplasia. In all cases, E6-E7 transcription and dysplastic features were highly correlated with cellular proliferation, as assessed by Ki-67 (MIB-1) antigen expression. Moreover, high levels of E6-E7 transcription and expression of p21cip1 protein in the basal layer seemed to be mutually exclusive. We conclude that expression of E6-E7 in the basal cells associated with increased proliferation in the absence of detectable p21cip1 protein is apparently necessary but not sufficient for immortalization, or for the loss of terminal differentiation, for which yet to be discovered additional events are required. The model system described in this study provides a valuable tool to analyze alterations in viral transcription regulation during HPV-mediated cell transformation.

Cell Division↗

The carboxyl-terminal region of the human papillomavirus type 16 E1 protein determines E2 protein specificity during DNA replication.

The mechanism of DNA replication is conserved among papillomaviruses. The virus-encoded E1 and E2 proteins collaborate to target the origin and recruit host DNA replication proteins. Expression vectors of E1 and E2 proteins support homologous and heterologous papillomaviral origin replication in transiently transfected cells. Viral proteins from different genotypes can also collaborate, albeit with different efficiencies, indicating a certain degree of specificity in E1-E2 interactions. We report that, in the assays of our study, the human papillomavirus type 11 (HPV-11) E1 protein functioned with the HPV-16 E2 protein, whereas the HPV-16 E1 protein exhibited no detectable activity with the HPV-11 E2 protein. Taking advantage of this distinction, we used chimeric E1 proteins to delineate the E1 protein domains responsible for this specificity. Hybrids containing HPV-16 E1 amino-terminal residues up to residue 365 efficiently replicated either viral origin in the presence of either E2 protein. The reciprocal hybrids containing amino-terminal HPV-11 sequences exhibited a high activity with HPV-16 E2 but no activity with HPV-11 E2. Reciprocal hybrid proteins with the carboxyl-terminal 44 residues from either E1 had an intermediate property, but both collaborated more efficiently with HPV-16 E2 than with HPV-11 E2. In contrast, chimeras with a junction in the putative ATPase domain showed little or no activity with either E2 protein. We conclude that the E1 protein consists of distinct structural and functional domains, with the carboxyl-terminal 284 residues of the HPV-16 E1 protein being the primary determinant for E2 specificity during replication, and that chimeric exchanges in or bordering the ATPase domain inactivate the protein.

Adenosine Triphosphatases↗

Transcription factor YY1 represses cell-free replication from human papillomavirus origins.

We have established cell-free replication for the human papillomavirus type 18 (HPV-18) origin of replication (ori)-containing DNA by using purified HPV-18 E1 and E2 gene products expressed as fusion proteins in Escherichia coli. The transcription factor YY1 has been shown to regulate RNA transcription by binding to a sequence overlapping the putative E1 protein binding site in the HPV-18 ori. We show that exogenously added YY1 fusion protein inhibited HPV-18 ori replication. Cotransfection of YY1 expression vectors also inhibited transient replication in 293 cells. However, inhibition did not appear to be mediated by binding to its cognate site in the ori as YY1 also inhibited the replication of the HPV-11 ori, which does not have a known or suspected YY1 binding site. Moreover, inhibition was not alleviated by the inclusion of YY1 binding oligonucleotides in the replication reaction mixtures. Rather, we demonstrated a direct interaction between purified fusion E2 protein and fusion YY1 protein by the pull-down assay and a partial restoration of replication activity by an elevated E2 protein concentration. These results suggest that YY1 can inhibit HPV ori replication by interfering with E2 protein functions.

Cell-Free System↗

A technique for enhancing union of allograft to host bone.

The aim of limb-salvage surgery in malignant bone tumours in children is to restore function and eradicate local disease with as little morbidity as possible. Allografts are associated with a high rate of complications, particularly malunion at the allograft-host junction. We describe a simple technique which enhances union of allograft to host bone taking advantage of the discrepancy in size between the adult allograft and the child's bone. This involves lifting a flap of periosteum before resection from the host bone, which is then telescoped into the allograft medullary canal, which may require internal burring or splitting, for a distance of 1.5 to 2 cm and covering the bone junction with the periosteal flap. This is more stable than conventional end-to-end opposition. For each centimetre of telescoping the surface area available for bony union is increased more than three times. The periosteal flap also augments union. Additional surface fixation with a plate and screws is not necessary. We have used this technique in nine children, in eight of whom there was complete union at a mean of 16 weeks. Delayed union, associated with generalised limb osteoporosis, occurred in one. Early mobilisation, with weight-bearing by three weeks, was possible. There was only one fracture of the allograft.

Bone Neoplasms↗

Post-transcriptional induction of p21cip1 protein in condylomata and dysplasias is inversely related to human papillomavirus activities.

Infections of the genital and oral epithelia by human papillomaviruses cause condylomata, papillomas, and squamous intraepithelial neoplasms, some of which can progress to invasive cancers. We describe an induction of p21cip1/WAF1/sdi1 protein in a fraction of the spinous cells in benign lesions and in cervical intraepithelial neoplasia grades I and II. The induction appears to be post-transcriptional and independent of p53. p21cip1 antigen-positive cells were sporadic in cervical intraepithelial neoplasia III and rare and focal in carcinomas. In contrast, p21cip1 protein was below or at the threshold of detection in the differentiated cells of normal squamous epithelia from different body sites despite an up-regulation of p21cip1 RNA. In cervical intraepithelial neoplasias from patients who were also positive for the human immunodeficiency virus, there was an additional increase in p21cip1 RNA in the upper spinous cells without concomitant p21cip1 protein induction. A consistent inverse relationship was observed between the p21cip1 protein induction and abundant human papillomavirus DNA and RNAs. We propose that p21cip1 protein induction is a novel host response that inhibits viral DNA replication and thus prevents elevated viral transcription. This hypothesis can partly account for the heterogeneity and the differentiation-dependent viral activities commonly observed in benign human papillomavirus lesions.

Adenocarcinoma↗

Targeted expression of activated erbB-2 to the epidermis of transgenic mice elicits striking developmental abnormalities in the epidermis and hair follicles.

The erbB-2 proto-oncogene belongs to a receptor tyrosine kinase family that includes the epidermal growth factor receptor, erbB-2, erbB-3, and erbB-4. erbB-2 is expressed in basal cells of the squamous epithelia and the outer root sheath of the hair follicles, but its function in epidermal development has not been well studied. To investigate its role in the skin, we created transgenic mice harboring an activated erbB-2 oncogene under the control of the human keratin 14 promoter. The keratin 14 promoter directed its expression to cells in which erbB-2 is normally expressed, whereas the activated receptor gene ensured increased signaling. All transgenic founder mice exhibited extensive and striking skin phenotype, including epidermal hyperplasia, preneoplasia, papilloma, hyperkeratosis, and dyskeratosis. The majority of the hair follicles were replaced by bizarre hyperproliferative intradermal squamous invaginations, whereas the rest of the follicles exhibited severe hyperplasia and disorganization. All but one of the transgenic mice died before or shortly after birth, probably as a consequence of defects in the skin and esophagus. These observations demonstrate that the skin is sensitive to erbB-2 signaling, suggesting an important role for this receptor tyrosine kinase in epidermal growth, differentiation, and hair follicle morphogenesis.

Animals↗

The differential expression of the HER-2/neu oncogene among high-risk human papillomavirus-infected glandular lesions of the uterine cervix.

OBJECTIVE: Our purpose was to examine the relationship between HER-2/neu expression and human papillomavirus infection in cervical glandular neoplasia. STUDY DESIGN: Cases of cervical adenocarcinoma in situ and invasive adenocarcinoma were selected for study. Human papillomavirus typing was performed by in situ hybridization. HER-2/neu was detected by in situ hybridization and immunohistochemistry. Fisher's exact test was used to assess for statistical significance. RESULTS: Fifteen cases of adenocarcinoma in situ and invasive adenocarcinoma were analyzed. In situ hybridization detected HER-2/neu messenger ribonucleic acid in 8 cases, whereas immunohistochemistry detected protein in 5 cases. Overall, HER-2/neu activity was present in 10 cases (66.7%). HER-2/neu messenger ribonucleic acid was detected more commonly in lesions associated with human papillomavirus type 16 versus type 18 (85.7% vs 25.0%, p = 0.04). CONCLUSION: HER-2/neu is frequently expressed in human papillomavirus-infected glandular lesions of the cervix. In situ hybridization may provide a more sensitive indicator of HER-2/neu activity over immunohistochemistry. Preferential expression of HER-2/neu messenger ribonucleic acid was detected in human papillomavirus type 16 versus type 18 lesions. Further study is warranted to examine relationships between human papillomavirus infection and HER-2/neu expression.

Adenocarcinoma↗

Co-existing pleomorphic and tubular basal cell adenomas of the parotid gland.

We report a hitherto undescribed case of co-existence of a pleomorphic adenoma and a tubular basal cell adenoma affecting the superficial lobe of the left parotid gland of a 53-year-old man. The histology of the pleomorphic adenoma is also of interest in that the prominent adipose metaplasia of its myxoid stroma yielded an appearance reminiscent of myxoid lipoma. The tubular basal cell adenoma showed gross cystic change, and its solid portion consisted of closely packed tubules lined by double layers of cuboidal cells with little intervening stroma. Unlike Warthin's tumour and membranous basal cell adenoma, both pleomorphic and tubular basal cell adenomas exhibit no propensity towards multicentricity or bilaterality. We, therefore, believe that their co-existence in the superficial lobe of the parotid gland of our patient is a mere coincidence rather than association.

Adenoma↗