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Biomedical subjects

K C Ho

Publications and source records attributed to K C Ho.

At least 19 recordsLinked to original sources

Fulminant progression of demyelinating disease after valproate-induced encephalopathy.

We report the clinical, radiologic, and pathologic features of a patient who had fulminant demyelinating disease and who experienced acute progression of his disease after an episode of valproate-induced hyperammonemic encephalopathy. The role hyperammonemia played in the progression of the demyelination is uncertain. This case raises concern of a possible risk with the use of valproic acid in the subset of patients with fulminant demyelinating disease.

Adult

Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis.

About 10% of gastric carcinomas including lymphoepithelioma-like carcinoma and adenocarcinoma are associated with Epstein-Barr virus (EBV) infection. In EBV-associated gastric carcinomas, the tumor cells express Epstein-Barr nuclear antigen 1 (EBNA-1) but not EBNA-2, -3A, -3B, or -3C, leader protein, or latent membrane proteins (LMPs) because of gene methylation. Only a few exceptional cases have LMP1 expression in tumor cells as demonstrated by immunohistochemical studies. To elucidate the biological effects of LMP1 and the significance of its restricted expression in EBV-associated gastric carcinomas, the LMP1 gene was transferred into EBV-negative gastric carcinoma cell lines (SCM1 and TMC1) and into EBV-negative nasopharyngeal carcinoma (NPC) cells (HONE-1) as a control. The biological effects of LMP1 in gastric carcinoma cells were monitored in vitro and in vivo. These results showed that the consequence of LMP1 expression is a growth enhancement in NPC cells, but it is a growth suppression in gastric carcinoma cells. The LMP1-expressing gastric carcinoma cells had a reduced growth rate, colony-forming efficiency, mean colony size, and tumorigenicity and a lower malignant cytological grade. The reduced growth rate, colony-forming efficiency, and mean colony size were partially reversible in vitro with treatment with LMP1 antisense oligonucleotide. In addition, enhanced apoptosis was found in the LMP1-expressing gastric carcinoma cells. This suggests that LMP1 may negatively modulate the malignant potential of gastric carcinoma cells via an enhancement of apoptosis. We concluded that the restriction of LMP1 expression in EBV-associated gastric carcinomas may lead to a growth advantage for tumor cells by avoiding LMP1 apoptotic effects and immunologically mediated elimination.

Adenocarcinoma

Bilateral choroidal metastases as the initial presentation of a small breast carcinoma: a case report.

Most ocular tumors metastasize from systemic origins in breast carcinoma in females, and bronchial carcinoma in males. Here, we report a case of choroidal carcinoma metastasis from the breast with visual problems being the only initial manifestations. In this case, both eyes were involved at almost the same time, with initial manifestation of blurred vision which progressed to complete visual loss. At first, the patient was diagnosed with malignant melanoma, and enucleation of the right eye was performed in another hospital. However, the tumor had already metastasized rapidly to numerous organs, including the lungs, brain and bone, although it had not affected the liver. Clinical presentations were, therefore, not compatible with those of malignant melanoma, which has usually been reported to metastasize to the liver. Persistent hypercalcemia and raised carcinoembryonic antigen (CEA) concentrations prompted investigations into the possibility of systemic malignancy. A very small breast nodule was finally located by thorough physical examination, and a lumpectomy was performed. A detailed review of the histopathology showed the tumors from the breast and the right eye to have the same origin. Simultaneous bilateral choroidal metastases from other malignancies is not uncommon; however, it is quite rare for breast carcinoma to present with visual problems as a first manifestation. Detailed history taking and physical examination are therefore essential when searching for a primary tumor, so that appropriate therapy can be given earlier.

Adult

CuTira brachytherapy: a new combination of radioactive copper isotopes and the hypoxic cytotoxin, tirapazamine, for targeted tumor therapy.

We previously showed a significant enhancement of tirapazamine-induced cytotoxicity and DNA damage after binding with copper. This result suggests that conjugates of tirapazamine with radioactive copper, i.e., 64Cu and 67Cu, may offer potential for targeted therapy of a wide range of advanced stage tumors including a possible treatment for patients with solitary hepatocellular carcinoma by intrahepatic arterial infusion. Major supporting considerations include: (a) tirapazamine having a high selective toxicity against hypoxic cells; (b) the nature of radioactive decay of these copper isotopes and obtainable high specific activity; and (c) simple procedure for the production of copper-tirapazamine complex.

Brachytherapy

Contrast media of high and low molecular weights in the detection of recurrent herniated disks.

PURPOSE: Our goal was to compare contrast enhancement of recurrent herniated disk fragments and scar after intravenous injection of a new high-molecular-weight contrast medium, Gadomer 17 (gadomer), with that after injection of a low-molecular-weight contrast medium, (gadopentetate dimeglumine). METHODS: Recurrent herniated disks were modeled in dogs by placing a fragment of intervertebral disk cartilage in the epidural space at laminectomy. MR imaging was performed with one of the contrast media at 20 and 50 days and with the other medium at 22 and 52 days. The changes in signal intensity from baseline in the disk fragment and in the adjacent scar tissue was measured at 2, 22, and 45 minutes. Differences were tested for significance with a student t-test. RESULTS: At 50 days after surgery, signal intensity in the intervertebral disk fragment increased by an average of 0.52 at 2 minutes after injection of gadomer and by an average of 0.90 after injection of gadopentetate. For scar, the increases in signal intensity were 1.41 (gadomer) and 1.62 (gadopentetate). At 22 and 45 minutes after injection, the signal intensity change in the disk fragment continued to be significantly greater after gadopentetate than after gadomer injection. In comparison with the changes at 50 days, both scar and disk fragment tended to show greater signal intensity changes at 20 days. Signal intensity changes in the disk fragments were significantly less after gadomer than after gadopentetate. Signal intensity changes in scar were slightly less with gadomer than with gadopentetate. CONCLUSION: Greater contrast is achieved between scar and recurrent herniated disk with a higher-molecular-weight contrast medium than with one of lower molecular weight. The difference between the high- and low-molecular-weight contrast media increases with maturation of the scar tissue.

Animals

Cytochrome oxidase in Alzheimer's disease: biochemical, histochemical, and immunohistochemical analyses of the visual and other systems.

Defects in oxidative metabolism have been implicated in Alzheimer's disease (AD). The present study evaluated the level of cytochrome oxidase (C.O.), an indicator of neuronal oxidative capacity, in various brain regions of post-mortem AD and control patients. We found a statistically significant reduction in C.O. levels in all cortical areas examined, including the primary and secondary visual cortices. In addition, all layers of the dorsal lateral geniculate nucleus and sublaminae of the primary visual cortex in AD cases examined suffered a reduction in their relative C.O. activity and protein amount. Our results suggest a generalized suppression of oxidative metabolism throughout the cortex, as well as in a major subcortical visual center in AD. Such hypometabolism may form the basis for not only deficits in higher cortical functions, but also a variety of visual dysfunctions known to occur in AD.

Alzheimer Disease

Analysis of bcl-2 expression in normal, inflamed, dysplastic nasopharyngeal epithelia, and nasopharyngeal carcinoma: association with p53 expression.

To further characterize bcl-2 expression in nasopharyngeal carcinoma (NPC), the authors analyzed bcl-2 expression immunohistochemically in biopsy specimens from 101 cases of NPC, of which 65 had the component of normal nasopharyngeal epithelium (NPE), 24 with dysplastic lesions adjacent to carcinoma, and 14 with both primary and metastatic lesions. An additional 25 nasopharyngeal biopsies of NPE from patients with chronic inflammation of nasopharynx were also included. The percentage of detectable bcl-2 expression shown in NPC (80%) and adjacent dysplastic lesions (71%) was significantly higher than in adjacent NPE (37%) and NPE from patients with chronic inflammation of the nasopharynx (30%) (P < .05). In both normal and inflamed NPE, the detectable bcl-2 expression was restricted to the basal cells; however, in dysplastic lesions, the bcl-2 staining distribution was increased with the dysplastic cell layers, and in entire layers of epithelium in severe dysplasia or carcinoma in situ. In addition, the staining intensity of bcl-2 in carcinomas and adjacent dysplastic lesions was generally stronger than that of adjacent NPE. These observations suggest that the expression of bcl-2 in dysplasia and carcinoma is enhanced relative to that of adjacent NPE. Enhanced bcl-2 expression to prevent apoptosis seems to occur from the early stages and may play an important role in the carcinogenesis of NPC. Furthermore, up to 77% of NPC with the coexpression of bcl-2 and p53 was observed and suggested that the association of bcl-2 and p53 expression seems to occur from the early stages of the development of NPC. The overexpression of p53 protein in NPC suggests that the mutation of p53 gene or altered function of wild-type p53 protein may contribute to the pathogenesis. It is conceivable that the presence of both enhanced bcl-2 expression and altered p53 functions may play a crucial synergistic effect in the carcinogenesis of NPC.

Adult

Anatomic relationship of the oculomotor nuclear complex and medial longitudinal fasciculus in the midbrain.

PURPOSE: To compare the MR characteristics of the oculomotor nucleus with its appearance on anatomic images. METHODS: Specimens of cadaveric brains were imaged in a 3.0-T MR imager equipped with a 3.0-cm solenoid coil. The specimens were sectioned, stained, and examined histologically. On anatomic sections, the oculomotor nuclei, medial longitudinal fasciculus, red nuclei, and oculomotor nerve were identified. The MR images were then compared with the anatomic sections. RESULTS: The oculomotor nuclei, medial longitudinal fasciculus, red nuclei, and oculomotor nerve could be identified on MR images by their size, shape, signal intensity, and location. CONCLUSION: MR images show the anatomic relationship of the oculomotor nerve complex, medial longitudinal fasciculus, and related structures in the brain stem.

Abducens Nerve

Effect of degeneration of the intervertebral disk on the process of diffusion.

PURPOSE: To test the hypothesis that diffusion of contrast medium into the intervertebral disk is affected by the integrity of the nucleus pulposus and annulus fibrosus. METHODS: In canine intervertebral disks, defects were made in the annulus fibrosus and nuclear material was removed from the disk with a nucleotome. MR imaging was performed with intravenous contrast medium at 15, 30, 60, and 90 days after the procedure. The diffusion of contrast medium in the intervertebral disk was studied by visual inspection and by measuring changes in signal intensity. The intervertebral disk were classified at each MR study as normal or abnormal on the basis of the signal intensity on T2-weighted images. RESULTS: In untreated disks after intravenous injection of contrast medium, a band of increased signal intensity was observed near the endplates that became wider with time and approached the center of the disk. In six of the 12 treated disks, the band of increased signal intensity was visibly diminished or less discrete compared with that in the control disks. Weeks later, these treated disks showed diminished signal intensity on T2-weighted images and bulging of the annulus fibrosus. CONCLUSIONS: Intervertebral disks with defects in the annulus fibrosus and reduced cartilage content were characterized by abnormal diffusion of contrast medium into the disk, and changes characteristic of early disk degeneration were detected subsequently.

Animals

Spontaneous remission in acute myelogenous leukemia: a case report.

A 62-year-old woman with hypocellular acute myelogenous leukemia experienced spontaneous remission after repeated episodes of severe infections. Transient surge of profuse blasts in the peripheral blood was observed prior to the occurrence of spontaneous remission. The duration of the spontaneous remission was relatively short, and the disease relapsed five months later. A second complete remission was achieved after chemotherapy with low-dose cytosine arabinoside. The patient finally died of relapsed leukemia after a second remission of three year duration. Possible mechanisms implicated in the occurrence of spontaneous remission in this patient are discussed.

Antimetabolites, Antineoplastic

Malignant lymphomas of sinonasal region, including cases of polymorphic reticulosis: a retrospective clinicopathologic analysis of 34 cases.

BACKGROUND: Lymphomas occurring in nasal cavities and paranasal sinuses are uncommon neoplasms in Western, but are reported to be higher in Oriental, countries. A retrospective study was performed to analyze the clinical and pathological characteristics of sinonasal lymphomas/polymorphic reticulosis at Taichung Veterans General Hospital during a 14-year period. METHODS: At Taichung Veterans General Hospital, 37 patients with sinonasal lymphomas (including three patients with polymorphic reticulosis) were seen from November 1982 through September 1996. Excluding three patients without sufficient data, a total of 34 patients with their clinical records were reviewed. Clinical information regarding characteristics of the tumors, histological studies, treatment modalities and follow-up was collected for analysis. RESULTS: The 34 patients who underwent review showed a male-to-female ratio of 2.1:1. Median age was 60 years (range 13-83 years). The most common symptoms were nasal obstruction, nasal discharge/rhinorrhea and epistaxis. Median duration of symptoms at the time of diagnosis was two months. The most frequently involved sites were nasal cavities (right more than left side). There were 31 non-Hodgkin's lymphomas and three polymorphic reticuloses. The pathological classifications revealed 13 diffuse large cell lymphomas, 14 diffuse mixed small and large cell lymphomas and four pleomorphic T-cell lymphomas. Of the 21 adequately staged patients, 13 patients were in stage I; four, stage II; two, stage III and two, stage IV. The immunophenotypic study was performed in 20 patients. Eighteen (90%) of them were T-cell lymphomas and only two cases (10%) derived from B-cell. Though approach to therapy and follow-up periods varied during the time period covered by this study, the differences in survival according to treatment modalities were not statistically significant. The follow-up period ranged from 9 days to 130 months. The mean survival was 84.2 months. The overall five-year survival rate was 63%. CONCLUSIONS: The majority of the cases here were T-cell lymphomas. Most histologic grading by Working formulation belonged to the intermediate grade. Optimal treatment for such a group of patients still has no consensus, but adequate local control is important. If diagnosed and treated early, primary sinonasal lymphomas can be associated with a favorable outcome even with local treatment alone.

Adolescent

Tirapazamine (SR 4233) interrupts cell cycle progression and induces apoptosis.

Tirapazamine (Tira), a bioreductive agent, is highly toxic to cells under low oxygen conditions. Since active investigations of this agent are focusing on its potential as an adjunct of radiotherapy to improve overall effects on radioresistant hypoxic tumor cells, understanding its toxic mechanisms under aerobic conditions is important to the clinical application of this agent. Tira-treated V79 Chinese hamster cells were tested for cytotoxicity by colony assay and growth inhibition by the MTT assay. The survival of V79 cells after being exposed to 100 microM of Tira for 2 h was about 78% of untreated controls. The mitotic cell counts of V79 cells approached zero after 4 h treatment of Tira at 100 microM or 3 h at 300 microM. The fragmentation pattern of DNA isolated from cells 2 h after 300 microM Tira treatment showed characteristics of apoptotic cells. The induction of apoptosis by Tira was also detected by flow cytometric analysis and microscopic observation. These effects of Tira may be part of underlying toxic mechanisms to cells (including normal cells) under aerobic conditions.

Animals

Enhanced malignant progression of nasopharyngeal carcinoma cells mediated by the expression of Epstein-Barr nuclear antigen 1 in vivo.

Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) and mostly classified as poorly differentiated squamous cell carcinoma or undifferentiated carcinoma with early metastasis and a rapidly progressive clinical course. The EBV-encoded latent proteins, Epstein-Barr nuclear antigen 1 (EBNA 1) and latent membrane proteins (LMPs), may be expressed in NPC, but their biological effects are poorly understood. EBNA 1 may predispose B lymphocytes to lymphomagenesis in transgenic mice, but its biological effects in NPC are still unknown. This study investigated the biological effects of EBNA 1 by expressing it in an EBV-negative NPC cell line (HONE-1), which was then inoculated into both nude and severe combined immunodeficiency mice. The EBNA 1 caused HONE-1 cells to grow in a less differentiated pattern and to progress more rapidly, as well as increasing their tumourigenicity and metastatic capability. These data suggest that EBNA 1 may play a critical role in the progressive evolution of NPC.

Animals

Clinical, physiologic, and pathologic evidence for vagus dysfunction in a case of traumatic brain injury.

A trauma victim with locked-in syndrome demonstrated severely decreased bowel sounds, intact response to suppository, and elevated, but unchanging pulse. Absent cardiac response to tracheal suctioning, high gastric residual volumes, and pulmonary edema in response to a urecholine challenge demonstrated dysfunction in the automatic system. Symptoms persisted for 2 1/2 years until death. At autopsy, asymmetric bilateral involvement of the dorsal motor nucleus of the vagus and of the nerve tract in the medulla were demonstrated. In contrast, a control subject with locked-in syndrome caused by a stroke did not demonstrate these phenomena. In trauma patients with delayed gastric emptying, measurement of the heart rate response to deep suctioning may lead to the diagnosis of this vagus dysfunction syndrome.

Adult

Correlative MR-anatomic study of the median nerve.

OBJECTIVE: The purpose of our study was to evaluate the effectiveness of MR imaging for showing the intrinsic anatomy of a peripheral nerve. Cadaver wrist specimens that included the median nerve were imaged with MR imaging at 3 T, then sectioned, stained, and inspected grossly and microscopically. The size, shape, and signal intensity of the sheath and axonal structures in the median nerve were identified in MR images by comparison with anatomic sections. CONCLUSION: This study suggests that MR imaging with sufficiently high-resolution techniques shows the internal structure of peripheral nerves. These results suggest that MR imaging may be a means to distinguish neuritis, tumor, degeneration, or fatty proliferation in a peripheral nerve and to evaluate the nerve before microsurgical anastomosis.

Adipose Tissue

MR appearance of the internal architecture of Ammon's horn.

PURPOSE: To determine whether the four subdivisions of Ammon's horn and six layers of CA1 seen histologically can be demonstrated with MR imaging. METHODS: Specimens of cadaver brains were imaged in a 3.0-T MR imager with a 3.0-cm solenoid coil. The specimens were sectioned, stained, and examined histologically. On anatomic sections, the four subdivisions of Ammon's horn and six layers of CA1 were identified. The MR images were then compared with the anatomic sections. RESULTS: Using geographic characteristics, we identified the four subdivisions of Ammon's horn. In CA1, the six layers could be identified by variations in signal intensity, width, and location. CONCLUSION: This study suggests that, with MR imaging of sufficiently high resolution, the internal architecture of Ammon's horn may be identified.

Brain Mapping

Ionic versus nonionic paramagnetic contrast media in differentiating between scar and herniated disk.

PURPOSE: To compare the MR contrast enhancement produced by ionic and nonionic paramagnetic contrast media in herniated disk fragments with that in epidural scar tissue. METHODS: A recurrent herniated disk was modeled in canines by using laminectomy to place a fragment of disk cartilage in the epidural space. The dogs were studied 88 and 90 days after laminectomy with MR imaging enhanced with an ionic or a nonionic paramagnetic contrast medium. Contrast enhancement of the epidural scar tissue and the epidural disk fragment was measured at 2, 22, and 45 minutes after the injection. RESULTS: Contrast enhancement was consistently and significantly higher in scar tissue than in disk fragments, although the difference decreased between 2 and 45 minutes after administration of contrast medium. Enhancement of disk fragments was less with the ionic than with the nonionic contrast medium. Contrast between the disk fragments and scar was also greater with the ionic than with the nonionic medium. CONCLUSIONS: The contrast between recurrent disk fragments and scar tissue is affected by the timing of the scan and the choice of contrast medium. Scans obtained immediately after the injection of contrast medium show more contrast between disk fragment and scar than do delayed scans. Recurrent herniated disk fragments are more effectively shown by ionic than by nonionic media.

Animals