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Biomedical subjects

K C Ho

Publications and source records attributed to K C Ho.

At least 55 records · Page 3Linked to original sources

Selective internal radiation therapy with intra-arterial iodine-131-Lipiodol in inoperable hepatocellular carcinoma.

UNLABELLED: From August 1990 to June 1993, 26 patients with inoperable hepatocellular carcinoma were treated with intra-arterial iodine-131-Lipiodol (131I-L). METHODS: Iodine-131-Lipiodol was given through either an implantable arterial port (9 patients) or during hepatic angiography (17 patients). All 26 patients had multiple lesions, 3 had involved resection margin after surgical resection and 1 had diffuse infiltrative lesions. The median size of the largest tumor among 22 patients with a measurable lesion was 4.5 cm (2-9.5 cm). The end points are tumor response in terms of tumor size, change in serum alpha-fetoprotein level, toxicity of treatment and overall survival. RESULTS: Twenty-three patients received a single treatment of 1.11-2.22 GBq (30-60 mCi)131I-L. Three patients received 2.22-4.44 GBq (60-120 mCi)131I-L in three fractions. Considering both radiological regression and reduction in serum alpha-fetoprotein level as objective response criteria, the overall response rate was 52% (13 out of 25 patients with evaluable disease). Ten out of 15 patients who had raised alpha-fetoprotein levels had more than 50% reduction and 8 patients had more than 90% reduction in alpha-fetoprotein level. Since analysis, 19 patients have died and 7 remain alive, giving a minimum median survival of 6 mo (range 1.2-16.6 mo), with 4 surviving more than 1 yr calculated from the day of treatment. There was only one patient who had late deterioration of liver function compatible with radiation hepatitis. There was no bone marrow toxicity documented in any patients. CONCLUSION: Treatment with intra-arterial 131I-L was well tolerated in patients with inoperable hepatocellular carcinoma and produced an objective response of 52% with median survival of 6 mo. A fractionated dose of 131I-L was feasible and the radiation dose could be escalated safely.

Carcinoma, Hepatocellular↗

Destructive hostility: the Jeffrey Dahmer case. A psychiatric and forensic study of a serial killer.

We were involved as forensic experts in the case of the serial killer Jeffrey Dahmer. We discuss the scene and victim autopsy findings, with a brief consideration of the basic emotion of hostility. These findings support the thesis that at the basis of this serial killer's behavior were primary unconscious feelings of hate that he had channeled into a sadistic programmed destruction of 17 young men. The interview of the serial killer, the photographic scene documentation, and the autopsy findings stress the ambivalent homosexuality of the killer, his sexual sadism, his obsessive fetishism, and his possible cannibalism and necrophilia.

Adolescent↗

Utility of high-dose contrast enhancement for detecting recurrent herniated intervertebral disks.

PURPOSE: To study the utility of high-dose contrast enhancement in the detection of recurrent herniated disk fragments. METHODS: Recurrent herniated disks were modeled in nine dogs by placing a fragment of normal autologous disk tissue in the epidural space at laminectomy. MR was performed at 30, 60, and 90 days with 0.3 mmol/kg of gadoteridol and repeated 24 hours later with 0.1 mmol/kg of gadopentetate dimeglumine. Contrast enhancement in the disk and scar tissue was measured and conspicuousness of the disk fragments assessed. RESULTS: In 70% of the animals, disk fragments were more conspicuous with the larger dose of contrast medium than with the smaller dose. In 30% of animals the conspicuousness was approximately equal. Contrast between disk fragment and scar decreased with time elapsed since surgery, with time elapsed since contrast-medium injection, and with decreasing dose of contrast medium. CONCLUSION: In the experimental model, increased conspicuousness of disk fragments was achieved with the larger dose of contrast medium. A clinical study is needed to confirm that a contrast-medium dose of 0.3 mmol/kg improves detection of recurrent herniated disks over a dose of 0.1 mmol/kg.

Animals↗

Imaging white matter tracts and nuclei of the hypothalamus: an MR-anatomic comparative study.

PURPOSE: To evaluate the MR appearance of the hypothalamus and its associated white matter tracts. METHODS: Coronal and sagittal spin-echo images were obtained in cadaver brains. Gross and histologic sections were made of the cadaver brains. The size, shape, signal intensity, course, and pattern of structures in the hypothalamic region were identified in MR images by comparison with the anatomic sections. RESULTS: The mamillary bodies, paraventricular zone of hypothalamic nuclei, postcommissural fornix, mammillothalamic fasciculus, and anterior commissure were identified on the MR images. CONCLUSION: This study suggests that, with MR imaging of sufficiently high resolution, some of the tracts and nuclei in the hypothalamus may be identified.

Humans↗

A complex response element in intron 1 of the androgen-regulated 20-kDa protein gene displays cell type-dependent androgen receptor specificity.

The androgen-regulated 20-kDa protein gene consists of four exons that code for a major secretory protein of rat ventral prostate. Analysis of its potential cis-acting transcriptional regulatory elements revealed that a large intron 1 region (In-1) had stronger androgen response element (ARE) activity than did the 5'-flanking DNA. In cotransfected CV1 cells, In-1 and its most active subfragment In-1c functioned as AREs but not glucocorticoid response elements (GRE). Nevertheless several ARE/GRE-like partial palindromic sequences are present in In-1c, and it bound both androgen receptors and glucocorticoid receptors in mobility shift assays. A cluster of three ARE/GRE-like sequences contained within a 39-base pair sequence of In-1c had both ARE and GRE activities when analyzed as an isolated oligonucleotide, suggesting that other elements within In-1c determined its ARE specificity. In addition to ARE/GRE-like sequences, In-1c contains putative response elements for the transcription factors AP1, CREB, AP2, OCT-1, C/EBP, and a number of inverted and direct repeats. The ARE specificity of In-1c observed in CV1 cells was diminished in PC3 and HeLa cells transiently cotransfected with an androgen receptor or glucocorticoid receptor expression vector together with an In-1c reporter vector; however, the ARE activity of In-1c was greater than its GRE activity in these cell lines. Interestingly, a 131-base pair subfragment of In-1c retained ARE specificity in all three cell lines.

Amino Acid Sequence↗

The etiology of focal spinal arachnoiditis. An experimental study.

Focal arachnoiditis and back pain have been attributed to potentially irritating substances leaking into the spinal canal from the lumbar intervertebral disc or facet joints. Through experimentation this hypothesis was tested: the nucleus pulposus (escaping from the intervertebral disc), lactic acid (from anaerobic glycolysis in the disc), chondroitin sulfate (a component of glycosaminoglycans in the disc), or synovial fluid (from degenerating facet joints) causes inflammation in the meninges if it contacts the dura mater. The test and control substances were injected into the epidural space of monkeys. Twelve weeks later the animals were killed; the dural sac was exposed by total lumbar laminectomy, grossly inspected, and then removed, fixed, sectioned, stained, and examined microscopically. Nucleus pulposus produced significant fibrosus in the arachnoid and epidural spaces; the other substances did not cause fibrosus or inflammation. The study suggests that leakage of nucleus pulposus into the epidural space causes an inflammatory response in the arachnoid and epidural spaces.

Animals↗

Vascularized iliac crest grafts: evaluation of viability status with marrow scintigraphy.

Forty-three vascularized iliac crest grafts in the femoral neck region in 38 patients were assessed with marrow scintigraphy. Twenty grafting procedures had been performed for treatment of fractures, 16 for nontraumatic osteonecrosis, and seven for focal bone lesions. Scintiscans were obtained preoperatively and in the early and late postoperative period. Anterior images of the hips were obtained 30 minutes after intravenous injection of 4 mCi (148 MBq) of technetium-99m tin colloid by using a gamma camera with a low-energy, general-purpose collimator. The viable graft was detected as an area of tracer uptake corresponding to the configuration of the graft on radiographs. Marrow scintigraphy at 12 weeks showed that 24 grafts were viable, 11 were nonviable, and eight were indeterminate. Early and late results concurred in 36 of 43 (84%) grafts. Nonviable grafts occurred most frequently in fractures in the elderly. In seven patients who subsequently required total hip replacement, six grafts were nonviable while one was indeterminate at 12 weeks. Results indicate that marrow scintigraphy is useful in the treatment of patients with vascularized iliac crest bone grafts.

Adolescent↗

Cytotoxicity and manganese superoxide dismutase induction by tumor necrosis factor-alpha and ionizing radiation in MCF-7 human breast carcinoma cells.

Both tumor necrosis factor-alpha (TNF) and ionizing radiation cause active-oxygen radical-mediated cell injuries and cell death. Thus cells treated by both TNF and radiation may suffer greater injuries than cells treated by either agent alone. On the other hand, TNF or radiation treatment can stimulate the expression of a mitochondrial superoxide scavenging enzyme, manganese superoxide dismutase (MnSOD), which can lower the cytotoxic effects of both agents. Thus, the induction of MnSOD by radiation may interfere with the cytotoxic action of TNF and vice versa. We used a human breast tumor cell line, MCF-7, to determine the interaction of TNF and radiation on cytotoxicity and MnSOD expression. TNF was found to be more effective as a cytotoxic agent when used before than after radiation treatment. These observations suggest that radiation induced-MnSOD was more effective in reducing the cytotoxic effect of TNF whereas TNF induction of MnSOD was less effective in counteracting the radiation action. Our results not only underscore the different effects of the treatment order of TNF and radiation, but also point to potential implication in the radiotherapy of breast tumors.

Breast Neoplasms↗

Molecular cloning of rat prostate transglutaminase complementary DNA. The major androgen-regulated protein DP1 of rat dorsal prostate and coagulating gland.

Complementary DNA (cDNA) that codes for a major androgen-dependent secretory protein of rat coagulating gland and dorsal prostate, dorsal protein 1 (DP1), was isolated by molecular cloning. Recombinant DP1 cDNA clones were identified from a bacteriophage lambda gt11 rat coagulating gland expression library using an affinity purified polyclonal antibody. Amino acid sequence deduced from DNA contained sequences identical with several DP1 cyanogen bromide cleavage fragments. Northern blot hybridization of poly(A) RNA isolated from intact rat dorsal prostate and coagulating gland revealed a predominant messenger RNA (mRNA) species of approximately 3200 nucleotides. Tissue-specific expression of DP1 mRNA was indicated by the absence of DP1 mRNA in ventral prostate and other tissues of the rat. Expression of DP1 mRNA was androgen-dependent, decreasing approximately 80% 7 days after castration and increasing rapidly following androgen replacement. Southern blot analysis of restriction enzyme-digested rat DNA indicated that DP1 is encoded by a single gene and that no major genomic rearrangements accounted for its lack of expression in the dorsal prostate-derived rat Dunning tumor. Sequence comparisons revealed that rat prostate DP1 shares sequence identity with Factor XIIIa and tissue transglutaminase, including the active center, GQCWVF, indicating that DP1 is a member of the transglutaminase gene family.

Amino Acid Sequence↗

Response elements of the androgen-regulated C3 gene.

Intron and 5'-flanking regions of the androgen-regulated C3 subunit gene contain potential cis-acting transcription control sequences including several 15-base pair (bp) partial palindromes resembling response elements for glucocorticoid (GRE) and progesterone (PRE) receptors. Specific DNA binding of the androgen receptor (AR) and androgen-dependent activation of transcription indicate that some of these GRE/PRE-like sequences are capable of functioning as androgen response elements (ARE). A 0.3-kilobase pair (kbp) 5'-flanking fragment including the promoter region contains one such sequence (element A) and a 0.5-kbp region of the first intron contains two sequences (elements B and C). Androgen-dependent enhancement of transcription was assayed by cotransfection of CV1 cells with a rat AR expression vector, pCMVrAR, and C3 genomic fragments or synthetic elements cloned into the reporter vector ptkCAT. Enhancement of chloramphenicol acetyltransferase activity with the 0.5-kbp first intron fragment was 16 +/- 4-fold, while with the 0.3-kbp 5'-flanking fragment no response was detected and element C alone was greater than B or A. Binding of AR in the mobility shift assay correlated with androgen-dependent enhancement of chloramphenicol acetyltransferase activity. The intensity of transcriptional enhancement with the 0.5-kbp intron fragment suggested that other regulatory sequences within this intron region potentiated the ARE activities of elements B and C. ARE activity of the strongest C3 gene response element (C) was similar to that of a potent GRE (element M) of the mouse mammary tumor virus gene.

Amino Acid Sequence↗

Effect of lidocaine on the meninges in an experimental animal model.

Arachnoiditis has been reported in patients who had received previous epidural injections of anesthetic agents. The purpose of this study was to determine if epidural injections of lidocaine are sufficient to cause arachnoiditis. Four monkeys that received a single epidural injection of lidocaine hydrochloride 1% were compared to four controls that had epidural injections of 0.9% saline. Four dogs that had multiple epidural injections of lidocaine hydrochloride 1% were compared to four controls that had multiple injections of saline. All animals were killed on the eighty-fourth day of the experiment. The dural sac, containing nerve roots and spinal cord, was removed intact from the lumbar spinal canal, fixed, sectioned, stained, and examined microscopically for evidence of arachnoid inflammation and fibrosis. No significant changes were found in the treated animals. Lidocaine hydrochloride 1% injected singly or repeatedly in the epidural space does not appear to be a cause of significant chronic meningeal reaction.

Animals↗

Hyperthermia enhances the cytotoxic effects of reactive oxygen species to Chinese hamster cells and bovine endothelial cells in vitro.

Hyperthermia is under intensive investigation as a treatment for tumors both alone and in combination with other therapeutic agents. Hyperthermia has a profound effect on the function and structural integrity of tumor microvasculature; this has often been cited as a reason for its effectiveness in treatment of tumors. To test the role of hyperthermia in cytotoxic effects of active oxygen species, Chinese hamster, V79, and bovine endothelial cells were treated by the active oxygens, O not equal to 2 and H2O2, generated from the hypoxanthine/purine and xanthine oxidase reactions. It was found that cytotoxicity to V79 cells depends on the concentrations of purine and xanthine oxidase. A high level of cytotoxicity may be initiated in hyperthermia-treated tumors because high xanthine oxidase activity is known to be associated with tumors and endothelial cells, and degradation processes produce high concentrations of xanthine oxidase substrates in tumors. Since the cytotoxic effect can be reduced by the xanthine oxidase inhibitor, allopurinol, and the H2O2 removal enzyme, catalase, the cytotoxic effect in this experimental system is dependent on xanthine oxidase and H2O2. Adding erythrocytes at the same time as purine and xanthine oxidase could also prevent the cytotoxicity. Elevated temperatures stimulated the reaction of purine and xanthine oxidase and resulted in an increased cytotoxic effect. A similar effect is observed in growth inhibition and colony formation in endothelial cells without adding xanthine oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Response of erythrocytes to heat in the presence of D2O, glycerol, and anisotonic saline.

Mammalian erythrocytes that lack cytoplasmic organelles and a nucleus are a useful model for studying the effect of heat on the cell membrane and cytoskeleton. The effect of heat on the membrane bilayer and cytoskeleton of erythrocytes is remarkably similar to that observed in nucleated cells. Some concentrations of D2O and glycerol can effectively protect erythrocytes from heat-induced damage to the membrane and cytoskeleton. These results are similar to observations in nucleated cells. Heating erythrocytes in some concentrations of anisotonic NaCl solutions reduced damage, an observation that does not apply to enhanced killing of nucleated cells. This difference implies that some components of the cytoplasm or nucleus, or both, may contribute to the enhancement of cytotoxicity of nucleated cells when they are heated in the anisotonic NaCl solution. Incremental heating, dividing a heat treatment into two fractions, and preheating of erythrocytes all modify the effect of heat on erythrocytes slightly, but the results suggest little, if any, development of thermotolerance. The response of chicken erythrocytes is similar to that of mammalian erythrocytes, although higher temperatures are required to produce a heat effect in chicken erythrocytes. These observations suggest that the characteristic differences in heat sensitivity in nucleated and enucleated cells involve components other than the cell membrane.

Acclimatization↗

Evidence that UGA is read as a tryptophan codon rather than as a stop codon by Mycoplasma pneumoniae, Mycoplasma genitalium, and Mycoplasma gallisepticum.

Molecular cloning and sequencing showed that Mycoplasma gallisepticum, like Mycoplasma capricolum, contains both tRNA(UCA) and tRNA(CCA) genes, while Mycoplasma pneumoniae and Mycoplasma genitalium each appear to have only a tRNA(UCA) gene. Therefore, these mycoplasma species contain a tRNA with the anticodon UCA that can translate both UGA and UGG codons.

Base Sequence↗

Effect of repeated injections of chymopapain in the epidural space.

Because arachnoiditis occurred in a previous experimental study, the authors performed additional experimental injections of chymopapain in the epidural space. Four monkeys received epidural injections of 100 units of chymopapain in 1.2 mL of saline on days 1, 8, and 16 of the experiment; four control animals received injections of 1.2 mL of 0.9% saline on the same days. Both groups were killed on the 84th day. The dural sac was removed, fixed, sectioned, stained, and examined microscopically. No significant changes were found in the arachnoid, dura, or epidural space of the treated animals. Chymopapain, even if injected repeatedly into the epidural space, does not cause significant scarring in the meninges.

Animals↗

Canine intervertebral disks: correlation of anatomy and MR imaging.

Because the structure, maturation, and degeneration of canine intervertebral disks resemble those of humans, the authors developed a model of acute intervertebral disk degeneration in dogs. Herniated disks of 18 dogs were examined with magnetic resonance (MR) imaging and then sectioned with a freezing microtome. On the basis of their morphologic appearance in the freezing microtome sections, most of the lumbar intervertebral disks could be categorized as one of six types. Each type has characteristic features and a distinctive appearance on MR images. Findings of this study--including decreased signal intensity from the intervertebral disk, altered signal intensity in contiguous bone marrow, bulging of the anulus fibrosus, herniation of the nucleus pulposus, and contrast enhancement after intravenous administration of gadolinium diethylenetriaminepentaacetic acid (DTPA)--resemble observations from human clinical studies. Classification of degenerating disks and identification of MR imaging characteristics of each type may improve the interpretation of MR images and recognition of early disk degeneration in humans.

Animals↗

Age-related changes in the cervical facet joints: studies with cryomicrotomy, MR, and CT.

The cervical facet joints of 20 cadavers were studied systematically with MR, CT, cryomicrotomy, and histologic sections to determine the anatomic changes that occur with age. Uniform layers of cartilage and subarticular cortical bone characterize the cervical facet joints in cadavers under 20 years of age. Most adult cervical facet joints have only a discolored or microscopically thin layer of cartilage and have irregularly thickened subarticular cortical bone. The appearance of the cervical facet joints changes significantly with aging.

Adult↗