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Biomedical subjects

K L Ho

Publications and source records attributed to K L Ho.

At least 73 records · Page 4Linked to original sources

3-Methylcholanthrene-induced expression of the cytochrome P-450c gene.

Transcriptional control of 3-methylcholanthrene-dependent cytochrome P-450c nuclear RNA induction was directly observed in an in vitro rat liver nuclear transcription system. Mercurated and radiolabeled ribonucleotides were incorporated into nuclear RNA transcribed in vitro, which was then isolated using thiopropyl-Sepharose 6B affinity chromatography. Dot hybridization experiments were carried out using bacteriophage M13 subclones of pRSA57 (a cDNA clone for rat serum albumin), pEB339 (a cDNA clone for rat cytochrome P-450c), and clone 46 (a cDNA clone for mouse cytochrome P1-450). The results of these studies demonstrate that 3-methylcholanthrene does not significantly influence the transcription of the rat serum albumin gene, but does increase the transcription of the cytochrome P-450c gene. Nuclear RNA precursors to the cytochrome P-450c mRNA were characterized by Northern blot analysis. Clone 46 hybridized to nuclear RNA species of 6.7 and 4.0 kb, in addition to the 3.0-kb cytochrome P-450c mRNA. pA8 (a genomic clone for rat cytochrome P-450c), hybridized to the same nuclear RNA species in addition to nuclear RNA species of 4.3, 3.4, and 2.2 kb. M13pd15 (a genomic clone containing information for the first intron of the cytochrome P-450c gene) hybridized to nuclear RNA species of 6.7 and 4.3 kb. All of these nuclear RNA species are polyadenylated. The mRNA coding for cytochrome P-450c was induced maximally in hepatic nuclei at 3 h following 3-methylcholanthrene administration. Maximal accumulation of cytochrome P-450c mRNA in hepatic cytosol has been previously shown to occur at approximately 15 h following 3-methylcholanthrene administration (Bresnick, E., Brosseau, M., Levin, W., Reik, L., Ryan, D. E., and Thomas, P. E. (1981) Proc. Natl. Acad. Sci. USA 78, 4083-4087). These data implicate a possible role of nuclear RNA transport in the regulation of induction of cytochrome P-450c, although further investigations are indicated.

Animals↗

Ultrastructure of cerebellar capillary hemangioblastoma. IV. Pericytes and their relationship to endothelial cells.

Electron microscopy and computerized morphometric techniques were employed to examine pericyte ultrastructure and to assess quantitatively their relationship to endothelial cells in five cases of cerebellar capillary hemangioblastoma. A total of 97 cross-sectioned capillary profiles were studied. Pericyte coverage of capillary ranged from 30.2% to 97.3% with a mean value of 68.7%, which is higher as compared with the available data from the cerebral cortex, skeletal and cardiac muscle, and pulmonary capillaries. The higher pericyte coverage of capillary suggests that pericyte is an active component of cerebellar capillary hemangioblastoma and may have a close functional relationship to endothelial cells. Pericytes contained bundles of parallel microfilaments along the adluminal side and in the terminal processes, and exhibited an intimate "peg-and-socket" relationship with endothelial cells, suggesting a contractile function of pericytes and their possible role in regulating capillary lumina and focal blood flow. The finding of abundant micropinocytic vesicles along the abluminal side of the cytoplasmic membrane indicates an active metabolic exchange between pericytes and the interstitium. It is possible that in cerebellar hemangioblastoma pericytes may act as a mechanical and metabolic monitor barrier for endothelial cells.

Adolescent↗

Ultrastructure of cerebellar capillary hemangioblastoma. III. Crystalloid bodies in endothelial cells.

The endothelial cells of three cases of cerebellar capillary hemangioblastoma were studied by means of electron microscopy. Crystalloid bodies, not previously described in the vessels of the central nervous system (CNS), were found in 5%-10% of the endothelial cells, more often in the capillaries with small irregular lumens. They were not observed in the pericytes or stromal cells. They were round to polygonal, 0.5-1.0 micron in size and composed of substructural units of parallel thick and thin electron-dense lines with a periodicity of 180-220 A. They coexisted occasionally with Weibel-Palade bodies but shared no structural correlation with them. The nature and significance of these crystalloid bodies are as yet unknown. Their close association with pinocytic vesicles suggests that the substructural crystalline might be the result of reconstruction of absorbed material from either the vascular lumen or the interstitium. Their subsequent development, associated with lysosomal activity, into intracytoplasmic dense bodies is postulated. Since crystalloid bodies were found only in endothelial cells, particularly those active in proliferation, they may play a pathophysiologic role in relation to angiogenesis.

Capillaries↗

Acute inflammation and endothelial injury in vein grafts.

An experimental study of autogenous vein graft morphology 6 hours after arterial implantation was performed in dogs. The animals were divided into five groups. The first control group had veins harvested and stored but not implanted. The endothelium showed excellent preservation by routine histology and scanning electron microscopy. The second control group had grafts implanted and flow decreased to 30 to 50 ml/minute. There was a massive acute inflammatory response with subendothelial and transmural accumulation of neutrophils causing widespread endothelial sloughing. A third group had grafts implanted, but flow was not reduced (mean, 170 ml/minute). Although an inflammatory response was also present, it was much less severe than in the low flow grafts and the endothelium remained grossly intact. Two other groups had low flow grafts implanted, but were treated with either lidocaine or steroids. Lidocaine had no effect on the inflammatory response or endothelial injury. High doses of alpha-methylprednisolone succinate almost completely prevented both endothelial loss and inflammatory infiltration. This study supports the premise that an acute inflammatory response can initiate endothelial injury after autogenous grafting, an effect that is much more prominent in low flow than high flow grafts. It also demonstrated that steroids can almost totally suppress the injury during the initial 6 hours after implantation.

Animals↗

Neuropathologic findings in thanatophoric dysplasia.

Neuropathologic study of eight cases of thanatophoric dysplasia (dwarfism) reveals developmental abnormalities including hypoplasia of posterior fossa, megalencephaly, cerebral gyral disorganization, hippocampal malformation, neuronal heterotopia, nuclear dysplasia, and abnormal axonal bundles. There are no noticeable differences in CNS abnormalities between thanatophoric dysplasia with and without cloverleaf skull (Kleeblattschädel). The CNS abnormalities, likely the result of abnormal neuronal migration and cytoarchitectonic disarrangement, are apparently not caused by skeletal abnormalities. The observation suggests that CNS abnormalities represent a characteristic and distinct manifestation of thanatophoric dysplasia.

Basal Ganglia↗

Ultrastructure of cerebellar capillary hemangioblastoma. II. Mast cells and angiogenesis.

The topographic distribution, population density, and ultrastructural features of mast cells were studied in six cases of cerebellar capillary hemangioblastoma. The vascular area of tumor tissue contained large numbers of mast cells (6.3 cells/high power field, X 400) in comparison with hyalinized area (0.3 cell) and adjacent cerebellar tissue (less than 0.1 cell). Close association of mast cells with endothelial cells and stromal cells was found. The morphology of mast cell granules and their degranulation through dissolution of granule contents and exocytosis were illustrated. The findings suggest that an increased number of mast cells may represent one of the characteristic histological features of capillary hemangioblastoma, and continuous degranulation of mast cell granules with release of heparin may play an important pathophysiologic role in the vascular proliferation and expansion of the tumor.

Adolescent↗

The role of alkaline protease in the development of cardiac lesions in myopathic hamsters: effect of verapamil treatment.

The role of alkaline protease in the development of myocardial lesions in myopathic hamsters was studied. There was abnormal elevation of alkaline protease in the myopathic heart at 1 month of age, preceding the development of cardiac lesions. In vivo treatments of verapamil were carried out in 1-month-old myopathic animals for 30 days. Results indicated that the drug treatment was effective in preventing the occurrence of the severe myocardial lesions found in the untreated animals at 2 months of age. Reduced lesion development was associated concomitantly with lowered levels of alkaline protease activity. Withdrawal of drug treatment caused the return of severe lesions and high levels of alkaline protease. The study of the alkaline protease activity in the skeletal muscle of the myopathic hamster also showed a parallel relationship between the enzyme levels and severity of lesions. The results are discussed in light of possible involvement of a serine protease and a Ca2+-activated protease in producing the cardiac lesions.

Aging↗

The enhancement of specific gene transcription in isolated nuclei by added HeLa whole cell extract.

Transcription was carried out in isolated rat liver nuclei by endogenous RNA polymerase with the addition of HeLa whole cell extract (HWCE) in the presence of nucleoside 5'-[gamma-S]triphosphate. The resulting 5'-gamma-thiophosphate on the synthesized RNA allows separation of in vitro initiated RNA from bulk RNA by mercury-agarose chromatography. HWCE not only increased initiation of new RNA chains greater than 3 times but also had no effect on the RNA synthesis by RNA polymerase II. The initiation of transcription of albumin and alpha-fetoprotein genes in an isolated nuclei system was selectively enhanced by HWCE. Using this system, we studied the effect of glucocorticoid on albumin and alpha-fetoprotein gene expression in vitro.

Albumins↗

Ultrastructure of cerebellar capillary hemangioblastoma. I. Weibel-Palade bodies and stromal cell histogenesis.

Ultrastructural study of three cases of cerebellar capillary hemangioblastoma demonstrated three major component cells: endothelial cells, pericytes and stromal cells. The stromal cells exhibited ultrastructural features reminiscent of the endothelial cells. Weibel-Palade bodies, cylindrical cytoplasmic organelles specific to endothelial cells, were found in the endothelial cells and stromal cells, but not in the pericytes. The finding supported the concept that stromal cells are closely related to endothelial cells and are likely derived from the angiogenic mesenchymal cells. Since von Willebrand protein has been shown to be concentrated in Weibel-Palade bodies, the finding of these bodies in the stromal cells provided a morphological evidence for the immunocytochemical expression of factor VIII/von Willebrand factor of the stromal cells in those cases in which it has been reported.

Adolescent↗

Basophilic degeneration of skeletal muscle in hypothyroid myopathy. Histochemical and ultrastructural studies.

Morphologic and histochemical studies of basophilic degeneration (BD) of skeletal muscle were performed on a 64-year-old woman with hypothyroid myopathy. The BD had staining characteristics of polysaccharide and similarity to the deposits described in cardiac muscle in five of six muscle groups studied and was absent in the diaphragm. The frequent occurrence of BD at the myotendinous junction suggested the necessity of including this area in muscle biopsy specimens of suspected hypothyroid myopathy. Review of the literature indicated a need for more detailed examination of muscle specimens of these patients to determine the clinical implication and biochemical nature of the BD. To my knowledge, the demonstration of a close association of BD and leptomeres and the presence of crystalline structures within the BD have not been described previously.

Arteriosclerosis↗

Concurrence of subependymoma and heterotopic leptomeningeal neuroglial tissue.

Heterotopic neuroglial tissues in the leptomeninges are generally regarded as developmental malformations. They are uncommon in the general population (1%) but are more often found in patients with other CNS maldevelopments (25%). Of the 22 cases of subependymoma available for our study, four (18.2%) had concurrent heterotopic neuroglial tissue. The great majority of these neuroglial heterotopias were located over the brain stem and were topographically close to the subependymomas. Since the histogenetic nature of subependymoma, whether it represents a local maldevelopment (hamartoma) or a true neoplasm, is still uncertain, the concurrence of subependymoma and heterotopic leptomeningeal neuroglial tissue seems to support the concept that the tumor is a maldevelopment rather than a true neoplasm.

Aged↗

Neoplastic aneurysm and intracranial hemorrhage.

A case of fatal intracerebral hemorrhage due to rupture of a neoplastic aneurysm in a 68-year-old man with a history of bronchogenic carcinoma is reported. Intracranial neoplastic aneurysms resulting from metastatic tumor embolization of the cerebral vessels are more often associated with cardiac myxoma and choriocarcinoma. Of the 23 reported cases, eight ruptured and caused intracerebral or subarachnoid hemorrhage. Like mycotic aneurysm, they are small and located in the peripheral branches of cerebral artery, and may easily be obscured by hemorrhage when ruptured.

Adolescent↗

Tumors of the cerebral aqueduct.

Two cases of tumor of the cerebral aqueduct are described. Case 1 is a pilocytic astrocytoma in a 16-year-old girl with a two-year history of intermittent increase of intracranial pressure. The tumor was completely confined within the lumen of the aqueduct. Case 2 is a subependymoma of a 68-year-old man. The tumor extended beyond the aqueduct to the periaqueductal gray matter and produced signs and symptoms suggesting normal pressure hydrocephalus. The literature contains 18 other cases of tumor of the aqueduct: 13 gliomas and five vascular malformations. All, except one, produced clinical manifestations of generalized hydrocephalus lasting from 20 days to six years. The result generally did not correspond to the histologic type of the tumor. Like gliomas of the brainstem in general, those in the aqueduct tend to occur in childhood and adolescence and affect male more than female patients.

Adolescent↗