Biomedical subjects

K L Ho

Publications and source records attributed to K L Ho.

At least 37 records · Page 2Linked to original sources

PubMed1995

Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex.

BACKGROUND AND PURPOSE: Most brain lesions that develop after an artery is occluded evolve from an initial stage of "ischemic injury" (probably reversible) to an infarct or an area where most neurons become necrotic. There is scant information on the time that must elapse after the arterial occlusion for neurons to undergo irreversible injury. The objective of these experiments was to chart the time course and the topographic distribution of the neuronal necrosis that follows the occlusion of a large cerebral artery. METHODS: One hundred fifty-one adult rats (including 15 controls) were used in this study. One hundred forty-seven had the right middle cerebral artery occluded for variable periods ranging from 30 minutes to 7 days. After processing the brains for histology, a meticulous structural evaluation of each specimen, including quantitation of necrotic neurons, was followed by a detailed statistical analysis of the neuronal counts. RESULTS: Few neurons in isolated sites showed morphological signs of necrosis during the initial 4 hours; the first significant increase in the percentage of necrotic neurons (15%) was observed within the territory of the occluded artery after 6 hours (P < .05); 12 hours after the arterial occlusion most neurons (65%) had become necrotic (P < .0001). Pannecrosis involving neurons, glial cells, and blood vessels was observed at 72 to 96 hours. However, even at this time pannecrosis involved only the preoptic area and the lateral putamen; a few intact neurons remained visible in the cortex, and scattered necrotic neurons could be identified beyond the edges of the "area of pallor," which does not become clearly demarcated until 4 to 5 days after the arterial occlusion. CONCLUSIONS: There is a predictable progression in the development of neuronal necrosis after a permanent arterial occlusion. Irreversible changes appear first in the caudoputamen and then spread to the cortex. The causes for the progression of the lesion are not known; however, therapeutic interventions that start within the first 1 to 2 hours after the arterial occlusion may alter the histopathologic responses to this form of injury. It remains to be determined whether the extent of the neurological deficit induced by an arterial occlusion correlates with the number of necrotic neurons.

Animals↗

PubMed1995

Primary craniofacial chordoma: case report.

A 37-year-old man presented with right facial pain and a nonpalpable mass over the malar eminence. An incisional biopsy via the intraoral route was performed and interpreted as a vascular malformation with degenerative changes. His symptoms persisted, and a repeat biopsy was suggestive of an epithelioid nerve sheath tumor. Total resection of the tumor was planned to include the infraorbital and malar regions, the infratemporal fossa, and the pterygopalatine fossa. At surgery, the tumor was removed with tumor-free margins obtained along the course of the maxillary nerve just before its entrance into the cavernous sinus. The pathological findings and the immunohistochemistry demonstrated a typical chordoma with no chondroid or sarcomatous dedifferentiation. We think that with greater use of immunohistochemical markers and electron microscopy, patients with chordoma in this location may be diagnosed promptly and accurately.

Adult↗

PubMed1995

Immunolocalization of cathepsin B in human glioma: implications for tumor invasion and angiogenesis.

The poor prognosis of patients with malignant gliomas is at least partially due to the invasive nature of these tumors. In this study, the authors investigated the possibility that the cysteine protease cathepsin B (CB) is a participant in the process of glial tumor cell invasion. To accomplish this, an immunohistochemical analysis was made of the localization of antibodies to CB in biopsies of five specimens of normal brain, 16 astrocytomas, 33 anaplastic astrocytomas, and 33 glioblastomas multiforme. Staining was scored according to the percentage of positive cells and the intensity of the stain, graded from 0 to 3+. Staining for CB was not seen in any of five samples of normal brain except for occasional neuronal cell bodies and microglia. Only five (31%) of 16 astrocytomas showed a small percentage of positive cells (0.01%-3%) that were stained in a light, diffuse cytoplasmic pattern (1+). Twenty-nine (87.8%) of 33 anaplastic astrocytomas showed positive light, granular staining in 2% to 40% of cells. In anaplastic astrocytoma, the staining within a tumor was heterogeneous with intensities of 1+ (17%), 1+ to 2+ (29%), or 2+ (55%). In contrast, all 33 (100%) glioblastomas were positive in 10% to 90% of cells. The staining was present in a coarse, granular pattern with an intensity of 2+ (12%) or 3+ (88%). Tumor cells infiltrating into brain adjacent to malignant gliomas stained positively in 26 cases that could be evaluated for glioblastoma multiforme; these invading cells frequently followed penetrating blood vessels as typical "secondary structures of Scherer." Moderate to intense CB staining associated with endothelial proliferation in high-grade tumors was also observed, especially in regions of tumor infiltration into adjacent normal brain. These results provide evidence consistent with the hypothesis that CB is functionally significant in the process of tumor invasion and angiogenesis in the clinical progression of the malignant phenotype in astrocytes.

Antibodies, Monoclonal↗

PubMed1993

Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation.

Marked neointima formation occurs after balloon injury to the intima of rat arteries. Angiotensin II has been implicated as a growth factor in this process, since angiotensin converting enzyme (ACE) inhibitors block neointima formation after injury. However, ACE is an important kininase, and its inhibitors may act in part by a kinin-mediated mechanism. Kinins are also known to stimulate synthesis of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) and prostacyclin, both of which have antigrowth effects. To determine whether the effect of ACE inhibitors on neointima formation is due to blockade of angiotensin II synthesis alone and/or inhibition of kinin inactivation, we followed two approaches. First, we compared the inhibition of neointima formation induced by the AT1-type angiotensin II receptor antagonist losartan with that caused by the ACE inhibitor ramipril. We also studied whether a kinin receptor antagonist, Hoe 140, blocks the effect of two different ACE inhibitors, ramipril and enalapril, on neointima formation. In addition, we studied whether the effect of ramipril is blocked by an NO synthesis inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME). Although both ramipril and losartan significantly reduced neointima formation, ramipril had a more marked effect (p < 0.05 for ramipril versus losartan). The kinin antagonist Hoe 140 reduced the inhibitory effect of ramipril and enalapril by 73% and 62%, respectively. The remaining effect of the ACE inhibitors was now similar to that of losartan. Inhibition of neointima formation by ramipril was also blocked by the NO synthesis inhibitor L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1993

Rat CYP1A1 negative regulatory element: biological activity and interaction with a protein from liver and hepatoma cells.

Rat CYP1A1 promoter activity was suppressed by the presence of a cis negative regulatory element (NRE) at position -843 to -746 in transiently transfected rat H4IIE and human HepG2 hepatoma cells. Removal of the NRE from the promoter-fusion gene constructs caused an increase in the basal promoter activity of 2-6-fold. Co-transfection of the NRE-containing or non-NRE-containing CYP1A1 promoter-fusion gene constructs with a cloned rat NRE, i.e., pNRE, into HepG2 cells caused a 2-fold or greater reduction in constitutive and induced promoter activities. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced expression of the endogenous human CYPA1 was also inhibited by transfection of pNRE into HepG2 cells. Deletion of the sequence from base pairs (bp) -658 to -269 in the NRE-containing construct caused a dramatic decrease of constitutive expression in transiently transfected HepG2 cells, compared with an identical construct that lacked the NRE. Deletion of the sequences between bp -658 and -158 in the CYP1A1 promoter did not affect reporter gene activity, indicating a second site of interaction. At least three different rat liver nuclear proteins bound to the rat NRE, as determined by gel mobility shift and DNase I footprinting assays. A 32-bp sequence within the rat NRE, with significant sequence identity to the 26-bp c-myc, fos/jun-octamer-binding, NRE, was protected from DNAse I cleavage by rat liver nuclear extracts. These data suggested a role for this region in the negative regulation of rat CYP1A1.

Animals↗

PubMed1992

Kinins mediate the antiproliferative effect of ramipril in rat carotid artery.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to inhibit neointimal proliferation in response to endothelial injury in the rat carotid artery. Since ACE inhibitors block degradation of kinins, our objective in this study was to determine whether kinins mediate the antiproliferative effect of the ACE inhibitor ramipril. Endothelial denudation was achieved in the left carotid artery of male Sprague-Dawley rats using a balloon catheter. The rats were divided into four groups: a) vehicle (saline); b) DuP 753 10 mg/kg/day; c) ramipril 5 mg/kg/day; and d) ramipril 5 mg/kg/day plus Hoe 140 70 micrograms/kg/day. Ramipril markedly reduced neointimal proliferation compared to control (vehicle) (p less than 0.05) and DuP 753-treated groups (p less than 0.05). When ramipril was given together with Hoe 140 its effect was significantly blunted (p less than 0.05). These results show that kinins are important mediators in the antiproliferative effect of ACE inhibitors.

Angiotensin II↗

PubMed1992

Isolated granulomatous angiitis of the spinal cord.

We describe a 31-year-old diabetic man, with granulomatous angiitis confined to the spinal cord, who developed rapidly progressive spastic paraplegia, clinically interpreted as being secondary to a spinal cord infarct. At the time of autopsy, vasculitis was limited to the spinal cord, without involvement of cerebral vessels. The inflammatory cells were predominantly CD4+ T lymphocytes, with few CD8+ T and B lymphocytes. The phenotypical composition of the inflammatory infiltrate is similar to that described in other granulomatous disorders such as sarcoidosis and tuberculin reaction.

Adult↗

PubMed1992

Ciliary claws: their existence in various epithelial cysts of the central nervous system.

We describe claw-like projections and their associated structures as encountered at the tips of cilia in a cerebellar epithelial cyst, an intraspinal bronchogenic cyst and two colloid cysts of the third ventricle. Ciliary claws appear either as a single structure or as a cluster of two to five projections measuring 22-28 nm in length and 8-10 nm in diameter, extending from the plasma membrane of the ciliary tip. The transmembranous fibrils of the ciliary claws are bound to a multilayered electron-dense disc which is attached by the distal ends of axonemal microtubules. These observations suggest that ciliary claws are common in several types of epithelial cysts of the central nervous system; the presence of these structures supports the premise that the corresponding epithelium is of endodermal origin.

Adult↗

PubMed1992

Colloid cysts of the third ventricle: ultrastructural features are compatible with endodermal derivation.

The histogenesis of colloid cyst of the third ventricle remains unsettled. Ultrastructural and immunohistochemical analyses have suggested the following possible origins: (a) neuroepithelium, including paraphysis, ependyma, choroid plexus and tela chorioidea; and (b) endoderm, including respiratory and enteric epithelium. This report describes the ultrastructural features of the lining epithelium in four cases of colloid cyst. Six distinct cell types were recognized: (1) ciliated cells with occasional abnormal cilia; (2) non-ciliated cells with microvilli coated with granulofibrillary material; (3) goblet cells showing discharge of secretory granules; (4) basal cells with prominent tonofilaments and desmosomes; (5) basal-located cells with elongated electron-lucent cytoplasm and scattered membrane-bound dense-core granules (150-350 nm); and (6) small undifferentiated cells with scanty organelles. Junctional complexes were present in the former four cell types but absent in the latter two. The types of epithelial cells and their topographic distribution within the epithelium are both very similar to those of normal respiratory epithelium and to the lining epithelium of intraspinal bronchogenic cyst. The observations made in the present study are compatible with the hypothesis that colloid cysts of the third ventricle originate from the endoderm, most likely the respiratory epithelium.

Adult↗

PubMed1992

Cauda equina tumor with ependymal and paraganglionic differentiation.

We describe the case of a 31-year-old woman who was first treated for a pigmented choroid plexus papilloma of the fourth ventricle. Ten year later, she developed a new tumor in the region of the cauda equina. This second neoplasm contained areas of papillary ependymoma that displayed phosphotungstic acid hematoxylin-positive glial fibers and immunoreactivity for glial fibrillary acidic and S-100 proteins. Areas of ependymoma merged with others that displayed the appearance of a paraganglioma, including lobules and nests of chief cells immunoreactive for neuron-specific enolase, synaptophysin, chromogranin, and serotonin. Satellite cells, but not chief cells, stained for glial fibrillary acidic and S-100 proteins. Electron microscopy showed features of both ependymal and paraganglionic differentiation, including intercellular lumina with microvilli, junctional complexes, cell processes with closely packed filaments, and dense core granules. Our case represents a rare example of a cauda equina neoplasm with simultaneous ependymal and paraganglionic differentiation. To our knowledge, this is the first described example of a tumor of this region showing features of both ependymoma and paraganglioma.

Adult↗

PubMed1992

A combination of adoptive transfer and antigenic challenge induces consistent murine experimental autoimmune encephalomyelitis in C57BL/6 mice and other reputed resistant strains.

Adoptive EAE was induced in SJL mice by the transfer of MBP-primed and in vitro-stimulated donor lymph node cells into naive syngeneic recipients. Priming donor mice with OVA instead of restimulating MBP-primed donor cell with OVA resulted in no transfer of EAE. This apparent lack of disease, however, could be overcome if the recipients were subsequently challenged with MBP. When this transfer-challenge technique was applied to BALB/c and C57BL/6 mice, these reputed (MBP)EAE-resistant strains developed consistent and severe disease similar to that seen in susceptible strains. In fact, a survey of eleven (MBP)EAE-resistant strains, defined on the basis of their inability to mount an encephalitogenic response in recipient mice following the transfer of MBP-primed and in vitro activated lymph node cells, revealed that EAE could be induced in all these strains. Since the surveyed strains represented a wide spectrum of genetic backgrounds as well as the common MHC congenic haplotypes (H-2b,d,k,m,r,s,v), it is concluded that the machinery for recognition of MBP, i.e. MHC genes and the appropriate T cell receptors, is functionally intact in these resistant mice. While MHC and T cell receptor genes are required for T cell responses, they are not the limiting factors that confer resistance in murine EAE.

Animals↗

PubMed1992

In vivo and in vitro study of the lesions produced with a computerized radiofrequency system.

For many years, radiofrequency-generated lesions have been used for the treatment of pain and abnormal movements. However, the reliability of this method has been questioned because of the variation in the size of lesions produced by the electrode at different times and temperatures. A 500-kHz radiofrequency generator with different electrodes was used to determine the size of lesions, using different time and temperature exposures. A computerized feedback mechanism kept the tip temperature constant during the production of the lesion, regardless of varying tissue impedance. Eight electrodes of different size and tip characteristics were evaluated at different temperatures and time settings, both in vitro and in vivo. Graphic display of the curves in time were obtained at 65, 70, 75, 80, 85 and 90 degrees C. The effects of thermo-coagulation were studied in vitro in fresh egg whites, using time intervals of 20, 40, 60, 80 and 100 s, and in vivo, in the subcortical white matter of 20 adult New Zealand white rabbits. Animals were sacrificed after 7 days. Lesions were photographed and measured under magnification. In all cases, the coagulated masses were ellipsoid, with regular, well-demarcated borders. A two-way statistical analysis of variance was done. The coagulum size increased with higher temperatures and with larger probes. The increase was significant in both diameter and length (p = 0.001). In contrast, the use of different times at the same level of temperature showed no significant increase in most of the electrodes. There were two statistical significant time effects, for both diameter and length, with the monopolar 2-mm electrode. The use of real-time monitoring with graphic display and the feedback information provided for the computerized control of power and current allows high precision of the temperature at the electrode tip during the production of the lesion.

Analysis of Variance↗

PubMed1992

Pathology of hypertensive arteriopathy.

The material covered in this article is divided into two parts: the initial portion summarizes information pertaining to the definition of structural abnormalities, attributed to arterial hypertension, that affects the intraparenchymal cerebral blood vessels. After a brief mention of the brain parenchymal lesions that accompany hypertensive arteriopathies, important modern mechanistic concepts that are derived primarily from animal observations are summarized.

Brain↗

PubMed1991

A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review.

Cocaine, especially in its alkaloidal or "crack" form, has been increasingly associated with cerebrovascular disease. Before the crack epidemic, cocaine hydrochloride (HCl) was also implicated as a cause of stroke. However, less is known about the differences in stroke subtypes, age at stroke onset, or presence of underlying structural cerebrovascular disease with different forms of cocaine use. We compared 26 patients (previously reported) from our four institutions plus 16 cases reported in the literature of stroke associated with alkaloidal cocaine to 63 (57 reported in the literature and six not previously reported from our four institutions) cases of stroke associated with cocaine HCl. Ischemic and hemorrhagic strokes are equally likely after alkaloidal cocaine use, whereas cocaine HCl is more likely (approximately 80% of the time) to cause hemorrhagic stroke, with approximately half the intracranial hemorrhages occurring from ruptured cerebral saccular aneurysms or vascular malformations. The presence of an underlying cerebral aneurysm was more common among patients with cocaine HCl-associated strokes than alkaloidal cocaine-associated strokes. Cerebral infarction was significantly more common among the alkaloidal cocaine users than in all the cocaine HCl users, and this was also true when alkaloidal cocaine users were compared with parenteral cocaine HCl (intravenous and intramuscular) users. Only hemorrhagic stroke has been reported with intravenous cocaine HCl use. We conclude that the pathogenesis of cocaine-related stroke is heterogeneous, and depends, in part, on the form of cocaine used.

Administration, Intranasal↗

PubMed1991

Accuracy and reliability of two methods of screening for hypoglycemia in neonates.

Two hundred and six neonates were screened for hypoglycemia using two glucose test strips and their results compared with a simultaneous blood sugar obtained from the Beckman's glucose analyser. Both test strips, Reflotest hypoglycemia and the Reflolux (BM test glycemia 20-800) gave rapid estimates of blood sugar readings. In this study, these two strips were assessed in their accuracy and reliability to detect neonatal hypoglycaemia (blood sugar levels less than 2.2 mmol/L). The sensitivity and specificity of the two test strips are 0.82 and 0.90 for Reflotest, and 0.88 and 0.81 for Reflolux respectively. Hence we conclude that both Reflotest and Reflolux are sensitive in detecting blood sugar levels at or below 2.2 mmol/L (40 mg/dl) although Reflolux is less specific. A laboratory result is mandatory before the diagnosis and prognosis of hypoglycemia is made.

Birth Weight↗

PubMed1990

Cerebrovascular complications of the use of the "crack" form of alkaloidal cocaine.

BACKGROUND AND METHODS: The use of cocaine, especially one of its alkaloidal forms ("crack"), has been increasingly associated with cerebrovascular disease. To clarify the clinical, radiologic, and pathological features of the events associated with cocaine use, we identified 28 patients at four medical centers who had stroke temporally related to the use of alkaloidal cocaine (during or within 72 hours of use). RESULTS: The 28 patients had the following types of cerebrovascular event: cerebral infarction (n = 18 [2 hemorrhagic; 1 fatal]) in the areas supplied by the middle cerebral artery (n = 10), anterior cerebral artery (n = 3), posterior cerebral artery (n = 1), and vertebrobasilar arteries (n = 4); subarachnoid hemorrhage (n = 5); intraparenchymal hemorrhage (n = 4); and primary intraventricular hemorrhage (n = 1). Eighteen patients (64 percent) had acute neurologic symptoms immediately or within one hour of using cocaine. Fifteen patients (45 percent) with either occlusive or hemorrhagic strokes had sever headache as an early symptom. Vasculitis was not suggested by radiography in any patient, nor was it identified on pathological examination in one patient who died. All the patients were young (mean age, 34 years; range, 23 to 49) and had no other apparent, direct cause of stroke. Other risk factors for stroke among the patients included mild mitral-valve prolapse (n = 4), hypertension (n = 4), cigarette smoking (n = 8), and regular alcohol use (n = 6). CONCLUSIONS: There is a strong temporal association of the use of alkaloidal cocaine with both ischemic and hemorrhagic cerebrovascular events. Cocaine-related stroke probably has many causes. A thorough history focusing on the use of cocaine and toxicologic screening of urine and serum should be part of the evaluation of any young patient with a stroke.

Adult↗

PubMed1990

Intercellular septate-like junction of neoplastic cells in myxopapillary ependymoma of the filum terminale.

Septate junction, a common intercellular feature of invertebrate epithelium, is absent in most vertebrate tissues. In an ultrastructural study of three cases of myxopapillary ependymoma of the filum terminale, structures similar to septate junction were observed in two cases. They were circumferential bands around the finger-like processes of neoplastic cells in which slightly widened 30-40-nm intercellular spaces (as compared to 15-20 nm in non-junctional region) were transversed at regular intervals by parallel septa resulting in characteristic ladder-like appearance. The electron-dense septa, 30-40 nm in cross-length and 20-30 nm in width, were arranged in a periodicity of 40-50 nm. The septa connected to the outer leaflets of the apposing cytoplasmic membranes which appear undisrupted. Most junctions were short; the longest one contained 15 septa in a length of 1.4 microns. Hemiseptate-like junctions with septa of the same measurements were noted between the processes and the investing basement membrane. Junctional complexes such as zonula adherens and gap junction were present in the vicinity. They may represent a specific intercellular feature of myxopapillary ependymoma, and function as cellular adhesions and a mechanical support of the neoplastic cells.

Adult↗

PubMed1990

Histogenesis of sarcomatous component of the gliosarcoma: an ultrastructural study.

This report describes the ultrastructural findings of the sarcomatous component in five cases of gliosarcoma. The tumor contained a heterogenous population of cells with collagen scattered in the interstitium. Three main cell types were found: histiocyte-like cells, fibroblast-like cells and undifferentiated cells. The histiocyte-like cells had oval nuclei, short and flat rough endoplasmic reticulum, prominent Golgi apparatus, lysosomes, phagocytic vacuoles, ruffled cytoplasmic membrane with filopodia, segmental basal lamina and occasional intercellular junctions. The fibroblast-like cells had elongated nuclei, prominent cisterns of rough endoplasmic reticulum and microfilaments. The undifferentiated cell cytoplasmic processes suggesting differentiation toward histiocyte-like cell. In addition, intermediate cells, myofibroblasts, multinucleated giant cells and xanthomatous cells were also present. Occasional glial processes were interposed between tumor cells. Some were enclosed by cytoplasmic processes of histiocyte-like cells and others engulfed within the cytoplasm. Capillary showed surface infoldings, fenestrations of endothelial cells, thickened basal lamina, occasional pericytes and scattered collagen. Some capillaries were surrounded by aggregating histiocyte-like cells and undifferentiated cells. The present findings suggest that (a) the sarcomatous component in gliosarcoma is likely derived from undifferentiated cells with a broad differentiation into histiocytic, fibroblastic and other cell types, (b) endothelial cells and pericytes may not participate in sarcomatous development, (c) capillaries within the sarcomatous component are of non-gliomatous type, and (d) the histiocyte-like cells are capable of phagocytizing glial elements.

Adult↗