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Biomedical subjects

I L Kwee

Publications and source records attributed to I L Kwee.

At least 55 records · Page 3Linked to original sources

Sorbitol accumulation in heart: implication for diabetic cardiomyopathy.

Sorbitol levels in heart were determined in streptozotocin-induced diabetic rats. Significantly higher levels were found in hearts of diabetic rats compared to normal rats. The findings are compatible with either significantly higher de novo synthesis of sorbitol in heart than is generally believed or uptake of circulating sorbitol by heart as previously indicated by nuclear magnetic resonance (NMR) in vivo metabolic imaging. Sorbitol accumulation in heart tissue may play a role in the pathogenesis of diabetic cardiomyopathy as has been implicated in cataract formation.

Animals↗

Phospholipid profile of the human brain: 31P NMR spectroscopic study.

Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, and ethanolamine plasmalogen represent the six most abundant phospholipids of brain cell membrane. The ratio of the phospholipid contents (phospholipid profile) of the brain is remarkably consistent under various metabolic conditions and alteration of the phospholipid profile is believed to reflect changes in the membrane system. We describe here a simple but sensitive method to analyze the phospholipid profile of the human brain utilizing the acidified chloroform-methanol lipid extraction method of Folch et al. and 31P nuclear magnetic resonance (NMR) spectroscopy. Unique regional phospholipid profiles were consistently obtained. Although the large chemical-shift anisotropy of the 31P confined to rigid structures such as the cell membrane precludes direct observation of phospholipid profiles in living tissue, a reflection of the membrane phospholipid profiles can nevertheless be obtained by studying "NMR visible" water soluble intermediate metabolites of membrane phospholipids in vivo.

Adult↗

Fluorine-19 NMR imaging of glucose metabolism.

Metabolic imaging reflecting glucose metabolism in the glycolytic and aldose reductase sorbitol (ARS) pathways was performed noninvasively in rat using fluorinated glucose analogs, 2-fluoro-2-deoxy-D-glucose (2-FDG) or 3-fluoro-3-deoxy-D-glucose (3-FDG), and fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging. 19F images of 2-FDG-6-phosphate, a main metabolite of 2-FDG in the glycolytic pathway, showed high glucose utilization in the brain, spinal cord, and heart. Images of 3-fluoro-3-deoxy-D-sorbitol (3-FDSL), a main metabolite of 3-FDG in the ARS pathway, demonstrated the heterogeneous nature of the spatial distribution of aldose reductase activities, being highest in the brain and lens. The extremely low toxicity of 3-FDG indicates promise for clinical application of 3-FDG NMR imaging.

Animals↗

F-19 MR imaging of glucose metabolism in the rabbit.

Noninvasive metabolic magnetic resonance (MR) imaging reflecting glucose metabolism in the aldose-reductase-sorbitol (ARS) pathway was performed in the rabbit head; after administration of the fluorinated glucose analogue 3-fluoro-3-deoxy-D-glucose (3FD-glucose), fluorine-19 images were generated. Images of 3FD-glucose showed significant 3FD-glucose uptake by adipose tissue, indicating its buffering effects in case of excess loads of glucose. Images of 3-fluoro-3-deoxy-D-sorbitol (3FD-sorbitol) demonstrated the spatial distribution of aldose reductase activities and significant sorbitol accumulation in the lens. Images of 3-fluoro-3-deoxy-D-fructose (3FD-fructose) showed preferential uptake of fructose by muscle tissue. The extremely low toxicity of 3FD-glucose indicates promise for its clinical application in metabolic imaging.

Aldehyde Reductase↗

Seesaw nystagmus. Role of visuovestibular interaction in its pathogenesis.

Elevation and intorsion of one eye and synchronous depression and extorsion of the other eye characterize a half cycle of seesaw nystagmus. Reversal of these movements constitutes the second half cycle, forming the "seesaw"-like movements. Based on analysis of the ocular oscillation characteristics of the cases of seesaw nystagmus reported in the literature, including the two new cases we present, we postulate that seesaw nystagmus is another type of ocular oscillation brought about by an unstable visuovestibular interaction control system. Nonavailability of retinal error signals to the inferior olivary nucleus essential for vestibuloocular reflex adaptation due to complete chiasmal dissection makes the system less stable. This system instability is further accentuated by the pursuit feedback element. The intact inferior olivary nucleus-nodulus connections in seesaw nystagmus would explain the 180 degrees phase difference that distinguishes it from the midline form of oculopalatal myoclonus, where these connections are likely disrupted.

Adult↗

Noninvasive evaluation of effects of an aldose reductase inhibitor in rat brain by 19F FDG NMR spectroscopy.

The inhibitory effects of an aldose reductase inhibitor, sorbinil (Pfizer, NY), on cerebral glucose metabolism were investigated noninvasively in rat brain using 19F nuclear magnetic resonance (NMR) spectroscopy and 2-fluoro-2-deoxy-D-glucose (2-FDG). Sorbinil given orally in the daily recommended doses (25 mg/kg) for man for the treatment of diabetic complications inhibited 2-FDG flux into the aldose reductase sorbitol (ARS) pathway, demonstrated as a reduction in the intensity of the ARS index resonance as well as an increase in the resonance area ratio between the pentose monophosphate shunt (PMS) and ARS index resonances (PMS/ARS ratio). Spatial metabolite mapping using rotating frame one-dimensional zeugmatography indicated that the inhibitory effect is spatially nonspecific. The present study is the first direct noninvasive observation of the effects of a pharmacological agent on cerebral enzymatic activities.

Aldehyde Reductase↗

31P NMR spectroscopy of the stomach by zig-zag coil.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopic investigations of the rat stomach were performed utilizing a 1-cm2, three-turn, zig-zag coil. A zig-zag coil of this dimension produced an effective B1 field that extends only within a 4-mm distance from the plane of the surface coil, rendering it possible to obtain high-resolution 31P spectra localized to the stomach without contamination from surrounding tissues. Normal stomach showed a characteristic spectral pattern with resonances reflecting inorganic phosphate (Pi), phosphocreatine (PCr), and the alpha-, beta-, and gamma-phosphates of adenosine triphosphate (ATP). Ischemia-induced changes in Pi, PCr, and ATP resonances were readily followed in vivo with a time resolution of 2.13 min. Indomethacin-induced ulcer revealed a low intracellular pH and a decrease in the PCr to Pi ratio indicating the partially ischemic conditions of ulcerative lesions of the stomach as has been previously suggested. The present studies indicate that 31P NMR spectroscopy utilizing a zig-zag coil is a powerful tool to study local pathology of the gastrointestinal (GI) tract. Since zig-zag coils suitable for fiberscopic devices are easily constructed, clinical applications of the present technique are apparent.

Animals↗

Limbic lymphoma.

Two cases of metastatic malignant lymphoma confined to the limbic-hypothalamic region are presented. The non-specific nature of the neurological symptoms associated with these lesions such as memory loss, impotence and confusion made neurological localization of the disease process difficult. While non-contrast computed tomography (CT) was unremarkable, contrast CT was diagnostic, showing bilateral homogenous enhancement of specific limbic-hypothalamic structures without significant mass effect. Since lymphomatous involvement of the limbic-hypothalamic area tends to be infiltrative without attendant mass effect, detection of metastasis may be elusive unless special attention is directed to this region. As lymphoma is often chemoresponsive and highly radiosensitive, early recognition of limbic-hypothalamic involvement of this disease is important.

Hodgkin Disease↗

Heterogeneity of regional cerebral glucose metabolism demonstrated in situ in rat brain by 19F NMR rotating frame zeugmatography: one dimensional chemical shift imaging of normal and gliosarcoma implanted brain.

Using 19-fluorine (19F) as nuclear magnetic resonance (NMR) signal probe and 2-fluoro-2-deoxy-D-glucose (2-FDG) as metabolic probe, one dimensional "imaging" (metabolite mapping) of pathway specific glucose metabolism in the pentose monophosphate shunt (PMS) and aldose reductase sorbitol (ARS) pathways were performed in situ in rat brain utilizing one dimensional rotating frame zeugmatography. Normal brain showed highest PMS activities in the brainstem consonant with known spatially heterogeneous concentration of glucose-6-phosphate dehydrogenase, the rate limiting enzyme for the PMS. The brain harboring sufficiently large gliosarcoma in the cerebrum showed a higher PMS/ARS area ratio indicating higher PMS activities in tumor which was localized by zeugmatography. The present study demonstrated the feasibility of studying regional glucose metabolism in the PMS and ARS utilizing 2-FDG.

Aldehyde Reductase↗

Noninvasive demonstration of in vivo 3-fluoro-3-deoxy-D-glucose metabolism in rat brain by 19F nuclear magnetic resonance spectroscopy: suitable probe for monitoring cerebral aldose reductase activities.

The metabolism of 3-fluoro-3-deoxy-D-glucose (3-FDG) in rat brain in vivo was investigated noninvasively using 19F nuclear magnetic resonance (NMR) spectroscopy. Following an intravenous infusion of 3-FDG, 400 mg/kg, four resonances assigned to the alpha and beta anomers of 3-FDG, 3-fluoro-3-deoxy-D-sorbitol, and 3-fluoro-3-deoxy-D-fructose were clearly resolved in brain, a result indicating that 3-FDG is metabolized primarily into the aldose reductase sorbitol (ARS) pathway. An orally administered aldose reductase inhibitor, sorbinil, caused reduction of the flux of 3-FDG into the ARS, an observation suggesting that the method can be applied in quantitative studies of ARS pathway activities. Studies of 24-h urine specimens showed that in addition to the two metabolites observed in brain, F- was excreted into the urine. 3-FDG appears to be a suitable metabolic probe for assessing glucose metabolism in the ARS pathway by in vivo 19F NMR spectroscopy.

Aldehyde Reductase↗

Oculopalatal myoclonus.

Five cases of oculopalatal myoclonus (OPM) were studied. Three exhibited the lateral form, characterized by jerky nystagmoid eye movements with simultaneous oblique and rotatory components, associated with lateralized palatal myoclonus, and 2 the midline form, characterized by vertical to-and-fro pendular eye movements with symmetric bilateral palatal myoclonus. Structural studies using computed tomography (CT) and proton nuclear magnetic resonance (NMR) imaging indicated that the integrity of the flocculus was preserved in all 5 cases. We postulate that the generation of ocular oscillations in OPM involves vestibulo-ocular reflex (VOR) adaptation mediated by the flocculus. The lateral form represents unilateral disease, whereas the midline form represents bilateral disease.

Brain Diseases↗

Noninvasive in vivo demonstration of 2-fluoro-2-deoxy-D-glucose metabolism beyond the hexokinase reaction in rat brain by 19F nuclear magnetic resonance spectroscopy.

The metabolism of 2-fluoro-2-deoxy-D-glucose (FDG) in vivo was observed noninvasively in rat brain using 19F nuclear magnetic resonance (NMR) spectroscopy following an intravenous injection of FDG (400 mg/kg). At 3 h after infusion, four resonances with discrete chemical shifts were resolved. Chemical shift analysis of these resonances suggested the chemical identity of two of the resonances to be FDG and/or FDG-6-phosphate and 2-fluoro-2-deoxy-delta-phosphogluconolactone and/or 2-fluoro-2-deoxy-6-phosphogluconate. The chemical identities of the other two resonances remain to be elucidated. The present study indicates that the metabolism of FDG in vivo is more extensive than is previously recognized and demonstrates the feasibility of using 19F NMR spectroscopy to follow the 19F-containing metabolites of FDG in vivo.

Animals↗

Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy.

We studied a thiamine-dependent enzyme, transketolase, from fibroblasts of a diabetic patient who developed Wernicke's encephalopathy when treated with tolazamide, in order to delineate if this patient also had transketolase abnormality [high Km for thiamine pyrophosphate (TPP)], as previously reported in postalcoholic Wernicke-Korsakoff syndrome. In addition to this patient, we also studied this enzyme from three diabetic kindreds without any history of Wernicke's encephalopathy and from four normal controls. We found that the above-mentioned patient and one of the diabetic kindreds with no history of Wernicke's encephalopathy had abnormal transketolase as determined by its Km for TPP. These data suggest a similarity between postalcoholic Wernicke-Korsakoff syndrome and the patient with tolazamide-induced Wernicke's encephalopathy from the standpoint of transketolase abnormality.

Fibroblasts↗

Subacute diencephalic necrosis and dural arteriovenous malformation.

We report a case of congestive venous necrosis involving the diencephalon symmetrically, presumably precipitated by a dural arteriovenous malformation (AVM). The patient presented with a 1-month history of intermittent confusion and gait ataxia. The initial radiological work-up revealed a dural AVM. The patient's subsequent deterioration was accompanied by computed tomographic findings of diencephalic congestion. Pathological examination showed subacute necrosis of the diencephalon. We discuss the pathogenesis of this case of subacute diencephalic necorsis and its possible relationship to the entity of subacute diencephalic angioencephalopathy.

Brain Diseases↗

Transfer of language dominance.

It has been suggested that recovery from aphasia may depend on the ability of the nondominant hemisphere to subserve language functions. We describe a patient who illustrates a possible "transfer" of language dominance. The patients sustained two infarcts two years apart, one in each hemisphere, involving mirror image territories in the temporoparietal area. The clinical course of each infarct was almost identical, consisting of an initial Wernicke's aphasia which evolved into anomic aphasia during recovery.

Anomia↗