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Biomedical subjects

A Kamei

Publications and source records attributed to A Kamei.

At least 55 records · Page 3Linked to original sources

Monitoring of the intracranial hemodynamics and oxygenation during and after hyperventilation in newborn rabbits with near-infrared spectroscopy.

Oxyhemoglobin, deoxyhemoglobin, total hemoglobin, and oxidized cytochrome aa3 were monitored, blood pressure and heart rate were continuously recorded, and cerebral hemodynamic changes were analyzed during and after hyperventilation (arterial CO2 tension < 2.67 kPa) and/or hyperoxemia (100% O2 inhalation) in 11- to 12-d-old rabbits. Oxyhemoglobin, deoxyhemoglobin, total hemoglobin, and oxidized cytochrome aa3 were monitored by means of near-infrared spectroscopy. Near-infrared spectroscopy ideally demonstrated decreases in oxyhemoglobin and total hemoglobin and an increase in deoxyhemoglobin during hyperventilation and a return to the previous values after hyperventilation. Cytochrome aa3 decreased during hyperventilation. On hyperventilation with 100% O2 inhalation, however, cytochrome aa3 was not reduced, although the changes in oxyhemoglobin and total hemoglobin were more significant. This reduction of cerebral oxygenation during hyperventilation without the administration of oxygen may induce hypoxic-ischemic brain damage. Noninvasive monitoring of cerebral oxygenation and hemodynamics, for which near-infrared spectroscopy is useful, is a requisite for the prevention of brain injury caused by severe hypocarbia in hyperventilation therapy.

Animals↗

The relationship between properties of antipsychotic drugs and cataract formation.

It has been reported that antipsychotic drugs such as phenothiazine derivatives, dibenzyl derivatives and others with calmodulin antagonism induce cataracts, which are generically called phenothiazine-induced cataracts. In the ophthalmologic field, the mechanism of cataractogenesis by such drugs is a problem urgently requiring a solution. This paper reports the relationship between the properties of such drugs and cataract formation. In this experiment, phenothiazine derivatives (chlorpromazine, trifluoperazine, prochlorperazine and perphenazine), dibenzyl derivatives (imipramine and amitriptyline), and other drugs (cyproheptadine and calmidazolium) were investigated. As a result, it was clarified that phenothiazine derivatives and calmidazolium have high lipophilicity, strong inhibition activity against phosphodiesterase, and a large permeability constant, and that those drugs induce high levels of Ca2+ accumulation in the lens. It was also revealed that those drugs were distributed only at the peripheral region of the lens after they had penetrated into the lens. From these findings, we inferred that the cataract formation may be caused by lens protein aggregation followed by the inactivation of calmodulin-dependent Ca-ATPase and subsequent Ca2+ accumulation in the lens. Furthermore, we have been convinced that it is necessary to lower at least the lipophilicity of these drugs to suppress the side effect of antipsychotic drugs inducing cataractic formation.

Animals↗

Peroxisomal disorders in children: immunohistochemistry and neuropathology.

Immunohistochemical studies with antisera against four peroxisomal enzymes, catalase and beta-oxidation enzymes (acyl-coenzyme A oxidase, bifunctional protein, and 3-ketoacyl-CoA thiolase), were performed on brain, liver, and kidney specimens from patients with peroxisomal disorders, as well as specimens from three control subjects, by using conventional paraffin-embedded autopsy material. The patients included eight with Zellweger syndrome and one with neonatal adrenoleukodystrophy. In the liver and kidney specimens from all patients, except one with Zellweger syndrome, diffuse immunostaining with all antisera in the cytoplasm of hepatocytes and renal tubular epithelium suggested an absence of peroxisomes but the presence of peroxisomal enzymes. Examination of brain specimens indicated a weak or negative reaction of neurons in the cerebral cortex and a weak reaction of glial cells in the white matter, which suggested maturational delay compared with control subjects. The delayed immunoreactive pattern of peroxisomal enzymes in Zellweger syndrome and neonatal adrenoleukodystrophy may be related to the significant neuropathologic features of polymicrogyria and dysmyelinogenesis. One patient with Zellweger syndrome had a unique finding of a positive granular catalase reaction and a negative reaction with antisera to 3-ketoacyl-coenzyme A thiolase, which suggested a diagnosis of pseudo-Zellweger syndrome. This study validates the application of these immunohistochemical methods to the study of peroxisomal enzymes. Use of these methods improves the accuracy of diagnosis of peroxisomal disorders.

Acetyl-CoA C-Acyltransferase↗

Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) was used to monitor human visual cortical function during and after photic stimulation (PS) in five adult volunteers. Cerebral blood volume (CBV) increased on the occipital surface during PS, but NIRS parameters did not change on the frontal surface. The increase in CBV was caused by a rapid increase in oxyhemoglobin with but a small increase in deoxyhemoglobin, suggesting cerebral vascular dilatation with decreased oxygen consumption. After PS stopped, CBV promptly decreased and then slightly increased again. Cytochrome aa3 did not show any change during and after PS. These phenomena reappeared following repeated PS in all five subjects. These results may represent the first step in the development of NIRS imaging.

Adult↗

Clinicopathological study of pontosubicular necrosis.

Clinicopathological features were examined in 65 neonates and 8 stillborn infants with pontosubicular necrosis (PSN) compared to 57 neonates and 19 stillborn infants without PSN. Twelve out of 65 neonates with PSN had congenital heart disease and 3 out of 65 neonates showed persistent fetal circulation. On neuropathological examination, the frequency of neonates with PSN who also showed karyorrhetic/eosinophilic neurons in other regions of the brain stem, basal ganglia and thalamus was higher than in controls. The results of this study suggest that acute ischemia is an important underlying pathogenetic factor and PSN occurs in the prenatal as well as postnatal period.

Asphyxia Neonatorum↗

Responses of cerebral blood volume and oxygenation to carotid ligation and hypoxia in young rabbits: near-infrared spectroscopy study.

After ligation of the bilateral common carotid arteries with exposure to hypoxia in young rabbits, cerebral blood oxyhemoglobin, deoxyhemoglobin, and total hemoglobin were measured by near-infrared spectroscopy. Ligation of common carotid arteries decreased oxyhemoglobin, increased deoxyhemoglobin, and slightly decreased total hemoglobin. Exposure to hypoxia with bilateral carotid ligation more remarkably decreased oxyhemoglobin and increased deoxyhemoglobin than that without carotid ligation. However, the total cerebral blood volume did not change very much. This marked reduction in the cerebral oxygenation may cause brain damage and may be an important monitoring marker for the prevention of hypoxic-ischemic encephalopathy.

Animals↗

Glutathione levels of the human crystalline lens in aging and its antioxidant effect against the oxidation of lens proteins.

This paper reports the role of glutathione (GSH) in the crystalline lens as an antioxidant against the oxidation of lens protein. GSH levels in normal lenses decreased gradually with increasing age, from approximately 5 mumol per g lens (wet weight) to 3 mumol per g lens (wet weight). On the other hand, levels of oxidized GSH in the lenses increased until the age of 40. After that, it remained almost constant at the level of approximately 0.9 mumol per g lens. Protein-bound GSH levels in both soluble and insoluble lens proteins dropped noticeably in the 50-year and older age groups, although there were significant differences in levels between both fractions. A decrease of tryptophan and tyrosine residues in lens proteins was proportional to a decrease in GSH levels in the lens as a result of aging. Those residue levels in the cataractous lenses were approximately half those in the normal lens proteins, and GSH levels in such lenses were almost one-tenth that in the normal lens. This study revealed that GSH may play an important role in preventing the oxidation of lens proteins from various oxidants. Furthermore, it is conceivable that these normal changes in GSH levels in the lenses increase the vulnerability of the lens to senile cataractogenesis.

Adolescent↗

Assessment of chemoembolization therapy for primary liver cancer using a stabilized adriamycin-lipiodol suspension.

We formulated a new lipiodol-Adriamycin suspension (ADM/lipiodol, 50 mg/10 ml) that remained stable for 48 h (half-life, 25 +/- 3 days). In five cases of hepatocellular carcinoma (HCC) resected after intra-arterial infusion of this agent, the ADM concentration in the tumor was quite high and the tumor necrosis rate was more than 80% on histological examination. Over a 5-year period, 180 patients with unresectable HCC underwent transcatheter arterial embolization therapy (TAE) in the presence or absence of this agent. The regimens consisted of suspension injection alone (A, n = 54), suspension injection + TAE using gelatin sponge (B, n = 29), TAE followed by suspension injection (C, n = 34), and TAE alone (D, n = 63). The estimated 1-year survival values determined for patients treated with these regimens were 70%, 73%, 43%, and 39% respectively, and the corresponding 3-year survival values were 27%, 31%, 15%, and 10%. The survival achieved using suspension injection was thus superior to that obtained using conventional TAE, and combined therapy with suspension injection followed by TAE seemed to enhance survival, although there were some biases in tumor size and in the stage of tumor progression. For patients with tumors measuring 5 cm or more in diameter, the survival obtained using regimen A was lower than that achieved using regimen D, but the combination of TAE and suspension injection improved the 1-year survival value obtained using regimen D from 34% to 52%. For patients with tumors measuring less than 5 cm in diameter, the survival achieved using regimen A was markedly better than that obtained using regimen D, although no difference was found between the survival value achieved using regimen A and that obtained using regimens B and C. On the basis of these results, our newly formulated ADM-lipiodol suspension was surmised to be effective by itself against relatively small HCC tumors, whereas it enhanced the efficacy of conventional TAE in large lesions.

Aged↗

Glycation and insolubility of human lens protein.

To learn whether glycation plays a role in insolubilization or in senile cataractogenesis, the reactivity of lens protein from normal and senile cataractous lenses and individual crystallin prepared from human lens with various sugars [glucose, glucose-1-phosphate (G-1-P), glucose-6-phosphate (G-6-P) and fructose], and the insolubility of those proteins were determined. The reactivity of human lens protein to glucose was increased in a dose-dependent manner, and it was demonstrated that 17.9, 18.5 and 24 kDa proteins were susceptible to glycation with sugars. The study also showed that alpha-, beta-crystallins and high molecular weight (HMW) aggregate obtained from cataractous lens have some weak reactivity against sugars. It was demonstrated that the proteins obtained from normal lens of older age and from cataractous lenses have higher insolubilities to glucose than do normal younger ones. Measurement of glycosylated protein by affinity column chromatography revealed that cataractous lenses contained a larger amount of glycosylated protein than normal ones. These results suggest that there is an age-related increase of glycation in normal human lens protein, and that such glycation increases the amount of insolubilized protein with the effect of aging. The author also speculates that an abnormal acceleration of glycation in the human lens may induce senile cataract formation.

Cataract↗

Possible process of insolubilization of lens proteins--direct effect of glucose.

The effect of glucose on the insolubilization of lens proteins was investigated in the presence of visible light. The amount of glucose-induced insolubilization of lens proteins showed a dose-dependent increase. The velocity of insolubilization accelerated under acidic conditions. These results suggest that this phenomenon may be due to the direct action of glucose rather than glycosylation. 1H-NMR spectroscopy results suggest that the action of glucose might be to induce conformational changes, and aggregation of the proteins. The in vitro observation of glucose-derived insolubilization of the lens proteins may be similar to that observed in diabetic mellitus. Elevated free glucose per se may have a role in diabetic cataractogenesis in addition to the metabolism of glucose to sorbitol and osmotic changes to the lens. Protein structural perturbation by glucose was demonstrated with isolated proteins from the aged normal human lenses over 40 years and may contribute to senile cataractogenesis. The results suggest that elevated lens glucose may act directly as one of the triggers of cataractogenesis.

Aging↗

Contribution of glycation to human lens coloration.

To study the contribution of glycation or the Maillard reaction to the spontaneous coloration of human crystalline lens in aging, we determined 1-deoxyfructosyl adduct and the fluorescent material, which are produced in the early stage of glycation, in the proteins of normal and colored human lenses of different ages. The amount of both glycation products in the lens increased significantly in proportion to aging or the advance of lens coloration. The insolubility of lens protein also increased with the advance of glycation. In addition, the present study showed that glucose and glucose-6-phosphate have higher reactivities with human lens protein than fructose and glucose-1-phosphate. This paper demonstrates that the deeper colored or older aged lens contains larger amounts of glycation products, and that glycation between lens protein and various sugars in vivo may be a serious factor in human lens coloration or insolubilization of lens protein.

Animals↗

Characterization of water-insoluble proteins in normal and cataractous human lens.

The mechanism of lens protein aggregation with age and/or cataract formation was investigated using the peptides resolubilized from the insoluble protein fraction of normal and cataractous human lenses. The insoluble fraction was treated with reductants for cleaving disulfide bonds, or with chelating agents for removing calcium ions from the aggregates. This study demonstrates that the insoluble protein aggregates consist of an approximately 400 Kd complex, which is formed by the peptides with lower molecular weight. Protein aggregation in the cataractous lens might be caused by disulfide bonds whereas, in aging, the aggregate might be preferentially formed by calcium ion bridges rather than by disulfide bonds. It was observed that the aggregate from the cataractous lenses involved a peptide with a molecular mass lower by 1 Kd or 2 Kd than the peptides found in the normal lens. The composition of crystallins in aggregating proteins and their secondary structures were also different in the normal and the cataractous lenses. Such changes of molecular weight, conformation, and/or crystallin species in the lens may lead to the disintegration of the orderly arrangement of crystallins, resulting in the diffused reflection and lens opacities which are seen in senile cataract.

Aged↗

Characterization of peptide inducing cataractogenesis in lens of hereditary cataractous rat (ICR/f RAT).

A material with inhibitory action to Na+/K+ ATPase was found in the lens of the ICR/f rat, a recessive hereditary cataractous rat. The material also induced lens opacification in vitro. From the results of amino acid analysis and by secondary ion mass spectroscopy, it was suggested that the material might contain approximately equimolar amounts of four amino acids, ie, aspartic acid, serine, glutamic acid and glycine, and that the molecular weight was 444. These facts suggested that this material with Na+/K+ ATPase inhibitory action might be a peptide. However, there is not yet any corroborating evidence to show whether this peptide is only a single material or not. The peptide significantly increased with aging in the lens of the ICR/f rat until approximately 90 days, when cataract became manifest, but its content decreased thereafter. This study suggests that one of the causes of cataractogenesis in the ICR/f rat might be this peptide, which is transformed in the lens with aging, and also that the peptide might accelerate lens opacification after cataractogenesis.

Aging↗

The evaluation of therapeutic efficacy of hachimi-jio-gan (traditional Chinese medicine) to mouse hereditary cataract.

This study was of a series of the evaluation of Hachimi-Jio-Gan (Rehmannia Eight Formula, pa-wei-ti-huang-wan or Bawei dihuang wan) to the various cataracts. In this study, the drug was evaluated for its therapeutic efficacy to mouse hereditary cataract from the delay effect of cataract appearance age and the suppression rates of variation of some biochemical parameters. The dose of 200 mg of Hachimi-Jio-Gan/day/100 g of mouse body weight significantly delayed the cataract appearance age by 4 days as compared to that of non-treated group. We estimated that the delay effect of 4 days in mouse may be corresponded to 13.9 years, when it was converted into the case of human. This drug also suppressed variation of sodium and potassium ions level in the lens with cataractogenesis. Furthermore, the drug dramatically reactivated the sodium-potassium ATPase activity damaged with the cataract formation, and also had a slight action of reducing agent. From these facts, we presumed that the drug may have a prophylactic efficacy to the cataract caused by the inhibition of sodium-potassium ATPase activity and also the oxidation of lens protein.

Administration, Oral↗

The evaluation of therapeutic efficacy of hachimi-jio-gan (traditional Chinese medicine) to rat galactosemic cataract.

Hachimi-jio-gan (Rehmannia Eight Formula, pa-wei-ti-huang-wan or Bawei dihuang wan) is one of traditional Chinese medicines which has been used for treating various senile disease for a few hundred years. This drug was evaluated for its therapeutic efficacy to rat galactosemic cataract from the suppressive rate of variance of some biochemical parameters, whose variation with cataractogenesis or the advance of cataract have been reported already. The dose of 500mg of Hachimi-jio-gan/day/200g of rat body weight suppressed significantly the variations of hydration rate, Na/K ratios, and calcium ion level in the lens with the advance of galactosemic cataract, especially when the drug was administered by the pre- or concurrent-administration before or with 30% of galactose diet respectively. This drug also could delay the progressive rate of lens opacification. However, the drug had no effect to suppress the galactitol accumulation in the lens. From these results, we presume that a drug action of Hachimi-jio-gan may control the balance of sodium, potassium and calcium ions which are important in relation to the maintenance of lens transparency. Then, we realized, that this drug may have a prophylactic efficacy to diabetic cataract, though a more detail study should be needed to apply this drug to human cataract disease.

Animals↗