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Biomedical subjects

K Wakabayashi

Publications and source records attributed to K Wakabayashi.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of plasma levels of lipid hydroperoxides and antioxidants in hyperlipidemic Nagase analbuminemic rats, Sprague-Dawley rats, and humans.

The levels of lipid hydroperoxides and antioxidants in plasma samples from Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR) were measured in comparison with those from normal human subjects. Cholesteryl ester hydroperoxide (CE-OOH) was detected, but phosphatidylcholine hydroperoxide was not. The levels of CE-OOH and the ratios of CE-OOH/CE were found to increase significantly in the order of human < SDR < NAR, suggesting that oxidative stress increases in the same order. NAR have a significantly lower level of ascorbate and lower ratio of ubiquinol/ubiquinone concentrations than SDR. This also suggests that NAR are subject to more oxidative stress than SDR, since ascorbate and ubiquinol are the most effective plasma antioxidants against oxygen radicals.

Adult↗
PubMed1992

Small-angle synchrotron x-ray scattering reveals distinct shape changes of the myosin head during hydrolysis of ATP.

In the energy transduction of muscle contraction, it is important to know the nature and extent of conformational changes of the head portion of the myosin molecules. In the presence of magnesium adenosine triphosphate (MgATP), fairly large conformational changes of the myosin head [subfragment-1 (S1)] in solution were observed by small-angle x-ray scattering with the use of synchrotron radiation as an intense and stable x-ray source. The presence of MgATP reduced the radius of gyration of the molecule by about 3 angstrom units and the maximum chord length by about 10 angstroms, showing that the shape of S1 becomes more compact or round during hydrolysis of MgATP. Comparison with various nucleotide-bound S1 complexes that correspond to the known intermediate states during ATP hydrolysis indicates that the shape of S1 in a key intermediate state, S1-bound adenosine diphosphate (ADP) and phosphate [S1**.ADP.P(i)], differs significantly from the shape in the other intermediate states of the S1 adenosine triphosphatase cycle as well as that of nucleotide-free S1.

Adenosine Triphosphate↗
PubMed1992

Presence of nuclear factors bound to both cAMP-responsive element and AP1 factor binding site in the porcine anterior pituitary.

Factors binding to consensus sequences of the cAMP-responsive element (CRE) and the AP1 factor binding site (AP1) were investigated using porcine anterior pituitary nuclear extracts. Each element showed specific gel mobility shifts. By reciprocal competition for the AP1 and CRE binding, CRE prevented AP1 binding completely. On the other hand, AP1 decreased the CRE binding considerably to 20%, suggesting that approximately 80% of the total CRE binding is due to factors which bind to a common site shared by both CRE and AP1, whereas proteins binding to AP1 alone are absent. Relative binding affinities of AP1 against CRE estimated from the reciprocal competition data were 0.17 for CRE binding and 0.56 for AP1 binding. UV cross-linking experiments showed that CRE and AP1 gave different patterns consisting of different molecular size. Inconsistency of the relative binding affinities and the multiple molecular size of binding factors, cannot be explained simply by the presence of two types of binding factor, common CRE/AP1-binding and specific CRE-binding factors. A more likely explanation is that the CRE/AP1-binding factors alter the dimer form by changing each respective partner to bind CRE and/or AP1.

Animals↗
PubMed1992

Immunocytochemical localization of synaptic vesicle-specific protein in Lewy body-containing neurons in Parkinson's disease.

We carried out an immunocytochemical examination of the brainstem and sympathetic ganglia of 5 autopsied patients with Parkinson's disease, using monoclonal antibodies against microtubule-associated protein 2 (MAP2) and synaptic vesicle-specific 38 kDa protein (SVP38). Lewy bodies (LBs) in the nerve cell somata were often immunoreactive for MAP2. Immunoreactivity of SVP38 in the somata of nerve cells was rarely demonstrated in the peripheral portion of the LBs. On the other hand, SVP38-immunoreactive (IR) LB-containing nerve cell processes were frequently found in the brainstem and sympathetic ganglia, considerably outnumbering MAP2-IR LB-containing nerve cell processes. These findings suggested that SVP38 is stored in LB-containing nerve cell processes and indicate that the majority of these processes are axons.

Aged↗
PubMed1992

Food-derived mutagens and carcinogens.

Cooked food contains a variety of mutagenic heterocyclic amines. All the mutagenic heterocyclic amines tested were carcinogenic in rodents when given in the diet at 0.01-0.08%. Most of them induced cancer in the liver and in other organs. It is noteworthy that the most abundant heterocyclic amine in cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, produced colon and mammary carcinomas in rats and lymphomas in mice but no hepatomas in either. 2-Amino-3-methylimidazo[4,5-f]quinoline induced liver cancer in monkeys. Formation of adducts with guanine by heterocyclic amines is presumably involved in their carcinogenesis. Quantification of heterocyclic amines in cooked foods and in human urine indicated that humans are continuously exposed to low levels of them in the diet. These low levels of heterocyclic amines are probably insufficient to produce human cancers by themselves. However, a linear relationship between DNA adduct levels and a wide range of doses of a heterocyclic amine was demonstrated in animals. It suggests that even very low doses of heterocyclic amines form DNA adducts and may be implicated in the development of human cancer under conditions in which many other mutagens-carcinogens, tumor promoters, and factors stimulating cancer progression exist.

Amines↗
PubMed1992

Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats.

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.

Animals↗
PubMed1992

Primary leptomeningeal glioma: ultrastructural and laminin immunohistochemical studies.

We studied a case of primary leptomeningeal glioma (PLG) on the left parietal lobe of a 74-year-old woman and compared the tissue with heterotopic glial tissue from another case. The PLG tumor consisted of spindle-shaped cells with marked nuclear atypism, which tended to be arranged in a fascicular pattern, and the majority of its cells were positive for glial fibrillary acidic protein. Ultrastructural examination demonstrated that most of the tumor cells contained intermediate filaments and often junctional complexes were present on their plasma membranes. Frequently, basal lamina-like structures surrounding the tumor cell surfaces were observed. Laminin immunohistochemistry clearly demonstrated a fine network of linear positive staining around the cytoplasm and processes of the tumor cells. The ultrastructure of the heterotopic glial tissue consisted of many astrocytes partially surrounded by basal lamina. These findings strongly suggest that PLG is a distinct tumor, which arises from the heterotopic astrocytes within the subarachnoid space.

Aged↗
PubMed1992

Correlation of computed tomography with the histopathology of primary malignant lymphoma of the brain.

The authors present seven autopsy cases of non-AIDS primary malignant lymphoma of the central nervous system to correlate the pathology with the findings of the most recent pre-mortem computed tomogram (CT). Of 10 primary contrast-enhancing (CE) lesions treated by chemotherapy alone, radiotherapy alone, radiochemotherapy, or surgery combined with radiochemotherapy, all but one completely disappeared after the initial course of therapy. However, in six of the seven patients, the final pre-mortem CT demonstrated CE lesions. In three cases CE lesions were at the same site as the primary lesion, in one case in a remote location, and in two cases in diffuse and multiple locations. In all but one case these CE lesions corresponded histologically to tumor nodules or to white matter densely infiltrated by tumor cells. The sole exception was diagnosed pathologically as delayed radiation necrosis. The final CT also showed five low-density areas (LDAs) which had evolved from CE lesions after the completion of therapy. These LDAs corresponded to rarefied or necrotic parenchyma in which tumor cells remained, mainly in the perivascular spaces. One case exhibited diffuse tumor infiltration of periventricular structures which appeared to have normal density and no CE on the final pre-mortem CT.

Aged↗
PubMed1992

Indirect effects of progesterone on the synthesis and secretion of prolactin in mammotroph-enriched cells.

To elucidate the role of steroid hormones in the synthesis and secretion of prolactin (PRL), a mammotroph-enriched cell preparation was made by centrifugal elutriation of trypsin-dispersed anterior pituitary cells from adult male rats. The mammotrophs were enriched by about 2-fold in comparison with those in the initial cell suspension. On the other hand, the ratio of enrichment of gonadotrophs, thyrotrophs and somatotrophs was less than onetenth. The separated mammotrophs were incubated in media containing 17 beta-estradiol and/or progesterone. 17 beta-estradiol increased the levels of PRL in the medium and the cells of 300% and 140%, respectively, and the content of messenger RNA (mRNA) to 193%, whereas progesterone had no such effects. Furthermore, progesterone had no influence on the 17 beta-estradiol-induced increase in the levels of PRL and the contents of PRL mRNA. These results suggest that 17 beta-estradiol regulates PRL synthesis and secretion in mammotrophs, whereas progesterone does not.

Animals↗
PubMed1992

A delayed response to acute stimulation with human chorionic gonadotropin in scorbutic rats.

Since our previous study revealed low basal testosterone (T) levels and a failure in response to an acute stimulation with human chorionic gonadotropin (HCG) despite of a good response to chronic stimulation in scorbutic mutant rats, time course of the response to HCG was studied and plasma LH level was measured in young adult rats deficient in ascorbic acid for 3 weeks. A single subcutaneous injection of HCG (200 IU) elevated T levels only slightly in plasma and not in testicular tissues of scorbutic rats 1 h after the injection when the levels in ascorbutic rats reached a maximum, while it yielded the same response pattern as in ascorbutic rats after 3 h. A pretreatment with HCG to scorbutic rats for 1 or 4 days resulted in the same response of plasma T as in ascorbutic rats. Plasma LH levels in unstimulated scorbutic rats were about 40% of those in ascorbutic rats. These findings indicate that a prolonged deficiency of ascorbic acid decreases plasma LH, and may reduce the sensitivity of testes to LH.

Animals↗
PubMed1992

Induction of preneoplastic lesions by a low dose of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the livers of rats treated with carbon tetrachloride.

The multifactorial nature of carcinogenesis in man has impelled us to study the effects of various chemicals and conditions in combination. In the present investigation, we examined the effects of low doses of 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) in combination with carbon tetrachloride (CCl4) on the formation of glutathione S-transferase placental form (GST-P)-positive foci in rat liver. Administration of diet containing MeIQx at 0.4, 4 or 40 p.p.m., representing one-thousandth, one-hundredth and one-tenth of the dose proved to induce hepatocellular carcinomas (400 p.p.m.), for 8 or 12 weeks did not induce GST-P-positive foci. However, 40 p.p.m. of MeIQx when co-administered with CCl4 (0.7 ml/kg, s.c. twice a week) induced preneoplastic lesions: 7- and 3-fold increases in the numbers and areas of GST-P positive foci in week 8, and 8- and 6-fold increases respectively in week 12, over those with CCl4 alone. Furthermore, a marked increase in the number of hyperplastic nodules was observed in this group of rats in week 12. No significant increases of GST-P-positive foci were observed at doses of 0.4 or 4 p.p.m. MeIQx in combination with CCl4. Thus, it is predicted that chronic exposure to 40 p.p.m. of MeIQx eventually results in induction of hepatocellular carcinomas in injured rat liver.

Animals↗
PubMed1992

Suppression of spontaneous hepatocellular carcinoma development in C3H/HeNCrj mice by the lipophilic ascorbic acid, 2-O-octadecylascorbic acid (CV-3611).

The study was performed to examine the effects of the lipophilic ascorbic acid, 2-O-octadecylascorbic acid (CV-3611), with a strong scavenging capacity for active oxygen species, on the spontaneous development of liver tumors in male C3H/HeNCrj mice. Animals were given a diet containing 0.1% CV-3611 for a total experimental period of 16 months. Hepatocellular carcinomas developed in 2/39 (5%) of these experimental mice and in 11/43 (26%) of control mice fed a basal diet. The numbers of carcinoma per mouse were 0.05 +/- 0.22 and 0.33 +/- 0.61 respectively. Thus, CV-3611 clearly suppressed the development of hepatocellular carcinomas. However, the scavenger did not affect either the incidence or the number of hepatocellular adenomas, suggesting that active oxygen species might be involved in the conversion of adenomas to carcinomas in spontaneous liver carcinogenesis in C3H/HeNCrj mice.

Animals↗
PubMed1992

Clinical values of intraoperative ultrasonography for spinal tumors.

Intraoperative ultrasonography was conducted in 52 cases of spinal tumor, at 7.5 MHz, mainly by means of linear scanning, to evaluate its clinical usefulness. The procedure was effectively applied in such clinical purposes as: 1) locating the tumor, 2) deciding the resectability of intramedullary tumors, 3) deciding the site for intraspinal biopsy or shunt tube insertion, 4) establishing the topical relationship between the spinal cord and the tumor, and 5) differentiating neurilemoma from meningoma. Of 10 patients with intramedullary tumors, 5 (50%) were removed, because extirpation was possible when the spinal cord and the tumor were well demarcated on the ultrasonogram. Intratumorous cysts were found to exist in 73% of neurilemoma and 14% of meningioma cases, enabling the differential diagnosis between the two tumors. Intraoperative ultrasonography is an uninvasive method to reveal intradural and extradural conditions and thus constitutes a valuable diagnostic means to ensure safe and precise spinal surgery.

Adolescent↗
PubMed1992

Detection of 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine in broiled beef.

2-Amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine (4'-OH-PhIP) showed mutagenicity in Salmonella typhimurium TA98 in the presence of S9 mix, inducing 180 revertants per 100 micrograms. Since creatinine, tyrosine and glucose, which are present in meat, are expected to be involved in the formation of 4'-OH-PhIP, its presence in broiled beef was examined. 4'-OH-PhIP was detected in broiled beef by high-performance liquid chromatography and UV-spectrometry after extraction with 0.1 N HCl and purification by blue cotton treatment and ion exchange column chromatography. Its level was estimated to be 21.0 ng per g of broiled beef, which is comparable to that of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

Animals↗
PubMed1992

Adduct formation at C-8 of guanine on in vitro reaction of the ultimate form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine with 2'-deoxyguanosine and its phosphate esters.

We examined the reactivity of the N-hydroxyamino derivative of a carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), after its O-acetylation with four 2'-deoxyribonucleoside 3'-monophosphates. 32P-Postlabeling analysis demonstrated that the levels of adducts with 2'-deoxyguanosine 3'-monophosphate were much higher than those with the other three nucleotides. 1H-NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N-acetyoxy-PhIP with 2'-deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C-8 position of guanine, as previously demonstrated with other heterocyclic amines.

Acetic Anhydrides↗
PubMed1992

Relation between monocytes in peripheral blood and development of atherosclerosis in hypercholesterolemic rabbits.

The relation among circulating monocytes, serum cholesterol and LDL cholesterol in manifestation of atherosclerosis was investigated in hypercholesterolemic rabbits. Serum cholesterol increased sharply and reached a plateau at 12 weeks after the start of cholesterol diet feeding; LDL cholesterol gradually increased until 24 weeks, and the number of monocytes in blood started to decrease abruptly around 12 weeks and resulted in less than 1% total white blood cells at 24 weeks, as reflected by a severe progression of atheroma formation. This result indicated that the decrement of monocyte number in blood was predictive of the presence of severe atherosclerotic plaques.

Animals↗
PubMed1992

Multiple genetic alterations in human carcinogenesis.

Cancer development in man appeared to be a multistage process as suggested by epidemiological studies on commonly occurring gastric, colon, and breast cancers and also on human retrovirus-related leukemia, and by the finding by physicians and surgeons of precancerous lesions for many types of neoplasias. In the last 10 years it has become evident that human cancers have multiple genetic alterations caused by point mutations, recombinations, amplifications, and/or deletions. The genes affected include both oncogenes and tumor-suppressor genes and genes that accelerate cell proliferation and metastasis. Cancers with more malignant properties and poorer prognosis are generally associated with larger numbers of genetic alterations. These multiple genetic alterations are considered to be a direct reflection of the multiple steps involved in carcinogenesis. The multiple genetic alterations are caused by multiple environmental carcinogenic substances or factors, each of which usually exists only at minute concentrations and does not exert any major impact alone except under particular occupational, iatrogenic, and locally geographic conditions. The fact that carcinogenesis is a multistep process involving multiple genetic alterations clearly needs to be taken into consideration in assessing the risks of environmental carcinogenic substances or factors. The increasing incidence of multiple primary cancers is also most easily understood from the viewpoint of multiple steps in carcinogenesis. Possible multiple approaches to cancer prevention should therefore be considered in relation to multistep carcinogenesis and multiple carcinogenic factors.

Animals↗