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Biomedical subjects

H Shinoda

Publications and source records attributed to H Shinoda.

At least 91 records · Page 5Linked to original sources

[Establishment and characterization of strain KE-24 derived from human colonic cancer].

Strain KE-24 of colonic cancer cells was established from human colonic cancer diagnosed histopathologically as poorly differentiated adenocarcinoma. Doubling time of the cancer cell line was 32.4 hrs, and the karyotype was 46, xy, t (1q:?), 6p-, 14q+. The cancer cells could be heterotransplanted in 66% of nude mice. The plating efficiency was 17% in a soft agar plate with an inoculum size of 1 x 10(3) cells/dish. The tumor cells produced and released CEA and CA19-9 in the spent medium and these cancer cells were stained with both anti-CEA and anti-CA19-9 antibodies by the immunohistological staining method. Strain KE-24 of the cancer cells could be cultured in the serum-free medium (Media-I) for more than 100 passages.

Adenocarcinoma↗

Comparison of mutagenicity and theoretical reactivity of 2,4-dinitrobenzaldehyde and 2,6-dinitrobenzaldehyde in bacterial mutation assay and molecular orbital method.

The mutagenicities and theoretical reactivity indices of 2,4-dinitrobenzaldehyde (2,4-DNBAl) and 2,6-dinitrobenzaldehyde (2,6-DNBAl) were investigated using Salmonella typhimurium strains TA98, TA98NR, TA98/1,8-DNP6, and TA100, TA100NR and TA100/1,8-DNP6, by means of the modified intermediate neglect of differential overlap/3 (MINDO)/3) method. The mutagenic activities of 2,4-DNBAl in TA98NR and TA98/1,8-DNP6 were lower than in TA98, whereas the activity in TA100NR was higher than in TA100 and TA100/1,8-DNP6. The mutagenic activity of 2,6-DNBAl in TA100 and that in TA100 and TA100/1,8-DNP6 decreased. These results suggest that the mutagenicities of 2,4-DNBAl and 2,6-DNBAl are dependent either on the microbial nitroreduction and subsequent acetylation or the presence of an aldehyde group. Among the reactivity indices examined, the frontier electron density values were correlated to the mutagenicities of 2,4-DNBAl and 2,6-DNBAl in TA100, TA100NR and TA100/1,8-DNP6 and the values of energy of the lowest unoccupied molecular orbit were correlated to the mutagenicities of several substituted dinitrobenzenes.

Acetylation↗

Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats.

The rats maintained on a thiamine-deficient diet for 30 days showed hypothermia, and their histamine levels increased significantly in both the anterior and posterior hypothalamus. When these rats were administered, thiamine disulfide and/or provided with thiamine-added diet for a further 30 days, the rats recovered from hypothermia, and histamine levels were decreased to the normal level. Thus, it is probable that the increased histamine levels in the hypothalamus, especially those in its anterior region, are closely related to the hypothermia in thiamine-deficient rats.

Animals↗

Brain region and gene specificity of neuropeptide gene expression in cultured astrocytes.

Astrocytes have many neuronal characteristics, such as neurotransmitter receptors, ion channels, and neurotransmitter uptake systems. Cultured astrocytes were shown to express certain neuropeptide genes, with specificity for both the gene expressed and the brain region from which the cells were prepared. Somatostatin messenger RNA and peptides were detected only in cerebellar astrocytes, whereas proenkephalin messenger RNA and enkephalin peptides were present in astrocytes of cortex, cerebellum, and striatum. Cholecystokinin was not expressed in any of the cells. These results support the hypothesis that peptides synthesized in astrocytes may play a role in the development of the central nervous system.

Animals↗

In vivo circumvention of vincristine resistance in mice with P388 leukemia using a novel compound, AHC-52.

A novel compound partially analogous to nifedipine, AHC-52, was found to sensitize multidrug-resistant tumor cells. AHC-52 at 0.5 microgram/ml completely reversed the in vitro resistance to vincristine (VCR) in VCR-resistant P388 cells (P388/VCR). Of various regimens examined for the in vivo treatment of P388/VCR-bearing mice, the combination of 0.05 mg/kg of VCR with 100 mg/kg twice a day of AHC-52 daily demonstrated the best result with a 206% increase in life prolongation. This result was comparable with that observed in parental P388-bearing mice treated with the optimal dose of VCR alone, indicating almost complete circumvention of resistance by combination VCR-AHC-52 therapy. In addition, the combination of both agents exhibited therapeutic effects in the treatment of P388-bearing mice with some long term survivors. This result was presumably due to the elimination of heterogeneity of VCR sensitivity in this cell population. These results suggest that combination chemotherapy using a sensitizing agent such as AHC-52 will be effective in not only circumvention of multidrug resistance but also retardation of its occurrence.

Animals↗

Amygdaloid kindling of rats increases preprosomatostatin mRNA and somatostatin without affecting glutamic acid decarboxylase (GAD) mRNA or GAD.

The levels of preprosomatostatin (preproSS) mRNA, somatostatin-like immunoactivity (SS-LI) (also known as somatotropin-release inhibitory factor, or SRIF), glutamic acid decarboxylase (GAD) activity and GAD mRNA were determined in several brain regions of amygdaloid-kindled rats. SS mRNA and SS increased in the cortex and striatum, while only SS increased in the hippocampus. No changes were detected in either GAD activity or GAD mRNA in any brain region. The data suggest that somatostatin may be one of the factors involved in the chain of events leading to kindled seizures.

Amygdala↗

Pancreatic alpha- and beta-cell function and metabolic changes during oral L-alanine and glucose administration: comparative studies between normal, diabetic and cirrhotic subjects.

The present study investigated whether or not, in addition to the oral glucose tolerance test, oral alanine loading was a useful diagnostic tool for hormonal and metabolic diseases. Fifty g of L-alanine was administered orally in 14 normal, 12 diabetic, and 8 liver cirrhotic subjects. The influence of oral alanine loading on hormones and metabolites was compared with the results of 100 g oral glucose loading. The results obtained were as follows: 1) In the normal subjects and cirrhotics, lactate and pyruvate concentrations gradually increased with time and reached their peak levels at 60 min, whereas they remained unchanged throughout the course in the diabetic group at glucose loading. 2) Alanine administration accelerated ureogenesis but did not affect blood glucose levels. 3) In both glucose and L-alanine administration, free fatty acid, glycerol and ketone body levels declined nonspecifically in all groups. 4) Serum glucagon levels during L-alanine loading increased in all groups, especially in liver cirrhotics. 5) L-alanine was a potent stimulus for insulin secretion in diabetics, while no insulin release during glucose loading was observed. 6) The molar ratio of insulin levels (during glucose loading)/glucagon levels (during L-alanine loading) was a good indicator of systemic glucose homeostasis from the hormonal aspect. It is suggested that, in addition to the oral glucose tolerance test, the oral administration of L-alanine can be a useful tool for the diagnosis of the status in diabetes mellitus and cirrhosis.

Administration, Oral↗

Globoid cell leukodystrophy is a generalized galactosylsphingosine (psychosine) storage disease.

Galactosylsphingosine (psychosine) in somatic organs from a patient with globoid cell leukodystrophy and from the twitcher mouse, an animal model of human globoid cell leukodystrophy was assayed. There was an abnormal accumulation of galactosylsphingosine as in nervous tissues, albeit the concentrations being lower than those in nervous tissues. Galactosylsphingosine accumulation in the kidney of the twitcher mouse increased with age. These findings indicate that globoid cell leukodystrophy is a generalized galactosylsphingosine storage disease.

Age Factors↗

Accumulation of galactosylsphingosine (psychosine) in the twitcher mouse: determination by HPLC.

We developed a sensitive and simple procedure for determination of galactosylsphingosine (psychosine), using HPLC. The method involved extraction of lipids, separation by cation-exchange and C18 reverse-phase columns, and derivatization with o-phthalaldehyde. The fluorescent galactosylsphingosine was detected by HPLC. The amount of galactosylsphingosine was accurately assayed by simultaneous determination of glucosylsphingosine, as the internal standard. The detection limit was 0.5 ng/assay tube, and the quantitative range of the method was up to 750 ng. This procedure was applied to tissue from the twitcher mouse, an animal model of human globoid cell leukodystrophy, as well as tissue from normal and carrier mice. In the latter mice, a small amount of galactosylsphingosine was detected in the spinal cord (21.6-37.2 ng/100 mg wet weight) but not in the cerebrum and sciatic nerve. Marked accumulation of galactosylsphingosine was noted in the nervous tissues of the twitcher strain, even on postnatal day 4. The concentration of galactosylsphingosine was greater in the peripheral than in central nervous tissues. The spinal cord and brainstem contained more galactosylsphingosine than did the cerebrum and cerebellum. The concentration increased with age from 764 ng/100 mg in the sciatic nerve at 4 days to 5,910 ng/100 mg at 37 days. These data correlate well with the pathological changes; tissues containing higher concentrations of galactosylsphingosine show earlier and more severe pathological changes than those containing lower concentrations, thereby indicating the close link of galactosylsphingosine to the pathogenesis of the twitcher mouse.

Animals↗

Electrophysiological study on limb myokymia in three women.

Physiological studies on three women with limb myokymia were carried out. The patients had diabetic neuropathy, neuromyotonia, and autonomic polyneuropathy, respectively. The EMG discharge pattern, coincident with myokymia, in a patient with myokymia and neuromyotonia differed from those with myokymia without neuromyotonia. In only the first patient did the electrical stimulation of nerves evoke "late repetitive response" (LRR), which resembled the wave forms of the myokymic discharge. Epidural and peripheral nerve blocks abolished myokymia in the first and second cases, but peripheral nerve block was without effect in the third patient. These findings indicate that myokymia originates in multiple sites of alpha motor neurons and that the pathophysiology may vary.

Adult↗

Diurnal rhythms in calcium and phosphate metabolism in rodents and their relations to lighting and feeding schedules.

Diurnal fluctuations in serum Ca, inorganic phosphorus, Mg, and alkaline phosphatase activity and their relations to lighting and feeding schedules were investigated in nocturnal rats and diurnal asiatic chipmunks. The following results were obtained: all parameters in the animals fed ad libitum and adapted to a regulated light-dark cycle (with light from 7.00 to 19.00 h) showed diurnal rhythms; under the same experimental condition, the patterns of the rhythms in the nocturnal rat and the diurnal asiatic chipmunk were nearly 180 degrees out of phase with each other; under the continuous lighting condition for more than 10 days, the diurnal rhythms of the parameters in rats decreased in their amplitudes, and phase shifts or marked modulations in the diurnal curves occurred when the time of availability of food was restricted from 9.00 to 17.00 h without altering the lighting schedule. The above findings support an idea that the rhythmicity is one of the essential features involved in the Ca metabolism. It is demonstrated that the environmental photofraction is one of the essential factors in generating or in maintaining the circadian rhythm of Ca metabolism as in other physiological processes and that the feeding time also could have a marked effect on the diurnal rhythm in the Ca metabolism.

Alkaline Phosphatase↗

Plasma adrenocorticotropin and cortisol responses to ovine corticotropin-releasing factor in patients with adrenocortical insufficiency due to hypothalamic and pituitary disorders.

Plasma ACTH and cortisol responses to intravenous injection of 100 micrograms synthetic ovine corticotropin-releasing factor (CRF) were studied in 4 patients with hypothalamic hypopituitarism, 2 patients with Sheehan's syndrome, 2 patients with isolated ACTH deficiency and 10 normal subjects. All 4 patients with hypothalamic hypopituitarism had exaggerated plasma ACTH responses to CRF compared to normal subjects and gradual but definite increases in plasma cortisol from low basal levels. Of 2 patients with Sheehan's syndrome, one had slight ACTH and cortisol increases after CRF injection, whereas the other had no increase in either. In 2 patients with isolated ACTH deficiency, plasma ACTH and cortisol remained undetectable (ACTH less than 10 pg/ml, cortisol less than 0.6 microgram/dl) after CRF injection. These results suggest that the CRF test is a useful tool in evaluating patients with secondary adrenocortical deficiency.

Adolescent↗

Structure-activity relationships of various bisphosphonates.

A variety of bisphosphonates with aliphatic side chains of increasing length, as well as 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP, formerly APD), dichloromethylene-bisphosphonate (Cl2MBP, formerly Cl2MDP), and dibromomethylene bisphosphonate (Br2MBP, formerly Br2MDP), were compared in vitro and in vivo to find (a) a possible relationship between structure and activity in order to give some indication about their mechanism(s) of action on bone and (b) the most efficient and safe compound having an effect on bone resorption. Some relationship was found between inhibition of calcium phosphate precipitation in vitro and of mineralization in vivo. No correlation existed, however, between any parameter measured and bone resorption. The number of calvaria cells in culture was decreased by compounds with a chain length greater than 5-C, by AHPrBP, Cl2MBP, and Br2MBP. Lactate production by these cells in vitro was increased by the long chain bisphosphonates and AHPrBP, and was decreased by Cl2MBP. No good correlation existed between the inhibition of bone resorption measured in vitro on calvaria and that seen in vivo on rat tibiae metaphyses. The latter was inhibited the most efficiently by the bisphosphonates longer than 5-C and by AHPrBP; these were 10 times more effective than Cl2MBP. Taking into account all factors, 1-hydroxypentylidene-1,1-bisphosphonate and AHPrBP seem to be the most active compounds to inhibit bone resorption.

Alkaline Phosphatase↗

Study on hydroxamic acids and their urease inhibitory potency by quantum chemistry calculation.

The electronic structures of 34 hydroxamic acids [R-(CONHCH2(n-CONHOH, R = aromatic or aliphatic, n = 1 or 0] were calculated by the INDO method and their urease inhibitory potencies were discussed in terms of the calculated electronic parameters and molar refraction. The charge distribution of -CONHOH residue which has been expected as a functional group for inhibition slightly be affected by the change of R - moiety and by the presence or absence of the -CONHCH2- residue. The best improved regression equation indicated that the inhibitory potency of hydroxamic acids was parabolically varied with the molar refraction and that the increase of the inhibitory potency by the presence of -CONHCH2- residue was explained by the variation of the charge density of a carbon atom directly bonding the -CONHOH group.

Chemical Phenomena↗