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Biomedical subjects

M Ichihashi

Publications and source records attributed to M Ichihashi.

At least 163 records · Page 9Linked to original sources
PubMed1991

Effect of dopa-loading on glutathione metabolising enzymes and tyrosinase in relation to 5-S-cysteinyl-dopa genesis in cultured B-16 melanoma cells.

The effect of DOPA and glutathione (GSH) on enzyme systems for 5-S-cysteinyl-DOPA (5SCD) genesis in murine melanoma cells cultured in tyrosine- and cystine-free medium were studied. DOPA at its optimum concentration (10(-5) M) when added alone did not alter tyrosinase, glutathione-S-transferase or gamma-glutamyl transpeptidase activities. In the presence of GSH at its optimum concentration (10(-5) M), DOPA loading did not cause any significant changes in tyrosinase or glutathione-S-transferase (GST) activities. This indicates that the higher 5SCD levels observed in the medium because of DOPA loading in the GSH dependent system results from increased substrate availability rather than the increased enzyme activity. An acute drop in 5SCD at DOPA concentrations above 10(-5) M observed in the GSH dependent system may be due to the inhibition of tyrosinase at high substrate concentrations (10(-4) M). Conversely, in the presence of DOPA, when GSH was increased, the resultant higher production of 5SCD could be explained by the increased activity of GST. When added alone, GSH (10(-5) M) caused a significant increase in GST (approximately 125%) and gamma-GTP (approximately 50%) activities. A drop in 5SCD in the medium when GSH was added beyond its optimum concentration (10(-5) M) in the DOPA-dependent system could be due to competitive inhibition of gamma-GTP by GSH. The data demonstrate that 5SCD genesis may be enhanced due to the accumulation of cytotoxic melanin precursors such as DOPA/DOPA quinone. The relative quantities of GSH at the sites of DOPA quinone formation and the levels of its metabolising enzymes can influence the type of product formed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Increase of sialylated tetraantennary sugar chains in parallel to the higher lung-colonizing abilities of mouse melanoma clones.

The N-linked sugar chains of melanoma cell membrane from five murine B16 melanoma clones (F1, F10, BL6, W1-4, and C4-1) with different degrees of metastatic abilities after intravenous and intrafootpad injections were released quantitatively as oligosaccharides by hydrazinolysis, and their structures were analyzed by serial lectin column chromatography, Bio-Gel P-4 column chromatography, and sequential glycosidase digestion. Sugar chain structures of each clone have shown to consist of the same elemental oligosaccharides, but to differ in their percent compositions. More than 84% of the neutral oligosaccharides were high mannose-type sugar chains. Most complex-type sugar chains were sialylated, of which the major structure was tetraantennary sugar chain. Highly lung-colonizing F10 cells had 1.4 and 1.7 times more non-repeated tetraantennary sugar chains than moderately colonizing F1 and C4-1 cells, respectively, and 2.5 times more than poorly colonizing W1-4 cells. BL6 cells, which are also highly lung-colonizing, had 1.5 and 1.9 times more non-repeated tetraantennary sugar chains than F1 and C4-1 cells, respectively, and 2.8 times more than W1-4 cells. These results suggest that increase of sialylated tetraantennary complex-type sugar chains without N-acetyllactosamine repeating units of B16 melanoma cells might correlate with the higher lung-colonizing ability after intravenous injection.

Animals↗
PubMed1991

Studies on nilvadipine. I. Synthesis and structure-activity relationships of 1,4-dihydropyridines containing novel substituents at the 2-position.

The synthesis of new 1,4-dihydropyridine derivatives containing novel substituent at the 2-position of the nucleus via the key intermediate 2-formyl-1,4-dihydropyridines (X), is described. The aldehydes (X) were prepared by hydrolysis of the acetals (IX) which were obtained from aryl aldehyde (V) and alkyl 4,4-dialkoxyacetoacetate (VI) by the Knoevenagel reaction and treatment with alkyl 3-aminocrotonate (VIII) according to the modified Hantzsch method. The formyl group of the aldehydes (X) was reactive enough to be converted to a variety of functional groups such as hydroxymethyl, cyano, substituted iminomethyl, carbamoyl, semicarbazone, substituted vinyl, ethynyl, and so on. In all of the novel compounds we prepared, 2-hydroxymethyl- and 2-cyano-1,4-dihydropyridines (IV and XXII) were found to possess potent activities in preliminary biological evaluations on hypotension in normotensive rats and on an increase in coronary blood flow in pentobarbital-anesthetized dogs. Optimization research in order to obtain a more potent compound was accomplished in the 2-hydroxymethyl- and 2-cyano-1,4-dihydropyridine series. We selected isopropyl 2-cyano-3-methoxycarbonyl-4-(3-nitrophenyl)-6-methyl-1,4-dihydropyridine -5-carboxylate (XXIIj) as a candidate compound for further biological evaluation studies. Fortunately, XXIIj (nilvadipine) has been accepted in clinical use for the treatment of hypertension.

Animals↗
PubMed1991

[A case of corrosive esophagitis with stenosis].

A 41-year-old man was admitted to our hospital because of pharyngeal pain and vomiting after intentionally swallowing sodium hydroxide. Gradually esophageal stenosis took place. After 9 months from the taking poison the patient was operated. We tried blunt dissection of esophagus. But the procedure failed in because the wire of stripper was cut. So performed total esophageal resection under the right thoracotomy. The right side colon was used to re-construction through antero-sternal space that was anastmosed to cervical esophagus and stomach. The postoperative course was uneventful.

Adult↗
PubMed1990

In situ detection of cutaneous melanoma by prompt gamma-ray spectrometry using melanoma-seeking 10B-dopa analogue.

10B1-para-boronophenylalanine (10B1-BPA), one of our boronated dopa analogues developed for thermal neutron capture therapy, has been found to have a selective affinity for malignant melanoma. We have established a method of 'in situ' detection of subcutaneous melanoma lesions, using this melanoma-seeking 10B-labeled compound. In this study, we applied an 'in situ' 10B microanalysis system via detection of the prompt gamma-ray from the 10B(n, alpha)7Li reaction triggered by irradiating the 10B-containing target with pure thermal neutrons, called prompt gamma-ray spectrometry, to hamsters bearing Greene's melanoma in subcutis and to a human patient whose occipital subcutaneous tumor was suspected of being a metastatic melanoma. In the hamsters, the time-dependent 10B dynamics showed increased 10B accumulation in melanoma, after 10B1-BPA administration, in contrast to that in non-melanoma normal skin. In the human patient, after subcutaneous injection of 10B1-BPA into perilesional sites 4 cm distant from the tumor margin, the average 10B concentration in the tumor was determined to be 24 ppm (microgram/g), in contrast to 3 ppm in skin covering the tumor and 1.1 ppm in blood, indicative of selectively high 10B1-BPA uptake by the tumor.

Aged↗
PubMed1990

Protein kinase C and linoleic acid-induced inhibition of melanogenesis.

Linoleic acid has been shown to inhibit melanogenesis in cultured B16 mouse melanoma cells. We report here the possible involvement of protein kinase C (PKC) in linoleic acid-induced inhibition of melanogenesis in B16 cells. A single PKC subspecies (alpha-PKC) was detected in B16 cells. The enzyme was activated by linoleic acid in vitro. The effective concentrations at which PKC was activated (25 microM; maximum response) were consistent with those for the inhibition of melanogenesis in cell culture system. In addition, the permeable diacylglycerol 1-oleoyl-2-acetyl glycerol that activates PKC also inhibits melanogenesis at 100 microM. These results suggest that activation of PKC plays a pivotal role in the linoleic acid-induced inhibition of melanogenesis in B16 cells.

Animals↗
PubMed1990

[Mandibular movement during chewing-gum chewing on the sagittal plane in children].

The purpose of this study was to investigate the changes of the mandibular movement during chewing-gum chewing in subjects ranging from children with deciduous dentition to adults with permanent dentition, and also to analyze the influences of malocclusion on the mandibular movement in children. The subjects were divided into three groups based on the developing stage of the dentition: ie., i) 7 children; mean age 4.6 yrs-with deciduous dentition, ii) 9 children; mean age 9.0 yrs with mixed dentition and iii) 10 adults; mean age 22.9 yrs with permanent dentition. In addition, 17 subjects who have malocclusion were also examined, who were subdivided into the cross-bite group (mean age 7.9 yrs) and progenia group (mean age 7.3 yrs). The mandibular movements were recorded with Saphon Visi-Trainer CII during chewing-gum chewing and the traces of mandibular movement recorded on the sagittal plane were then analyzed. The results obtained in the present study are summarized as follows; 1) The chewing pattern of children with deciduous dentition was characterized by narrow width and large posterior deviation of the opening and closing pathway. During growth, the width of the pathways increased and their posterior deviation decreased. The narrow width of the opening and closing pathways form the majority of the type of chewing pattern in children with deciduous dentition. On the other hand, the types of reversed and crossed pathways form the majority in adults. 2) The chewing pattern in children with malocclusion was characterized by small posterior deviation in the pathway. The type of reversed cycle was ranked first among the chewing patterns of progenia patients, while there were no significant differences of chewing types between cross-bite patients and children with normal occlusion. As far as the results of the present study is concerned, the changes of the mandibular movement on the sagittal plane following the dentitional growth were characteristic indicated. In addition, malocclusion such as cross-bite and progenia observed in the children may influence the chewing pattern.

Adult↗
PubMed1990

An acoustically investigated case of phonetic change in higher vertical dimension.

This report presents the phonetic changes of a patient whose occlusal vertical dimension is extended. His chief complaint is esthetic restoration of his anterior teeth, but his occlusal vertical dimension is abnormally shortened by long-time attrition. Therefore we extended his occlusal vertical dimension, and reconstructed his occlusion, and carried out acoustic observations.

Aged↗
PubMed1990

[Do OKT6 positive Langerhans cells play a role in the suppression of ultraviolet-induced carcinogenesis?].

Langerhans cells (LC) in epidermis are antigen presenting cells. LC may play a role in immune surveillance system and are considered to suppress development of ultraviolet (UV) induced skin cancers. We studied effect of UVB irradiation to LC of xeroderma pigmentosum (XP) and normal subjects by using OKT6 monoclonal antibody. When 3 minimal erythema dose (MED) of UVB were irradiated, density of OKT6 positive LC of XP began to decrease 6 hours after irradiation, and showed the least numbers on day 2 and returned completely to the pre-irradiation level on day 14. Further, after 3 MED irradiation, LCs of both normal subjects became the least on day 3 and returned to the pre-irradiation level on day 14. In XP variant and normal subjects, the number of LC in chronic sun-exposed skin decreased significantly in a similar way comparing to that of non-exposed skin. These results suggest that epidermal LC may not play an essential role in prevention of UV-induced tumor development.

Adult↗
PubMed1989

Melanogenic regulatory factors in coated vesicles from melanoma cells.

Coated vesicles have been found to contain much higher tyrosinase and gamma-glutamyl transpeptidase activities than premelanosomes. This indicates that similar to tyrosinase, gamma-glutamyl transpeptidase, an enzyme responsible for pheomelanogenesis, is highly concentrated in coated vesicles after its maturation in Golgi associated endoplasmic reticulum (GERL). Furthermore, in the pre- and post-dopaquinone melanogenic pathway, coated vesicles convert dopachrome to colorless indole compounds more quickly than in premelanosomes because of their higher dopachrome conversion factor activity. Melanosomes have been found to exhibit indole conversion factor activity, while coated vesicles show indole blocking factor activity. In moderately tyrosinase-rich premelanosomes, the levels of dopachrome conversion factor and indole blocking factor are lower than in coated vesicles or melanosomes. High levels of indole blocking factor in coated vesicles may indicate why melanin polymer formation does not occur there in vivo despite their high tyrosinase activity.

Coated Pits, Cell-Membrane↗
PubMed1989

Repair of 254 nm ultraviolet-induced (6-4) photoproducts: monoclonal antibody recognition and differential defects in xeroderma pigmentosum complementation groups A, D, and variant.

Repair kinetics of ultraviolet (UV) light-induced (6-4) photoproducts in xeroderma pigmentosum complementation group A, D, and variant cells were studied by the enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody raised against (6-4) photoproducts, together with unscheduled DNA synthesis (UDS) and loss of T4 endonuclease V-susceptible sites (ESS). Group AXP35KO cells completely failed to repair both ESS (cyclobutane pyrimidine dimers) and antibody-recognizing (6-4) photoproducts until tested 24 h after irradiation, and had 2% early-time UDS. Group DXP43KO cells showed about 10% removal of both (6-4) photoproducts and ESS in 24 h, despite showing a residually higher level of 40% early-time and cumulative UDS. Thus, the results substantiated the extreme UV hypersensitivity of XP group A and D cells. However, XP52KO variant cells exhibited the normal level of UDS and ESS loss, but a slightly reduced repair of antibody-recognizing (6-4) photoproducts at 6 and 12 h after irradiation, which may account for a small UV hypersensitivity of the XP variant cells.

Antibodies, Monoclonal↗
PubMed1989

Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound.

As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure.

Animals↗
PubMed1989

Clinical and photobiological characteristics of xeroderma pigmentosum complementation group F: a review of cases from Japan.

A 61-year-old female patient with xeroderma pigmentosum (XP), registered as XP46KO, was assigned to complementation group F by the cell fusion-complementation method. The XP46KO fibroblasts in culture exhibited a defective DNA repair capacity of 10-15% unscheduled DNA synthesis and a 3-fold sensitivity to the lethal effect of 254 nm ultraviolet light compared with normal cells. The patient had mild clinical symptoms consisting of numerous pigmented freckles and a small number of seborrheic keratosis-like papules. She had no skin cancers in the sun-exposed areas of the skin and so far no neurological abnormalities. A review of 11 Japanese group F patients revealed very mild skin symptoms with no ocular or neuro-psychiatric abnormalities. Single skin cancers occurred in only 3 of the 11 patients with an average age of 52 years for their first skin malignancy.

DNA↗
PubMed1989

Effects of various drugs on bladder function in conscious rats.

In the present study, we attempted to evaluate the effects of various intravenous administered drugs, which had been shown to influence bladder function in anesthetized animals, on the cystometrogram in conscious rats placed in a restraining cage. Thiopental, diazepam, baclofen, clonidine and flavoxate, considered to act on the micturition center in the brain stem, hardly increased bladder capacity (time to micturition in cystometrogram) in conscious rats, but morphine, indomethacin and lidocaine, considered to act on the micturition center in the sacral cord or bladder mechanoreceptors, increased it. In a chronic conscious rat, histopathological findings show that the bladder tissue at 2 days after implantation of the catheter to the bladder showed experimental cystitis characterized by severe edema in the submucosa and an increase in prostaglandin E2 content, which is thought to stimulate directly and/or indirectly the capsaicin-sensitive sensory fiber in the afferent branch of the micturition reflex, and there was hyperreflexia characterized by decreases in both bladder capacity and urine volume. In conclusion, cystometrography in conscious rats placed in a restraining cage is thought to be a useful model for evaluating the true effect of a newly developed agent on bladder function.

Animals↗