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Biomedical subjects

H Kondoh

Publications and source records attributed to H Kondoh.

At least 145 records · Page 8Linked to original sources
PubMed1990

[Four-week repeated dose oral toxicity study of BMY-28100 in juvenile rats].

In order to investigate the repeated dose oral toxicity of BMY-28100 in juvenile rats, the drug was administered orally to 4-day-old Crj: CD(SD) rats of both sexes at daily doses of 250, 750 and 1,500 mg/kg for 4 weeks. The results obtained are summarized as follows: 1. Soiling around the anus apparently correlated to soft stool or diarrhea was observed at 750 and 1,500 mg/kg and the incidence appeared to be dose-related. Three deaths including 1 death due to cannibalization occurred at 750 and 1,500 mg/kg, but they were considered to have been caused by misadministration. 2. Slightly depressed body weight gains were noted in the 750 and 1,500 mg/kg dose groups during early dosing period. 3. Slightly increased averages of food and water consumption observed predominantly in the 1,500 mg/kg dose group at later dosing period and the recovery period were considered as incidental and unrelated to the treatment. 4. Though average values of some blood chemical parameters were slightly suppressed or elevated compared with those of controls at the completion of the dosing and recovery periods, these differences appeared to be generally within normal ranges and to be irrelevant to the drug treatment. No definitive drug-related changes were detected in hematological examinations and urinalyses. 5. The average absolute and/or relative organ weights of the brain, thymus, lungs and liver from male rats in the 1,500 mg/kg dose group were lower than those of the corresponding organs from controls. However, these findings were not considered to be toxicologically significant because no corroborative changes were detected microscopically. 6. Macroscopic and microscopic examinations demonstrated dilatation of the cecum in a dose-related fashion. This phenomenon has been reported with other antibiotics and appears to be drug-related and reversible caused by an alteration of the gut flora. There were no other microscopic changes that were considered to be related to the administration of the drug. 7. Electron microscopic examination revealed no drug-related changes in the liver and kidneys from rats of the 1,500 mg/kg dose group. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 250 mg/kg/day for both male and female juvenile rats in the 4-week repeated dose oral toxicity study if the finding of cecum dilatation was not considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1990

Augmentation of antiproliferative activity of recombinant human tumor necrosis factor by delta 12-prostaglandin J2.

The effects of tumor necrosis factor (TNF) and cyclopentenone prostaglandins (PGA2 and delta 12-PGJ2), singly and in combination, against proliferation in three human gynecologic tumor cell lines (HeLa S3, HHUA, and CAOV-3) were examined in vitro. The HeLa S3 and CAOV-3 cells were unresponsive to TNF, and the HHUA cells exhibited a minimal degree of responsiveness to TNF. The HeLa S3 and HHUA cells were responsive dose-dependently to PGA2, and the CAOV-3 cells were slightly responsive to PGA2. All three cell lines were highly responsive to delta 12-PGJ2. The synergistic antiproliferative effect of TNF and delta 12-PGJ2 appeared in all three cell lines. Pretreatment with delta 12-PGJ2 enhanced the effectiveness of TNF in these cell lines, but not vice versa. A synergistic interaction between TNF and PGA2 was absent in these three cell lines. These results suggest that a combined treatment with TNF and delta 12-PGJ2 could provide a new approach to obtaining increased responses in clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Long-term results of cerebral arteriovenous malformations--surgical and conservative treatment].

During the past 20 years, we have treated 187 cases with cerebral arteriovenous malformations (AVMs). These 134 patients were treated surgically and the remaining 53 patients were managed non-surgically. The purpose of this study is to clarify the surgical indications of AVMs, based on a comparison of the long-term follow-up results between the surgical and nonsurgical groups. Consequently, good results were obtained in the surgical group: the operative mortality was 7.5% and the morbidity was 12.7%. The long-term follow-up results were as follows: Of the 124 followed cases in the surgical group, there were 16 cases with improvement of neurological deficits (13%) and 3 cases with neurological aggravation (2%). Of the 47 followed cases in the nonsurgical group, there were 5 cases with improvement of neurological deficits (11%) and 6 cases with neurological aggravation (13%). As for the incidence of AVM hemorrhage, there were 8 cases with hemorrhage in the nonsurgical group including 4 cases (3 rebleeding cases) which were fatal (11%), in contrast to one case (subtotal resection) in the surgical group. On follow-up angiography, the size of AVMs were unchanged in the majority of cases in the nonsurgical group, with the exception of 2 cases in which there were slight regressions. In the surgical group, on the other hand, enlargement in 2 cases and spontaneous regression in 3 of residual AVM occurred following incomplete resection. Particularly in 2 cases involving unresectable AVMs, a newly formed aneurysm was discovered in the follow-up angiography, emphasizing the fact that serious follow-up angiography is required in cases of untreated AVMs.

Adolescent↗
PubMed1989

Age-related changes in brush border enzymes under different dietary conditions.

We examined the age-related changes of renal brush border enzymes of male Donryu rats under different dietary conditions. High protein diet (51% casein) markedly decreased the activity of renal leucine aminopeptidase as compared with low protein diet (8% casein). No significant difference, however, was observed in the activity of renal maltase between high and low protein diets. Alkaline phosphatase activity from young adult (3-month-old) rats in the high protein diet group was significantly lower than that in the low protein diet groups. From these results, it is inferred that dietary conditions affect the age-related alteration of renal brush border enzymes. Together with the previous results, it is suggested that proteins of renal brush borders are altered differently during the aging process.

Aging↗
PubMed1989

Synergistic effects of interferon-gamma and tumor necrosis factor against proliferation of gynecologic tumor cell lines.

The cooperative effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon-gamma (rH-IFN-gamma) against the proliferation of four human gynecologic tumor cell lines (HHUA, ISHIKAWA, HeLa S3, and SCH) were examined in vitro. The effect of rH-IFN-gamma on TNF receptors was also examined. ISHIKAWA and SCH cells were highly responsive to rH-TNF alone, HHUA cells exhibited a minimal degree of responsiveness to rH-TNF, and HeLa S3 cells were unresponsive to rH-TNF alone. HHUA, HeLa S3, and SCH cells were responsive dose-dependently to rH-IFN-gamma, and ISHIKAWA cells were unresponsive to rH-IFN-gamma alone. A synergistic antiproliferative effect of rH-TNF and rH-IFN-gamma appeared in HHUA, ISHIKAWA, and HeLa S3 cells. The effectiveness of rH-TNF increased in these cell lines pretreated with rH-IFN-gamma, but not vice versa. rH-IFN-gamma did not change the binding affinity of TNF receptors in the four cell lines, but increased the number of binding sites for TNF in HeLa S3 and SCH cells. These findings suggest that there is no relationship between the increase in TNF binding sites by rH-IFN-gamma and the synergistic antiproliferative effect of rH-IFN-gamma and rH-TNF. The combination therapy of rH-IFN-gamma and rH-TNF will be a new approach against cancers.

Cell Division↗
PubMed1989

Stage-dependent expression of the chicken delta-crystallin gene in transgenic fish embryos.

To study the regulation of gene expression of vertebrate crystallin genes, the chicken delta-crystallin gene was introduced into a small freshwater fish, medaka (Oryzias latipes), which lacks this gene, and its expression was examined immunohistologically at several developmental stages before hatching. The gene expression was detected in the central fiber cells of the lens at an early stage, showing a stage-dependent expression. In non-lens tissues, the expression was barely detectable before tissue differentiation. It first became substantial mainly in mesodermal tissues and then later in a greater variety of tissues, including ectodermal and endodermal ones. Thus, the non-lens expression of delta-crystallin was also stage-dependent, with the stage being dependent on the tissue type. These results from lens and non-lens tissues are discussed in relation to tissue differentiation and two categories of delta-crystallin expression.

Animals↗
PubMed1989

New hepatoprotective triterpenes from Canarium album.

Canarium album has yielded seven triterpenes of which two appear to be novel. The new triterpenes, which were identified on the basis of spectral characteristics, are urs-12-ene-3 alpha, 16 beta-diol and olean-12-ene-3 alpha, 16 beta-diol. Both compounds exhibited hepatoprotective activity in primary cultured rat hepatocytes intoxicated with D-galactosamine.

Animals↗
PubMed1989

A mutagenic new iridoid in the water extract of catalpae fructus.

A mutagenic principle in the water extract from Catalpae Fructus (originated from Catalpa ovata G. DON) (Bignoniaceae) was isolated and characterized as a new iridoid named catalpin. The iridoid exhibited mutagenic activity towards Salmonella typhimurium strain TA100 in the presence and absence of rat liver homogenate (S9) mix in Ames' test.

Animals↗
PubMed1988

Elimination of undesirable immunoglobulin contaminants including aggregated IgG from gamma-globulin preparations by jackfruit lectin affinity chromatography.

Jackfruit lectin, jacalin, has been characterized to combine with IgA of only IgA1 subclass but not with IgA2 subclass and other immunoglobulins. However, we found in the present study that a lectin from another batch of jackfruit (Jacalin-H) showed a different nature in binding reaction. Jacalin-H combined with immunoglobulins of every class or subclass except monomer IgG. More interestingly, the Jacalin-H also combined with aggregated IgG. By means of the Jacalin-H affinity chromatography, we could efficiently eliminate aggregated IgG as well as immunoglobulins other than monomer IgG from commercial gamma-globulin preparations. Jacalin-H affinity chromatography is easy, inexpensive and efficient in the elimination of undesirable immunoglobulin contaminants in the commercial gamma-globulin preparations.

Chromatography, Affinity↗
PubMed1988

Exogenous delta-crystallin gene expression as probe for differentiation of teratocarcinoma stem cells.

We developed an experimental system in which differentiation of teratocarcinoma stem cell is probed by expression of stably introduced exogenous genes. We used chicken delta-crystallin gene (delta gene) and its derivative (Mo delta gene) driven by long terminal repeat (LTR) promoter of Moloney murine leukemia virus (Mo-MuLV). Neither of the genes was expressed in the undifferentiated condition. Differentiation to primitive endoderm induced by retinoic acid (RA) led to expression of delta but not Mo delta, while differentiation to more advanced endodermal cells by RA plus dibutyryl cAMP elicited Mo delta expression in addition to delta. These results are interpreted as a consequence of differential activation/suppression of gene expression through enhancer elements associated with the genes.

Alkaline Phosphatase↗
PubMed1988

Developmental regulation of the chicken delta 1-crystallin gene: analysis by transgenesis and gene dissection.

We previously reviewed what we had learned about the regulation of the delta 1-crystallin gene through experiments using gene transfer techniques [Kondoh et al. (1986) Cell Differ. 19, 151-160]. It was concluded then that regulatory genetic elements for the lens-specific expression are associated with the delta 1-crystallin gene, and that these chicken elements properly function in mammalian cells. In the last couple of years, we have made significant progress in the understanding of lens-specific delta-crystallin expression. This is owing to success in transgenesis of mouse with the delta 1-crystallin gene and in functional dissection of the gene which led us to the discovery of an intragenic enhancer as the major determinant for lens-specific expression. In this article, we summarize these recent advances.

Animals↗
PubMed1988

Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins.

N-myc expression is under stage- and tissue-specific regulation in mammalian development, but its function is totally unknown. We sought agents to block N-myc activity in order to infer from the effect the possible function of N-myc in the apparently complex processes. As candidates for such agents, we tested fusion genes encoding N-myc:beta-galactosidase fusion proteins for their effects on the formation of transformed foci of rat embryo primary fibroblasts as the result of transfection with N-myc and activated H-ras. One of the gene constructs very efficiently antagonized N-myc activity, as assessed by its effect on focus formation, but did not appreciably affect cell viability. The product of this gene was not only targeted to the nucleus but also accumulated in subnuclear loci which may represent the sites where normal N-myc proteins reside. The occurrence of antagonistic effect at a low stoichiometric ratio suggested that the fusion protein gene competed with the N-myc gene in a fashion analogous to a dominant negative mutation.

Animals↗
PubMed1988

Embryonic stem cell-mediated transfer and correct regulation of the chicken delta-crystallin gene in developing mouse embryos.

To study regulation of delta-crystallin expression during ontogeny, we transferred the gene from chicken into developing mouse embryos by first transforming an embryonic stem (ES) cell line of mouse and then producing chimaeric embryos by combining them with normal mouse embryos. Using this technique, genes were transferred into a variety of developing mouse tissues with high efficiency. Two delta-crystallin gene constructs were used: the wild-type gene with 2200 bp of the 5' flanking sequence, shown to be lens-specific in an assay using cultured mouse cells, and a mutant gene with 51 bp of the 5' flanking sequence, lacking the sequence required for expression in lens cells. Five independent lines carrying the former and two lines carrying the latter were employed in producing chimaeras. In the chimaeric embryos having the wild-type gene, delta-crystallin was expressed in the lens and in specific regions of the primitive central nervous system (CNS) as is seen in embryonic expression in the chicken. In adult mouse chimaeras also, expression was restricted to the lens and the CNS, in the pyramidal neurones of the piriform cortex and the hippocampus. delta-crystallin expression in these tissues is due to proper transcriptional regulation, since no expression was observed when chimaeras were produced with the ES lines carrying the mutant gene. The experimental results reported here demonstrate the advantage of ES-cell-mediated gene transfer in the study of embryonic gene regulation, because a number of gene constructs and chromosomal sites can be analysed shortly after embryo manipulation without requiring gene transmission to the next generation.

Animals↗
PubMed1988

14-Hydroxy-6-O-methylerythromycins A, active metabolites of 6-O-methylerythromycin A in human.

(14R)-14-Hydroxy-6-O-methylerythromycin A and (14S)-epimer have been isolated as active metabolites from human urine after oral administration of 6-O-methylerythromycin A (TE-031, A-56268). The structures of these metabolites were determined by means of mass, 1H and 13C NMR spectroscopies. Antimicrobial activities of (14R)-14-hydroxy-6-O-methylerythromycin A, a major metabolite, were comparable to those of the parent drug TE-031, whereas (14S)-14-hydroxy-6-O-methylerythromycin A was 4- to 8-fold less active than TE-031 against bacterial standard strains.

Chemical Phenomena↗
PubMed1988

Immunologic effects on peripheral lymphoid cells from patients with chronic hepatitis type B during administration of recombinant interleukin 2.

Nine patients with chronic hepatitis type B were treated with recombinant interleukin 2 (rIL-2). Side effects were limited to low-grade fever and headache, which were transient and tolerable for the patients. Seven normal volunteers and nine patients with chronic active hepatitis were administered by one bolus of 500 units of rIL-2. Acute effects of rIL-2 administration on lymphoid cells included a rapid decrease in lymphocytes, especially in cytotoxic T cells and natural killer cells. These acute effects resolved within 24 hours. There was no difference in the changes of immunological parameters between normal volunteers and patients. The same effects were seen during 28 days of rIL-2 administration. The number of lymphocytes and CD4 positive cells was increased after rIL-2 administration for 28 days (P less than 0.01). Natural killer cell activity, especially that of CD16+ and Leu-7- cells was also increased (P less than 0.05). These effects may favour the elimination of virus-infected hepatocytes.

Adult↗