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Biomedical subjects

K Hanada

Publications and source records attributed to K Hanada.

At least 235 records · Page 13Linked to original sources
PubMed1992

Amplification of plasmid (L factor) DNA and increased production of a plasmid gene product (gamma-interferon) in mouse L cells.

It has previously been reported that composite DNAs derived from L factor, a polyoma-related mammalian plasmid, can be established in several mouse cell lines after transfection. Here, we report that the copy number of a plasmid composite DNA consisting of L factor, pBR DNA, dihydrofolate reductase (dhfr) gene, and gamma-interferon (gamma-IFN) gene was increased more than 10-fold after two successive adaptations of the plasmid-bearing mouse L cells to increasing concentrations of methotrexate (MTX), an inhibitor of dhfr. The structure of the amplified L factor plasmid remained intact during prolonged cell culture, but the copy number remained to be amplified only when the selective pressure (presence of MTX in the medium) has been exerted during the culture. Cells bearing the amplified plasmid produced a higher level of gamma-IFN compared with the original clone, which was likely to be derived from the plasmid gamma-IFN gene amplified along with L factor and the dhfr gene.

Animals↗
PubMed1992

Inhibitory effect of the leukotriene B4 receptor antagonist against hypomagnesic diet-induced dermatitis in hairless rats.

In vivo experiments have shown that magnesium deficiency elicits characteristic skin lesions in the hairless rat. However, the mechanism of the involvement is not clarified. From the results of previous studies, a product derived from arachidonic acid, but not via the cyclooxygenase pathway, has been considered as an etiological cause. In this study, the inhibitory effect of newly produced leukotriene B4 (LTB4) receptor antagonist (LTBRA) against these skin manifestation was examined in hairless mutants given a hypomagnesic diet. Control animals with treatment of LTBRA developed eruptions on their bodies with increasing serum levels of LTB4, but LTBRA-treated animals did not suffer from the cutaneous disorder. Increased serum levels of LTB4 in control rats were significantly higher than those in the pre-treated condition. The diminution of skin lesions by LTBRA strongly indicated that magnesium deficiency dermatitis may involve a lipoxygenase-mediated metabolite of arachidonic acid, presumably LTB4, and that the cutaneous changes in hairless rats fed with hypomagnesic diet might provide an easily identifiable indicator of LTB4-mediated dermatitis.

Animals↗
PubMed1992

Five confirmed human cases of gnathostomiasis nipponica recently found in northern Japan.

Five confirmed human cases of gnathostomiasis nipponica exhibiting creeping eruption and itching were found sporadically from the autumn of 1991 to the winter of 1992 in the northern region of the mainland of Japan. In all cases, a causative gnathostome with 3 transverse rows of hooklets on the head bulb was detected in biopsied skin. The morphological characteristics agreed with the advanced third-stage larvae of Gnathostoma nipponicum. Within a few weeks before development of symptoms, all patients had histories of eating raw freshwater fishes, kokanee (Salmo nerka nerka), carp (Cyprinus carpio), crucian carp (Carassius gibelio langsdorfi), or common ice-fish (Salangichthys microdon). However, they had never eaten raw loach, which is known as a source of human infections with G. nipponicum.

Adult↗
PubMed1991

Functional reconstitution of sphingomyelin synthase in Chinese hamster ovary cell membranes.

Sphingomyelin synthase (phosphatidylcholine:ceramide phosphocholinetransferase) activity in the membranes of Chinese hamster ovary cells was found to be detectable with a fluorescent ceramide analog, containing a short acyl chain, as a substrate. We developed a method for the functional reconstitution of sphingomyelin synthase in detergent-treated membranes. Treatment of membranes with 1.5% octyl glucoside in the absence of exogenous phosphatidylcholine resulted in almost complete loss of sphingomyelin synthase activity, even after removal of the detergent by dialysis. In contrast, membranes treated with the detergent in the presence of exogenous phosphatidylcholine showed partial activity and, after dialysis of this mixture, enzyme activity was restored to almost the same level as the activity in dialyzed intact membranes. The effects of various lipids on enzyme activity in this reconstitution system suggested that L-alpha-phosphatidylcholine was the environmental lipid essential for the functional reconstitution of the enzyme. Furthermore, diacylglycerol was suggested to serve as an inhibitory regulator of sphingomyelin synthesis.

4-Chloro-7-nitrobenzofurazan↗
PubMed1991

Polymorphism of apolipoprotein A-II (apoA-II) among inbred strains of mice. Relationship between the molecular type of apoA-II and mouse senile amyloidosis.

Three types of apolipoprotein A-II (apoA-II) proteins (A, B and C) were predicted from the nucleotide sequence of apoA-II cDNA. Substitution of amino acid residues was noted at four positions (type A: Pro-5, Asp-20, Met-26, Ala-38; B: Pro-5, Glu-20, Val-26, Val-38; C: Gln-5, Glu-20, Val-26, Ala-38). Each type was identifiable by digestion of amplified apoA-II DNA by PCR, using restriction-fragment-length polymorphism of the apoA-II gene for restriction enzymes Cfr13I and MspI. The molecular type of apoA-II was determined among 23 strains of mice including nine of the senescence accelerated mouse series developed in our laboratory. Examination of types of apoA-II and amyloid deposition in the F2 and F3 hybrid mice showed that apoA-II amyloid deposition was present only in the mice homozygous for type C apoA-II and which were 12-17 months of age. The molecular type of apoA-II may be a factor involved in the development of senile amyloidosis in mice.

Aging↗
PubMed1991

Cloning and structural analysis of cDNA and the gene for mouse transcription factor UBF.

The gene and protein structure of the mouse UBF (mUBF), a transcription factor for mouse ribosomal RNA gene, have been determined by cDNA and genomic clones. The unique mUBF gene consists of 21 exons spanning over 13 kb. Two mRNAs coding for mUBF1 and mUBF2 having 765 a.a. and 728 a.a., respectively, are produced by an alternative splicing of exon 8. It specifies 37 amino acids constituting a part of the regions homologous to high mobility group proteins (HMG box 2). A human UBF (hUBF) cDNA obtained by polymerase chain reaction also indicates the presence of two kinds of mRNAs, the shorter form lacking the same region as mUBF2. Comparison of the cDNAs from hUBF and mUBF revealed an unusual conservation of nucleotide sequence in the 3'-terminal non-coding region. We examined the relative amounts of expression of mUBF1 and mUBF2. The eight tissues studied contained both molecular species, although mUBF2 was the predominant form of UBF. The mRNA of mUBF1 was expressed one half of the mUBF2 in quiescent mouse fibroblasts but reached the same amount in growing state.

Amino Acid Sequence↗
PubMed1991

Evidence suggesting a role for cathepsin L in an experimental model of glomerulonephritis.

We have utilized specific, irreversible inhibitors of cysteine proteinases to examine the role of renal cathepsin B and cathepsin L in the proteinuria which occurs in an experimental model of human glomerular disease. Administration of trans-epoxysuccinyl-L-leucylamido-(3-methyl)butane (Ep475) a specific, irreversible inhibitor of cysteine proteinases, including cathepsins B and L, significantly reduced proteinuria in rats with experimentally induced, neutrophil-independent, anti-GBM antibody disease (controls: 10 +/- 1 mg/24 h, N = 8; anti-GBM antibody disease: 203 +/- 30 mg/24 h, N = 8; anti-GBM antibody disease + Ep475: 112 +/- 13 mg/24 h, mean +/- SEM, N = 6, P less than 0.05). There was a marked reduction in the activity of both cathepsin B and cathepsin L in renal cortices obtained from Ep475-treated rats compared to either saline-treated controls or rats treated with anti-GBM IgG only. Administration of Z-Phe-Tyr(O-t-butyl)CHN2, a specific, irreversible cysteine proteinase inhibitor with a high degree of selectivity toward cathepsin L, also caused a reduction in anti-GBM antibody-induced proteinuria (90 +/- 18 mg/24 h, N = 6, P less than 0.05). This reduction in proteinuria was accompanied by a marked decrease (-84%) in the specific activity of renal cortical cathepsin L in Z-Phe-Tyr(O-t-butyl)CHN2-treated rats. However, cathepsin B activity was unchanged. There was no significant change in the renal anti-GBM antibody uptake, plasma urea nitrogen, or plasma creatinine values in the Z-Phe-Tyr(O-t-butyl)CHN2-treated rats compared to rats treated with anti-GBM IgG only or saline-treated controls. These data document the ability of cysteine proteinase inhibitors to decrease the proteinuria which occurs in a neutrophil-independent model of human anti-GBM antibody disease and suggest an important role for cathepsin L in the pathophysiology of the proteinuria which occurs in this model.

Animals↗
PubMed1991

Structural and functional analysis of a polyoma-related mammalian plasmid (L factor): the enhancer activity and plasmid establishment.

L factor is a unique plasmid DNA which was originally discovered in a subclone (B822) of mouse L cells at a high copy number (more than 5,000 copies/cell). The presence of L factor caused no detectable abnormalities to the plasmid-bearing cells. We determined the total DNA sequence of the L factor I (and a part of L factor II) and compared it with that of polyoma DNA. Both DNA are common to the general construction of DNA frames such as early, late and noncoding regions, suggesting the two to be closely related. On the other hand, the L factor DNA sequences differ substantially from that of polyoma in the DNA sequences corresponding to the polyoma large T antigen, capsid proteins and a portion of the enhancer region. In order to investigate the mechanism of plasmid establishment of L factor, we compared the enhancer activity, capacity of DNA replication and efficiency of plasmid establishment of L factor with those of polyoma. The results indicate that L factor enhancer activity and DNA replication capacity were considerably lower than those of polyoma, suggesting that these altered (lowered) activities associated with L factor contribute to the plasmidal establishment and stable maintenance of L factor.

Animals↗
PubMed1991

Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vitro.

A series of new epoxysuccinyl peptides were designed and synthesized to develop a specific inhibitor of cathepsin B. Of these compounds, N-(L-3-trans-ethoxycarbonyloxirane-2-carbonyl)-L-isoleucyl-L-proli ne (compound CA-030) and N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-prol ine (compound CA-074) were the most potent and specific inhibitors of cathepsin B in vitro. The carboxyl group of proline and the ethyl ester group or the n-propylamide group in the oxirane ring were necessary, the ethyl ester group or the n-propylamide group being particularly effective for distinguishing cathepsin B from other cysteine proteinases such as cathepsins L and H, and calpains.

Animals↗
PubMed1991

Novel epoxysuccinyl peptides. A selective inhibitor of cathepsin B, in vivo.

New derivatives of E-64 (compound CA-030 and CA-074) were tested in vitro and in vivo for selective inhibition of cathepsin B. They exhibited 10,000-30,000 times greater inhibitory effects on purified rat cathepsin B than on cathepsin H and L: their initial Ki values for cathepsin B were about 2-5 nM, like that of E-64-c, whereas their initial Ki values for cathepsins H and L were about 40 200 microM. In in vivo conditions, such as intraperitoneal injection of compound CA-030 or CA-074 into rats, compound CA-074 is an especially potent selective inhibitor of cathepsin B, whereas compound CA-030 does not show selectivity for cathepsin B, although both compounds CA-030 and CA-074 show complete selectivity for cathepsin B in vitro.

Animals↗
PubMed1991

Responses of calcitonin gene-related peptide-immunopositive nerve fibres in the periodontal ligament of rat molars to experimental tooth movement.

Nerve fibres showing CGRP-immunoreactivity were exclusively distributed around blood vessels in the periodontal ligament of normal teeth. The CGRP-positive nerves as well as the vessels were more dense during tooth movement and reached a maximum density and intensity of immunoreaction after 3 days. After that, the immunoreactive nerves gradually disappeared, and returned to the control level by the 7th day. Some of the CGRP-nerves were adjacent to bone resorptive lacunae at 3 days when active remodelling of alveolar bone was taking place. These findings suggest that the distribution of CGRP-positive nerves is dynamically changed around the blood vessels in the periodontal ligament during tooth movement, and that CGRP might affect the regulation of blood flow in the ligament. CGRP is possibly involved in the tissue remodelling, directly or indirectly, in addition to its function as a neurotransmitter.

Animals↗
PubMed1991

Atypical depressive symptoms possibly predict responsiveness to phototherapy in seasonal affective disorder.

Phototherapy was administered to 24 depressed patients with seasonal affective disorder (SAD), of which 62%, 24%, and 14%, respectively, showed improvements of greater than or equal to 50%, 25-50%, and less than 25% based on the Hamilton rating scale for depression for SAD (HAMSAD). No patients showed aggravation or side effects. Although the improvement rate in HAMSAD correlated significantly with the pretreatment severity of atypical symptoms of depression, it did not correlate with that of typical symptoms. This suggests that phototherapy is a useful treatment in SAD and that responsiveness to phototherapy in SAD can possibly be predicted by the atypical depressive symptoms before treatment.

Adolescent↗