Congenital bilateral perisylvian syndrome and eating epilepsy.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M Moriya
Publications and source records attributed to M Moriya.
Is the growth of brown adipocytes necessary for cold acclimation in mice?
Chronic exposure to cold increases the growth of brown adipose tissue and the resistance to more severe cold, thus improving thermogenesis. The present study examined the possibility that dietary compounds can modify cold acclimation. Adenosine (ADO) or adenine (ADE) were administered in drinking water (0.05%, w/v) for 5 weeks to male ddY strain mice from 4 weeks of age. At 5 weeks of age, the mice were exposed to 4 degrees C for 4 weeks. After termination of this period, the interscapular brown adipose tissue (IBAT) and rectal temperature on acute exposure to severe cold (-20 degrees C) for 60 min were measured. Chronic exposure to cold increased the weight of IBAT and made mice resistant to a fall in rectal temperature on exposure to severe cold. The growth of IBAT and improvement in thermogenesis can be used as a cold acclimation profile in ddY mice. The growth of IBAT was selectively prevented by ingestion of ADO. The improvement in thermogenesis was reduced, but only a little, by the ingestion of either ADO or ADE. Thus, growth of brown adipocytes might not be necessary for cold acclimation in mice.
Acclimatization↗
Cellular response to exocyclic DNA adducts.
The mutagenic potential of three exocyclic DNA adducts was studied in Escherichia coli and simian kidney cells by incorporating them into single-stranded DNA. Differences in the mutagenic potency of the adducts were observed between hosts: 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine were more mutagenic in simian cells, whereas 1,N2-(1,3-propan-1,3-diyl)-2'-deoxyguanosine was more mutagenic in E. coli. To investigate the cellular response to DNA adducts, a double-stranded DNA vector system was developed. Use of this system showed that 1,N6-ethenodeoxyadenosine blocks DNA synthesis strongly, and DNA synthesis past this adduct was highly accurate in E. coli. The blockage of DNA synthesis was overcome in an error-free manner by the recombination repair mechanism (daughter-strand gap repair).
Animals↗
Cerebellar microfolia and other abnormalities of neuronal growth, migration, and lamination in the Pit1dw-J homozygote mutant mouse.
The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal formation of the anterior pituitary. In neonates and adults there is almost complete absence of growth hormone (GH), prolactin (PRL), thyroxin (T4), and thyroid-stimulating hormone (TSH). Since these hormones have been suggested to play a role in normal development of the central nervous system (CNS), we have investigated the effects of the Pit1dw-J mutation on the cerebellum and hippocampal formation. In the cerebellum, there were abnormalities of both foliation and lamination. The major foliation anomalies were 1) changes in the relative size of specific folia and also the proportional sizes of the anterior vs posterior cerebellum; and 2) the presence of between one and three microfolia per half cerebellum. The microfolia were all in the medial portion of the hemisphere in the caudal part of the cerebellum. Each microfolium was just rostral to a normal fissure and interposed between the fissure and a normal gyrus. Lamination abnormalities included an increase in the number of single ectopic granule cells in the molecular layer in both cerebellar vermis (86%) and hemisphere (40%) in comparison with the wild-type mouse. In the hippocampus of the Pit1dw-J homozygote mouse, the number of pyramidal cells was decreased, although the width of the pyramidal cell layer throughout areas CA1-CA3 appeared to be normal, but less densely populated than in the wild-type mouse. Moreover, the number of granule cells that form the granule cell layer was decreased from the wild-type mouse and some ectopic granule cells (occurring both as single cells and as small clusters) were observed in the innermost portion of the molecular layer. The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1.
Animals↗
Quantitative analysis of edema in the dorsal nerve roots induced by acute mechanical compression.
STUDY DESIGN: Edema in the dorsal nerve roots caused by acute compression was assessed quantitatively in the lumbar spine of the adult dog. OBJECTIVE: To establish quantitative evaluation of edema in the dorsal nerve roots and to observe changes after acute compression with time. SUMMARY OF BACKGROUND DATA: Mechanical compression induces an increase in microvascular permeability of the endoneurial capillaries and results in intraneural edema. However, there are no quantitative studies on edema in the nerve roots. METHODS: The seventh lumbar nerve root was compressed with a 60-g force clip for 10 minutes. The nerve roots were removed immediately and at 24 hours, 1 week, and 3 weeks after compression. Nerve roots from the control and the sham groups were also obtained. Before removing the nerve roots, Evans blue albumin was injected intravenously. Changes in edema were examined using fluorescence microscopy. Evans blue albumin emits a bright red fluorescence. The relative red fluorescent area was calculated using computer image analysis, and the data were used to indicate the degree of edema. RESULTS: In the compressed segment, edema was most pronounced just after decompression and reduced in nerves removed at 24 hours. In nerves removed at 1 week, edema was pronounced but was reduced at 3 weeks. In the segments closest to the spinal cord, edema was seen after 1 week and was significant after 3 weeks. In the segments closest to the dorsal root ganglion, edema was not detected at any time. CONCLUSION: In the dorsal nerve roots the degree and the area of edema changed with time elapsed after acute compression. The degree of edema 24 hours after decompression was one third the degree immediately after decompression. These results show that edema induced by mechanical compression can recover after decompression.
Animals↗
Mutagenic potential of stereoisomeric bay region (+)- and (-)-cis-anti-benzo[a]pyrene diol epoxide-N2-2'-deoxyguanosine adducts in Escherichia coli and simian kidney cells.
We have investigated the mutagenic potential of site-specifically positioned DNA adducts with (+)- and (-)-cis-anti stereochemistry derived from the binding of r7,t8-dihydroxy-t9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (BPDE) to N2-2'-deoxyguanosine (G1 or G2) in the sequence context 5'TCCTCCTG1 G2CCTCTC. BPDE-modified oligodeoxynucleotides were ligated to a single-stranded DNA vector and replicated in Escherichia coli or simian kidney (COS7) cells. The presence of (+)- or (-)-cis adduct strongly reduced the yield of transformants in E. coli, and the yield was improved by the induction of SOS functions. Both adducts were mutagenic in E. coli and COS cells, generating primarily G --> T transversions. In E. coli, the (-)-cis adduct was more mutagenic than the (+)-cis adduct, while in COS cells, both adducts were equally mutagenic. These results were compared with those obtained with stereoisomeric (+)- and (-)-trans adducts [Moriya, M., et al. (1996) Biochemistry 35, 16646-16651). In E. coli, cis adducts, especially (-)-cis adducts, are consistently more mutagenic than the comparable trans adduct. In COS cells, trans adducts yield higher frequencies of mutations than the two cis adducts and, with the exception of the high-mutation frequency associated with the (+)-trans adduct at G2, relatively small differences in mutation frequencies are observed for the three other adducts. In E. coli, mutation frequency is a pronounced function of adduct stereochemistry and adduct position. These findings suggest that the fidelity of translesional synthesis across BPDE-dG adducts is strongly influenced by adduct stereochemistry, nucleotide sequence context, and the DNA replication complex.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
Novel dithiocarbamate carbapenems with anti-MRSA activity.
A new series of 1beta-methyl carbapenems, in which a disubstituted-aminothiocarbonylthio moiety was attached to the C-2 position of the carbapenem nucleus, were prepared and evaluated for anti-MRSA activity. These derivatives showed good in vitro antibacterial activity against high-level MRSA, and the finding of good affinity for PBP-2' supported these results. Some of the compounds having favorable protein-binding affinity showed excellent in vivo anti-MRSA activity.
Animals↗
Spontaneous rupture of the uterus caused by placenta percreta at 28 weeks of gestation: a case report.
Placenta percreta is a rare complication of pregnancy. Rupture of the uterus due to placenta percreta is one of the most urgent obstetrical catastrophes. Recently, we observed a patient who developed placenta percreta accompanied by spontaneous uterine rupture at 28 weeks of gestation. A 29-year old gravida 3, para 1, who had a history of one cesarean section and one miscarriage with dilatation and curetage, was seen at 28 weeks of gestation. An acute abdomen and shock were diagnosed. Immediate laparotomy revealed a transverse rupture on the fundus of the uterus. A hysterectomy was performed. Pathological examination of the uterus showed placenta percreta. Rupture of the uterus due to placenta percreta before the onset of labor is extremely rare.
Adult↗
Auditory projections from the IC to the SCN by way of the LG in the mole, Mogera.
To study morphological substrates for sensory specialization in subterranean mammals, we investigated both auditory and visual pathways in the mole. The inferior colliculus (IC), an auditory relay, projects not only to the medial geniculate, the major gateway to the auditory cortex, but also to the lateral geniculate (LG), the major gateway to visual cortex. Further evidence is that the LG does not send many fibers to the cortex in the mole. Instead, the auditory inputs to the LG are likely to be conveyed to the suprachiasmatic hypothalamic nucleus (SCN), which plays a role in photoperiodic functions in common mammals. Auditory inputs to the SCN may subserve periodic reproductive behaviors in the exclusively separated territorial domains of subterranean mammals.
Animals↗
New xenograft model of multiple myeloma and efficacy of a humanized antibody against human interleukin-6 receptor.
A new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 x 10(6) KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti-IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6-dependent KPMM2 cells.
Animals↗
Enhanced nonshivering thermogenic activity of the heat-tolerant FOK rat.
Explore the source record for details and available documents.
Adipose Tissue, Brown↗
[Effects of phenylalanine and tyrosine on cold acclimation in mice].
The effects of phenylalanine (PHE) and tyrosine (TYR) on cold acclimation were studied in mice of the ddY strain. At 5 weeks of age, mice were maintained at 4 degrees C for 4 weeks. Test groups of mice were supplied with a 0.05% (w/v) solution of PHE or TYR as drinking water in addition to water. We measured changes in body weight, intake of water and food, rectal temperature upon acute exposure to -20 degrees C, weight of interscapular brown adipose tissue (BAT) and the levels of glucose, nonesterified fatty acids (NEFA) and 3H-butyrate in the blood prior to and after exposure to the lower temperature of -20 degrees C. Chronic exposure to cold (4 degrees C) reduced body-weight gain for the first two weeks but weight gain recovered within the next two weeks. PHE and TYR partially inhibited the gain in body weight under exposing to cold. TYR reduced the gain of body weight under room temperature. Exposure to cold stimulated the daily consumption of food. Both PHE and TYR somewhat enhanced the food intake when exposed to cold. Exposure to cold rendered mice resistant to severe cold (-20 degrees C). Both PHE and TYR did not reduce this resistance except in the early state in the case of TYR. Exposure to cold increased the weight of BAT but both PHE and TYR prevented this increase. The effect of TYR was determined in the case fed under room temperature. Cold exposure changed the utilization of glucose, NEFA and 3H-butyrate in the blood when exposed to severe cold (-20 degrees C). Both PHE and TYR prevented the change in NEFA. It remains to be confirmed whether the growth of brown adipocytes is always necessary when mice acclimate to cold.
Acclimatization↗
[Effects of adenosine and adenine on cold acclimation in mice].
The effects of adenosine (ADO) and adenine (ADE) on cold acclimation were studied in mice of the ddY strain. At 5 weeks of age, mice were maintained at 4 degrees C for 4 weeks. Test groups of mice were supplied with a 0.05% (w/v) solution of ADO or ADE as drinking water in addition to water. We measured changes in body weight, intake of water and food, rectal temperature upon acute exposure to -20 degrees C, weight of interscapular brown adipose tissue (BAT) and the levels of glucose, nonesterified fatty acids (NEFA) and 3H-butyrate in the blood prior to and after exposure to the lower temperature of -20 degrees C. Chronic exposure to cold (4 degrees C) reduced body-weight gain for the first two weeks but weight gain recovered within the next two weeks. ADO partially but selectively inhibited the gain in body weight. This effect was marked in mice maintained at room temperature. Such an inhibitory effect was the case of ADE in the room temperature. Exposure to cold stimulated the daily consumption of food. ADO further and selectively enhanced food intake, but ADE enhanced that in room temperature. Cold increased in daily intake of water. Both ADO and ADE accelerated the intake of water. This effect was marked in mice maintained at 4 degrees C and the effect of ADE was considerable. Mice chose to drink the water that contained ADO, while the choice of water that contained ADE was apparent only during exposure to cold. Exposure to cold rendered mice resistant to severe cold (-20 degrees C). ADO and ADE partially reduced this resistance. Exposure to cold increased the weight of BAT but ADO selectively prevented this increase. Cold did not change the levels of the various compounds measured in the blood. In mice exposed to 4 degrees C for 4 weeks, acute exposure to severe cold decreased the glucose level and increased the levels of NEFA and 3H-butyrate. ADO selectively prevented the changes in the levels of NEFA and 3H-butyrate. It remains to be confirmed whether the growth of brown adipocytes is always necessary when mice acclimate to cold.
Acclimatization↗
Fidelity of translesional synthesis past benzo[a]pyrene diol epoxide-2'-deoxyguanosine DNA adducts: marked effects of host cell, sequence context, and chirality.
We have used a site-specific approach to investigate the mutagenic potential of (+)- and (-)-trans-anti-benzo[a]pyrene diol epoxide (BPDE) DNA adducts. Oligodeoxyribonucleotides (5'TCCTCCTG1G2-CCTCTC), modified at the exocyclic amino groups of G1 or G2, were incorporated into a single-stranded shuttle vector and introduced into Escherichia coli or simian kidney (COS) cells. This experimental system permits translesional synthesis to proceed in the absence of DNA repair. The presence of (+)- or (-)-BPDE-N2-dG adducts strongly inhibited translesional synthesis in E. coli; induction of cellular SOS functions reduced this blocking effect. Vectors containing (+)-BPDE adducts at G1 or G2 generated mutation frequencies of 19% and 3%, respectively; these values were not altered significantly by induction of SOS functions. In COS cells, (+)-BPDE-modified vectors generated mutation frequencies of 13% at G1 and 45% at G2. In E. coli, the (-)-BPDE adduct generated mutation frequencies of < or = 2% at G1 and G2 and, in COS cells, 13% at G1 and 21% at G2. The predominant mutations in E. coli and COS cells were G-->T transversions targeted to the site of the lesion; however, when G2 was modified, a significant number of targeted G-->A and G-->C mutations were observed in COS cells. We conclude from this study that (+)-and (-)-BPDE-N2-dG adducts pair preferentially to dCMP and dAMP during translesional synthesis in a process that is strongly influenced by the stereochemistry of the adduct, by the bases flanking the lesion, and by host cell factors.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
1,N6-ethenodeoxyadenosine, a DNA adduct highly mutagenic in mammalian cells.
1,N6-Ethenodeoxyadenosine (epsilon dA) is one of four exocyclic DNA adducts produced by chloroethylene oxide and chloroacetaldehyde, reactive metabolites of vinyl chloride, a human carcinogen. epsilon dA has also been detected in DNA of the liver of humans and untreated animals, suggesting its formation from endogenous sources. The mutagenic potential of epsilon dA was studied using a single-stranded shuttle vector system in several E. coli strains and in simian kidney cells (COS7). This vector system enables quantitative analysis of translesional synthesis past a site-specifically placed DNA adduct in both hosts owing to the lack of the complementary strand. In experiments with five strains of E. coli, a very limited number of targeted mutations (one epsilon dA-->T, one epsilon dA-->dC, and two epsilon dA-->single base deletion) were observed among 756 transformants in hosts preirradiated with UV; no targeted mutations were observed among 563 transformants in nonirradiated hosts. These results indicate that nonmutagenic base pairings of epsilon dA:T are the almost exclusive events in E. coli. In COS7 cells, the frequency of targeted mutations was 70%, consisting of epsilon dA-->dG (63%), epsilon dA-->T (6%), and epsilon dA-->dC (1%), indicating that the insertion of dCMP opposite the adduct is predominant. When compared with the results for 3,N4-ethenodeoxycytidine (epsilon dC), which was studied previously in the same system [Moriya et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 11899-11903], the results of this study indicate that the intrinsic mutagenic potency of epsilon dA is comparable to that of epsilon dC in mammalian cells.
Acetaldehyde↗
Crossed projection neurons are generated prior to uncrossed projection neurons in the lateral superior olive of the rat.
The present study examined in the lateral superior olive (LSO) of the rat whether LSO neurons projecting to the ipsilateral inferior colliculus (IC) might be generated later than those projecting to the contralateral IC. Rat fetuses were exposed in utero to 5-bromodeoxyuridine (BrdU), a thymidine analogue, to label neurons proliferating at different embryonic stages from day E11 through to E20. Upon reaching adulthood, the rats were given unilateral injections of fluoro-gold (FG), a retrograde fluorescent tracer, into the IC. Subsequently, the tissue sections of the brains obtained from the rats were immunostained for BrdU to simultaneously detect neurons that were BrdU-positive and/or FG-positive. BrdU-positive LSO neurons were found in the rats which had been exposed to BrdU during E12-E16. In E12 and E13 BrdU-exposure cases, the vast majority of doubled-labeled (BrdU-positive and FG-positive) neurons were seen on the contralateral side to the FG injection. In E14, E15 and E16 BrdU-exposure cases, in contrast, all double-labeled neurons were found on the ipsilateral side to the FG injection. The distribution of these double-labeled neurons within the nucleus was diffuse in all the BrdU-exposure cases. Thus, the results indicate that LSO neurons are generated during E12-E16, that the crossed projection neurons are generated 1-4 days earlier than the uncrossed projection neurons, and that no topographical relationships exist between the early- and the late-generated populations of the LSO neurons.
Animals↗
Brain capillary endothelial cells express two forms of erythropoietin receptor mRNA.
To study the existence of the erythropoietin receptor (Epo-R) mRNA in brain capillary endothelial cells, the reverse transcription (RT) PCR was performed using total RNAs from rat brain capillary endothelial cells (RBECs) and MBEC4, which is one of the established mouse brain capillary endothelial cell lines. Southern analysis of the RT-PCR products indicated that both RBECs and MBEC4 expressed an authentic form of Epo-R mRNA as a minor form and an intron-5-inserted form of Epo-R mRNA, thus a soluble form of Epo-R mRNA, as a major form. Furthermore, the effect of recombinant human erythropoietin (rHuEpo) on the DNA synthesis in RBECs was analyzed. rHuEpo showed a dose-dependent mitogenic action on RBECs as a competence factor. Radioiodinated rHuEpo was bound specifically to RBECs with time, cell number and dose dependencies. Binding studies with 125I-rHuEpo showed that RBECs had a single class of receptors with low-affinity (Kd = 860 pM) and that the number of sites/cell (10300) was abundant. These results suggest that brain capillary endothelial cells express not only an authentic form of Epo-R but also a soluble form of Epo-R and that erythropoietin acts directly on brain capillary endothelial cells as a competence factor.
Animals↗
Immunohistochemical localization of the calcium/calmodulin-dependent protein phosphatase, calcineurin, in the mouse testis: its unique accumulation in spermatid nuclei.
Immunohistochemical localization of a calmodulin-dependent protein phosphatase, calcineurin, was studied in the mouse testis in relation to previous observations showing that calmodulin is unusually rich in spermatogenic stages from mid-pachytene spermatocytes to elongating spermatids. The antibodies raised against calcineurin from scallop testis reacted with subunit B, but not subunit A, of calcineurin isoforms from mouse brain and testis. Indirect immunofluorescence using these antibodies on the mouse testis revealed positive reactions only in the nuclei of round or elongating spermatids: calcineurin started to accumulate in nuclei from the acrosomal cap phase, peaked at the initial stage of nuclear elongation, and decreased thereafter. There was almost no signal in the cytoplasm; spermatogenic cells at other stages, including spermatogonia, spermatocytes, mature sperm, and other somatic cells in the seminiferous tubules were totally negative. Immuno-electron microscopy gave the same result, on the basis of measuring the density of immunogold particles. These results suggest a role for calcineurin in remodeling of the nuclear chromatin in metamorphosing spermatids.
Animals↗