Biochemistry 29, . The sequences of three genomic clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5'-flanking region from the major transcription site to nucleotide position -1105, and compared with those of the CYP3A7 gene, a fetal-specific form of cytochrome P450 in humans. The results showed that the identity of 5'-flanking sequences between CYP3A4 and CYP3A7 genes was 91 %, and that each 5'-flanking region had characteristic sequences termed as NFSE (P450N,-specific element) and HFLaSE (P450HFLa specific element), respectively. A basic transcription element (BTE) also lay in the 5'-flanking region of the CYP3A4 gene as seen in many CYP genes [Yanagida, A., Sogawa, K., Yasumoto, K. & Fujii-Kuriyama, Y. (1990) Mol. Cell. Biol. 10, 1470-14751. The BTE binding factor (BTEB) was present in both adult and fetal human livers.To examine the transcriptional activity of the CYP3A4 gene, DNA fragments in the 5'-flanking region of the gene were inserted in front of the simian virus 40 promoter and the chloramphenicol acetyltransferase structural gene, and the constructs were transfected in HepG2 cells. The analysis of the chloramphenicol acetyltransferase activity indicated that (a) suecific element(s) which could bind with a fa&or(s) in livers was present in the the transcriptional activity.Cytochrome P450 is a heme-containing enzyme which plays central roles in the oxidative and reductive metabolism of a variety of endogenous as well as exogenous compounds. It is generally known that there are numbers of forms of cytochrome P450, which are classified into families according to the homology of their nucleotide sequences 111.Among families of cytochrome P450, the CYP2C and CYP3A families are unique in that there are many forms in each family, and that these enzyme proteins are present in larger amounts in human liver microsomes, compared with other forms of cytochrome P450 121. The CYP3A, CYP3A4 (P450N,.) and CYP3 A7 (P450HFLa) proteins have been purified from human adult and fetal livers, respectively [3-51.Correspondence to T. Kamataki, Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, N12W6, Kitaku, Sapporo, Hokkaido, 060 JapanAhhreviations. BTE, basic transcription element ; BTEB, BTE binding factor; CAT, chloramphenicol acetyltransferase; CUP, cytochrome P450; DMEM, Dulbecco's modified Eagles medium; ER, estrogen receptor; ERE, estrogen response element; GR, glucocorticoid receptor; GRE, glucocorticoid response element; HFLaSE, P450HFLa-specific element; HNF-4, hepatic nuclear factor-4 ; HNF-5, hepatic nuclear factor-5 ; NFSE, P450,,-specific element; PR, progesterone receptor; PRE, progesterone response element; SV40, simian virus 40.Enzymes. Cytochrome P450 (EC 1.14.14.1 .); chloramphenicol acetyltransferase (EC 2.3.1.28.).Note. The 5'-flanking sequence data of CYP3A4 gene published here have been deposited with the DDBJ/EMBL/GenBank and are available under the accession number D11131. ~, I5'-flanking region of the CYP3A4 gene to show In addition, f...

1. Activities of 35 taste-responsive neurons in the cortical gustatory area were recorded with chronically implanted fine wires in freely ingesting Wistar rats. Quantitative analyses were performed on responses to distilled water, food solution, and four taste stimuli: sucrose, NaCl, HCl, and quinine hydrochloride. 2. Taste-responsive neurons were classified into type-1 and type-2 groups according to the response patterns to licking of the six taste stimuli. Type-1 neurons (n = 29) responded in excitatory or inhibitory directions to one or more of the taste stimuli. Type-2 neurons (n = 6) showed responses in different directions depending upon palatability of the liquids to rats: neurons showing excitatory (or inhibitory) responses to palatable stimuli exhibited inhibitory (or excitatory) responses to unpalatable stimuli. 3. Correlation coefficients of responses to pairs of stimuli across neurons suggested that palatable stimuli (water, food solution, sucrose, and NaCl) and unpalatable stimuli (HCl and quinine) elicited reciprocal (excitatory vs. inhibitory) responses in type-2 neurons, whereas type-1 neurons showed positively correlated responses to specific combinations of stimuli such as food solution and NaCl, sucrose and HCl, NaCl and quinine, and HCl and quinine. 4. A tendency toward equalization of effectiveness in eliciting responses among the four basic taste stimuli was detected on the cortex. The ratios of mean evoked responses in 29 type-1 neurons in comparison with spontaneous rate (4.4 spikes/s) were 1.7, 1.9, 1.8, and 1.9 for sucrose, NaCl, HCl, and quinine, respectively. 5. The breadth of responsiveness to the four basic taste stimuli was quantified by means of the entropy measure introduced by Smith and Travers (33). The mean entropy value was 0.540 for 29 type-1 neurons, which was similar to 0.588 previously reported for rat chorda tympani fibers, suggesting that breadth of tuning is not more narrowly tuned in a higher level of the gustatory system in the rat. 6. Convergent inputs of other sensory modalities were detected exclusively in type-1 neurons. Thirteen (45%) of 29 type-1 neurons also responded to cold and/or warm water, but none of 6 type-2 neurons responded to thermal stimuli. Two (7%) of 29 type-1 neurons responded to almond and acetic acid odors, but the 6 type-2 neurons did not. Two (13%) of 16 type-1 neurons responded to interperitoneal injection of LiCl, which is known to induce gastrointestinal disorders, with a latency of approximately 5 min, but 4 type-2 neurons tested were not responsive to this stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The responses of 90 cortical neurons in the somatosensory and gustatory areas were recorded with chronically implanted fine wires in freely moving Wistar rats. The responses were analyzed mainly while the animals were freely licking solutions and eating dry pellets. Cortical neurons were classified into several groups according to their response properties. 2. "Mechanosensitive" neurons (n = 20) showed rhythmic phasic activity in different phases of the licking cycle, depending on the location of their receptive field in the peripheral orofacial region. 3. "Movement-related" neurons (n = 27) changed their activities tonically during licking, chewing, or grooming behavior. The responses were either excitatory or inhibitory. Receptive fields and adequate stimuli could not be identified. These neurons might receive somatosensory (except light tactile) inputs from wide or deep areas of intra- or perioral regions, or might be related to orofacial active movement. 4. "Taste" neurons (n = 35) increased or decreased their discharge rates during licking of particular taste solutions. Some taste neurons received convergence from somatosensory inputs. 5. "Temperature" neurons (n = 2) responded exclusively to water of temperatures lower or higher than room temperature. The responses were opposite in direction between cold and warm stimuli. 6. "Anticipation" neurons (n = 4) increased their impulse discharges before the start of licking in the situation in which the animal expected access to the drinking tube. 7. "Attention" neurons (n = 2) responded to arousal stimulation such as sound, a flash of light, and body touch. These neurons showed only a slightly increasing response during ingestive behavior. 8. The locations of 56 of 90 units were histologically identified. Mechanosensitive neurons were located in the appropriate parts of the somatotopic pattern within the primary somatic sensory area in the granular cortex. Taste neurons were found evenly in the dysgranular cortex and the agranular insular cortex. Other types of neurons were located mainly in the dysgranular cortex between the granular cortex and agranular insular cortex, and some were intermingled with taste neurons in the agranular insular cortex. 9. The present study has shown that cortical neurons in the orolingual somatosensory and taste areas have different response characteristics related to each aspect of ingestive behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

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Vital tooth-derived demineralized dentin matrix (DDM) has a bone-inductive ability, while non-vital tooth-derived DDM lost it. Acid treatment for dentin provides the increase of surface area, the release of matrix-binding growth factors such as BMPs, and the decrease of the infection risk. Human autograft of vital toothderived DDM was achieved first in Japan 2002, while first bone autograft was noted in Italy 1820. This paper introduced dentin/bone biology and a unique clinical case, combined with two types of non-vital tooth-derived DDM (roots, granules) for lateral bone augmentation. A 63-year-old woman revealed highly atrophic mandible in 2015. Three non-vital teeth were extracted, changed in shape, demineralized in 2% HNO 3 , were rinsed, and were grafted immediately. The CT images at 3 months after the graft showed remarkable lateral augmentation. DDM scaffolds were received to host, and two fixtures were placed into the DDM-augmented bone. The patient was successfully restored with their own DDM scaffolds and implant surgery.

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