[Sucrose content in pharmaceutical syrups].
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Biomedical subjects
Publications and source records attributed to N Maeda.
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In rats, the effects of L-thyroxine (T4; 0.2 micrograms/g body weight), hydrocortisone (HC; 5 micrograms/g body weight) and mastication on the postnatal development of the facial part of the skull were examined. Administration of T4 and/or HC to rats for 5 consecutive days from day 5 after birth induced a precocious increase in the ratio of the facial length to the head length. The effects of these hormones decreased with the progression of weaning, and after the 20th postnatal day, the hormones had no effects on the postnatal development of either (facial and head) part of the skull. Moreover, these hormones played an additive role in the growth of facial part. On the other hand, continuous suckling from birth to the 30th postnatal day caused a significant decrease in the ratio of the facial length to the head length. These results suggest that increases in the circulating levels of T4 and HC in suckling rats and mastication in the weaning period are involved in development of the postnatal development of the facial part of the skull.
A histological study has been made on the jaw-closing muscle, Adductor mandibulae, of 2 species of Cyprinidae, Zaco platypus and Carassius gibelio langsdorfi, which show completely different feeding behaviour. The former swims up to the food with its mouth open in rapid current, and the latter sucks food from the bottom into its mouth by enlargement of the buccal and opercular cavities in quite mild current. The latter's feeding behaviour was made repeatedly. The A. mandibulae was divided into its anterior and posterior parts in both fish. The anterior part in Z. platypus was divided into 2 portions, and that of C. gibelio langsdorfi into 3 portions. In each portion of the muscle of both fish, SDH activity in the muscle fibers decreased from the medial to the lateral side. Both fish had 3 types of the fibers on the basis of SDH activity, whereas the combinations of each fiber type were more complex in C. gibelio langsdorfi than in Z. platypus. Moreover, the ratio of fibers with higher SDH activities was larger in C. gibelio langsdorfi than in Z. platypus. And, differences in the number of capillaries per fiber in the same fiber type between the 2 fish suggest a complex adaptation of the jaw-closing muscle to the environmental circumstances of the fish.
The aggregation (especially the 'rouleau' formation) of human erythrocytes induced by polysaccharide and polyglutamic acid was quantitatively examined by using a low-shear rheoscope combined with a television image analyzer and a computer. (1) The morphological characteristics of rouleaux induced by these macromolecules are presented. (2) Polysaccharides with high molecular weights of 70 400 and 494 000 and poly(glutamic acids) with weights of 50 000 and 66 000 formed the rouleaux (then the three-dimensional aggregates). But polysaccharides with the low molecular weights of 10 300 and 42 500 and poly(glutamic acids) with weights of 8000 and 20 000 did not. The dependences of the velocity of rouleau formation on the macromolecule concentration and on the shear rate are shown. (3) The erythrocyte aggregation induced by high-molecular-weight polysaccharides was inhibited by low-molecular-weight polysaccharides and glucose, but was not affected by low-molecular-weight poly(glutamic acids). (4) The aggregation induced by high-molecular-weight poly(glutamic acids) was inhibited by poly(glutamic acid) with a molecular weight of 8000, but was accelerated by that of 20 000. The poly(glutamic acid)-induced aggregation was not affected by low-molecular-weight polysaccharides. (5) The stereochemical structure-dependent interaction (or the mode of bridging) of macromolecules with erythrocytes was stressed for the mechanism of erythrocyte aggregation.
We tested the inhibitory effects of phenothiazine derivatives on bone in vivo and osteoblastic cells in vitro. Chlorpromazine (CPZ) and trifluoperazine (TFPZ) dose-dependently decreased alkaline phosphatase activity in calvariae of rats: half-maximal inhibitory effects of CPZ and TFPZ were at 2.0 and 4.0 mg/kg, respectively. These effects were more specific for calvaria and ileum than for liver and duodenum. CPZ inhibited the proliferation of osteoblastic clone MC3T3-E1 cells to a greater extent than that of liver epithelial clone RLC-18(4) cells in vitro. CPZ, TFPZ and perphenazine (PNZ) also affected rather specifically alkaline phosphatase activity and collagen synthesis and were not cytotoxic. These in vivo and in vitro findings suggest inhibitory effects on osteoblastic cell function(s). However, promethazine (PMZ) had little effect in vivo and in vitro. In addition, increases in serum calcium and phosphate induced by CPZ indicate its possible involvement in bone resorption.
The nucleotide sequences of cDNAs coding for human salivary proline-rich proteins (PRPs) were determined. Clones cP1 and cP2 contain repetitive regions in which sites for the restriction enzyme HaeIII occur repeatedly; they code for the precursors of acidic PRPs. Clones cP3 to cP7 contain repetitive regions in which BstNI sites occur repeatedly; they code for precursors of basic and glycosylated PRPs. The clones cP3, cP4, and cP5 are identical except that cP4 and cP5 are missing 399 and 459 base pairs, respectively, from the repetitive region of cP3. The sequences at these deletion end points are homologous to the consensus sequences of RNA splicing donor and acceptor sites. This strongly suggests that all three cDNAs are derived from the transcript of a single gene via differential RNA splicing. All of the precursor proteins share a feature--the N-terminal region, following the signal peptide, is acidic, while the remainder of the molecule, made of proline-rich repeats of about 21 amino acids, is basic. Each precursor can generate multiple PRPs by various post-translational cleavages on the carboxylic side of specific arginine residues. The data show how differential RNA splicing and post-translational cleavages could generate a large number of proteins, such as those found in saliva, from a much smaller number of genes.
Thirty-three kilobase pairs (kb) of human DNA containing the haptoglobin (Hp) and haptoglobin-related (Hpr) gene pair were cloned, and the nucleotide sequence of 21-kb DNA was determined. The two genes are closely linked, with Hpr being 2.2 kb downstream of Hp. Six hundred nucleotides of DNA occur between the two genes that are not found either 5' to the Hp gene or 3' to the Hpr gene. After the duplication event, the first intron of the Hpr gene acquired a 9-kb insert consisting mainly of a retrovirus-like element with a potential primer-binding site homologous to a mouse isoleucine tRNA. The element forms a repeated family in the human genome that I name RTVL-I (retrovirus-like element-isoleucine). In the coding region of the Hpr gene, there are no frameshift or nonsense mutations and its exon-intron splicing sites, 5' flanking and 3' flanking sequences do not show any obvious defects. There are 28 amino acid differences between the decoded amino acid sequences of the Hpr and Hp genes. Sixteen of these differences occur in the hpr beta chain, and all appear to be located on the surface of the molecule in places not thought to be involved in the hemoglobin binding function of haptoglobin. The structure of the Hpr gene suggests that the gene may be expressed and give rise to a functional product.
The deformability of human erythrocytes was measured in a rheoscope, as a function of intracellular calcium content (varied with ionophore (A23187) and CaCl2) without complete ATP depletion and echinocytic transformation. Loading calcium into intact erythrocytes (calcium content: 16.8 mumol/1 packed cells = 1.48 amol per cell), the cell volume and energy charge gradually decreased. Further, the membrane fluidity of the lipid portion decreased without crosslinking of membrane proteins. A distinct transition from deformable to undeformable cells was observed by the rheoscope technique: i.e., 50% transition occurred at 40-50 mumol calcium/1 packed cells (= 3.5-4.0 amol per cell) and more than 90% above 100 mumol/1 packed cells (= 6.5 amol per cell) at a shear stress of 140 dyn/cm2. The deformable cells maintained their deformability to ellipsoidal disks independent of the average calcium content. The underformable cells, separated as high-density cells by density gradient centrifugation after calcium-loading, showed lower glucose-6-phosphate dehydrogenase activity than low-density-deformable cells; thus, the calcium-loaded, undeformable cells were presumably in vivo aged cells. The younger cells, fractionated as low-density cells from intact erythrocytes, were more deformable than aged cells. Upon calcium-loading, the younger cells restored their cell volume and deformability, while the aged cells, containing originally more calcium and less ATP, decreased their volume and became undeformable. Therefore, calcium accumulation by ionophore-CaCl2 takes place in preference to aged cells of lower energy metabolism, and leads to cellular dehydration and loss of deformability, due to condensed hemoglobin and altered membrane organization.
The effects of forskolin on differentiation of osteoblastic cells (clone MC3T3-E1) cultured in alpha-minimum essential medium containing 0.1% bovine serum albumin were investigated by assays of intracellular cyclic AMP level and alkaline phosphatase activity in the cells. Forskolin increased cyclic AMP production in the cells in a dose-related manner, the maximum increase being 250-fold above that of the controls. Alkaline phosphatase activity in the cells was also elevated as early as 24 h and rose to nearly its maximum at 48 h. The elevation was dose-dependent, with a maximum increase at 5 X 10(-6) M forskolin. Forskolin and prostaglandin E2 showed a supraadditive effect on cyclic AMP production in the cells and had an additive effect on alkaline phosphatase activity, whereas forskolin and dibutyryl cyclic AMP had little additive effect on either cyclic AMP production or enzyme activity. These results suggest that cyclic AMP is closely linked to the differentiation of osteoblastic cells in vivo.
We investigated the stimulative effect of prostaglandin E2 (PGE2) on an osteoblastic cell line, clone MC3T3-E1, in serum-free medium. PGE2 elevated collagen and non-collagen protein syntheses in a dose-related fashion up to 2 micrograms/ml, the maximal increases being 2- and 3-fold, respectively, over that in the control. Its stimulative effect was evident as early as 12 h. PGE2 slightly increased DNA content, but its effect was less than that on collagen and non-collagen protein syntheses. Moreover, PGE stimulated an increase in prolyl hydroxylase activity with a maximal effect at 1-2 micrograms/ml, the activity being 15-fold over that of the control. These results strongly indicate that PGE2 directly enhances total protein synthesis including that of collagen in osteoblasts in vitro, suggesting its direct effect on bone formation in vivo as well.
DNA studies suggest that six loci control the synthesis of human salivary proline-rich proteins (PRPs). Genes at two of these loci (proposed names, PRH1 and PRH2) contain regions that strongly hybridize to a probe made from a cDNA in which sites for the restriction enzyme HaeIII occur repeatedly; they code for the acidic PRPs. Genes at the remaining four loci (PRB1, PRB2, PRB3, and PRB4) contain regions that strongly hybridize to a probe with repeated BstN1 sites; they probably code for the basic and glycosylated PRPs. In contrast to these data suggesting six loci forming two gene subfamilies, studies of protein polymorphisms and families have led to the postulation of 13 loci with 11 common null alleles. The discrepancy in the number of loci is partly resolved by the hypothesis that the three acidic PRPs, Db, Pa, and PIF, are coded for by alleles at one of the HaeIII-type loci rather than by three discrete loci.
The formation of the anulospiral ending of Ia fibers in muscle spindles was investigated in the masseter muscle of developing mice. Before 15 days after birth, the complete anulospiral ending was not observed in almost all of the muscle spindles examined. With the growth of mice, the Ia fiber began to construct the spiral ending, and by the 40th postnatal day after weaning, almost all of the Ia fibers of the muscle spindles had complete coiled endings, though the formation still continued in some spindles. The continuous formation of anulospiral endings for a long period after weaning indicates that muscle spindle morphogenesis may be affected by muscle tension in the masseter muscle due to the movement activated after weaning.
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