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Biomedical subjects

T Shimada

Publications and source records attributed to T Shimada.

At least 163 records · Page 9Linked to original sources

CYP2A6 genetic polymorphisms and liver microsomal coumarin and nicotine oxidation activities in Japanese and Caucasians.

Genotypes of CYP2A6, namely CYP2A6(*)1 (wild-type), CYP2A6(*)2, and CYP2A6(*)3, were examined in liver DNA of 39 Japanese and 43 Caucasians using two-step polymerase chain reaction (PCR) methods. We first amplified a DNA fragment (1725 bp) located between near middle of exon 1 and end of exon 4 of the CYP2A6 gene and further amplified using a forward primer 't' or 'mut' (middle of exon 3) and a reverse primer 'E3R' (middle of intron 3) for the detection of CYP2A6(*)2-genetic polymorphism. The 1725 bp fragment was also used for the amplification between exon 3 and near middle of intron 3 of the CYP2A6 gene and the fragment thus obtained digested with XcmI or DdeI to detect and confirm the CYP2A6(*)2- and CYP2A6(*)3-types, respectively. Only one DNA sample from a Japanese origin (J18) was not amplified by CYP2A6-specific primers; liver microsomes from this individual had very low activity of coumarin 7-hydroxylation and were devoid of protein(s) immunoreactive to anti-CYP2A6 antibody. Thus, this individual was suggested to be due to the gene deletion in CYP2A6. By analyzing the remaining 38 Japanese and 43 Caucasians, we found that there were no cases of CYP2A6(*)3-type polymorphism in the samples examined in this study, and no cases of CYP2A6(*)2-type polymorphism in the Japanese samples. Of Caucasians studied two individuals were classified into heterozygous CYP2A6(*)1/(*)2-type. Liver microsomal coumarin 7-hydroxylation activities in these two Caucasians were found to be lower than those of the other 41 Caucasians. Kinetic analysis showed that two CYP2A6(*)1/(*)2 individuals had a very low ratio of V(max) to K(m) for nicotine C-oxidation as well as coumarin 7-hydroxylation in liver microsomes, compared with those of homozygous CYP2A6(*)1-type. These results suggest that among 39 Japanese and 43 Caucasians examined one Japanese is classified to be CYP2A6 gene deletion and two Caucasians are heterozygous CYP2A6(*)1/(*)2-genotype. Thus the race-related differences in the occurrence of CYP2A6 genetic polymorphisms were supported.

Aryl Hydrocarbon Hydroxylases↗

Mapping of c-Fos in the trigeminal sensory nucleus following high- and low-intensity afferent stimulation in the rat.

Although previous studies have suggested that nociceptive afferents from intra-oral and facial structures are organized differently in the trigeminal sensory nucleus (TSN), more detailed data are needed. The present study aimed to fill this gap, by examining the changes in the expression of c-Fos within the rat TSN following high- and low-intensity electrical stimulation applied to the Gasserian ganglion (GG). A low-intensity stimulus (0.1 mA) induced c-Fos in many neurons in the dorsomedial subdivision (Vodm) of the oral subnucleus (Vo; mean +/- SEM in a certain segment = 163.0 +/- 42.7), in the medial part of the dorsomedial subdivision (Vidm) of the interpolar subnucleus (Vi; 120.5 +/- 40.1), in the medial corner of the magnocellular zone (VcIII/IV; 47.5 +/- 10.5), and in the superficial layers (VcI/II; 1330.0 +/- 65.6) along the entire length of the dorsomedial-ventrolateral axis of the caudal subnucleus (Vc). A modest number of Fos-positive neurons were induced in the dorsal principal subnucleus (Vp; 10.0 +/- 4.9) and in the lateral VcIII/IV (11.5 +/- 1.6). A high-intensity stimulus (1.0 mA) significantly increased the number of Fos-positive neurons in each subdivision compared with the low-intensity stimulus (Vp 32.3 +/- 10.8; Vodm 270.3 +/- 75.3; Vidm 189.3 +/- 38.5; medial VcIII/IV 77.5 +/- 18.2; lateral VcIII/IV 24.8 +/- 9.3; VcI/II, 2155.8 +/- 470.2). At both low- and high-intensity stimulation, the fields where Fos-positive neurons appeared are restricted to the dorsal or dorsomedial subdivisions of the rostral subnuclei, Vp, Vo and Vi, where the main projectional fields of primary afferents from the intraoral structures are found, while Fos-positive neurons were distributed in the entire VcI/II, along the dorsomedial-ventrolateral axis of Vc, where the main projectional fields of primary afferents from the facial skin are found. The threshold to induce c-Fos is, however, different according to the fields. These results suggest that nociceptive processing in the intra-oral region is mediated through the entire length of the rostro-caudal axis of TSN, but is mediated primarily through VcI/II in the facial region.

Afferent Pathways↗

Molecular structure of a novel gypsy-Ty3-like retrotransposon (Kabuki) and nested retrotransposable elements on the W chromosome of the silkworm Bombyx mori.

We previously characterized a female-specific randomly amplified polymorphic DNA (RAPD), designated W-Kabuki, derived from the W chromosome of the silkworm, Bombyx mori. To further analyze the W chromosome of B. mori, we obtained a lambda phage clone which contains the W-Kabuki RAPD sequence and sequenced the 18.1-kb DNA insert. We found that this DNA comprises a nested structure of at least seven elements; three retrotransposons, two retroposons, one functionally unknown insertion, and one Bombyx repetitive sequence. The non-LTR retrotransposon BMC1, the retroposon Bm1, a functionally unknown inserted DNA (FUI), and a copia-like LTR retrotransposon (Yokozuma) are themselves inserted into a novel gypsy-Ty3-like LTR retrotransposon, named Kabuki. Furthermore, this Kabuki element is itself inserted into another copy of Bm1. The BMCI and Yokozuna elements inserted in the Kabuki sequence are intact. Moreover, the Kabuki element is largely intact. These results suggest that many retrotransposable elements have accumulated on the W chromosome, and these elements are expected to evolve more slowly than those on other chromosomes.

Amino Acid Sequence↗

Identification and characterisation of a silkworm ABC transporter gene homologous to Drosophila white.

In the silkworm, Bombyx mori, many eye- and egg-colour mutations affecting the synthesis and accumulation of ommochrome pigments have been described. In order to understand the pigment precursor transporters involved, ABC transporter genes homologous to the Drosophila white gene were isolated from the silkworm. Reverse transcriptase-polymerase chain reactions (RT-PCR) using embryonic mRNA amplified three cDNA fragments, named Bmwh1, Bmwh2 and Bmwh3 that showed homology to the white gene. Since Bmwh3 shows the highest degree of sequence identity and a similar expression pattern to the Drosophila homologue, we characterised this gene further. A 2667-bp Bmwh3 cDNA isolated from an embryonic library has one ORF encoding a polypeptide of 687 amino acids. The predicted protein has one ATP-binding domain, six transmembrane-spanning segments and high similarity to the Drosophila WHITE protein. Southern analysis indicates that Bmwh3 is a single-copy gene. Polyadenylated Bmwh3 transcripts about 2.7 kb long were detected in eggs, Malpighian tubules and pupal heads, but not in testes, posterior silk glands or fat body cells. The level of Bmwh3 mRNA was reduced in w3 and w3ol mutants but normal in other egg- and eye-colour mutants, suggesting that Bmwh3 correspond to the w3 locus. Genetic analysis was used to map the cloned gene to chromosome 10.

ATP-Binding Cassette Transporters↗

Expression of bone morphogenetic proteins and rat distal-less homolog genes following rat femoral fracture.

Expression of the genes encoding bone morphogenetic proteins (BMPs), BMP type IA receptor (BMPR-1A), and rat distal-less homolog (rDlx) was studied in bone, callus, and the surrounding soft tissue following rat femoral closed fracture, using RT-PCR-based techniques. Before fracture, the genes encoding BMP-5, BMP-6, and BMPR-1A were found to be expressed in both bone and the surrounding soft tissue, whereas the BMP-2 gene was expressed only in bone and BMP-7 was not expressed in either tissue. Expression of these genes was unaffected by fracture. The gene encoding BMP-4 was also expressed in both bone and the surrounding soft tissue before fracture. Moreover, although unchanged in bone, 6 h after fracture BMP-4 expression was increased tenfold in the surrounding soft tissue. The increased BMP-4 expression was transient and returned to prefracture levels within 72 h. Expression of rDlx was also increased in bone after fracture, but at later times than were observed with BMP-4: elevated rDlx expression was detected after 48 h and persisted for 30 days or more. No expression of rDlx was observed in the surrounding soft tissue before or after fracture. These findings indicate that BMP-4 and rDlx are selectively expressed following femoral fracture in the rat, and also suggest that they are involved in the formation of the callus at an early point during the postfracture healing of bone.

Alkaline Phosphatase↗

Transduction of fibroblasts and CD34+ progenitors using a selectable retroviral vector containing cDNAs encoding arylsulfatase A and CD24.

Metachromatic leukodystrophy (MLD) is an autosomal recessive, inherited, lysosomal storage disease caused by a deficiency in arylsulfatase A (ASA). This disease is characterized by progressive demyelination leading to severe neurological symptoms. Allogenic bone marrow transplantation at an early stage of clinical course is only effective treatment currently available. Accordingly the corrective transfer of the ASA gene into hematopoietic stem cells is thought to be an important option for curative treatment for MLD. We have recently developed a selectable vector system based on ex vivo sorting of transduced cells (Migita et al. 1995). In this study, we applied this selectable system for development of MLD gene therapy. A bicistronic retroviral vector containing ASA cDNA and CD24 cDNA as a selectable marker gene was constructed. This vector was successfully transduced on fibroblasts from MLD patients, ASA activity was increased 7-fold compared to normal untransduced cells. PCR Southern analysis of hematopoietic colonies showed that transduction efficiency of CD34+ cells was 11-22%. However, after fluorescence-activated cell sorting using anti-CD24 antibody, 75-100% of colonies became vector positive. The sorting raised the ASA activity several fold compared to untransduced CD34+ progenitors. These results suggest that a bicistronic ASA vector containing a CD24 selectable marker could be a useful component of gene therapy for MLD.

Antigens, CD↗

Association between single nucleotide polymorphisms in the hMSH3 gene and sporadic colon cancer with microsatellite instability.

The association between three single nucleotide polymorphisms (SNPs) in the hMSH3 gene and sporadic colon cancer with microsatellite instability (MSI) was analyzed. Of the three SNPs observed in this population, SNPs at residues 235 and 693 were novel, while that at residue 3133 was previously described. The SNPs at residues 235 and 3133 caused amino acid substitutions, V79I and T1045A, respectively. We analyzed the allele frequencies of the three SNPs in samples from 19 patients with sporadic colon cancer with MSI and 90 healthy controls. We found that the V79 allele frequency was significantly higher in the tumor samples than in controls. In addition, the frequency of the G693 allele showed a higher trend in the tumor samples than in controls. These results indicated that some SNPs in the hMSH3 gene were associated with colon cancer with MSI.

Alleles↗

Esophageal carcinoma with nonrecurrent inferior laryngeal nerve.

Occurrence of a nonrecurrent inferior laryngeal nerve is quite rare. We present the case of a 70-year-old man with carcinoma of the esophagus. An abnormal right subclavian artery was detected preoperatively. This anomaly suggested that the right inferior laryngeal nerve branched directly from the vagal trunk. A carcinoma of the esophagus was resected, and lymph nodes were dissected. The right inferior laryngeal nerve was fully preserved, and the esophagus was primarily repaired.

Aged↗

GABA(A) receptor-mediated effects on expression of c-Fos in rat trigeminal nucleus following high- and low-intensity afferent stimulation.

We examined the effects of systemic administration of a GABA(A) receptor agonist, muscimol, or antagonist, bicuculline, on the expression of c-Fos protein induced 3h after electrical stimulation of the trigeminal ganglion at low (0.1 mA) or high intensities (1. 0 mA) in the urethane-anesthetized rat. In saline-treated rats, 10 min stimulation of the trigeminal ganglion induced c-Fos-immunopositive neurons throughout the full extent of the ipsilateral superficial layers of the trigeminal nucleus caudalis, and dorsal or dorsomedial part of the nuclei rostral to obex (trigeminal nucleus principalis, dorsomedial nucleus of trigeminal nucleus oralis, dorsomedial nucleus of trigeminal nucleus interpolaris). Animals stimulated at 1. 0 mA induced a significantly higher number of labeled neurons in all trigeminal sensory nucleus than animals stimulated at 0.1 mA. In rats treated with 1mg/kg i.p. muscimol and stimulated at 0.1 mA, the numbers of Fos-positive neurons in trigeminal nucleus caudalis, dorsomedial nucleus of trigeminal nucleus interpolaris, and dorsomedial nucleus of trigeminal nucleus oralis were significantly decreased. However, after stimulation at 1.0 mA, the numbers of Fos-positive neurons in the superficial layers of trigeminal nucleus caudalis was increased and no changes occurred in the numbers of Fos-positive neurons in the magnocellular zone of trigeminal nucleus caudalis, the dorsomedial nucleus of trigeminal nucleus interpolaris, or dorsomedial nucleus of trigeminal nucleus oralis compared to saline-treated controls. In rats treated with 2mg/kg i.p. bicuculline and stimulated at 0.1 mA, the number of Fos-positive neurons increased in the superficial layers of trigeminal nucleus caudalis and trigeminal nucleus principalis. However, after stimulation at 1.0 mA, the number of Fos-positive neurons was unchanged in superficial layers of trigeminal nucleus caudalis, but decreased in the magnocellular zone of trigeminal nucleus caudalis, dorsomedial nucleus of trigeminal nucleus interpolaris and dorsomedial nucleus of trigeminal nucleus oralis. There was a specific loss of Fos-positive neurons in the maxillary and ophthalmic divisions (ventrolateral half) of trigeminal nucleus caudalis. These results indicate that the expression of c-Fos in the trigeminal nucleus is differentially regulated through GABA(A) receptors in a manner that is dependent on the nucleus and the type of primary afferents that are activated by different stimulus intensities.

Afferent Pathways↗

Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation.

BACKGROUND: Plasma brain natriuretic polypeptide (BNP) levels have been used as biochemical markers of systolic left ventricular (LV) dysfunction. Although in vitro studies have shown the existence of BNP messenger RNA in the atria, the main production site of BNP is believed to be the ventricle. The hypothesis that the atrium could be a source of BNP was examined in patients with lone atrial fibrillation (AF), the most common type of sustained arrhythmia. METHODS AND RESULTS: We studied 16 controls and 21 patients with lone AF. Plasma samples for BNP were selectively and serially obtained from the aorta, anterior interventricular vein (AIV), and coronary sinus (CS). Atrial natriuretic polypeptide (ANP) levels were also measured to determine whether the CS samples contained significant amounts of atrial venous drainage. Of the 3 sample locations, the CS had the greatest ANP levels, confirming transcatheter sampling position accuracy. BNP levels were significantly greater in the CS than AIV in the patients with AF (279 +/- 226 v 126 +/- 97 pg/mL; P < .01). Consequently, plasma BNP levels were also greater in the patients with AF than controls (103 +/- 90 v 5 +/- 2 pg/mL; P < .001). LV ejection fraction was significantly less in patients with AF than control patients. Atrial production of BNP decreased significantly after successful DC cardioversion of AF in the 5 restudied patients (182 +/- 139 v 59 +/- 64 pg/mL; P < .05). CONCLUSION: The data suggest that AF is a condition in which BNP is produced in the atrium itself.

Adult↗

Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human oral squamous cell carcinomas: implications for lymph node metastasis.

We measured the production levels of seven different matrix metalloproteinases (MMP-1, 2, 3, 7, 8, 9 and 13) and two tissue inhibitors of metalloproteinases (TIMP-1 and 2) in the homogenates of human oral squamous cell carcinomas and control normal squamous epithelia by the corresponding sandwich enzyme immunoassay systems. The levels of MMP-1, 2, 3, 8, 9, 13 and TIMP-1 were significantly higher in the carcinoma samples than in the control. Among them, only the production level of MMP-2 was significantly higher in the carcinomas with cervical lymph node metastasis than in those without metastasis (P < 0.05). Gelatin zymography demonstrated that activation ratio of the zymogen of MMP-2 (proMMP-2) is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or normal control (P < 0.01). Quantitative RT-PCR for membrane-types 1, 2 and 3 MMPs (MT1, 2 and 3-MMPs), which activate proMMP-2 in vitro, demonstrated that MT1-MMP is predominantly expressed in the carcinoma tissues, and the expression level is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or the control samples (P < 0.05). Although MT2-MMP and MT3-MMP were detected in approximately 30% of the carcinoma cases, their expression levels were extremely lower compared with that of MT1-MMP. There was a direct correlation between the MT1-MMP expression level and proMMP-2 activation ratio (r = 0.62, P < 0.01). In situ hybridization and immunohistochemistry indicated that carcinoma cells and stromal cells adjacent to carcinoma cell nests express MT1-MMP transcripts and protein. MMP-2 and TIMP-2 were also immunolocalized to the carcinoma cells in the carcinoma samples. By in situ zymography, gelatinolytic activity was demonstrated in the carcinoma cell nests and abolished by the treatment with an MMP inhibitor, BB94. These results suggest that among seven different MMPs, the production of proMMP-2 and its activation mediated by MT1-MMP play an important role in the cervical lymph node metastasis of the human oral squamous cell carcinomas.

Base Sequence↗

The effects of aspirin on antioxidant defences of cultured rat gastric mucosal cells.

BACKGROUND: Helicobacter pylori-associated inflammation leads to exposure of the gastric epithelium to reactive oxygen species (ROS) generated in the gastric mucosa. In some pathological conditions, such as those induced by nonsteroidal anti-inflammatory drugs, the gastric mucosa may become more susceptible to ROS. AIM: To examine the effects of aspirin on antioxidant defenses as well as on oxidant injury in cultured rat gastric mucosal cells. METHODS: Primary monolayer cultures of rat gastric fundic mucosa were exposed to an ROS-generating system, hypoxanthine/xanthine oxidase (XOD). Cytotoxicity was quantified by measuring 51Cr release from prelabelled cells. The effects of aspirin on antioxidants and on cellular injury brought about by the ROS-generating system were determined. RESULTS: XOD, in the presence of hypoxanthine, caused a dose-dependent increase in specific 51Cr release, which corresponded to the ability of XOD to produce ROS (as assessed by the production of uric acid from hypoxanthine). Incubation of cells with aspirin (1-100 microM) produced a dose-dependent increase in XOD-induced 51Cr release. Aspirin did not affect cellular glutathione content or activity of glutathione peroxidase, glutathione reductase or endogenous catalase. By contrast, aspirin caused a dose-dependent reduction in mucus synthesis. as assessed by incorporation of [3H]-glucosamine hydrochloride into the cells. CONCLUSIONS: Aspirin at therapeutically relevant concentrations rendered cultured gastric cells more susceptible to subsequent exposure to ROS. Aspirin affected neither the glutathione redox cycle nor catalase activity. Thus, the enhancement of ROS-induced injury by aspirin may be accomplished through diminished gastric mucus synthesis, since mucus is a potent scavenger of ROS. These findings provide insight into how gastric inflammation and injury (such as that induced by H. pylori infection) in human gastric mucosa is modulated by the administration of nonsteroidal anti-inflammatory drugs.

Animals↗

Fatal cardiac rupture: a case of subepicardial aneurysm after myocardial infarction.

We report a case in which 2-dimensional echocardiography established the diagnosis of a left ventricular subepicardial aneurysm that was followed by rupture and sudden death before surgery. Two-dimensional echocardiography is of great help in detecting this rare complication after myocardial infarction. Urgent surgical treatment is warranted for this condition.

Aged↗

Lymphatic drainage of carbon particles injected into the pleural cavity of the monkey, as studied by video-assisted thoracoscopy and electron microscopy.

OBJECTIVES: The aim of this study was to clarify the dynamics of lymphatic drainage of the pleural cavity to understand the mechanism of malignant pleural effusion. METHODS: We injected carbon particles into the pleural cavity of monkeys subjected to general anesthesia. We then observed the parietal pleura with a video-assisted thoracoscope and scanning and transmission electron microscopes to examine the regions of the parietal pleura where the carbon particles had been absorbed. RESULTS: The video-assisted thoracoscope showed that the carbon particles had gone directly to the costal, mediastinal, and diaphragmatic pleura by 10 to 15 minutes after injection. From the scanning and transmission electron microscopes, we found that the parietal pleura in the costal and mediastinal regions consisted of 3 elements: a layer of small mesothelial cells, the macula cribriformis, and lymphatic lacunae. Stomata (3-5 microm in diameter) were found between the small mesothelial cells. The macula cribriformis was composed of densely packed collagen fibrils and had many foramina (3-10 microm in diameter). Intrapleurally injected carbon particles were carried into the lymphatic lacunae via the stomata and vesicles of the mesothelial cells and the foramina of the macula cribriformis. The lymphatic lacunae filled with carbon particles were richly distributed in both the anterior costal pleura and the mediastinal pleura. CONCLUSION: We suggest that the mesothelial stomata and the macula cribriformis are structures essential to the absorption of macromolecules and cellular elements from the pleural cavity into the lymphatic system.

Animals↗

Ethnic-related differences in the frequency distribution of genetic polymorphisms in the CYP1A1 and CYP1B1 genes in Japanese and Caucasian populations.

1. Race-related differences in the frequency distribution of genetic polymorphisms in the CYP1A1 and CYP1B1 genes were studied in 39 Japanese and 45 Caucasians. 2. Four types of CYP1A1 polymorphism, namely m1 (a nucleotide change at T6235C in the 3'-flanking region), m2 (A4889G at exon 7), m3 (T5639C in the 3'-flanking region) and m4 (C4887A at exon 7), and three types of CYP1B1 genetic polymorphism, namely m1 (C488G and G701T leading to Arg48Gly and Ala119Ser exchanges respectively), m2 (C1294G leading to a Leu432Val exchange) and m3 (A1358G leading to an Asn453Ser exchange) were studied. 3. The distribution of the m1-, m2-, m3-, and m4-types of CYP1A1 polymorphism in the Japanese population was 30.8, 17.9, 0 and 0% respectively; those in Caucasians were 3.3, 6.7, 0 and 2.2% respectively. Two types (m1, and m2) of CYP1B1 polymorphism were expressed at 14.1 and 21.8% respectively in the Japanese, and by 28.9 and 37.5% respectively in the Caucasian. Ethnic differences were also noted in the m3-type CYP1B1 polymorphism in which the incidence in Caucasians was 23.9%, whereas no cases in the 39 Japanese subjects were observed. 4. No apparent association was found in the incidence in each of the genetic polymorphisms of CYP1A1 and CYP1B1 genes, nor in methylenetetrahydrofolate reductase gene, except that the occurrence of the m2-type of CYP1A1 genetic polymorphism was related to that of the m1-type CYP1A1 polymorphism in the Japanese population. 5. These results suggest that there are race-related differences in the occurrence of genetic polymorphisms in both CYP1A1 and CYP1B1 genes in Japanese and Caucasian populations and that these differences in P450 genetic polymorphisms may, in part, cause differences in the occurrence of lung and breast cancers in these ethnic groups.

Alleles↗

Photosynthesis, plant growth and N allocation in transgenic rice plants with decreased Rubisco under CO2 enrichment.

Ribulose-1,5-bisphosphate carboxylase (Rubisco) efficiency for CO2-saturated photosynthesis was examined in leaves of rice (Oryza sativa L.). The amount of Rubisco in a leaf was calculated to be 30-55% in excess for the light-saturated rate of photosynthesis at 100 Pa CO2. Long-term exposure to CO2 enrichment decreased the amount of Rubisco protein. However, N was not reallocated from decreased Rubisco to other components limiting photosynthesis, and the decrease in Rubisco was simply due to a decrease in total leaf-N content by CO2 enrichment. Thus, rice plants did not optimize N allocation into Rubisco at elevated CO2. Transgenic rice plants with decreased Rubisco were obtained by transformation with the rbcS antisense gene. The transformant with 65% wild-type Rubisco was selected as a plant with optimal Rubisco content for CO2-saturated photosynthesis at the level of a single leaf. This selected transgenic plant had 20% lower rates of photosynthesis at normal CO2 (36 Pa), but 5-15% higher rates of photosynthesis at elevated CO2 (100 Pa) for a given leaf N content. However, such transgenic plants did not necessarily show greater production of biomass even under conditions of CO2 enrichment. Although they had a higher N-use efficiency for plant growth under such conditions during the middle stage of growth, the growth rate was lower during the early stage of growth. Thus, improvement of N-use efficiency by a single leaf did not necessarily lead to greater production of biomass by the whole plant.

Carbon Dioxide↗

Regulation of hepatic vitamin A storage in a rat model of controlled vitamin A status during aging.

It is currently unknown whether the capacity of the liver to esterify and store vitamin A (VA) changes as a function of long-term VA intake or age. The objective of this study was to investigate whether age and/or VA status are factors for the hepatic expression of cellular retinol-binding protein (CRBP), the esterification of retinol by lecithin:retinol acyltransferase (LRAT) and the accumulation of VA and lipids in liver. Two factors, VA intake and age, were studied in a 3x3 design. Diets denoted as VA-marginal, control and supplemented contained 0.35, 4 and 25 mg retinol equivalents/kg diet, respectively; male Lewis rats were fed these diets from weaning until the ages of 2-3 mo (young), 8-10 mo (middle-aged) and 18-20 mo (old) (n = 6/group. Liver CRBP mRNA differed (two-way ANOVA) with dietary VA (P<0.0001) and age (P<0.05). Hepatic LRAT activity increased with dietary VA (P<0.0001). Age was not a factor (P = 0.47) although there was an interaction of age and dietary VA (P<0.0001). Hepatic LRAT activity was correlated (r = 0.633, P<0.0001) with plasma retinol at physiologic concentrations. In VA-supplemented rats of all ages, the plasma molar ratio of total retinol:retinol-binding protein (RBP) exceeded 1, and liver VA and total lipid concentrations were elevated. However, tests of liver function had previously been shown to be within normal values. Thus, the capacity of the liver for retinol esterification by LRAT was not diminished by age or the accumulation of VA and other lipids. We conclude the following: 1) hepatic LRAT activity is regulated across a broad, physiologic range of dietary VA; 2) LRAT activity is regulated throughout life; and 3) the capacity for hepatic VA storage is high throughout life.

Acyltransferases↗