Biomedical subjects

K Tsukamoto

Publications and source records attributed to K Tsukamoto.

At least 19 recordsLinked to original sources

PubMed2002

Complete, long-lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian herpesvirus vector expressing VP2 antigens.

Marek's disease herpesvirus is a vaccine vector of great promise for chickens; however, complete protection against foreign infectious diseases has not been achieved. In this study, two herpesvirus of turkey recombinants (rHVTs) expressing large amounts of infectious bursal disease virus (IBDV) VP2 antigen under the control of a human cytomegalovirus (CMV) promoter or CMV/beta-actin chimera promoter (Pec promoter) (rHVT-cmvVP2 and rHVT-pecVP2) were constructed. rHVT-pecVP2, which expressed the VP2 antigen approximately four times more than did rHVT-cmvVP2 in vitro, induced complete protection against a lethal IBDV challenge in chickens, whereas rHVT-cmvVP2 induced 58% protection. All of the chickens vaccinated with rHVT-pecVP2 had a protective level of antibodies to the VP2 antigen at the time of challenge, whereas only 42 and 67% of chickens vaccinated with rHVT-cmvVP2 or the conventional live IBDV vaccine, respectively, had the antibodies. The antibody level of chickens vaccinated with rHVT-pecVP2 increased for 16 weeks, and the peak antibody level persisted throughout the experiment. The serum antibody titer at 30 weeks of age was about 20 or 65 times higher than that of chickens vaccinated with rHVT-cmvVP2 or the conventional live vaccine, respectively. rHVT-pecVP2, isolated consistently for 30 weeks from the vaccinated chickens, expressed the VP2 antigen after cultivation, and neither nucleotide mutations nor deletion in the VP2 gene was found. These results demonstrate that the amount of VP2 antigen expressed in the HVT vector was correlated with the vaccine efficacy against lethal IBDV challenge, and complete protective immunity that is likely to persist for the life of the chickens was induced.

Animals↗

PubMed2001

Exclusive association of paraoxonase 1 with high-density lipoprotein particles in apolipoprotein A-I deficiency.

Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated protein which removes peroxidized lipids from lipoproteins. It has been proposed that apolipoprotein A-I (apoA-I) is an important determinant for its stabilization on HDL. However, little is known about its existence and activity in an apoA-I-deficient state in humans. To characterize the nature of PON1 in apoA-I deficiency, we investigated PON1 in an apoA-I-deficient patient. When serum was analyzed on fast protein liquid chromatography, PON1 protein was distributed almost exclusively on HDL despite the absence of apoA-I; on the other hand, 38.5% of PON1 protein was found in the lipoprotein-free fraction when the lipoproteins were fractionated through ultracentrifugation. The stability of PON1 activity in the patient serum was almost the same as in the normal control sera throughout incubation at 14 degrees C for 7 days. However, when the sera were incubated at 37 degrees C for 24 h, its activity declined more than those in the normal controls (19% versus 4% reduction of the initial values). Our results demonstrated that PON1 protein possesses a preferential association with HDL even in the absence of apoA-I, although apoA-I is a crucial factor for the maximal activity and stabilization of PON1.

Aged↗

PubMed2001

Validation of an analytical method for a potent antitumor agent, TZT-1027, in plasma using liquid chromatography-mass spectrometry.

A sensitive and specific analytical method for a potent antitumor agent, TZT-1027, in plasma has been developed using liquid chromatography-mass spectrometry (LC-MS) with [2H4]TZT-1027 as an internal standard (I.S.). A plasma sample was purified by solid-phase extraction on a C18 cartridge, followed by solvent extraction with diethyl ether. The extract was then injected into the LC-MS system. Chromatography was carried out on a C18 reversed-phase column using acetonitrile-0.05% trifluoroacetic acid (TFA) (55:45) as a mobile phase. Mass spectrometric analysis was performed in atmospheric pressure chemical ionization (APCI) mode with positive ion detection, and the protonated molecular ions ([M+H]+) of TZT-1027 and I.S. were monitored to allow quantitation. The method was applied to the determination of TZT-1027 in human, monkey, dog, rat and mouse plasma. As far as the sample preparation was concerned, good recoveries (73.5-99.1%) were obtained. The calibration curves were linear over the range of 0.25-100 ng per 1 ml of human, dog and rat plasma, per 0.5 ml of monkey plasma, and per 0.1 ml of mouse plasma. From the intra- and inter-day accuracy and precision, the present method satisfies the accepted criteria for bioanalytical method validation. TZT-1027 was stable when stored below -15 degrees C for 6 months in human plasma and for 3 weeks in plasma from other species. TZT-1027 was also stable in plasma through at least three freeze-thaw cycles.

Animals↗

PubMed2001

ATP-binding cassette transporter-1 induces rearrangement of actin cytoskeletons possibly through Cdc42/N-WASP.

Positional cloning approaches revealed that Tangier disease (TD), a genetic high density lipoprotein deficiency, is associated with mutations in the ATP-binding cassette transporter-1 (ABCA1) gene. However, the biological function of ABCA1 is still not fully investigated. Recently, we have reported that the cells from the patients with TD had abnormal actin cytoskeletons in association with decreased expression of Cdc42, a member of RhoGTPases family. In the present study, we have found that actin cytoskeletons were altered in HEK293 cells transfected with human ABCA1 (hABCA1) cDNA. Cells expressing hABCA1 were divided into the following two groups by the distinct morphology with altered actin cytoskeletons: one had increased formation of filopodia (designated as Type I) and the other had long protrusions (designated as Type II). Type I cells had morphology similar to that of cells transfected with dominant active form of Cdc42 (Cdc42-DA, V12Cdc42Hs-DA). Type II cells had morphology similar to that of cells transfected with neural Wiskott-Aldrich Syndrome Protein (N-WASP),one of the established downstream effector molecules of Cdc42. We have obtained the data showing a possible pathway of ABCA1/Cdc42/N-WASP by the following experiments. Introduction of mutant of Cdc42 (dominant negative form of Cdc42, N17Cdc42Hs-DN) and N-WASP (N-WASP lacking verprolin homology domain, N-WASPDeltaVPH), both of which are supposed to have potential to inhibit rearrangement of actin cytoskeletons, significantly inhibited the morphological changes induced by expression of hABCA1. Immunoprecipitation study with FLAG-tagged ABCA1 (hABCA1-FLAG) revealed that Cdc42 was coimmunoprecipitated with hABCA1-FLAG. In addition, we have demonstrated possible intracellular colocalization of these two molecules in the overexpressing cells by the confocal laser microscopy. These results may suggest that hABCA1 regulates actin organization through the possible interaction with Cdc42Hs.

ATP Binding Cassette Transporter 1↗

PubMed2001

Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells.

Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone. BCRP-overexpressing cells show cross-resistance to camptothecin derivatives such as irinotecan, SN-38 (the active metabolite of irinotecan), and topotecan. To test whether BCRP confers SN-38 resistance, we selected two SN-38 resistant sublines from PC-6 human small-cell lung cancer cells by SN-38, and then characterized these cells. Compared to PC-6 cells, the resistant sublines PC-6/SN2-5 and PC-6/SN2-5H were approximately 18- and 34-fold resistant, respectively. The intracellular SN-38 accumulation was reduced in the sublines, and BCRP mRNA was overexpressed in proportion to the degree of SN-38 resistance. These findings suggest that BCRP confers SN-38 resistance in the sublines. To confirm this hypothesis, PC-6/SN2-5 cells were transfected with antisense oligonucleotides complementary to portions of BCRP mRNA. The antisense oligonucleotides significantly suppressed BCRP mRNA expression, and enhanced SN-38 sensitivity in the subline. These data indicate that BCRP is directly involved with SN-38 resistance, by efflux transport of SN-38.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2001

Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E.

Apolipoprotein E is a multifunctional protein synthesized by hepatocytes and macrophages. Plasma apoE is largely liver-derived and known to regulate lipoprotein metabolism. Macrophage-derived apoE has been shown to reduce the progression of atherosclerosis in mice. We tested the hypothesis that liver-derived apoE could directly induce regression of pre-existing advanced atherosclerotic lesions without reducing plasma cholesterol levels. Aged low density lipoprotein (LDL) receptor-deficient (LDLR(-/-)) mice were fed a western-type diet for 14 weeks to induce advanced atherosclerotic lesions. One group of mice was sacrificed for evaluation of atherosclerosis at base line, and two other groups were injected with a second generation adenoviruses encoding human apoE3 or a control empty virus. Hepatic apoE gene transfer increased plasma apoE levels by 4-fold at 1 week, and apoE levels remained at least 2-fold higher than controls at 6 weeks. There were no significant changes in plasma total cholesterol levels or lipoprotein composition induced by expression of apoE. The liver-derived human apoE gained access to and was retained in arterial wall. Compared with base-line mice, the control group demonstrated progression of atherosclerosis; in contrast, hepatic apoE expression induced highly significant regression of advanced atherosclerotic lesions. Regression of lesions was accompanied by the loss of macrophage-derived foam cells and a trend toward increase in extracellular matrix of lesions. As an index of in vivo oxidant stress, we quantitated the isoprostane iPF(2 alpha)-VI and found that expression of apoE markedly reduced urinary, LDL-associated, and arterial wall iPF(2 alpha)-VI levels. In summary, these results demonstrate that liver-derived apoE directly induced regression of advanced atherosclerosis and has anti-oxidant properties in vivo that may contribute to its anti-atherogenic effects.

Adenoviridae↗

PubMed2001

Molecular phylogeny and evolution of the freshwater eel, genus Anguilla.

A molecular phylogenetic analysis was conducted on all of the known catadromous eel species of the genus Anguilla to assess their relationships and evolutionary history. The analyses of a total of 1427 bp of the mitochondrial 16S ribosomal RNA and 1140 bp of the complete cytochrome b gene sequences suggested that the genus Anguilla was monophyletic in origin, with A. borneensis as the most basal species. Four clades/species groups that correspond to their geographical ranges were indicated, Indo-Atlantic (three species), Oceania (two species), tropical Pacific (two species), and Indo-Pacific (five species), with ambiguous positions for A. japonica and A. reinhardti. This grouping conflicts with that of a previous morphological study, since the broad undivided maxillary and short-fin type, which were thought to be phylogenetically important, were paraphyletic in the molecular analysis. However, the molecular phylogeny and the present geographic distribution of species suggested historical dispersion of the genus Anguilla according to the Tethys corridor hypothesis, which proposed that anguillid eels originated near present-day Indonesia and dispersed westward along paleo-circumglobal equatorial currents. The westward-moving strain entered the paleo-Atlantic through the Tethys Sea and was ancestral to present-day European and American species.

Anguilla↗

PubMed2001

A mitogenomic perspective on the basal teleostean phylogeny: resolving higher-level relationships with longer DNA sequences.

A recent study demonstrated that mitochondrial genomic (mitogenomic) data comprising nucleotide sequences from the concatenated protein-coding (no 3rd codon positions) plus transfer RNA (stem regions only) genes reproduced the expected phylogeny of teleosts with high statistical support. We reexamined the interrelationships of the five major, basal teleostean lineages (Osteoglossomorpha, Elopomorpha, Clupeomorpha, Ostariophysi, and Protacanthopterygii; given various rankings) using mitogenomic data for which five alternative phylogenetic hypotheses have been previously proposed on the basis of both morphological and molecular analyses. In addition to previously determined complete mitochondrial DNA (mtDNA) sequences from eight basal teleosts and two outgroups, we determined the complete mtDNA sequences (excluding a portion of the control region) for two, purposefully chosen species of Osteoglossomorpha (Osteoglossum bicirrhosum and Pantodon buchholzi), and the data were subjected to maximumparsimony and maximum-likelihood analyses. The resultant tree topologies from the two methods were congruent, although they differed from any of the previously proposed hypotheses. Furthermore, the mitogenomic data confidently rejected all of these hypotheses with high statistical significance.

Animals↗

PubMed2001

Complete mitochondrial DNA sequence of Conger myriaster (Teleostei: Anguilliformes): novel gene order for vertebrate mitochondrial genomes and the phylogenetic implications for anguilliform families.

The complete nucleotide sequence of the mitochondrial genome was determined for a conger eel, Conger myriaster (Elopomorpha: Anguilliformes), using a PCR-based approach that employs a long PCR technique and many fish-versatile primers. Although the genome [18,705 base pairs (bp)] contained the same set of 37 mitochondrial genes [two ribosomal RNA (rRNA), 22 transfer RNA (tRNA), and 13 protein-coding genes] as found in other vertebrates, the gene order differed from that recorded for any other vertebrates. In typical vertebrates, the ND6, tRNA(Glu), and tRNA(Pro) genes are located between the ND5 gene and the control region, whereas the former three genes, in C. myriaster, have been translocated to a position between the control region and the tRNA(Phe) gene that are contiguously located at the 5' end of the 12S rRNA gene in typical vertebrates. This gene order is similar to the recently reported gene order in four lineages of birds in that the latter lack the ND6, tRNA(Glu), and tRNA(Pro) genes between the ND5 gene and the control region; however, the relative position of the tRNA(Pro) to the ND6-tRNA(Glu) genes in C. myriaster was different from that in the four birds, which presumably resulted from different patterns of tandem duplication of gene regions followed by gene deletions in two distantly related groups of organisms. Sequencing of the ND5-cyt b region in 11 other anguilliform species, representing 11 families, plus one outgroup species, revealed that the same gene order as C. myriaster was shared by another 4 families, belonging to the suborder Congroidei. Although the novel gene orders of four lineages of birds were indicated to have multiple independent origins, phylogenetic analyses using nucleotide sequences from the mitochondrial 12S rRNA and cyt b genes suggested that the novel gene orders of the five anguilliform families had originated in a single ancestral species.

Amino Acid Sequence↗

PubMed2001

Effects of all-trans retinoic acid on melanogenesis in pigmented skin equivalents and monolayer culture of melanocytes.

The effects of all-trans retinoic acid (RA) on melanogenesis and the mechanism of its action in topical treatment have not been elucidated. The purpose of this study was to determine the effects of RA on melanogenesis in the pigmented skin equivalent as well as in monolayer culture of melanocytes, and to determine whether RA, hydroquinone (HQ), and hydrocortisone (HC) show synergistic depigmenting effects in combined treatments of each other. The suppressing effect of RA on melanogenesis was not observed in pigmented skin equivalents and monolayer culture of murine and human melanocytes, although HQ showed strong inhibition of melanogenesis. The synergistic effects between RA, HQ, and HC were not particularly seen. The results suggested that RA neither has direct inhibitory effects on melanogenesis of melanocytes, nor influences the cell-cell interactions between melanocytes, keratinocytes and fibroblasts, such as paracrine actions with regard to melanin production. The role of RA in bleaching treatments appears to be in other specific actions, such as promotion of keratinocytes proliferation and acceleration of epidermal turnover.

Animals↗

PubMed2001

Genetic analysis of phytosterolaemia.

Two women with multiple xanthomas, intermittent arthritis and thrombocytopenia were diagnosed as phytosterolaemia, an autosomal-recessive lipid storage disease, based on their increased serum concentrations of beta-sitosterol, campesterol and sitostanol. The gene responsible for this disease is located within a distance of 18 cM between microsatellite markers of D2S 1788 and D2S1352 at chromosome 2p21. We genotyped the patients and their family members with 16 microsatellite markers around this locus. The results from the homozygosity mapping of one family suggested that the gene was located within the distance of 12.6 cM between D2S2328 and D2S1352. We have shortened the genetic distance by 5.4 cM.

Adult↗

PubMed2001

HHV8-negative primary effusion lymphoma of the peritoneal cavity presenting with a distinct immunohistochemical phenotype.

Primary effusion lymphoma (PEL) has been recognized as a body-cavity-based lymphoma that was originally reported to be associated with human herpes virus 8 (HHV8) infection, and was frequently found in human immunodeficiency virus-positive (HIV) patients. Here we describe an autopsy case of PEL of the peritoneal cavity in an immunocompetent patient. Cytological analysis of tumor cells within ascites revealed immunocytochemical features of keratin positivity and CD45 negativity. At autopsy, the presence of a massive volume of ascites as well as diffuse tumor cell infiltrates within the serosa of the intestine and mesenterium were observed. Tumor cells were morphologically similar to anaplastic large-cell lymphoma, but were immunohistochemically positive for keratin and epithelial membrane antigen (EMA). They also showed no reactivity to representative lymphocyte surface markers including CD45, in addition to being negative for CD30 and p80NPM/ALK. Molecular analysis of the tumor cells revealed monoclonality of the immunoglobulin heavy-chain gene rearrangement which demonstrated a lymphoma of the B-cell lineage. Furthermore, HHV8 was not detected by immunohistochemical analysis, PCR or nested PCR technique. Based on these results, we consider the present case to be an HHV8-negative PEL with keratin and EMA positivity.

Adult↗

PubMed2001

Cytochrome P450 enzymes involved in the metabolic pathway of the histamine 2 (H2)-receptor antagonist roxatidine acetate by human liver microsomes.

Roxatidine acetate hydrochloride (ROX, 2-acetoxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide hydrochloride, CAS 78273-80-0), a histamine 2 (H2)-receptor antagonist, has been clinically applied for the treatment of gastritis, gastric and duodenal ulcers. There is no report on the identification of the metabolic enzyme of M-1 (2-hydroxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide), the pharmacologically active metabolite, in humans. In this study, the Cytochrome P450 (CYP or P450) enzymes which participate in the metabolism of ROX were identified using human liver microsomes and S9 fractions. M-1 was converted to M-4 (3-[m-(1-piperidinyl-methyl)phenoxy]propylamine) by the enzyme reaction with the S9 but not with microsomes. M-4 was further metabolized to M-5 (3-[m-(1-piperidinylmethyl)phenoxy]propanol) by microsomes. The metabolism was inhibited by coumarin and anti-CYP2A1 serum. (3-[m-(1-piperidinylmethyl)-phenoxy]propionic acid) and M-3 (m-(1-piperidinylmethyl) phenol) formation from M-5 were inhibited by quinidine and anti-CYP2D6 serum. Moreover, M-5 was converted to M-2 and M-3 by cDNA-expressed CYP2D6. In conclusion, this study shows that microsomal enzymes do not participate in the clearance of the active metabolite M-1, CYP2A6 primarily catalyzes M-5 formation from M-4, and CYP2D6 primarily catalyzes M-2 and M-3 formation from M-5 in humans.

Chromatography, High Pressure Liquid↗

PubMed2001

Oestrogen receptor-alpha gene polymorphism is associated with endometriosis, adenomyosis and leiomyomata.

Endometriosis, adenomyosis and leiomyomata develop in women of reproductive age and regress after menopause or ovariectomy, suggesting that they grow in an oestrogen-dependent fashion. We investigated whether polymorphism in the oestrogen receptor-alpha (ERalpha) gene is related to oestrogen-dependent benign uterine disease. A total of 203 women with regular menstrual cycles underwent laparotomy or laparoscopy and were diagnosed histologically with endometriosis, adenomyosis and/or leiomyomata. Patients with cervical carcinoma in situ, tubal occlusion or adhesion but no other gynaecological disease were considered to be disease-free. A total of 179 women undergoing annual health examination were grouped as reference population. The distribution of PVUII genotypes (PP, Pp, and pp) of the ERalpha gene was different between each pair of the four groups of endometriosis, adenomyosis/leiomyomata, disease-free, and reference population (P = 0.022-0.0005), except between the former two groups. The PP genotype was less frequent in the groups of endometriosis (P = 0.0002) and adenomyosis/leiomyomata (P = 0.002) as compared to that in the disease-free group. In the endometriosis group, there was no difference in the distribution of PVUII genotypes due to complicating diseases (adenomyosis and/or leiomyomata) or severity of the clinical stages. These results suggest that the PVUII polymorphism of the ERalpha gene is associated with the risk for endometriosis, adenomyosis, and leiomyomata.

Adult↗

PubMed2001

Progesterone inhibition of functional leptin receptor mRNA expression in human endometrium.

Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors (OB-R). Leptin is involved in the stimulation of reproductive functions, and local expression of leptin and OB-R in the ovary, oocyte, embryo, and placenta might play a role in early development. The mRNA and protein of the long form leptin receptor (OB-R(L)) but not of leptin are expressed in the human endometrium and the abundance of OB-R mRNA expression varies during the menstrual cycle with a peak in the early secretory phase. We examined the steroidal regulation of OB-R(L) mRNA expression. Northern blot analyses showed that in organ-cultured proliferative endometrial specimens, oestradiol (10(-9) and 10(-8) mol/l) had no acute effect on the OB-R(L) mRNA expression, whereas oestradiol plus progesterone (10(-8), 10(-7) and 10(-6) mol/l) or medroxyprogesterone acetate (10(-8) and 10(-7) mol/l) suppressed the expression by approximately 50%. This progestin-induced suppression was blocked by a concomitant addition of mifepristone. Additionally, incubation of endometrial specimens in the presence of leptin resulted in the phosphorylation of its intracellular target, STAT3 (signal transducer and activator of transcription 3). These results indicate that, in the human endometrium, progestins act via the progesterone receptors to suppress functional OB-R(L) mRNA expression, and may thereby alter the sensitivity of the endometrium to leptin.

Adult↗

PubMed2001

Identification of a genetic determinant of pathogenicity in chicken anaemia virus.

The molecular basis of pathogenicity of the chicken anaemia virus (CAV) needs to be clarified in order to develop a safe, live virus vaccine. In this study, several high- and low-pathogenic infectious DNA clones were obtained from field virus samples after 12 or 38 passages in MDCC-MSB1 cells. The high-pathogenic clones induced a low haematocrit, low weight gain and high mortality. Nucleotide sequence analyses identified one amino acid, at residue 394 of the VP1 capsid protein, as a major determinant of pathogenicity. To determine the role of this amino acid in pathogenicity, chimeric infectious DNA clones and point-mutated clones were used for chicken pathogenicity tests. These analyses clearly demonstrated that residue 394 of VP1 was crucial for the pathogenicity of CAV; all of the cloned viruses with glutamine at this position were highly pathogenic, whereas those with histidine had low pathogenicity. Low-pathogenic CAV, based on an infectious DNA clone, is a candidate for a genetically homogeneous and stable CAV live vaccine.

Amino Acid Sequence↗

PubMed2001

Imported parakeets harbor H9N2 influenza A viruses that are genetically closely related to those transmitted to humans in Hong Kong.

In 1997 and 1998, H9N2 influenza A viruses were isolated from the respiratory organs of Indian ring-necked parakeets (Psittacula Krameri manillensis) that had been imported from Pakistan to Japan. The two isolates were closely related to each other (>99% as determined by nucleotide analysis of eight RNA segments), indicating that H9N2 viruses of the same lineage were maintained in these birds for at least 1 year. The hemagglutinins and neuraminidases of both isolates showed >97% nucleotide identity with those of H9N2 viruses isolated from humans in Hong Kong in 1999, while the six genes encoding internal proteins were >99% identical to the corresponding genes of H5N1 viruses recovered during the 1997 outbreak in Hong Kong. These results suggest that the H9N2 parakeet viruses originating in Pakistan share an immediate ancestor with the H9N2 human viruses. Thus, influenza A viruses with the potential to be transmitted directly to humans may be circulating in captive birds worldwide.

Amino Acid Sequence↗

PubMed2001

Gastric emptying in diabetic gastroparetic dogs: ffects of SK-951,a novel prokinetic agent.

We examined whether delayed gastric emptying could be produced by diabetes in dogs. Diabetes was produced by a single injection of streptozotocin (30 mg/kg i.v.), and diabetic hyperglycemia was observed from 2 to 15 months after injection. The plasma acetaminophen concentration, which is an indirect indicator of the gastric emptying rate, was delayed in 2 of 5 diabetic dogs from 15 months after the induction of diabetes. The effects of SK-951, a benzofuran derivative, on delayed gastric emptying were also examined in diabetic gastroparetic dogs in comparison with those of cisapride. SK-951 (1 mg/kg i.v.) significantly enhanced delayed gastric emptying in diabetic dogs, but cisapride (1 mg/kg i.v.) had no effect. In addition, SK-951 increased the plasma glucose levels in a manner correlated with its effect on gastric emptying. The present study suggested that SK-951 may be useful in the treatment of diabetic gastroparesis.

Acetaminophen↗