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Biomedical subjects

S Yamazaki

Publications and source records attributed to S Yamazaki.

At least 181 records · Page 10Linked to original sources

The alpha1L-adrenoceptor subtype in the lower urinary tract: a comparison of human urethra and prostate.

OBJECTIVE: To identify the alpha1-adrenoceptor subtypes present in the human urethra, by comparing the affinity of prazosin for alpha1-adrenoceptors in the rabbit, dog and human prostatic urethra, and in the dog and human prostate. MATERIALS AND METHODS: The study comprised samples of human prostate and prostatic urethra, obtained by open prostatectomy of patients with benign prostatic hyperplasia, and of the proximal urethra and prostate from male Beagle dogs and rabbits. Specimens were homogenized, filtered and pelleted by centrifugation. Nonspecific binding was determined in the presence of 1 mmol/L prazosin when assessing [3H]YM-617 (tamsulosin) binding, and 10 mmol/L phentolamine when assessing [3H]prazosin binding. Specific binding was defined as the difference between total binding and nonspecific binding. RESULTS: The dissociation constant for [3H]prazosin in the human prostate (0.088 nmol/L) was less than that in the rabbit urethra (0.299 nmol/L), dog urethra (0.604 nmol/L), dog prostate (0.482 nmol/L) and human urethra (0.254 nmol/L). The affinity of prazosin was also investigated by determining the potency of the inhibition of [3H]YM-617 binding. The affinity of prazosin for alpha1-adrenoceptors in the human urethra (Ki, 2.5 nmol/L) was lower than its affinity for alpha1-adrenoceptors in the human prostate (Ki, 0.25 nmol/L) and all of the cloned subtypes (Ki, 0.26-0.44 nmol/L). CONCLUSION: The alpha1L-adrenoceptor subtype is more prominent in the human, rabbit and dog urethra and dog prostate than in the human prostate.

Adrenergic alpha-Antagonists↗

Antibacterial activity of bovine lactoferrin and its peptides against enterohaemorrhagic Escherichia coli O157:H7.

The antimicrobial activities of bovine lactoferrin (bLF), its pepsin hydrolysate (bLFH) and the active peptide lactoferricin B (LFcinB) against four clinical isolates of enterohaemorrhagic Escherichia coli O157:H7 were studied. The MICs against these isolates were 3 mg ml-1 for bLF, 0.1-0.2 mg ml-1 for bLFH and 8-10 micrograms ml-1 for LFcinB in 1% Bactopeptone broth. LFcinB killed these bacteria within 3 h at concentrations above 10 micrograms ml-1. Transmission electron microscopy findings suggested that LFcinB acts on the bacterial surface and affects cytoplasmic contents. LFcinB was shown to influence the levels of verotoxins in the culture supernatant fluid of an E. coli O157:H7 strain. These results demonstrate that E. coli O157:H7 strains are susceptible to the antimicrobial effects of bLF and its peptides.

Animals↗

A novel donor splice site mutation in the C1 inhibitor gene of a patient with type I hereditary angioneurotic edema.

We studied the molecular genetic basis of a C1 inhibitor deficiency in a patient with type I hereditary angioneurotic edema using both the polymerase chain reaction and nucleotide sequencing. A single nucleotide change (T-->A) at the GT 5' donor splice recognition motif in the seventh intron of the C1 inhibitor gene was detected. A restriction site analysis of the C1 inhibitor gene in the patient's family indicated that this mutation is correlated with a decreased level of C1 inhibitor activity. A northern blot analysis demonstrated C1 inhibitor mRNA to have a normal size, but its contents were reduced by about 50% compared with a normal subject. As the donor splice site is essential for an excising of the intron during mRNA processing, aberrant mRNA splicing may cause a rapid degradation of the transcript, thus resulting in the onset of hereditary angioneurotic edema.

Adult↗

Combined effects of clenbuterol and various concentrations of protein on performance of broiler chickens.

1. The effects of the beta-adrenergic agonist, clenbuterol (1 mg/kg diet) on the growth and muscle composition in female broiler chickens (14 to 32 d of age) fed on diets containing various concentrations of protein (220, 240 or 260 g protein/kg) were examined. 2. Body weight gain over the 18 d period increased linearly with increasing protein intake. The rate of gain was significantly higher in clenbuterol-treated chickens than in control birds. 3. Dietary clenbuterol increased thigh muscle weight and protein concentration of breast and thigh muscle, regardless of dietary protein content. Protein/DNA ratio in thigh muscle was enhanced by clenbuterol feeding, and the magnitude of difference of the ratio was higher in chickens fed on the 240 and 260 g CP/kg diets than in those fed the 220 g CP/kg diet. 4. It was concluded that clenbuterol-treated chickens require increased dietary protein to maintain maximal growth, and that increased protein consumption is an important factor in improving growth in clenbuterol-fed broilers.

Adipose Tissue↗

Identification of potential regulatory elements for the transport of Emp24p.

To examine the possibility of active recycling of Emp24p between the endoplasmic reticulum (ER) and the Golgi, we sought to identify transport signal(s) in the carboxyl-terminal region of Emp24p. Reporter molecules were constructed by replacing parts of a control invertase-Wbp1p chimera with those of Emp24p, and their transport rates were assessed. The transport of the reporter was found to be accelerated by the presence of the cytoplasmic domain of Emp24p. Mutational analyses revealed that the two carboxyl-terminal residues, leucine and valine (LV), were necessary and sufficient to accelerate the transport. The acceleration was sequence specific, and the terminal valine appeared to be more important. The LV residues accelerated not only the overall transport to the vacuole but also the ER to cis-Golgi transport, suggesting its function in the ER export. Hence the LV residues are a novel anterograde transport signal. The double-phenylalanine residues did not affect the transport by itself but attenuated the effect of the anterograde transport signal. On the other hand, the transmembrane domain significantly slowed down the ER to cis-Golgi transport and effectively counteracted the anterograde transport signal at this step. It may also take part in the retrieval of the protein, because the overall transport to the vacuole was more evidently slowed down. Consistently, the mutation of a conserved glutamine residue in the transmembrane domain further slowed down the transport in a step after arriving at the cis-Golgi. Taken together, the existence of the anterograde transport signal and the elements that regulate its function support the active recycling of Emp24p.

Amino Acid Sequence↗

Characterization of a multi-copper enzyme, nitrous oxide reductase, from Rhodobacter sphaeroides f. sp. denitrificans.

The nitrous oxide reductase from the photodenitrifier, Rhodobacter sphaeroides f. sp. denitrificans, has been purified. The enzyme is composed of two identical subunits of 66 kDa, and contains four copper atoms per subunit. Copper supplementation of the medium resulted in a 3.5-fold increase in the enzyme yield with doubly enhanced specific activity. The activity of the purified nitrous oxide reductase was completely inhibited by 100 microM zinc ions.

Copper↗

Cloning and characterization of the genomic RNA sequence of the mumps virus strain associated with a high incidence of aseptic meningitis.

cDNA clones of the mumps virus wild-type strain, associated with a high incidence of aseptic meningitis (ODATE-1 strain), were isolated and analyzed from genomic nucleotide position 22 to 8520 containing the NP, P, M, F, SH and HN protein coding region. The ODATE-1 strain exhibited a RFLP profile identical to that of the Urabe vaccine strain in spite of the fact that the virus was isolated from non-vaccinated cases. However, a comparison of nucleotide and amino acid sequences among the ODATE-1 strain, Urabe strain and Miyahara strain revealed that the ODATE-1 strain was not related to the Urabe strain.

Animals↗

FK317, a novel substituted dihydrobenzoxazine, exhibits potent antitumor activity against human tumor xenografts in nude mice.

The antitumor effects of FK317, a novel substituted dihydrobenzoxazine, were evaluated using human tumor xenografts (small cell lung cancer, non-small cell lung cancer, stomach cancer, colon cancer, pancreatic cancer, breast cancer, cervical cancer and ovarian cancer). Tumor growth-inhibitory effects and the effective dose-range of FK317 were much stronger and broader, respectively, than those of reference drugs such as mitomycin C, adriamycin, cisplatin, taxol and irinotecan. Furthermore, the body weight decrease and myelosuppression in FK317-treated mice were less than in the animals given any of the reference drugs. To explain this tumor selectivity, the distribution of FK317 was investigated after dosing tumor-bearing mice with the 14C-labelled compound. The concentration of FK317 in tumor tissues was relatively low, and long tumor retention was not observed. However, thin-layer chromatographic separation revealed that the radioactivity in the tumor resided mainly in strongly cytotoxic metabolites, while that in other tissues resided mainly in non-cytotoxic metabolites. These results suggest that FK317 shows strong antitumor activity without side effects, and one reason for this is its specific metabolite pattern. FK317 is now undergoing phase I clinical trials.

Adenocarcinoma↗

TNF-alpha, RANTES, and MCP-1 are major chemoattractants of murine Langerhans cells to the regional lymph nodes.

We have previously reported that lymph node cells generated chemotactic factors for Langerhans cells (LCs) in the induction phase of contact dermatitis. In order to clarify the chemotactic factors involved in migration to the regional lymph nodes, we investigated the migratory activity of murine LCs toward several cytokines and chemokines in vitro. One-day cultured LC-enriched epidermal cells were added to the upper compartment of a modified Boyden chamber and cytokines were added to the lower compartment. We counted dendritic cells migrated to the lower chamber as LCs under phase contrast microscopy. About 99% of migrated dendritic cells were positively reacted with anti-Ia(d) and NLDC145 antibodies and considered to be LCs. We could detect LC migration more accurately by this direct examination than by counting the migrated cells in the filter membrane of a Boyden chamber. In our system, migration of murine epidermal LCs was stimulated by TNF-alpha, RANTES and MCP-1, but not by GM-CSF, IL-1beta, IL-4, and IL-6. TNF-alpha induced LC migration at concentrations from 4 x 10(3) U/ml to 5 x 10(4) U/ml. RANTES at concentrations from 10 to 100 ng/ml and MCP-1 at a concentration of 100 ng/ml induced LC migration in a dose-dependent manner. These data confirmed that TNF-alpha, RANTES, and MCP-1 induced LC migration from epidermis during contact sensitization.

Animals↗

Complete nucleotide sequence and genetic organization of Aichi virus, a distinct member of the Picornaviridae associated with acute gastroenteritis in humans.

The complete nucleotide sequence of a novel enteric virus, Aichi virus, associated with nonbacterial acute gastroenteritis in humans was determined. The Aichi virus genome proved to be a single-stranded positive-sense RNA molecule with 8,251 bases excluding a poly(A) tail; it contains a large open reading frame with 7,302 nucleotides that encodes a potential polyprotein precursor of 2,433 amino acids. The genome contains a 5' nontranslated region (NTR) with 712 bases and a 3' NTR with 240 bases followed by a poly(A) tail. The structure of the genome, VPg-5' NTR-leader protein-structural proteins-nonstructural proteins-3' NTR-poly(A), was found to be typical of a picornavirus. The VP0-VP3 and VP3-VP1 cleavage sites were determined to be Q-H and Q-T, respectively, by N-terminal amino acid sequence analyses using purified virion proteins. Possible cleavage sites, Q-G, Q-A, and Q-S, which cleave P2 and P3 polyproteins were found to be similar to those of picornaviruses. A dendrogram based on 3Dpol proteins indicated that Aichi virus is genetically distinct from the known six genera of picornaviruses including entero-, rhino-, cardio-, aphtho-, and hepatovirus and echovirus 22. Considering this together with other properties of the virus (T. Yamashita, S. Kobayashi, K. Sakae, S. Nakata, S. Chiba, Y. Ishihara, and S. Isomura, J. Infect. Dis. 164:954-957, 1991), we propose that Aichi virus be regarded as a new genus of the family Picornaviridae.

Acute Disease↗

Circadian behavior and plasticity of light-induced c-fos expression in SCN of tau mutant hamsters.

In hamsters homozygous for the circadian clock mutation tau, the photic history dramatically affects the magnitude of light-induced circadian phase shifts. The maximum amplitude of phase shifts produced by 1-h light pulses presented at CT 14 was less than 2 h in animals that had been in DD for 2 days, whereas animals that had been kept in DD for 49 days could be shifted by more than 8 h. In this study, the authors compared the effect of previous light history on the amplitude of circadian phase shifts and on c-fos expression in the SCN of tau mutant hamsters. Although the maximum amplitude of behavioral phase shifts was drastically different between animals that had been held for either 2 or 49 days in DD, maximal fos induction was not significantly different in these two groups. However, photic thresholds for light-induced behavioral phase shifts, c-fos mRNA, and Fos immunoreactivity were closely correlated within both groups, and these thresholds were lower (more sensitive to light) after 49 than after 2 days in DD. The correlation between phase shifting and Fos induction thresholds, under conditions where both responses are dramatically altered by the previous light history, demonstrates an association between changes in circadian behavioral phase-shifting responses of tau mutant hamsters and plasticity of light-induced c-fos expression in SCN. However, because the maximum amplitudes of Fos induction and phase shifting were not correlated in animals that had been in DD for 2 days, we speculate that the level of c-fos expression does not directly determine phase shift amplitude.

Animals↗

[Analysis of contact dermatitis by cytokines. III.--Sensitization and crossreaction of phenolic compounds].

We examined sensitization and crossreaction by the guinea pig maximization test (GPMT) with phenolic compounds. Skin specimens were collected from earlobes of BALB/c mice on 24 h after elicitation phase of contact hypersensitivity reaction (CHR) with phenolic compounds. The expression of cytokines of skin specimens was examined by the reverse transcriptase/polymerase chain reaction (RT-PCR) method. Consequently, phenolic compounds which showed positive reaction in GPMT expressed IL-2 and IFN-gamma on 24 h after elicitation, and some phenolic compounds showed marked crossreaction. Therefore, it was found that on several phenolic compounds, dimerization of these compounds from monomer to dimer decrease sensitization.

Animals↗

Inhibition of adrenaline-induced lipolysis by ginseng polypeptide and its modified peptides.

The anti-lipolysis by ginseng polypeptide and its modified peptides was examined using porcine adipose cells. Ginseng polypeptides modified by amino acid substitution or proteolyzation reduced or lost the inhibiting activity of adrenalin-induced lipolysis. Correlation between the anti-lipolytic activity of ginseng polypeptide and its Mg(2+)- and ribose-binding activities is discussed.

Adipose Tissue↗

Trehalose as osmoprotectant in Rhodobacter sphaeroides f. sp. denitrificans IL106.

The photosynthetic bacterium Rhodobacter sphaeroides f. sp. denitrificans IL106 can grow in high osmolarity. The accumulation of intracellular inorganic ions and organic solutes in cells grown in a synthetic medium containing different concentrations of NaCl was examined. Together with potassium ion, trehalose was the major organic osmoprotectant and its accumulation depended on the external salt concentration. Intracellular levels of glycine betaine and other osmoprotectants such as proline did not change when osmolarity increased.

Betaine↗

Molecular phylogeny of zooxanthellate bivalves.

The aim of this research was to analyze the phylogenetic relationships of zooxanthellate bivalves belonging to the genera Tridacna, Hippopus, Fragum, and Corculum as well as to the closely related azooxanthellate bivalves belonging to Vasticardium and Fulvia. The small-subunit ribosomal RNA genes (18S rDNAs) from these bivalves were amplified by polymerase chain reaction with universal eukaryotic primers and were then sequenced. The sequence data from each species were analyzed by the neighbor-joining, maximum parsimony, and maximum likelihood methods, and phylogenetic trees were constructed. The results were essentially consistent with the morphological taxonomy of these bivalves. Thus, the zooxanthellate clams branch into two lineages, one composed of the genera Fragum and Corculum in the family Cardiidae, and the other composed of the genera Tridacna and Hippopus in the family Tridacnidae. However, present results indicate that the azooxanthellate clams analyzed (Vasticardium flavum and Fulvia mutica) are more likely to form a clade with the species of Tridacna and Hippopus than with those of Fragum and Corculum. This topology suggests that either the symbiosis with zooxanthellae occurred independently in each of two lineages, Tridacna-Hippopus and Corculum-Fragum, or the symbiosis was established in clams ancestral to the lineages of both the zooxanthellate clams and the azooxanthellate clams Vasticardium and Fulvia, and the latter lost the symbiotic relationship after the symbiotic clam lineages had diverged.

Animals↗

[Probability of leaving cancer tissue unresected by limited operation in patients with peripheral, stage I non-small cell lung cancer].

To study the probability of leaving metastatic lymph nodes or intralobar metastasis unresected by limited surgery, we reviewed histopathologically 189 patients who had major pulmonary resection and complete lymph adenectomy for peripheral, p-T 1 or T 2 non-small cell lung cancer from 1975 to 1997 at our hospital. Lymph node involvements and or intralobar metastasis were found in 25 (26.0%) of 96 cases with tumor smaller than 3.0 cm and 44 (47.3%) of 93 cases with tumor larger than 3.0 cm. There was no difference between histological types of lung cancer. From this result, it was suggested that the risk of leaving cancer by limited operation would not be low. In conclusion, we believe that limited operation is not an alternative to the standard resection in patients with peripheral, stage I non-small cell lung cancer.

Aged↗

[A case of hepatic metastasis of rectal cancer with familial adenomatous polyposis treated by transarterial administration of low-dose leucovorin and 5-FU].

A 37-year-old man was diagnosed as having a rectal cancer with familial adenomatous polyposis, with the mutation of APC gene, and gastric polyposis, hypertrophy of the retinal pigment epithelium and a lipoma of the left arm. The patient underwent a total colectomy for the rectal cancer and a partial resection of the liver for metastasis (S3) which was detected on laparotomy, followed by cannulation in the hepatic artery. After the operation, 5-FU alone and low doses of CDDP and 5-FU were administered, but the level of serum CEA elevated and CT scanning showed multiple liver metastases. Then, low doses of leucovorin (30 mg/body bolus) and 5-FU (500 mg/body/h) were injected through an injection port every week. After 6 months, the level of serum CEA reduced and CT scanning showed minor response (about 30% on the decrease rate), without side effects, including diarrhea, stomatitis and bone marrow suppression.

Adenomatous Polyposis Coli↗

[Paclitaxel (taxol): a review of its antitumor activity and toxicity in clinical studies].

Paclitaxel (Taxol) is a new class of anti-tumor agents which act by promoting the assembly and inhibiting the disassembly of microtubules. Single-agent studies have shown its significant activity for advanced cancers in various organs including ovary, lung, breast, and head and neck. Combination therapies with other anticancer agents have been extensively investigated in these cancers. Paclitaxel combined with cisplatin is now considered to be the standard treatment for advanced ovarian cancer. In other cancers, promising results have been obtained in several studies of paclitaxel-based chemotherapy. Major toxicities of paclitaxel-monotherapy are hypersensitivity reaction, neutropenia, and peripheral neuropathy. Combination of other cytotoxic agents sometimes leads to severer toxicities such as neurotoxicity with cisplatin and cardiotoxicity with anthracycline. Although further evaluation is needed, paclitaxel will be a main agent in the treatment of advanced solid tumors.

Antineoplastic Agents, Phytogenic↗