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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 235 records · Page 13Linked to original sources

Immunomodulatory constituents from an ascomycete, Microascus tardifaciens.

Fractionation guided by the immunosuppressive activity of the defatted AcOEt extract of an Ascomycete, Microascus tardifaciens, afforded eight constituents, questin (emodin 8-O-methylether) (1), rubrocristin (2), 5,7-dihydroxy-4-methylphthalide (3), cladosporin (asperentin) (4), cladosporin 8-O-methylether (5), tradioxopiperazine A [cyclo-L-alanyl-5-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (6), tradioxopiperazine B [cyclo-L-alanyl-7-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (7), and asperflavin (8), among which 6 and 7 were new compounds. Compounds 1 and 2 showed considerably high immunosuppressive activity, 6 was moderate and, 3, 4, 5, 7 and 8 showed low activity.

Anthracenes↗

Monoamine oxidase inhibitory naphthoquinone and/or naphthalene dimers from Lemuni Hitam (Diospyros sp.), a Malaysian herbal medicine.

From the extract of a Malaysian herbal medicine, Lemuni Hitam (Diospyros sp.), which exhibited monoamine oxidase (MAO) inhibition, three new naphthoquinone and/or naphthalene dimers (lemuninols A-C, 1-3) were isolated together with 4,6-dihydroxy-5-methoxy-2-methyl-naphthalene (8) and six known monomers (4-7, 9 and 10). The structures were determined by spectroscopic methods including 2D-NMR techniques. Among them, lemuninol A showed 45% inhibition of MAO (mouse liver) at 5.0 x 10(-6) g/ml, and lemuninols B and C and a naphthoquinone (9) indicated weak activity. Some related quinones were also tested for their MAO inhibitory activities.

Animals↗

Immunomodulatory constituents from three ascomycetes, Gelasinospora heterospora, G. multiforis, and G. longispora.

Three new 2-pyrones (2H-pyran-2-ones) called multiforisins G (3), H (1), and I (4), and a known hexaketide sordarial (2) have been isolated from an Ascomycete Gelasinospora heterospora. Among them, 1, 2, and 3 have been proved to be the immunosuppressive components of the fungus. Compounds 1, 3, and 4 have also been isolated from G. multiforis together with multiforisin A (5), which was formerly isolated from this fungus as its main immunosuppressive feature, and 1-5 have also been isolated from G. longispora. The absolute stereostructure of 2, which was not previously certain, has finally been determined to be (3'R,4'S). It has been found that the multiforisins 1, 3, and 5 in which one of the two substituents at positions 3 and 5 is a hydroxymethyl group and the other is a formyl or an acetoxymethyl group, show high immunosuppressive activity; the immunosuppressive activity of 3 does not seem to be due to inhibition of interleukin 2 (IL-2) production.

Adjuvants, Immunologic↗

Induction of GM-CSF production of macrophages by advanced glycation end products of the Maillard reaction.

We previously reported that AGEs can induce macrophage growth. In this paper, we examined whether advanced glycation end products (AGE) of protein induced GM-CSF production of macrophages. AGE of bovine serum albumin markedly stimulated not only the expression of GM-CSF mRNA, but also GM-CSF secretion in macrophage supernatant. Thus GM-CSF is suggested to be an endogenous signal for macrophage growth induction by AGEs.

Animals↗

Spatial and temporal distribution of CD44 and osteopontin in fracture callus.

The multifunctional adhesion molecule CD44 is a major cell-surface receptor for hyaluronic acid (HUA). Recent data suggest that it may also bind the ubiquitous bone-matrix protein, osteopontin (OPN). Because OPN has been shown to be a potentially important protein in bone remodelling, we investigated the hypothesis that OPN interactions with the CD44 receptor on bone cells participate in the regulation of the healing of fractures. We examined the spatial and temporal patterns of expression of OPN and CD44 in healing fractures of rat femora by in situ hybridisation and immunohistochemistry. We also localised HUA in the fracture callus using biotinylated HUA-binding protein. OPN was expressed in remodelling areas of the hard callus and was found in osteocytes, osteoclasts and osteoprogenitor cells, but not in cuboidal osteoblasts which were otherwise shown to express osteocalcin. The OPN signal in osteocytes was not uniformly distributed, but was restricted to specific regions near sites where OPN mRNA-positive osteoclasts were attached to bone surfaces. In the remodelling callus, intense immunostaining for CD44 was detected in osteocyte lacunae, along canaliculi, and on the basolateral plasma membrane of osteoclasts, but not in the cuboidal osteoblasts. HUA staining was detected in fibrous tissues but little was observed in areas of hard callus where bone remodelling was progressing. Our findings suggest that OPN, rather than HUA, is the major ligand for CD44 on bone cells in the remodelling phase of healing of fractures. They also raise the possibility that such interactions may be involved in the communication of osteocytes with each other and with osteoclasts on bone surfaces. The interactions between CD44 and OPN may have important clinical implications in the repair of skeletal tissues.

Animals↗

Electrochemotherapy against colorectal carcinoma: comparison of in vitro cytotoxicity of 5-fluorouracil, cisplatin and bleomycin.

Effectiveness of electrochemotherapy against colorectal carcinoma (CRC) was investigated in vitro using murine CRC cell lines. Electropermeabilization did not increase the sensitivity of CRC cells to 5-fluorouracil or cisplatin. Conversely, electropermeabilization markedly increased the sensitivity of CRC cells to bleomycin (BLM), resulting in 1,000-fold higher susceptibility. Subsequent analyses revealed that electropermeabilization significantly increased intracellular BLM levels of CRC cells. These results suggest that electrochemotherapy with BLM is a promising modality for the treatment of CRC, and that electrochemotherapy can be translated from the treatment of superficial tumors to the treatment of internal tumors including CRC.

Adenocarcinoma↗

Simultaneous detection of multiple STR loci on sex chromosomes for forensic testing of sex and identity.

The forensic usefulness of X and Y chromosomal STR loci has recently been demonstrated. One quadruplex-PCR, using 2 X- and 2 Y-STRs (STRX1/HPRTB and DYS390/ DYS393), and 2 duplex-PCRs, each using an X- and a Y-STR (ARA/DYS390 and ARA/DYS393), and detection of PCR products by using an automated DNA sequencer are reported herein. This approach allows us to determine not only the sex of the donor of a sample, but also the X- and/or Y-STR genotypes of the sample. A male biological specimen yields 4 amplified products in quadruplex-PCR and 2 amplified fragments in duplex-PCRs, whereas a female biological specimen yields only 2 amplified fragments of X-STR in quadruplex-PCR and one fragment, also of X-STR, in duplex-PCRs. Our study thus provides useful information for many activities in forensic practice, such as identity testing, paternity testing, especially of deficiency cases, compilation of population data, and sex determination of a biological sample from a single PCR.

Alleles↗

Effects of thromboxane synthetase inhibitor (RS-5186) on experimentally-induced cerebral vasospasm.

RS-5186, which inhibits thromboxane A2 (TXA2) synthetase activity, ameliorated delayed cerebral vasospasm in a canine two-hemorrhage model. Subarachnoid hemorrhage was induced in 15 dogs, which were divided into two groups. In the RS-5186-treated group (9 dogs), 50 mg kg-1 of RS-5186 was administered twice a day for seven days. The remaining six dogs without administration of RS-5186 were used as a control group. In the RS-5186-treated group, the angiographic diameter of the basilar artery on Day 7 after subarachnoid hemorrhage was constricted to 60.9% +/- 11.6% (n = 9, mean +/- SD) of that on Day 0, before subarachnoid hemorrhage. The corresponding value was 42.8% +/- 6.1% (n = 6) in the control group. There was a statistically significant difference between these percentages. In the RS-5186-treated group, plasma thromboxane B2 level on Day 7 was 144.3 +/- 28.1 pg ml-1 (n = 4), which was lower than the 815.5 +/- 162.0 pg ml-1 (n = 4) in the control group (p < 0.0005). The plasma 6-keto-prostaglandin F1 alpha level on Day 7 was 180.5 +/- 66.5 pg ml-1 (n = 4) in the RS-5186-treated group, and higher than 107.3 +/- 12.4 pg ml-1 (n = 4) in the control group (p = 0.0734). Thus, administration of RS-5186 reduced TXA2 plasma level and had a beneficial effect on angiographically-detected delayed vasospasm.

Animals↗

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents: special references to bacteria isolated between July 1996 and June 1997].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 20 facilities in Japan since July 1982. This paper describes the results obtained during period from July 1996 to June 1997. The number of cases investigated as objectives was 217 for one year. A total of 406 strains were isolated from 177 cases (81.6% of total cases). From primary infections 162 strains were isolated, and from postoperative infections 244 strains were isolated, respectively. From primary infections, anaerobic bacteria were predominant, while from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was the highest. In postoperative infections, the majority of them were Enterococcus faecalis, while in primary infections, many of them were Enterococcus avium. The isolation rate of Staphylococcus spp., especially from postoperative infections, followed that of Enterococcus spp. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli and Enterobacter cloacae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. The isolation rate of aerobic Gram-negative bacillus has decreased with time, while those of anaerobes like B. fragilis group and of aerobic Gram-positive bacteria have gradually increased in both types of infections. We found vancomycin-resistant strains of neither Staphylacoccus aureus nor Enterococcus spp.; however, the MIC of arbekacin for one of strains of S. aureus was 100 micrograms/ml. Both the MIC90's of meropenem and imipenem/cilastatin against P. aeruginosa isolated in this term were 25 micrograms/ml, which were higher than those against the strains isolated in the previous years. Compared with the isolated strains in the year 1995, progress of resistance against carbapenem antibiotics was confirmed.

Anti-Bacterial Agents↗

[Recent advances in the management of severely burned patients].

With recent advances in the systemic care of burns, patients with burns covering 80% of their body surface can frequently survive. The percentage of total body surface area burn for an expected 50% mortality rate has improved to 98% for children and 72% for adults in one burn center in the USA. From the results of 11 burn units in Tokyo, the mortality rate of burn patients with a prognostic burn index of 90-100 was 51.4%. The improvement is attributable to advances in the understanding of the pathophysiology of severe burns as a systemic inflammatory response syndrome. Improved cardiopulmonary management of extensive burns and respiratory tract burns has also played a part in reducing the mortality rate. Individualized fluid resuscitation programs based on hemodynamic monitoring have reduced the incidence of burn shock and acute renal failure. Early eschar excision and wound closure by immediate grafting have further reduced the mortality rate from extensive full-thickness burns. The use of bilayer artificial skin has improved the survival and cosmetic results of early eschar excision in patients with massive full-thickness burns. Cultured autologous epidermal sheets hold promise if used on an appropriate dermal bed.

Adolescent↗

Effect of dexamethasone on the intestinal first-pass metabolism of indinavir in rats: evidence of cytochrome P-450 3A [correction of P-450 A] and p-glycoprotein induction .

Indinavir, a potent and specific inhibitor of HIV protease, is a known substrate of cytochrome P-450 (CYP) 3A and p-glycoprotein. The purpose of this study is to investigate and compare the inducing effect of dexamethasone (DEX) on CYP3A and p-glycoprotein in the hepatic and intestinal first-pass metabolism of indinavir in rats. Pretreatment of rats with DEX had little effect on the pharmacokinetics (Cl and T(1/2)) after i.v. administration of indinavir, whereas DEX markedly altered the peak concentration (C(max)) and bioavailability of indinavir after oral dosing. The C(max) decreased from 2.8 microM in control rats to 0.28 microM in DEX-treated rats, and bioavailability decreased from 28 to 12.4%. The decreased bioavailability after DEX pretreatment was due mainly to an increase in first-pass metabolism. Intestinal first-pass metabolism (E(G)) increased from 6% in control rats to 34% in DEX-treated rats, and hepatic first-pass metabolism (E(H)) increased from 65 to 82%. Analysis of in vitro kinetic data revealed that the increased intestinal and hepatic metabolism by DEX was attributed to an increase in the V(max), as a result of CYP3A induction, without a significant change in the K(m) values. DEX pretreatment also induced p-glycoprotein in the intestine and liver of rats. p-Glycoprotein appeared to increase the intestinal metabolism of indinavir whereas it had little effect on the hepatic metabolism of indinavir. Although it has been suggested that the role of intestinal metabolism for some drugs is quantitatively greater than that of hepatic metabolism in the overall first-pass metabolism, the contribution of intestinal metabolism to the overall first-pass metabolism of indinavir in rats is not quantitatively as important as the hepatic metabolism, regardless of DEX induction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Efficacy of intra-arterial chemotherapy on life prolongation in patients with hepatic metastasis from colorectal cancer].

The efficacy of intra-arterial chemotherapy for life prolongation was investigated in patients with hepatic metastasis from colorectal cancer who visited our hospital from Jan. 1989-Mar. 1999, but without any other remote metastasis when the presence of their hepatic metastasis was detected. The subjects were assigned to 4 groups; group A (n = 8) was only treated by hepatectomy, group B (n = 27) by intra-arterial chemotherapy combined with hepatectomy, group C (n = 42) with intra-arterial chemotherapy alone, and group D (n = 23) by systemic chemotherapy through intra-venous or oral administration. The survival rates of these groups were determined, and the recurrence risk after hepatectomy was compared between group A and B. Further, the survival rate of the patients treated by intra-arterial chemotherapy was compared between the cases of PD and not-PD (including CR, PR, and NC). The median survival in cases of H1 and H2 was 405 days for group A, 1,018 days for group B and 245 days for group C, showing that group B had a significantly more favorable prognosis than either group A or group C. There were also significant differences in the median survival of H3 cases between group C (422 days) and group D (113 days). One-year cumulative recurrence risks in the residual livers of group A and group B were 79% and 28%, respectively. Thus, significant differences in the recurrence risk were found in the two groups. Meanwhile, the median survival of PD and non-PD cases was 240 and 588 days, respectively. These results suggested that local control by intra-arterial chemotherapy is useful for life prolongation.

Antineoplastic Combined Chemotherapy Protocols↗

[Aseptic meningitis induced by high-dose gamma-globulin in an adult woman with antiphospholipid syndrome and chronic idiopathic thrombocytopenic purpura].

It is well known that the administration of high-dose gamma-globulin concentrate is effective in alleviating thrombocytopenia in patients with idiopathic thrombocytopenic purpura (ITP). However, treatment can sometimes induce aseptic meningitis. A 25-year-old Japanese woman with antiphospholipid syndrome and ITP was conditioned with high-dose gamma-globulin concentrate prior to splenectomy. Three days after the initial gamma-globulin course, she experienced severe headache, vomiting, and high-grade fever. Cerebrospinal fluid examination yielded a diagnosis of aseptic meningitis. The patient's clinical symptoms and abnormal cerebrospinal fluid findings disappeared immediately after the discontinuation of gamma-globulin therapy. Cases of aseptic meningitis induced by high-dose gamma-globulin therapy are uncommon in the literature, and most involve children. Moreover, to our knowledge, only 1 Japanese adult ITP case of gamma-globulin-induced aseptic meningitis has been reported to date. Aseptic meningitis may be one of the important adverse effects of the administration of high-dose gamma-globulin concentrate to pediatric as well as adult ITP patients.

Adult↗

[A case of relapsing polychondritis with oculobulbar symptoms and successful treatment of respiratory failure with BiPAP].

A 66-year-old man developed diplopia, ptosis, dysphagia, and acute respiratory failure. The initial diagnosis was myasthenia gravis and prednisolone had been administrated for three years. Because of recurrent upper respiratory infections, prednisolone was tapered off. Two months later, auricular chondritis, arthritis, and conjunctivitis appeared. He was diagnosed as having relapsing polychondritis on the basis of histological findings of the ear lobe biopsy. Reinstituted prednisolone had the effect on the auricular chondritis, arthritis, and conjunctivitis, but no effect on dysphagia, hoarseness, and respiratory failure caused by the deformity of the pharynx and airway. Tracheal collapse usually causes rapid death, so early tracheostomy and the use of endotracheal prostheses have been recommended in patients with airway obstruction from relapsing polychondritis, but such surgical management can only partially open up the large airways and has no effect on smaller airways. In this case tracheostomy and endoluminal stent placement have helped improve the patient's respiratory failure, but have had little effect on its aggravation at night in the supine position. The use of BiPAP after surgical management can be an effective treatment for airway involvement in relapsing polychondritis probably because it keeps the narrowed airways from collapsing, especially at night.

Acute Disease↗

Antitumor effect of electrochemotherapy on colorectal carcinoma in an orthotopic mouse model.

Electropermeabilization was shown to markedly increase the sensitivity of murine colorectal carcinoma (CRC) cells to bleomycin (BLM), resulting in more than 2,500-fold higher susceptibility to BLM. Subsequent in vivo electrochemotherapy with BLM revealed profound antitumor effects on subcutaneous CRC tumors. Furthermore, when electrochemotherapy with BLM was employed for the treatment of orthotopic CRC tumors in mice, significantly prolonged survival priods were observed. These results indicate the feasibility of electrochemotherapy with BLM for the treatment of CRC and demonstrate that electrochemotherapy can be translated from the treatment of cutaneous and subcutaneous tumors to the treatment of internal cancers including CRC.

Animals↗