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Biomedical subjects

T Mayumi

Publications and source records attributed to T Mayumi.

At least 145 records · Page 8Linked to original sources
PubMed1994

Chemical modification of natural human tumor necrosis factor-alpha with polyethylene glycol increases its anti-tumor potency.

Natural human tumor necrosis factor-alpha (TNF-alpha) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG-modified TNF-alpha depended on the reaction time as well as the initial molar ratio of PEG to TNF-alpha. The specific activity of modified TNF-alpha was gradually reduced with increase in the degree of PEG-modification, but the plasma half-life of TNF-alpha was increased by up to 40-fold. Modified TNF-alpha showed approximately 100 times greater anti-tumor potency than unmodified TNF-alpha. Covalent attachment of PEG to TNF-alpha thus increased the bioavailability of TNF-alpha, and may facilitate its potential therapeutic use.

Animals↗
PubMed1994

Intravenous administration of polyethylene glycol-modified tumor necrosis factor-alpha completely regressed solid tumor in Meth-A murine sarcoma model.

Complete regression of solid tumors was achieved by plural intravenous (i.v.) administrations of polyethylene glycol (PEG)-modified tumor necrosis factor-alpha (TNF-alpha), prepared by covalently modifying natural human TNF-alpha with N-succinimidyl succinate PEG. The anti-tumor efficacy of PEG-modified TNF-alpha (MPEG-TNF-alpha), in which 56% of the TNF-alpha-lysine residues were coupled with PEG, was compared with that of native TNF-alpha in the Meth-A murine fibrosarcoma model. MPEG-TNF-alpha and native TNF-alpha were given as i.v. injections twice a week for 2 weeks. The anti-tumor activity of MPEG-TNF-alpha was dose-dependent and was far superior to that of native TNF-alpha. Complete regression was observed in 3 of the 8 mice administered native TNF-alpha at the dose of 10,000 JRU (Japan reference unit), but 4 of the 5 remaining mice died during the therapeutic period. At 5,000 JRU of native TNF-alpha, no case of complete regression was observed. By contrast, complete regression was obtained in all 10 mice given 200 JRU of MPEG-TNF-alpha. No side-effects were observed at the dose of 500 JRU of MPEG-TNF-alpha, which was 2.5 times the minimal dose (200 JRU) of MPEG-TNF-alpha required for complete regression in all treated mice. MPEG-TNF-alpha appears to have potential as a candidate anti-tumor therapeutic agent.

Animals↗
PubMed1994

A comparison of drug transport through cultured monolayers of bovine brain capillary and bovine aortic endothelial cells.

To examine how efficient primary cultured brain capillary endothelial cells are as an in vitro blood-brain barrier (BBB) system with regard to drug transport, we compared bovine brain capillary endothelial cells (BBCEC) with bovine aortic endothelial cells (BAEC). Paracellular and transcellular transport were examined. [14C]Sucrose and fluorescein isothiocyanate-dextran (FITC-dextran)(average molecular weight about 4400 and 71200) were used as indices of paracellular transport. The permeability coefficients of [14C]sucrose and FITC-dextran through BBCEC monolayers were about 3 and 30-40 fold lower than those through BAEC monolayers, respectively. Transcellular transport was examined by means of [3H]leucine and [3H]alanine uptake studies. The Km value (Michaelis constant) of the amino acid uptake was lower in BBCEC than in BAEC. BBCEC had higher alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) activity than BAEC when cultured in vitro. These results suggest that BBCEC are suitable for drug transport studies across the BBB in vitro.

Alanine↗
PubMed1994

Amino acids and peptides. XXII. Preparation and antinociceptive effect of [D-Ala2]Leu-enkephalin-poly(ethylene glycol) hybrid.

The hybrid of poly(ethylene glycol) and [D-Ala2]Leu-enkephalin was prepared by the solution method and its antinociceptive effect and inhibitory effect on the electrically induced contractions of mouse vas deferens were examined. The hybrid was synthesized by the coupling of Boc-Tyr-D-Ala-Gly-Phe-Leu-OH and amino-poly(ethylene glycol), followed by trifluoroacetic acid treatment. The hybrid showed more potent antinociceptive activity in mice and 120 times higher inhibitory activity in mouse vas deferens preparation than intact [D-Ala2]Leu-enkephalin.

Amino Acid Sequence↗
PubMed1994

Amino acids and peptides. XX. Preparation of beta-cyclododecyl aspartate and its application to synthesis of fibronectin- and laminin-related peptides.

beta-Cyclododecyl aspartate was prepared and its application to peptide synthesis was examined. Derivatives of beta-cyclododecyl aspartate are more likely to crystallize and should be useful for peptide synthesis. The cyclododecyl ester was much stable to bases than the benzyl ester and rather more stable than the cyclohexyl ester. It was removable by HF treatment and trifluoromethanesulfonic acid treatment. beta-Cyclododecyl aspartate was used for synthesis of laminin- and fibronectin-related peptides by solid phase and liquid phase methods.

Amino Acid Sequence↗
PubMed1994

Amino acids and peptides. XXI. Laminin-related peptide analogs including poly(ethylene glycol) hybrids and their inhibitory effect on experimental metastasis.

Laminin-related peptides, Tyr-Ile-Gly-Ser-Arg analogs, were prepared and their inhibitory effects on experimental metastasis were examined. Of the amino acids in the Tyr-Ile-Gly-Ser-Arg sequence, L-Arg was very important and Ile was not essential for the inhibitory effect. To obtain a potent inhibitor of metastasis, hybrids of Tyr-Ile-Gly-Ser-Arg-Gly and 2 types of poly(ethylene glycol) were prepared. The inhibitory effects of the hybrids were more potent than that of Tyr-Ile-Gly-Ser-Arg-Gly.

Amino Acid Sequence↗
PubMed1994

Acetic acid intoxication by rectal administration.

The enhanced toxicity of acid instilled directly into the rectum, without benefit of dilution and neutralization in the upper intestine, is evident in a case of acetic acid intoxication by accidental rectal administration of 50 mL of 9% acetic acid to a 5-year-old boy. The complications included necrosis of the colon, acute renal failure, acute liver dysfunction, disseminated intravascular coagulopathy (DIC) and sepsis.

Acetates↗
PubMed1994

[Hyperbaric oxygen therapy in the Hokkaido University Hospital].

We surveyed the hyperbaric oxygen therapy during the past seven years in the Hokkaido University Hospital. The mean number of patients was 27 per year. The average number of the therapy was 328 per year. There were neither complications nor accidents attributable to the hyperbaric oxygen therapy. Three representative diseased states hypoxic brain damage, sudden deafness and occlusion of retinal arteries, showed remarkable recovery by this therapeutic modality. A safety standard has been revised in 1991. We have been operating the hyperbaric oxygen therapy according to the revised standard. The inter-departmental approach in this therapeutic modality is mandatory in order to achieve effective outcome.

Female↗
PubMed1993

Effect of T cells on the complement production by monocytes.

We studied the role of T cells in the regulation of C3 or C4 production by monocytes. While cocultured T cells reduced C3 production, they enhanced C4 production by monocytes in a number-dependent manner. Interleukin-2 enhanced these effects of T cells on C3 and C4 production, indicating that activated T cells had greater effects on complement production by monocytes. CD4+ T cells had greater effects than those of CD8+ T cells on the C3 or C4 production by monocytes, indicating that CD4+ T cells were mainly involved in the regulation of C3 and C4 production by monocytes. T-cell-conditioned medium (T-CM) also decreased C3 and enhanced C4 production, but the effect of T-CM on C3 and C4 production was less remarkable than that of T cells. T cells separated by transwell inserts from monocytes had similar effects as those of T-CM on complement production. Anti-IFN-gamma antibody completely blocked the suppressing effect on C3 production and partially blocked the stimulating effect of T cells on C4 production. These results indicate that T cells regulate C3 or C4 production by monocytes via IFN-gamma as a humoral factor. Moreover, the stimulating effect of T cells on C4 production was partially blocked when monocytes and T cells were incubated with anti-CD2, anti-LFA-1, and anti-HLA-DR antibodies, and anti-CD2 partially blocked the suppressing effect of T cells on C3 production by monocytes. These results indicate that T cells modulate the C3 and C4 production by monocytes not only via a humoral factor but also via a direct interaction with monocytes.

Cell Communication↗
PubMed1993

Does a lidocaine patch reduce the pain at venous cannulation in adults?

In this study we evaluated whether a lidocaine patch reduces the pain relating to a venous cannulation in adults. The patch is consisted of the base containing 50% lidocaine on a thin polyester membrane. Its surface area is 15 cm2. Twenty-six adult patients scheduled for elective surgery (11 males and 15 females) were randomly divided into two groups according to application periods: Group A for 15 min and Group B for 30 min. Either the dorsal part of the hand or the radial side of the wrist was chosen and covered with the patch. Pain assessment was made by patients using a 0-100 point visual analog scale (VAS). In 7 patients of Group A, plasma lidocaine levels were measured 15 min after application by homogeneous enzyme immunoassay. The levels were further measured 30 and 60 min after application in 3 of those patients. The mean VAS score was 28.4 +/- 13.1 (mean +/- SD) for Group A and 51.8 +/- 15.9 for Group B, and the difference was statistically significant (P < 0.05). Plasma lidocaine levels were always below 0.2 microg.ml(-1). The results indicate that the skin was partially anesthetized by the lidocaine patch. A lidocaine patch may be useful and safely applicable for venous cannulation in adult patients.

Clinical Trial↗
PubMed1993

Does preoperative oral clonidine inhibit salivary secretion during general anesthesia?

Clonidine is known to inhibit salivary secretions and cause dryness of the mouth. We evaluated the effect of preoperative oral clonidine on salivary secretions before and during general anesthesia. Twenty-eight adult patients, equally divided into four groups, received the following premedication 2 hr prior to induction of anesthesia. Group 1 patients received oral ranitidine 5 mg.kg(-1) alone. Groups 2 and 3 patients received oral clonidine 1 microg.kg(-1) and 3 microg.kg(-1) respectively with oral ranitidine 5 mg.kg(-1). Group 4 patients received no premedication and served as control. The volume of salivary secretions was determined by calculating the change in weight of four cotton wool cylinders placed in the oral space 10 min before and 30, 60 and 120 min after induction of anesthesia. Salivary volume was significantly less in the clonidine treatment groups before induction of anesthesia. After induction of anesthesia, there were no significant differences in salivary secretions among the four groups. No severe hypotension or bradycardia was seen in any patient of four groups. Preoperative oral ranitidine 5 mg.kg(-1) had no effect on salivary secretion. In conclusion, clonidine did not decrease salivary secretions further over the already decreased level during general anesthesia.

Journal Article↗
PubMed1993

End-tidal CO2 changes under constant cardiac output during cardiopulmonary resuscitation.

OBJECTIVES: To evaluate a) whether end-tidal CO2 values change under constant cardiac output during cardiopulmonary resuscitation (CPR), and b) what factors are responsible for the change. DESIGN: A cohort study. SETTING: University research laboratory. SUBJECTS: Nine mongrel dogs. INTERVENTIONS: Ventricular fibrillation was electrically induced. After 2 mins, open-chest cardiac massage was initiated to maintain cardiac output at 0.2 L/min (23% of baseline cardiac output) by the measurement of blood flow with an electromagnetic flow probe on the ascending aorta. The cardiac massage was kept constant until 50 mins after the induction of ventricular fibrillation. MEASUREMENTS AND MAIN RESULTS: Before and during ventricular fibrillation, end-tidal CO2, minute volume of alveolar ventilation, and CO2 excretion were continuously monitored. Blood gases and oxygen saturation values were also measured in arterial and the mixed venous blood samples. CO2 content was calculated. After induction of ventricular fibrillation, end-tidal CO2 decreased and thereafter continued to increase until the end of the experiment. Two mechanisms may have contributed to the early reduction in end-tidal CO2. One mechanism is a further decrease in CO2 excretion compared with the reduction in alveolar ventilation and the other is an increase in alveolar deadspace (estimated from the increase in the difference between PaCO2 and end-tidal CO2). The subsequent increase in end-tidal CO2 was mainly due to a change in CO2 excretion. There are two hypotheses concerning the subsequent increase in CO2 excretion: the increase in pulmonary capillary blood flow (estimated from the change in the arteriovenous CO2 content gradient) and the increase in CO2 production itself. CONCLUSIONS: End-tidal CO2 changes under constant cardiac output during CPR. When end-tidal CO2 is used to estimate the effectiveness of the cardiac massage, this type of change must be recognized.

Animals↗
PubMed1993

Effect of a monoclonal anti-sperm antibody (A-1) on in vitro fertilization in the mouse.

We prepared four monoclonal antibodies raised against mouse spermatozoa. The ability of the hybridoma culture supernatants to inhibit in vitro mouse fertilization was determined. One of these monoclonal antibodies, termed A-1, strongly inhibits sperm penetration into zona pellucida of egg in a concentration-dependent fashion. On the other hand, even in the presence of the same concentration of A-1 antibody, sperm binding to comulus-free eggs was slightly inhibited and sperm-egg fusion was not inhibited at all. Immuno-fluorescence studies with A-1 showed that it recognizes an antigen(s) localized in the acrosome of mouse spermatozoa. In the case of unfixed sperm, the acrosome-intact sperm (i.e., sperm bound to egg zona pellucida) and unbound sperm were slightly immunostained with A-1 antibody (1.6% and 9.0%, respectively). All the full acrosome reacted sperm (i.e., sperm penetrating into the perivitelline space) were not immunoreacted. On the other hand, when sperm were fixed with methanol, approximately 80% of unbound sperm were immunoreacted with this antibody. Furthermore, almost all of zona-binding sperm were immunostained, whereas acrosome reacted, penetrating sperm were not. These data suggested that the antigen recognized by A-1 was located inside the plasma membrane of spermatozoa, and appeared on the surface of the spermatozoa during the period of penetration into egg zona pellucida. After sperm penetration into the perivitelline space this antigen must be released from the sperm.

Animals↗
PubMed1993

Effect of bredinin on early embryonic development in mice.

Bredinin, an immunosuppressive agent, had a teratogenic effect and a decreasing effect in litter size in mice and in rats. We investigated the direct effect of bredinin on the development of mouse preimplantation embryos in vitro. Bredinin strongly inhibited the first differentiation step from the morula to the blastocyst stage, whereas the steps from the two-cell embryo to the morula stage were not inhibited. At 10(-6) or 10(-5) M of bredinin, only one or none of the morula embryos developed to a blastocyst after a 48 h culture; while approximately 90% of the embryos developed to blastocysts in the absence of bredinin. To determine whether the bredinin inhibition was reversible, the morula embryos were cultured with 10(-5) M of bredinin for 48 h. The embryos were transferred to bredinin-free culture conditions, and their development was observed. The inhibitory effect of bredinin was reversible. The expansion of zona-free blastocyst was also inhibited by bredinin. When blastocyst embryos were cultured in the presence of bredinin (10(-6) M), the mean size of the embryos was reduced to half the initial size. In addition, the steps of hatching from the zona pellucida and attaching to the substratum were significantly inhibited by bredinin. Trophoblast outgrowth was completely inhibited by 10(-6) M bredinin; however, the area of trophoblast outgrowth was expanded to 18-fold the initial size after a 96 h culture in the absence of bredinin. Thus, the decrease in the number of offspring is due to the direct effect of bredinin on mice embryos.

Animals↗
PubMed1993

Amino acids and peptides. XIX. Preparation of enkephalin-poly(ethylene glycol) hybrid and evaluation of its analgesic activity.

The poly(ethylene glycol) hybrid of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) was prepared and its analgesic activity was examined. Poly(ethylene glycol) #4000 was converted to amino-poly(ethylene glycol) and coupled with the N alpha-protected pentapeptide, followed by trifluoroacetic acid treatment to give the hybrid. The hybrid was soluble in water or various organic solvents. The analgesic activity of Leu-enkephalin was markedly potentiated by hybrid formation with poly(ethylene glycol).

Amino Acid Sequence↗
PubMed1993

[Alcoholic liver injury accompanied with various metabolic and endocrinological disorders--a case report].

We report a young female case of alcoholic liver injury accompanied with various metabolic and endocrinological disorders. A 29 year-old woman was admitted because of general fatigue and hyperlipidemia. She was a heavy drinker. Laboratory data on admission revealed liver dysfunction and hyperlipidemia (type II b) with a quite high serum gamma-glutamyltranspeptidase (gamma GTP) level. The microscopic finding of the liver biopsy specimen showed fatty metamorphosis and ballooning of hepatocytes, and she was diagnosed as heavy alcoholic liver injury. The endocrinological examination revealed the elevated plasma cortisol level, though the urinary 17-hydroxycorticoids (17-OHCS) and 17-ketosteroids (17-KS) excretion and the plasma adrenocorticotropic hormone (ACTH) level were reduced. Cortisol secretion showed the normal circadian rhythm and the normal response to ACTH provocation. The levels of plasma triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also reduced. These endocrinological and metabolic disorders were normalized in company with recovery of the liver function by temperance, diet therapy and nutritional education. Thus, these abnormalities were considered to be resulted from the alcoholic liver injury and the effect of the ethanol to the hypothalamic-pituitary system.

Adult↗