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Biomedical subjects

M Matsuo

Publications and source records attributed to M Matsuo.

At least 325 records · Page 18Linked to original sources
PubMed1994

Synthesis and structure-activity relationships of antiallergic N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamides possessing both antihistaminic and anti slow-reacting substance (SRS) activities.

A series of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanamide derivatives were synthesized and tested for in vivo antianaphylactic activity and in vitro anti slow-reacting substance (SRS) activity. Among the compounds synthesized, N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2- thiazolyl]propanamide (7) was the best balanced compound (antianaphylactic activity, ED50 = 0.92 mg/kg p.o.; anti-SRS activity, IC50 = 0.89 microgram/ml). Regarding the biological activities of 7, we ascribe the antianaphylactic activity to its potent antihistaminic activity and the anti SRS activity to the inhibition of 5-lipoxygenase.

Amides↗
PubMed1994

[Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta). (1) Acute oral toxicity to rats].

Acute oral toxicity (LD50-value) of organic chemicals to rats was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. Certain parabolic correlations were established between logarithm of LD50-value (mmol/kg body weight, rats) and delta c of all the collected chemicals (n = 144, R = 0.578), alcohols (n = 29, R = 0.587), ketones (n = 7, R = 0.962), aldehydes (n = 9, R = 0.621), ethers (n = 5, R = 0.890), acetates (n = 7, R = 0.670) and aromatics (n = 84, R = 0.736). Introducing molar volume (Vc) to the above equations could not improve the correlation. In the study, we assumed that as for acute toxicity, chemicals taken into the mammals through biological membrane first disturb the homeostasis, which causes certain biological reactions (i.e. death) and that amounts of the chemicals intaken are regulated by their solubility in the membrane. Based on the assumption, we drew a theoretical equation, which describes LD50 by a parabolic function of delta c. A regression analysis using the equation gave significant correlations as stated above, which incarnates the assumption. A solubility parameter of 2.30 x 10(4) (J/m3)1/2 was also determined for the biological membrane (absorption site) of rats. For comparison, log P was used to describe LD50 of all the chemicals, but no correlation was established (R = 0.164-0.443).

Acetates↗
PubMed1994

[Analysis of acute toxicity (LD50-value) or organic chemicals to mammals by solubility parameter (delta) (2). Acute oral toxicity to mice].

Acute oral toxicity (LD50-value) of organic chemicals to mice was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. As it was observed in the previous study with rats, parabolic correlations were established between logarithm of LD50-value (mmol/kg body weight, mice) and delta c of all the collected chemicals (n = 85, R = 0.626), alcohols (n = 10, R = 0.683), ketones (n = 7, R = 0.631) and aromatics (n = 62, R = 0.645). Introducing molar volume (Vc) to the above equations did not improve the correlations. Although statistically significant correlations were not found in alcohols and ketones with mice, we successfully assured the theoretical equation regardless of species difference by establishing significant correlations with all the collected chemicals and aromatics. By analysis, we could determine the solubility parameter of 2.27 x 10(4) (J/m3)1/2 for the biological membrane (absorption site) of mice. As the delta c-values which dip the LD50-values are approximately the same for mice and rats, common deleterious effects and mechanism may be working at common target sites. In addition, no species difference in sensitivity (toxicity) was found for the aromatics. For comparison, log P was used to describe LD50 of all the collected chemicals, but no correlation was established (R = 0.004-0.418).

Acetates↗
PubMed1994

[Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta) (3). Acute dermal toxicity to rabbits].

Acute dermal toxicity (LD50-value) of organic chemicals to rabbits was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. As it was observed in the previous studies with rats and mice, parabolic correlations were also established between logarithm of LD50-value (mmol/kg body weight, rabbits) and delta c of all the collected chemicals (n = 56, R = 0.498), alcohols (n = 19, R = 0.857), ketones (n = 7, R = 0.711), aldehydes (n = 7, R = 0.633) and aromatics (n = 20, R = 0.613). Introduction of molar volume (Vc) to the above equations did not improve the correlations. In the study, we assumed that chemicals absorbed dermally by the mammals similarly disturb the homeostasis, as in acute oral toxicities of organic chemicals to rats and mice. We successfully confirmed the theoretical equation regardless of species and routes of administration by establishing statistically significant correlations with all the collected chemicals, alcohols and aromatics. By analysis, we could determine the solubility parameter of 2.24 x 10(4) (J/m3)1/2 for the biological membrane (absorption site) of rabbits. As the dermal delta c-values which dip the LD50-values for rabbits are approximately the same as in acute oral toxicities with rats and mice, common deleterious effects and mechanism may be working at the common target sites. The regression curves of LD50-values of rabbits, however, are slightly higher than those of rats and mice, which may reflect the difference in amounts of the chemicals absorbed by the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1994

Pharmacological profile of FK480, a novel cholecystokinin type-A receptor antagonist: comparison to loxiglumide.

The pharmacological profile of FK480[(S)-(+)-N-<1-(2)-fluorophenyl)-3,4,6,7-tetra hydro-4-oxo-pyrrolo(3,2,1-jk) (1,4)benzodiaze-pine-3-yl>-1H-indole-2- carboxamide], a novel cholecystokinin type-A (CCK-A) receptor antagonist, was compared with that of the CCK-A receptor antagonist, loxiglumide. Both FK480 and loxiglumide inhibited 125I-labeled CCK-8 (125I-CCK-8) binding to rat pancreatic and guinea-pig gallbladder membranes with IC50 values of 0.40 +/- 0.04 and 0.06 +/- 0.02 nM for FK480 and 330 +/- 66 and 66 +/- 10 nM for loxiglumide, respectively. These two agents also inhibited 125I-CCK-8 binding to guinea-pig brain (cerebral cortex) receptors with respective IC50 values of 72 +/- 11 nM and > 10 microM, indicating less affinity to central receptors. Intravenous administration of FK480 (ED50 = 18 micrograms/kg) was 2800 times more potent than that of loxiglumide (ED50 = 50 mg/kg) in inhibiting CCK-8-induced pancreatic amylase secretion in rats. Furthermore, FK480 had ED50 values of 10 and 8.4 micrograms/kg, respectively, in antagonizing CCK-8-induced inhibition of charcoal meal gastric emptying in mice when administered orally 1 or 5 hr before the CCK-8. Loxiglumide (ED50 = 23.5 mg/kg, when administered orally 1 hr before the CCK-8) also antagonized it, but its activity was 2400 times less than that of FK480. We conclude that FK480 is a potent, orally effective CCK-A receptor antagonist with long duration of action.

Amylases↗
PubMed1994

Amplification of selected exons by polymerase chain reaction enables determination of the translational reading frame of dystrophin mRNA resulting from deletion mutations.

Duchenne and Becker muscular dystrophies (DMD and BMD) are severe and mild phenotypes, respectively, of the mutated dystrophin gene. Based on the frameshift theory, an out-of-frame deletion causes DMD, while an in-frame deletion causes BMD. Amplification of deletion-prone exons by polymerase chain reaction (PCR) has been used for the screening of deletion mutations of the dystrophin gene. However, it is difficult to determine the resulting translational reading frame in deleted cases by amplification of the deletion-prone exons. To determine the resulting translational reading frame, we employed a method which selectively amplifies exons affecting the following translational reading frame. Using this method, thirty-three DMD/BMD patients with a deletion mutation in the central region of the dystrophin gene were examined. Twenty-seven of 29 DMD patients had out-of-frame deletions, while only two had in-frame deletions. All four BMD patients had in-frame deletions. Therefore, 93.9% patients fitted the frameshift theory. This method is very useful for clinical diagnosis because of its precision and convenience.

Base Sequence↗
PubMed1994

[Evaluation of changes in IL-6 in gynecological infections].

We administered imipenem/cilastatin sodium (IPM/CS) to patients with gynecological infections as initial treatment and evaluated changes in blood interleukin 6 (IL-6) as an infection marker. 1. The subjects consisted of 7 patients with chorioamnionitis, 4 with intrauterine infections, and 1 with subcutaneous abscess. IPM/CS (1-2 g/day) was intravenously drip infused. This therapy was markedly effective in 1 patient and effective in 11; the response rate was 100%. 2. IL-6 generally began to decrease earlier than CRP. Before drug administration, correlations were observed between IL-6 and CRP (r = 0.946) between IL-6 and elastase (r = 0.355), and between elastase and CRP (r = 0.579). During the entire course, correlations were observed between IL-6 and CRP (r = 0.581), between IL-6 and elastase (r = 0.303), and between elastase and CRP (r = 0.776). These results suggest that blood IL-6 reflects early the pathologic state and treatment effects, and is a useful infection marker in gynecological infections.

Adult↗
PubMed1994

[Clinical effects of imipenem/cilastatin sodium on gynecological infections].

We evaluated the effectiveness and safety of imipenem/cilastatin sodium (IPM/CS) in gynecological infections at gynecological departments at multiple institutions in Yamagata Prefecture. The subjects consisted of 64 patients with gynecological infections, 9 with urinary tract infections, and 21 with other infections. IPM/CS was intravenously drip infused at a dose of 1-2 g/day. The overall response rate was 97.9% (92/94); 96.9% (62/64) for gynecological infections, 100% (9/9) for urinary tract infections, and 100% (21/21) for other infections. Bacteriologically the response rate was 97.3% (36/37), and the eradication rate was 97% (32/33). As for subjective and objective side effects, only diarrhea was observed in 1 patient. Clinical laboratory examinations showed no abnormal values. These results suggest the usefulness of IPM/CS for gynecological infections.

Bacterial Infections↗
PubMed1994

[Retroperitoneal xanthogranuloma: a case report].

A 48-year-old man was admitted to our hospital for lumbago. Computerized tomographic (CT) scan, aortography and venacavography indicated a solid retroperitoneal tumor at the right renal hilus. The tumor was removed and right nephrectomy was conducted. Some of the tumor remained owing to strong adhesion to the inferior vena cava and lumbar spine. Histological diagnosis of the resected tumor was retroperitoneal xanthogranuloma. One year after surgery, the CT scan revealed a gradual decrease in size of the remaining retroperitoneal mass.

Granuloma↗
PubMed1994

Increased tissue factor pathway inhibitor levels in uremic patients on regular hemodialysis.

We investigated tissue factor pathway inhibitor (TFPI) levels in 44 non-dialysis uremic patients and 36 chronic dialysis patients, as well as the changes of TFPI levels during hemodialysis sessions using heparin (n = 14), low molecular weight heparin (n = 7), nafamostat mesilate (n = 5), and argatroban (n = 2). In non-dialysis uremic patients, TFPI levels increased (mean +/- SD: 178 +/- 37% of control pooled plasma) along with the impairment of renal function. In chronic hemodialysis patients, TFPI levels were even higher (265 +/- 72%) before dialysis, but did not depend on the etiology of renal failure (diabetic or non-diabetic), the interval between dialysis sessions (twice or three times a week), and the duration of hemodialysis. During hemodialysis sessions using heparin, TFPI levels increased 1.2- to 3.5-fold compared with the level before hemodialysis and the degree of increase in TFPI was correlated with the heparin concentration (r = 0.648, p = 0.0001, n = 29). During dialysis sessions using low molecular weight heparin, TFPI levels also increased, but the change was less marked than during dialysis with heparin. TFPI levels did not change during dialysis sessions using nafamostat mesilate or argatroban. In conclusion, TFPI levels were increased by renal failure and by long-term repeated injection of heparin, but the hemodialysis procedure itself did not alter the TFPI level.

Adolescent↗
PubMed1994

[A case of infrarenal left inferior vena cava with macrohematuria after contusion in the lumber region].

A 33-year-old woman was admitted with macrohematuria after contusion in the left lumber region. The excretory urogram showed no abnormal findings, but color doppler and RI-angiography revealed infrarenal left-sided inferior vena cava (left IVC). The pressure in the dilated left renal vein was higher than that in the right one. Renal contusion in addition to the congestion of the left renal vein due to left IVC was thought to be the cause of hematuria in this case. Hematuria disappeared after retrograde instillation of 0.2% AgNO3 water solution into the left renal pelvis. Left IVC rarely presents clinical symptoms, and is usually found by chance on CT scan or ultrasonography during examinations for upper abdominal organs. Our case is the 69th one of left IVC in Japan, and belongs to Type 2' according to our classification of left IVC.

Adult↗
PubMed1994

A novel point mutation (G-1 to T) in a 5' splice donor site of intron 13 of the dystrophin gene results in exon skipping and is responsible for Becker muscular dystrophy.

The mutations in one-third of Duchenne and Becker muscular dystrophy patients remain unknown, as they do not involve gross rearrangements of the dystrophin gene. We now report a defect in the splicing of precursor mRNA (pre-mRNA), resulting from a maternally inherited mutation of the dystrophin gene in a patient with Becker muscular dystrophy. This defect results from a G-to-T transversion at the terminal nucleotide of exon 13, within the 5' splice site of intron 13, and causes complete skipping of exon 13 during processing of dystrophin pre-mRNA. The predicted polypeptide encoded by the aberrant mRNA is a truncated dystrophin lacking 40 amino acids from the amino-proximal end of the rod domain. This is the first report of an intraexon point mutation that completely inactivates a 5' splice donor site in dystrophin pre-mRNA. Analysis of the genomic context of the G-1-to-T mutation at the 5' splice site supports the exon-definition model of pre-mRNA splicing and contributes to the understanding of splice-site selection.

Adult↗
PubMed1993

Studies on neurokinin antagonists. 3. Design and structure-activity relationships of new branched tripeptides N alpha-(substituted L-aspartyl, L-ornithyl, or L-lysyl)-N-methyl-N-(phenylmethyl)-L-phenylalaninamides as substance P antagonists.

As an extension of our study on discovering a novel substance P (SP) antagonist, we designed new branched tripeptides containing L-aspartic acid (2 and 5), L-ornithine (3 and 6), and L-lysine (4 and 7) by reconstructing the structure of the previously reported tripeptide SP antagonist [Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (1), FR113680]. The strategy for this design was based on the postulate that the dipeptide half D-Trp(CHO)-Phe-NMeBzl in 1 is essential for receptor recognition. Molecular modeling studies implied that these newly designed tripeptides could mimic the spatial orientations of the essential dipeptide structure. As expected, all of these compounds potently inhibited 3H-SP (1 nM) binding to guinea pig lung membranes in the 10(-8) M range. The 1H-indol-3-ylcarbonyl derivatives (5-7) were slightly more potent than the corresponding 1H-indol-2-ylcarbonyl derivatives (2-4), as predicted by the molecular modeling studies. The structure-activity relationships studies on the selected 1H-indol-3-ylcarbonyl derivatives indicated that the threonine moiety at the side chain can be modified into a variety of structures without any significant loss of the activity. Furthermore in the L-lysine series, even dipeptide compounds having nothing or a simple acyl group at the epsilon-amino group, such as N alpha-[N alpha-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenylmethyl)- L-phenylalaninamide (18b), exhibited potent activity. These dipeptides belong to a new structural class of SP antagonist.

Animals↗
PubMed1993

Several short interspersed repetitive elements (SINEs) in distant species may have originated from a common ancestral retrovirus: characterization of a squid SINE and a possible mechanism for generation of tRNA-derived retroposons.

Using labeled transcripts generated in vitro from squid total genomic DNA as a probe, we isolated and characterized a SINE that is present in the squid genome. The squid SINE appears to be derived from a tRNA(Lys). When the consensus sequences of five different SINEs with a tRNA(Lys)-like structure from distantly related species, including squid, were aligned, we found in the tRNA-unrelated region two sequence motifs that were almost identical among these five SINEs. This observation suggests a common evolutionary origin for these SINEs and/or some function(s) for these motifs. Similar sequences were unexpectedly found to be present in sequences complementary to the U5 regions of several mammalian retroviruses whose primer is a tRNA(Lys). On the basis of these findings, we present a model for the generation of SINEs. We propose that they are derived from a "strong-stop DNA" with a primer tRNA(Lys) that is an intermediate in the reverse transcription of certain retroviruses. Our model suggests that a certain group of SINEs may have been generated by horizontal transmission, although it is not clear whether information was transmitted via a similar retrovirus or via an RNA or DNA of a SINE.

Animals↗
PubMed1993

Mobility and molecular orientation of vitamin E in liposomal membranes as determined by 19F NMR and fluorescence polarization techniques.

To elucidate the molecular orientation and mobility of alpha-tocopherol (vitamin E) in membranes, 19F nuclear magnetic resonance (NMR) was applied. In bilayer phosphatidylcholine (PC) liposomes, 19F NMR spin-spin relaxation times (T2) of 19F-labeled methyl groups on either the chromanol moiety or the isoprenoid side chain of alpha-tocopherol were significantly decreased compared to those for alpha-tocopherol in solution (CDCl3), suggesting that the vitamin E molecule exists in the lipid core of membranes and that its motional freedom is significantly restricted. The difference in T2 values between the solution state and PC liposomes was greatest for the 5a-CF3 on the chromanol moiety compared with other methyl groups on the isoprenoid side chain. Hence, it is thought that the chromanol moiety of alpha-tocopherol may fit tightly near the surface of the membrane because of its hydrophilicity. When Pr3+ was added to the liposomal suspension, the intensity of the NMR signal for 5a-CF3 changed faster than those of the other methyl groups. When the surface of the liposomal membranes was positively charged using stearyl amine, the mobility of the 5a-methyl group, expressed as the correlation time (tau c), was quite similar to that in negatively charged membranes. These results indicate that the chromanol moiety of alpha-tocopherol may orient near the membrane surface, and that the hydroxyl group may be hydrogen bonded to the ester carbonyl of PC. For further confirmation of this conclusion, time-dependent changes in the fluidity of liposomes caused by the addition of Pr3+ were measured at the surface and inner region of liposomal membranes using a fluorescence polarization technique. The fluidity increased in the surface region and decreased in the inner region of liposomes containing alpha-tocopherol. These results show that when praseodymium ions may pass through the liposomal membrane, the hydrogen bonds between alpha-tocopherol and the ester carbonyl of PC may be broken, leading to the formation of an alpha-tocopherol-Pr3+ complex, thus causing the fluidity to increase. Based on the findings obtained, mobility and molecular orientation of vitamin E in membranes are proposed.

Fluorescence Polarization↗
PubMed1993

Effects of an NK1 receptor antagonist, FK888, on constriction and plasma extravasation induced in guinea pig airway by neurokinins and capsaicin.

The effects of FK888, an NK1 receptor antagonist, on airway constriction and airway plasma extravasation induced by neurokinins and capsaicin were investigated in guinea pigs. FK888 inhibited substance P (10(-8) M)- and neurokinin A (10(-9) M)-induced contraction of isolated guinea pig trachea, with IC50 values of 3.2 x 10(-8) and 4.2 x 10(-6) M, respectively. FK888 given i.v. inhibited substance P (13.5 micrograms kg-1)-induced airway constriction with an ED50 value of 0.40 mg kg-1 but did not inhibit neurokinin A (1.1 micrograms kg-1)- and capsaicin (3.1 micrograms kg-1)-induced airway constriction at a dose of 1 mg kg-1. On the other hand, FK888 given i.v. inhibited airway plasma extravasation induced by substance P (1.3 micrograms kg-1), neurokinin A (11 micrograms kg-1) and capsaicin (100 micrograms kg-1) with equal potency and ED50 values of 0.011, 0.0063 and 0.019 mg kg-1, respectively. When FK888 was given locally (into the airway directly) inhibitory activities were more potent than following i.v. administration. In this case FK888 inhibited substance P-, neurokinin A- and capsaicin-induced airway constriction with ED50 values of 3.2, 190 and 550 micrograms kg-1, respectively, suggesting that an about 100 times higher dose is required to inhibit neurokinin A- and capsaicin-induced airway constriction than substance P-induced constriction. FK888 given orally was also effective in substance P-, neurokinin A- and capsaicin-induced airway plasma extravasation with ED50 values of 4.2, 5.9 and 9.5 mg kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗