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Biomedical subjects

K Kitagawa

Publications and source records attributed to K Kitagawa.

At least 181 records · Page 10Linked to original sources
PubMed1994

Relationship between lipophilicity and skin permeability of various drugs from an ethanol/water/lauric acid system.

The in vitro skin permeability of 16 drugs with a wide range of lipophilicity (log P; -0.95-4.40) was evaluated by the use of an ethanol/water (60/40) binary vehicle with or without lauric acid as a permeation enhancer. The enhancing effect by the addition of lauric acid to the ethanol/water (60/40) binary vehicle could be observed from the aspect of both permeation rate and lag time. The permeation rate increased with an increase in the hydrophilicity of the drugs. It was considered that lauric acid exerts an effect on both the polar and nonpolar regions of lipids of the stratum corneum, and the cooperative interaction of ethanol and lauric acid increases the participation of the polar pathway of drugs. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/water (60/40) binary vehicle with lauric acid showed a parabolic shape, with its peak at a more hydrophilic range (log P; 0.19) compared with other past references (log P; 2-3). The ethanol/water (60/40) binary vehicle with lauric acid appears to be a good candidate as a vehicle for transdermal therapeutic systems for hydrophilic drugs.

1-Octanol↗
PubMed1994

Platelet-activating factor-acetylhydrolase activity in maternal and umbilical venous plasma obtained from normotensive and hypertensive pregnancies.

OBJECTIVE: To elucidate whether plasma platelet-activating factor-acetylhydrolase activities in women with pregnancy-induced hypertension and in their fetuses are different from those in normotensive mothers and fetuses. METHODS: We measured platelet-activating factor-acetylhydrolase activity in the plasma of 11 normotensive nonpregnant women, 39 normotensive pregnant women, 30 pregnant women with pregnancy-induced hypertension, 31 fetuses delivered from normotensive pregnant women, and 12 fetuses delivered from women with pregnancy-induced hypertension. RESULTS: Plasma platelet-activating factor-acetylhydrolase activity in normotensive pregnant women at 28-31 weeks' gestation was significantly lower than that in normotensive nonpregnant women (P < .001). In contrast, in women with pregnancy-induced hypertension at 28-31 weeks' gestation, the activity of this enzyme was significantly higher than that in gestational age-matched, normotensive pregnant women (P < .01). Platelet-activating factor-acetylhydrolase activity in the umbilical venous plasma of fetuses delivered from women with pregnancy-induced hypertension at 37-40 weeks' gestation was significantly higher than that in the gestational age-matched term fetuses of normotensive mothers (P < .001). CONCLUSION: These findings indicate that the hydrolysis of platelet-activating factor is decreased during a normal pregnancy and that such modulation does not occur in pregnant women with pregnancy-induced hypertension or in their fetuses.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

[Residential movement of persons with senile dementia within one year prior to death].

The purpose of this study was to clarify what factors were affecting the residential movement of persons with senile dementia, within one year prior to their death, and to find out ways to sustain the quality of life of the terminal period. We analyzed ninety-six cases of the members of the Association of Family Caring for the Demented Elderly, who died within the period from 1989 to 1991. 1. The average age of death of the elderly persons was 83.2 years. Seventy-four percent had severe dementia. Fifty-five percent had complications of cancer, cardiopathy or apoplexy. 2. Thirty-three percent of the patients in the analyzed cases died at home, sixty percent died in hospitals, and seven percent died elsewhere. Only a few had been hospitalized for more than one year. 3. There were four major movement patterns: care at home and death at home, periodic hospitalization before death at home, periodic hospitalization before death at hospital, and hospitalization and death at hospital. Each of the four patterns had unique characteristics regarding both physical and mental disorders. 4. Those persons with periodic hospitalization before death at home had more care in regards to discharge guidance than those with periodic hospitalization before death at hospital. From the above analysis, we concluded that persons with senile dementia in their terminal period require preventative treatments against advanced dementia and the various complications. In addition they need effective discharge planning at medical institutions.

Aged↗
PubMed1994

Age-associated decreases in the messenger ribonucleic acid level and the rate of synthesis of apolipoprotein A-II in murine senile amyloidosis.

BACKGROUND: Apolipoprotein A-II (apoA-II), an apoprotein of serum high density lipoprotein, is the serum precursor of murine senile amyloid protein fibril. Three types of apoA-II protein variants (type A, B, and C) were found among inbred strains of mice. We reported the decreased concentration and the accelerated clearance of serum apoA-II with advancing age in the senescence-accelerated mouse-prone (SAM-P/1) mice, a strain with a high incidence of severe senile systemic amyloidosis and type C apoA-II. EXPERIMENTAL DESIGN: Age-related changes in hepatic mRNA levels and rates of synthesis of apoA-II were investigated in SAM-P/1 and SAM-R/1, the latter of which has a low incidence of amyloidosis and type B apoA-II. RESULTS: At age 2 months, both strains had the same levels of hepatic apoA-II mRNA. However, in SAM-P/1 after age 4 months, we observed a remarkable age-associated decrease in apoA-II mRNA levels and the level at age 14 months was about 50% of that seen at age 2 months. On the other hand, in SAM-R/1, the level at age 17 months was still 77.4% of the level at age 2 months. No age-related decrease in mRNA levels of apoA-I, another major apolipoprotein of high density lipoprotein, was observed in either strain. Slight age-associated decreases in ApoE mRNA levels and age-associated changes in apoB mRNA levels were observed, with the same profiles for both strains. The rates of hepatic synthesis of apoA-II protein decreased significantly in SAM-P/1 and decreased slightly in SAM-R/1, with advancing age. The parallel changes observed between mRNA levels and rates of synthesis of apoA-II indicate that decrease in the rate of apoA-II synthesis reflects age-associated decreases in mRNA levels. CONCLUSIONS: These findings suggest that the decreased concentration of serum apoA-II protein with advancing age may be caused by a decrease in the level of its mRNA.

Aging↗
PubMed1994

[Clinical analysis of benign tumors of the lung].

Benign tumors of the lung occur in low frequency, but its differential diagnosis from malignant tumors such as lung cancer is important. This paper presents as analysis of clinical features of 26 cases operated on for benign tumor of the lung. Histologically there were 15 hamartomas, 8 sclerosing hemangiomas, 2 inflammatory pseudotumors and one clear cell tumor. The roentgenographic appearances were well defined circumscribed solitary nodules in 17 cases (65%), and lobulation and spiculation in 9. Histological diagnosis of benign tumors was not obtained in all cases preoperatively. Minimal resection procedures were performed in 22 cases (85%). No postoperative complications developed.

Adolescent↗
PubMed1993

APC gene messenger RNA: novel isoforms that lack exon 7.

The APC gene at human chromosome 5q21 is responsible for familial adenomatous polyposis coli. Furthermore, sporadic cancers of not only colon but also other digestive organs often contain mutations in the APC gene. A dominant mouse mutation Min that was generated by chemical mutagenesis and causes polyposis in the digestive tract is in the mouse homologue of the human APC gene. The APC mRNA is generated from 15 exons. Two mRNA isoforms were reported which are produced by alternative splicing in the 9th exon. Here, we report novel mRNA isoforms that lack the 7th exon in both mouse and human cells.

Animals↗
PubMed1993

Induced resistance and susceptibility to cerebral ischemia in gerbil hippocampal neurons by prolonged but mild hypoperfusion.

Brief periods of non-lethal cerebral ischemia can induce resistance against subsequent lethal ischemia. In this study, asymptomatic gerbils after unilateral carotid artery ligation were subjected to 5 min of forebrain ischemia. The prolonged but mild hypoperfusion, by carotid occlusion, induced susceptibility at 1 day and tolerance at 30 days to lethal ischemia in the hippocampal neurons. The neuroprotective effect correlated well with induction of heat shock protein 72 in the hippocampal neurons. These results suggested that neuronal cells possess a cellular response to sublethal hypoperfusion and can survive forthcoming ischemic stress.

Animals↗
PubMed1993

Development of congenic strains of mice carrying amyloidogenic apolipoprotein A-II (Apoa2c). Apoa2c reduces the plasma level and the size of high density lipoprotein.

A congenic strain of mice with amyloidogenic apolipoprotein A-II (Apoa2c) on the genetic background of the amyloidosis-resistant SAM-R/1 strain was produced by 12 generations of backcrossing. Genome mapping using endogenous murine leukemia proviral markers was done in the congenic strain, termed R1.P1-Apoa2c. We confirmed that only a small region surrounding the apoA-II gene on chromosome 1 was transferred from the genome of the donor SAM-P/1 strain. The level and particle size of plasma high density lipoprotein were decreased in R1.P1-Apoa2c mice compared to those in the progenitor SAM-R/1 mice. The function of apoA-II can be studied using this strain of mice.

Amyloidosis↗
PubMed1993

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease.

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scar-like fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.

Adenoma↗
PubMed1993

Molecular cloning and characterization of a novel neutrophil chemotactic factor from a filarial parasite.

To compare the molecular structure of a parasite-derived neutrophil chemotactic factor (NCF) with host-derived NCFs or other NCFs, molecular cloning of cDNA encoding NCF derived from Dirofilaria immitis adult worm (DiNCF) was performed. A D. immitis cDNA library was screened with an antibody to DiNCF, and one DiNCF cDNA clone (pD-4) was isolated. A fusion protein of pD-4 and gene 10 protein showed significant neutrophil chemotactic activity whereas gene 10 protein itself showed marginal neutrophil chemotactic activity. The total nucleotide sequence analysis revealed that pD-4 was 994 bp long with a 432 bp open leading frame encoding a 143 residue protein. The NH2-terminal amino acid sequence of the natural DiNCF and the deduced amino acid sequence from the cDNA showed that the mature functional protein was comprised of 112 amino acids. Although the deduced amino acid sequence of this protein did not show overall homology to host-derived NCFs or other known proteins, it contained a similar sequence (Met-Phe-Lys) to the known chemotactic peptides. The possibility of the functional epitope of DiNCF is discussed.

Amino Acid Sequence↗
PubMed1993

A proteolipid protein gene family: expression in sharks and rays and possible evolution from an ancestral gene encoding a pore-forming polypeptide.

The myelin proteolipid proteins (PLP and DM20) are believed to act as "adhesive struts" in the extracellular apposition of the CNS myelin sheath. These proteins have been considered late evolutionary developments, which arose de novo in the antecedents of early tetrapods. However, PCR primed with degenerate oligonucleotides corresponding to common segments of rat PLP/DM20 revealed three novel mRNAs in the brains of two elasmobranchs. These mRNAs are closely related to each other and to mammalian DM20, but lack the sequence that distinguishes PLP from DM20. We term the novel proteolipid proteins DM alpha, DM beta, and DM gamma. At least DM alpha and DM gamma are highly expressed in white matter in myelinating shark brain. The DMs not only are highly homologous to each other, but also contain regions bearing similarities with segments of channel-forming regions of the nicotinic acetylcholine receptor and the glutamate receptor macromolecular complexes. Significantly, we find that across these segments, DM alpha and DM gamma are more similar to the channel proteins than the two channel proteins are to each other.

Amino Acid Sequence↗
PubMed1993

Dietary soybean protein compared with casein retards senescence in the senescence accelerated mouse.

The effects of replacing dietary casein with soybean protein on mean life span, mean life span of the last one-tenth of a group, grading scores of senescence and deposition of senile amyloid were investigated in senescence accelerated mice (SAM-P/1) compared with a control strain (SAM-R/1). SAM-R/1 mice fed the soybean protein-containing diet had mean life spans of 618 +/- 42 d (males) and 578 +/- 62 d (females), 58% (males) and 44% (females) longer than those of corresponding casein fed mice (P < 0.01). Similarly, in SAM-P/1 mean life-spans were 265 +/- 16 d (males) and 307 +/- 23 d (females) in the soybean diet group, 27% (males) and 30% (females) longer than in the casein diet groups (P < 0.01). The mean life span of the last one-tenth of each group fed soybean protein was significantly longer than the corresponding group fed casein. In SAM-R/1 mice, pathological studies revealed that severe secondary amyloid deposition (amyloid A protein) in the kidneys, spleen, stomach and liver was significantly suppressed, in males only, by replacing casein with soybean protein (P < 0.01). The occurrence of contracted kidneys caused by the infiltration of amyloid A protein was suppressed in SAM-R/1 mice fed the soybean protein-containing diet (P < 0.05). The deposition of senile amyloid in SAM-P/1 mice with aging was retarded by replacing casein with soybean protein (P < 0.01). These results indicate that dietary protein source is important in modulating the advance of senescence in SAM mice.

Aging↗
PubMed1993

Differential activation of polymorphonuclear leukocytes from peripheral blood and exudate in surgical patients.

We examined the effects of surgical trauma on polymorphonuclear leukocyte (PMN) chemotaxis, production of phagocytosis-dependent intracellular chemiluminescence (CL) and production of phagocytosis-independent total CL in two groups: group A with esophageal cancer, and group B with gastric cancer. The scale of surgical trauma was quantified by measuring interleukin-6 in plasma and exudate from drainage tubes. We found a significant augmentation of chemotaxis, total CL and intracellular CL in both groups during the post-operative week. In group A, the increments in both chemotaxis and total CL of circulating cells were smaller than those in group B, but there was no significant difference in intracellular CL between the two groups. Exudate PMNs were more chemotactic, but produced smaller amounts of total CL than circulating cells. No significant difference in intracellular CL between exudate and circulating PMNs was detected, indicating that phagocytic activity was not affected. We conclude that severe surgical trauma causes circulating PMNs with high chemotactic activity to migrate to sites of injury, but that preactivated PMNs in exudate examined in vitro produce lower amounts of reactive oxygen metabolites in response to soluble chemoattractants in vitro than cells circulating in plasma.

Adult↗
PubMed1993

Effect of hydrophilic and lipophilic vehicles on skin permeation of tegafur, alclofenac and ibuprofen with or without permeation enhancers.

The effects of an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle, and an ethanol/water (60/40) system as a hydrophilic vehicle, with or without permeation enhancers for in vitro skin permeation and in vivo skin absorption of tegafur, alclofenac and ibuprofen with different lipophilicity, were evaluated. The in vitro and in vivo skin permeability of tegafur, alclofenac and ibuprofen was enhanced by the use of ethanol/panasate 800 (40/60) or ethanol/water (60/40) binary vehicles as a donor composition. However, the two vehicles showed contrastive properties in relation to the extent of permeation enhancement of the three drugs: tegafur > alclofenac > ibuprofen for the ethanol/panasate 800 (40/60) system, and ibuprofen > or = alclofenac > tegafur for the ethanol/water (60/40) system. When lauric acid, as a permeation enhancer, was added to both of the binary vehicles, the in vitro and in vivo skin permeability of three drugs further increased, and the in vivo absorption rate of the drugs from the ethanol/water (60/40) system was larger than that from the ethanol/panasate 800 (40/60) system. In conclusion, it was suggested that the ethanol/panasate 800 (40/60) lipophilic binary vehicle is useful for hydrophilic drugs, and conversely, the skin absorption of lipophilic drugs can be improved by the use of the ethanol/water (60/40) hydrophilic binary vehicle with or without lauric acid as a permeation enhancer.

Animals↗
PubMed1993

Evaluation of the final deprotection system for the solid-phase synthesis of Tyr(SO3H)-containing peptides with 9-fluorenylmethyloxycarbonyl (Fmoc)-strategy and its application to the synthesis of cholecystokinin (CCK)-12.

Acidolytic deprotection and cleavage conditions for an acid-labile Tyr(SO3H)-containing peptide were systematically examined with respect to acid, temperature, and scavenger. The 90% aqueous trifluoroacetic acid (TFA)-based reagent systems (90% aqueous TFA/m-cresol and 90% aqueous TFA/m-cresol/2-methylindole) at 4 degrees C were found to minimize the deterioration of Tyr(SO3Na) in the peptide. The latter deprotection/cleavage system was applied to the 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase synthesis of cholecystokinin (CCK)-12 on an acid-labile PAL-linked support (PAL = peptide amide linker), with Fmoc-Tyr(SO3Na)-OH as a building block.

Amino Acid Sequence↗
PubMed1993

[Prospective longitudinal studies on lens changes after vitrectomy--quantitative assessment by fluorophotometry and refractometry].

We prospectively evaluated lens changes after vitrectomy on 55 patients with vitreoretinal interface syndrome such as idiopathic epiretinal membrane, vitreomacular traction syndrome, and impending stages of idiopathic senile macular hole. Postoperative changes in crystalline lenses were assessed by fluorophotometric measurement of lens autofluorescence, measurement of refractive errors and biomicroscopic evaluation of progression of nuclear sclerosis. Examinations were repeated prior to surgery and at 1, 3, 6, and 12 months postoperatively. While autofluorescene and light transmittance of the lens were not affected by vitrectomy in patients less than 50 years old, older patients showed a significant increase of autofluorescence and decreased transmittance as early as 3 months after surgery. The refraction became myopic with time especially in the older patient group. Nuclear cataract was also found on biomicroscopic examination in the older patients as early as 1 month after surgery and progressed with time. The older the patients were, the more prominent those lens changes were.

Adult↗