Biomedical subjects

T Imai

Publications and source records attributed to T Imai.

At least 595 records · Page 33Linked to original sources

PubMed1993

Serum and immunohistochemical studies of NCC-ST-439 in breast cancer.

It has been thought that NCC-ST-439 antigen (ST-439) is a tumor-related carbohydrate antigen. The authors conducted serum and immunohistochemical studies to investigate the clinical significance of ST-439 in breast cancer. The level of serum ST-439 was elevated in advanced and recurrent breast cancers. In comparison with CEA and CA15-3, ST-439 was superior in sensitivity but inferior in specificity to these markers. The level of serum ST-439 showed no correlation with the levels of CEA or CA15-3. In the combination assay of these three markers, 80.6% of recurrent cases and 33.8% of primary cases were positive. Immunohistochemically, the expression of ST-439 was observed in 28.1% of noncancerous mammary duct epithelium and in 38.1% of the cancerous portion. From the above, we concluded that ST-439 was a tumor-related antigen and could be a tumor marker with high sensitivity in breast cancer.

Adenofibroma↗

PubMed1993

Effect of ethanol on the development and maturation of synapses in the rat hippocampus: a quantitative electron-microscopic study.

The effects of chronic ethanol administration on the development and maturation of synapses in the strata radiatum and lacunosum-moleculare of CA1 in the hippocampus were quantitatively examined in rats exposed to ethanol for the entire period of fetal life as well as the whole period of postnatal life. Synapse densities in the strata radiatum and lacunosum-moleculare of the ethanol-treated group were significantly lower than those of the control group at 2, 14, 21, and 70 days of age. However, the rates of density reduction did not change between either of the strata that receive different groups of afferent fibers. The ratio of axospinous to axoshaftic synapses also did not change between control and ethanol-treated groups. These data suggest that chronic administration of ethanol reduces the density of synapses in this area and that this effect is not specific to neither the type of afferent fibers nor the type of synapses.

Animals↗

PubMed1993

The effects of ethanol exposure on radial arm maze learning and behavior of offspring rats.

The effects of maternal drinking on offspring have been studied epidemiologically, in human beings, and experimentally, in rats. The physical growth of offspring of female alcoholic rats, including histological growth of brain, lung, thymus gland, liver, and kidney, was previously reported by us. In the present study, we observed the effect of ethanol intake by the mother rat on learning ability and behavior of offspring rats using an eight radical arm maze. At the same time histological observations of the cerebrum were carried out. The mother rat was exposed to ethanol from a young age to delivery (P-DEL) or to weaning (P-NURS). After weaning, the offspring was exposed to ethanol until the tests began (P-WEAN). Experimental groups, classified by length of ethanol exposure, as mentioned above, disclosed the following: (1) Number of trials required for fulfilling learning criterion was significantly large in P-DEL and P-NURS rat groups relative to the controls; that is, P-DEL and P-NURS rats were slow in learning. (2) Numbers of rats which did not fulfill the learning criterion were: Group P-DEL, one male of eight; Group P-NURS, three males of seven. The behavior of the rats in Group P-WEAN differed from those in other groups; while they were receiving acclimation training, they were, unlike ordinary rats, not watchful of the device, slow to find the feed, and indifferent. They seemed to lack carefulness and sometimes failed to eat the feed even though they succeeded in selecting correct arms. Their motion was abrupt and they ran at extraordinarily high speeds. (3) In the observations of correct choices in the first eight choices, groups P-DEL and P-NURS showed significantly low values. This suggested the lowering of their learning ability. (4) In the observations of continuous correct choices, Group P-DEL showed a significantly low value. This suggested the rats did not learn thoroughly enough to retain their acquisition long. (5) Body weight, learning ability, and hippocampal neurons were affected by ethanol exposure more severely in Group P-NURS than in Group P-DEL. An even more severe effect was observed in Group P-WEAN.

Animals↗

PubMed1993

Fifty sequenced-tagged sites on human chromosome 11.

Fifty novel sequenced-tagged sites (STSs) were identified from cosmid clones mapped to human chromosome 11. DNA sequences were determined for one or both cloning ends of 69 cosmid markers that had each been localized to 1 of 24 subchromosomal regions by means of hybridization to somatic cell hybrid panels. Proper primer sequences and appropriate conditions for a polymerase chain reaction (PCR) were determined for each marker. Twenty-one of the cosmids were not suitable for generating STSs, mainly because both of their ends contained repetitive elements such as Alu and L1 sequences; however, some were inappropriate because the sizes of their PCR products from human DNA, used as template, were same as those from yeast DNA. Finally, 50 STSs were established from 48 clones: 20 were derived from markers localized on the short arm and 30 from the long arm. These STSs can serve as new reagents for investigating human DNA in somatic cell hybrids and for isolating yeast artificial chromosomes to anchor large DNA contigs and fine-scale physical maps of chromosome 11.

Base Sequence↗

PubMed1993

Pharmacokinetics of flosequinan in elderly patients with chronic congestive heart failure.

We have investigated the pharmacokinetics of the direct vasodilator flosequinan in elderly patients with congestive heart failure. Eight patients received a single dose of 50 mg, and 8 patients received once-daily treatment with 25 mg for two weeks. In the single dose study, the tmax of flosequinan was 2.5 h, Cmax was 1.17 microgram.ml-1 and t1/2 was 5.63 h. The tmax of the metabolite BTS 53554 was 20.3 h, Cmax was 1.44 microgram.ml-1 and t1/2 was 62.0 h. BTS 53554 accumulated gradually in the 14-day repeated dose study and steady-state was reached after approximately 2 weeks. Flosequinan was not found to accumulate. Adverse reactions were not observed in either the single or repeated dose study. It is advisable to consider renal function and body weight when flosequinan is to be administered to elderly patients with congestive heart failure. The initial dose should be 25 mg.

Aged↗

PubMed1993

Influence of constant sustained positive airway pressure on right ventricular performance.

OBJECTIVE: The detrimental effect of positive airway pressure on right ventricular (RV) performance is controversial and the aim of this study was to determine the effects of constant positive airway pressure without ventilatory fluctuation on RV performance with the aid of a pulmonary arterial catheter equipped with a rapid response thermistor for measuring RV ejection fraction (RVEF) and RV end-diastolic volume index (RVEDVI). DESIGN: A prospective, clinical study. SETTING: The central operating theatre of a university hospital. PATIENTS: Nine patients who had major surgery and required right heart catheterization for normal clinical management. MEASUREMENTS AND RESULTS: Cold indicator was injected into the RV 4 or 5 times for each airway pressure (0, 10 or 20 cmH2O) which was maintained manually stable for 15 s, and 9 paired data were analyzed by repeated-measures analysis of variance. They are separated into two groups; RVEF at zero airway pressure greater (A group) or less (B group) than 0.4. In A group (7 patients), increasing airway pressures (0 vs 10 vs 20 cmH2O) did not affect RVEF (0.55 +/- 0.05 vs 0.54 +/- 0.06 vs 0.56 +/- 0.04), RVEDVI (69 +/- 36 vs 73 +/- 29 vs 58 +/- 20 ml.m-2), or stroke volume index (SVI: 38 +/- 18 vs 40 +/- 17 vs 33 +/- 13 ml.beat-1.m-2); however, in B (2 patients), RVEF (0.35 and 0.38 vs 0.31 and 0.28 vs 0.19 and 0.17) and SVI (35 and 28 vs 32 and 27 vs 27 and 23) decreased, while RVEDVI increased (99 and 73 vs 103 and 97 vs 146 and 132). CONCLUSIONS: In most patients, the changes in RVEF, SVI, and RVEDVI did not occur under constant positive airway pressure, therefore the changes reported in mechanically ventilated patients may not attributable to the extent of positive airway pressure but rather to abrupt increases in airway pressure. These appears, however, to be patients whose RV function is so disturbed that they cannot cope with increased afterloads.

Aged↗

PubMed1993

A 5-lipoxygenase inhibitor, FR110302, inhibits ozone-induced airway hyperresponsiveness in guinea pigs and dogs.

Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. In the present study we examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance (Rrs) was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve of Rrs to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 h. In a control group of guinea pigs, delta log PC100 (the index of the ozone-induced airway hyperresponsiveness) was 0.58 +/- 0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished delta log PC100 (10 mg/kg: 0.22 +/- 0.10; 100 mg/kg; 0.11 +/- 0.06). Dogs were exposed to 3 ppm ozone for 2 h. In a control group of dogs, delta log Dmin (another index of the ozone-induced airway hyperresponsiveness) was 1.24 +/- 0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg p.o.) significantly diminished delta log Dmin (1 mg/kg: 0.60 +/- 0.18; 3.2 mg/kg: 0.27 +/- 0.12). These results suggest that FR110302 may be a useful drug for attenuating airway hyperresponsiveness in asthmatic patients.

Acetylcholine↗

PubMed1993

Endothelin-1 is an autocrine/paracrine regulator of porcine granulosa cells.

We studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from porcine granulosa cells, and whether ET-1 acts directly on granulosa cells in an autocrine/paracrine fashion. The dilution curve of the conditioned medium from cultured porcine granulosa cells was parallel to a standard curve of ET-1 in RIA. Reverse-phase HPLC of the conditioned media from the granulosa cells revealed a major peak of ET-1-like immunoreactivity (ET-1-LI) coeluting with standard ET-1. ET-1-LI was released from cultured porcine granulosa cells as a function of time. Northern blot analysis demonstrated the expression of mRNA for prepro-ET-1 in the granulosa cells. We demonstrated the presence of ET-1 in the follicular fluid of porcine ovaries, and that the concentration of ET-1 in large follicles was higher than that in small-medium follicles. ET-1 dose-dependently stimulated cell growth and DNA synthesis in porcine granulosa cells. ET-1 inhibited the FSH- and hCG stimulated accumulation of progesterone in porcine granulosa cells in long-term incubation. These findings suggest that ET-1 produced by porcine granulosa cells may function as an autocrine/paracrine growth factor and modulator of steroidogenesis in ovarian granulosa cells.

Animals↗

PubMed1993

Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: a comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and Werdnig-Hoffmann disease.

This report concerns the expression of ubiquitin in anterior horn cells of various subgroups of adult and infantile motor neuron disease (MNDs); immunohistochemical techniques were employed. Ubiquitin-positive skein-like inclusions (SLIs) were found in all cases of adult-onset amyotrophic lateral sclerosis (ALS), including 16 cases with sporadic ALS, two cases of familial ALS with posterior column degeneration and Lewy body-like hyaline inclusions (LBHIs), two sporadic ALS cases with LBHIs, and three cases of sporadic ALS with dementia. SLIs were not found in anterior horn cells of 5 cases with Werdnig-Hoffmann disease (WHD). However, granular ubiquitin-positive deposits were seen in ballooned neurons of WHD patients. No ubiquitinated materials were found in the perikarya of two sporadic juvenile ALS patients with basophilic inclusions (BIs), but granular ubiquitin-immunoreactive deposits were occasionally observed in the BIs. These results suggest that ubiquitin-positive SLIs are characteristic features of various forms of adult-onset ALS and that aggregated ubiquitinated granules are characteristic of ballooned neurons of WHD. Ubiquitinated structures and their distribution patterns may reflect degenerative processes of anterior horn cells, and may be useful for classifying subgroups of motor neuron diseases.

Adult↗

PubMed1993

Tracing of corticospinal fibers by extracellular pressure-injection of biocytin into the motor cortex in rats.

The aim of this study was to determine if biocytin, a low molecular analog of biotin, could reliably label details of corticospinal fibers at the lumbar level in rats. Biocytin (5%) was injected extracellularly by pressure into the unilateral hindlimb area of the motor cortex. Frozen sections of the injection sites and the lumbar segments were incubated with avidin-horseradish peroxidase (HRP). Terminal labeling of corticospinal fibers at the lumbar segments could be observed within 2-3 days of the injection. These results indicate that anterograde tracing with biocytin can be applied to label axons in a long tract such as the corticospinal tract in rats. Biocytin stain provided a view of a higher level of detail than wheat germ agglutinin (WGA)-HRP.

Animals↗

PubMed1993

Structure and physical map of 64 variable segments in the 3'0.8-megabase region of the human immunoglobulin heavy-chain locus.

We have constructed the physical map of the 0.8 megabase DNA fragment which contains the 3' 64 variable region (V) gene segments of the human immunoglobulin heavy chain (H) locus. The organization of the VH locus showed several features that indicate dynamic reshuffling of this locus. The sequenced 64 VH segments include 31 pseudogenes, of which 24 are highly conserved except for a few point mutations. Comparison of the 64 germline VH sequences shows that each VH family has conserved sequences, suggesting that there might be some genetic or selection mechanisms involved in maintenance of each family. The total number of the human VH segments was estimated to be about 120, including at least 7 orphons.

Amino Acid Sequence↗

PubMed1993

Laparoscopic adrenalectomy for primary aldosteronism: a new operative method.

From January 17, 1992 to January 16, 1993, laparoscopic adrenalectomy was performed in 7 patients (3 men, 4 women) with primary aldosteronism ranging in age from 35 to 65 years (mean 48.7 years). Five of the adrenal lesions were on the left side and two were on the right. Five to six trocar-sheath units were used, and adrenal tumors were successfully removed with adjacent normal adrenal glands in all patients. The operative time ranged from 165 to 572 min (mean 302 min), operative blood loss was between 50 and 450 ml (mean 217.2 ml), and there was no major complication. In conclusion, laparoscopic adrenalectomy is a safe alternative operative method for primary aldosteronism, although application of this technique to other types of adrenal lesions remains to be examined.

Adrenal Gland Neoplasms↗

PubMed1993

Reduction of cell proliferative activities of gastric stump adenomatous hyperplasias after bile reflux diversion in rats.

Previously we reported the majority of lesions induced by bile reflux, in the absence of chemical carcinogens, in the rat remnant stomach to consist primarily of gastric type and secondarily of intestinal type cells, and that they are reversible after diversion of bile reflux. The present study was designed to evaluate changes in proliferative activities in cells of each type under these conditions. The frequency of adenomatous hyperplasia (AH) induced in the gastric stump mucosa by duodenal content reflux after Billroth II partial gastrectomy (BII) increased until the 54th week of the experiment. Roux-en-Y (RY) surgical procedure which prevents duodenal reflux performed at the 24th or 36th week after BII led to a decrease in AH. Cell content of the lesions was analyzed using routine H&E staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical concanavalin A, galactose oxidase Schiff and sialidase galactose oxidase Schiff reactions) and proliferation in each compartment evaluated by an immunohistochemical method using bromodeoxyuridine (BrdU) and a monoclonal antibody against BrdU. At the 54th week the number of BrdU-labeled cells per normal pyloric column was significantly (P < 0.05) increased to 10.63/pit after the BII operation, while it diminished to 5.23/pit after RY diversion, this being the same level as with the RY procedure alone. AH maintained a high rate of BrdU incorporation at 12.7% after BII operation, which was also significantly reduced (P < 0.01) to 7.0% by the RY surgery. The intestinal type cell showed highest (22.2%), the surface mucous type cell showed the next (16.5%) and the pyloric gland type cell showed lowest (5.2%) BrdU labeling indices after BII operation. All the cell types in AH showed similar proportional decreases in BrdU incorporation after RY diversion. Thus surgical intervention reverses the cell proliferation caused by bile reflux in the gastric stump.

Adenocarcinoma, Mucinous↗

PubMed1993

Heparin inhibits endothelin-1 and proto-oncogene c-fos gene expression in cultured bovine endothelial cells.

We studied the inhibitory effects of heparin, thrombin inhibitor, and protein kinase C (PKC) inhibitor on basal and thrombin-induced preproendothelin-1 (prepro-ET-1) and proto-oncogene c-fos mRNA expression in cultured bovine endothelial cells (ECs). Northern blot analysis using cDNA for bovine prepro-ET-1 as a probe showed that heparin lowered not only the basal but also the stimulated expression of prepro-ET-1 mRNA by thrombin. A selective thrombin inhibitor (argatroban) and a PKC inhibitor (staurosporine) also inhibited thrombin-induced but not basal prepro-ET-1 mRNA expression. Heparin similarly inhibited thrombin-induced c-fos proto-oncogene mRNA expression in ECs. These data suggest that heparin, in addition to its antithrombin effect, has an inhibitory effect on prepro-ET-1 mRNA expression, possibly via a PKC-dependent pathway.

Alkaloids↗

PubMed1993

Isolation of a cDNA encoding the largest subunit of TFIIA reveals functions important for activated transcription.

Transcription factor IIA has been shown to interact with the TATA-binding protein and to act early during preinitiation complex formation. The human factor is composed of three subunits (alpha, beta, gamma). A human cDNA clone encoding the largest subunit of TFIIA (alpha) was isolated. The recombinant alpha polypeptide, together with the beta and gamma subunits, was capable of reconstituting TFIIA activity. Studies using antibodies raised against recombinant alpha polypeptide demonstrate that TFIIA can be an integral component of the preinitiation complex. We demonstrate that TFIIA not only interacts with TBP but also can associate with the TFIID complex. Functional assays establish that TFIIA has no apparent role in basal transcription but plays an important role in activation of transcription. Interestingly, amino acid sequence analyses of the beta-subunit demonstrate these residues to be entirely contained within the carboxyl terminus of the cDNA clone encoding the alpha-subunit.

Amino Acid Sequence↗

PubMed1993

An in-vitro and in-vivo correlative approach to the evaluation of ester prodrugs to improve oral delivery of propranolol.

A series of ester prodrugs of propranolol was synthesized by incorporating substituents (straight alkyl, branched alkyl, acyloxyalkyl and cycloalkyl) into the beta-hydroxy function of propranolol with the aim of protecting the drug against first-pass metabolism following oral administration. The in-vitro hydrolysis rates of the prodrugs were, in increasing order, liver homogenate >> plasma > buffers. The pH-rate profile of the prodrugs showed maximum stability around pH 4.0; the hydrolysis rates were drastically increased over pH 6.8. QSAR analysis revealed hydrophobic (pi) and electronic (sigma) effects of the substituents play the main roles for prodrug hydrolysis in buffers and plasma, while hydrolysis in liver homogenate could not be well explained by any of these parameters. Four prodrugs (O-acetyl-, O-butyryl-, O-isovaleryl- and O-cyclopropanoyl-propranolol) were selected for oral administration based on their hydrolysis in-vitro. Following oral administration of prodrugs to beagle dogs the absolute bioavailabilities (F) of propranolol were about 2-4-fold that after an equivalent dose of propranolol. The prodrugs were rapidly absorbed and regenerated propranolol to attain peak plasma levels at 0-0.5h. Intact prodrug levels were also observed, which varied depending on their respective stabilities in in-vitro media. A linear relationship between F of propranolol and log P was obtained. F further appeared to be parabolically dependent on the observed hydrolysis rates of prodrugs in liver homogenate suggesting optimal design manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

Comparative study on inclusion complexation of maltosyl-beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin and beta-cyclodextrin with fucosterol in aqueous and solid state.

The complexation of fucosterol with three kinds of beta-cyclodextrin (beta-CyD) was investigated in aqueous solution and in the solid state. The solubility of fucosterol increased significantly on its complexation with maltosyl-beta-CyD and heptakis(2,6-di-O-methyl)-beta-CyD (DM-beta-CyD), while no appreciable increase was observed when complexed with beta-CyD. The stability constant of complexation with beta-CyD estimated from solubility determinations was greater for a 1:2 complex than for a 1:1 complex. On the other hand, 1:1 complexation of fucosterol with maltosyl-beta-CyD or DM-beta-CyD was greater than 1:2 complexation. The solid complexes were obtained in molar ratios of 1:2 and 1:3 for beta-CyD and maltosyl-beta-CyD complexes, respectively. The inclusion behaviour of fucosterol with maltosyl-beta-CyD was compared with beta-CyD in the solid state using DSC, powder X-ray diffractometry and CP/MAS 13C NMR. Maltosyl-beta-CyD showed different inclusion behaviour compared with beta-CyD, and produced an amorphous structure of fucosterol on complex formation. The dissolution rate of fucosterol-maltosyl-beta-CyD complex was significantly faster than other complexes due to its high aqueous solubility and amorphous structure.

Chemistry, Pharmaceutical↗

PubMed1993

Immunoelectron microscopy of acute graft versus host disease of the skin after allogeneic bone marrow transplantation.

AIMS: To clarify the pathological mechanisms of acute cutaneous graft versus host disease (GvHD) following allogeneic bone marrow transplantation. METHODS: Skin biopsy specimens from five patients were examined by immunoelectron microscopy. A panel of monoclonal antibodies against T cell and natural killer cell subpopulations was used, including anti-CD4, -CD8, -CD16b, -CD56, -CD57, and -TCR delta 1 antibodies. RESULTS: All the specimens contained CD8+ cells, CD4+ cells, and CD56+ cells infiltrating the epidermis. Cells stained with anti-CD16b, -CD57, or -TCR delta 1 were very sparse or absent. Most of the CD8+ cells in the epidermis displayed morphological features of activated cytotoxic T lymphocytes and apposition of such cells to degenerating keratinocytes was shown. CD4+ cells outnumbered CD8+ cells in the epidermis in all five cases. Noticeable intercellular as well as intracellular oedema of keratinocytes was observed at the site of prominent CD4+ cell infiltration, suggesting that these also have a role as actual effector cells by secreting cytotoxic cytokines. CD56+ cells infiltrating the epidermis did not exhibit the characteristic ultrastructural morphology of the natural killer cells thus far examined, and their lineage remained uncertain. CONCLUSIONS: These data provide direct evidence that CD8+ cytotoxic T cells attack keratinocytes, and further suggest that CD4+ cells as well as CD56+ cells participate in the cellular pathogenesis of acute cutaneous GvHD.

Adolescent↗