Biomedical subjects

K Sano

Publications and source records attributed to K Sano.

At least 55 records · Page 3Linked to original sources

PubMed2001

Decreased intraoral secretions during sedation-analgesia with propofol-ketamine and midazolam-ketamine combinations.

PURPOSE: To investigate salivary flow over time with a balanced sedation-analgesia technique using a propofol-ketamine (PK) or a midazolam-ketamine (MK) combination in human volunteers. METHODS: In the PK group, boluses of 1 mg.kg(-1) of propofol and 0.7 mg.kg(-1) of ketamine were initially administered. This was followed by an infusion, given over a 1-h period, of propofol (5 mg.kg(-1)) admixed with ketamine (0.7 mg.kg(-1)). In the MK group, 0.07 mg.kg(-1) of midazolam and 0.7 mg.kg(-1) of ketamine was followed by the infusion of a midazolam (0.07 mg.kg(-1)) and ketamine (0.7 mg.kg(-1)) admixture, also given over a period of 1 h. Salivary flow was measured prior to and at 10-min intervals during the sedation-analgesia, as well as for 30 minutes after its termination. RESULTS: Mixed intraoral secretions were significantly reduced, by 43% and 47%, on average, in the PK and MK groups, respectively, when compared with presedation levels, and had not returned to baseline levels 30 min after discontinuation of the infusion. CONCLUSION: Sedation-analgesia with PK and MK combinations controls intraoral secretions by reducing salivary flow.

Journal Article↗

PubMed2001

Can 3D-CTA surpass DSA in diagnosis of cerebral aneurysm?

After introducing of Helical scanning CT (HCT) and 3D-CTA (three-dimensional CT angiography), various improvements to these methods have been made every year to achieve better imaging quality. The current resolution permits visualisation of the internal structure of tumors, although as yet insufficiently clearly. We suggest that these improvements can be more efficient than conventional cerebral aneurysms angiography. In this study, we compared HCT and 3D-CTA with conventional cerebral angiography in patients with cerebral aneurysms at our facility. We also examined whether 3D-CTA has the possibility of independent clinical application and can surpass conventional DSA in diagnostic efficacy. In this paper, we found this information insufficient in clipping operations using 3D-CTA only when 1) It was difficult to distinguish a crooked infundibular dilation from an aneurysm, 2) Imaging threshold influenced the measured value of the vascular diameter and 3) It was also difficult to confirm whether the peripheral vessels adhere to the aneurysm. In conclusion, from the result of the comparison between 3D-CTA and DSA in this study, it was concluded that 3D-CTA is a reliable alternative method to conventional angiography in the diagnosis of anterior circulation and most aneurysms of regular size. In such cases it may be possible to obtain the same quality of preoperative information, but it is less invasive.

Adult↗

PubMed2001

Intracranial dysembryogenetic tumors: pathogenesis and their order of malignancy.

Dysembryogenetic tumors can be classified into three main categories: (1) tumors derived from embryonal cell rests in situ such as craniopharyngioma, Rathke's cleft cyst, chordoma, etc., (2) tumors derived from embryonal cells straying into the tissue ("verirrte Keime") such as so-called germ cell tumors, epidermoid, dermoid, lipoma, hamartoma, etc., and (3) included twin (fetus-in-fetu) tumors. The pathogenesis of the second one may be that the embryonic cells of various stages of embryogenesis are misplaced in the bilaminar embryonic disc at the time of the primitive streak formation, becoming involved in the stream of lateral mesoderm and carried to the neural plate area to become incorrectly enfolded into the brain at the time of neural tube formation. The third category of tumor may be related to sequestration of cells of the blastocyst before differential blocking of the genome has occurred. The author propounds the following hypothesis: intracranial dysembryogenetic tumors composed of cells resembling the cells that appear in the earlier stages of embryogenesis are more malignant than those composed of cells resembling those appearing in the later stages of embryogenesis.

Brain Neoplasms↗

PubMed2001

PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.

Inogranic pyrophosphate (PPi) inhibits hydroxyapatite deposition, and mice deficient in the PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) Plasma cell membrane glycoprotein-1 (PC-1) develop peri-articular and arterial calcification in early life. In idiopathic infantile arterial calcification (IIAC), hydroxyapatite deposition and smooth muscle cell (SMC) proliferation occur, sometimes associated with peri-articular calcification. Thus, we assessed PC-1 expression and PPi metabolism in a 25-month-old boy with IIAC and peri-articular calcifications. Plasma PC-1 was <1 ng/ml by enzyme-linked immunosorbent assay in the proband, but 10 to 30 ng/ml in unaffected family members and controls. PC-1 functioned to raise extracellular PPi in cultured aortic SMCs. However, PC-1 was sparse in temporal artery lesion SMCs in the proband, unlike the case for SMCs in atherosclerotic carotid artery lesions of unrelated adults. Proband plasma and explant-cultured dermal fibroblast NTPPPH and PPi were markedly decreased. The proband was heterozygous at the PC-1 locus, and sizes of PC-1 mRNA and polypeptide, and the PC-1 mRNA-coding region sequence were normal in proband fibroblasts. However, immunoreactive PC-1 protein was relatively sparse in proband fibroblasts. In conclusion, deficient extracellular PPi and a deficiency of PC-1 NTPPPH activity can be associated with human infantile arterial and peri-articular calcification, and may help explain the sharing of certain phenotypic features between some IIAC patients and PC-1-deficient mice.

Arteriosclerosis↗

PubMed2001

Expression of vascular endothelial growth factor in mouse tumours subjected to photodynamic therapy.

The aim of this study was to define the appropriate fractionation interval between photodynamic therapy (PDT) for the enhancement of its anti-tumour effects. Tumour reoxygenation and the kinetics of tumour vascular cells following PDT were evaluated in mice by means of immunohistochemical staining for the vascular endothelial growth factor (VEGF) and the proliferating cell nuclear antigen (PCNA), respectively. The VEGF labelling indices (LIs) of the tumour cells and the PCNA LIs of the tumour vascular cells were assessed at various time intervals after PDT. The tumour cell VEGF LIs of the experimental groups at time points from 0 to 6 h after PDT were significantly higher than those of the control groups, but subsequently returned to control levels at 24 h after PDT. The vascular cell PCNA LI of the experimental group at 24 h after PDT was significantly lower than that of the control group, but returned to the control level at 48 h. These results indicated that the tumour subjected to PDT might be reoxygenated, and that the maximum damage to the tumour vasculature emerged at 24 h after PDT. We propose here that the fractionation interval between PDTs should be 24 h.

Animals↗

PubMed2001

Design, synthesis, and biological evaluation of anti-HIV double-drugs. conjugates of HIV protease inhibitors with a reverse transcriptase inhibitor through spontaneously cleavable linkers.

Based on the prodrug concept as well as the combination of two different classes of anti-HIV agents, we designed and synthesized a series of anti-HIV double-drugs consisting of HIV protease inhibitors conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoins the two different classes of inhibitors has been investigated. Double-drugs using a succinyl amino acid linker were shown to release the parent drugs via spontaneous imide formation at a faster rate compared to compounds using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Among the double-drugs, KNI-1039 (3b) with a glutarylglycine linker exhibited extremely potent anti-HIV activity compared with that of the individual components. Double-drug 3b was relatively stable in culture medium, whereas it regenerated active species in cell homogenate. These results suggested that the synergistic enhancement of anti-HIV activities of 3b may be due to their ability to penetrate into the target cell and subsequent regeneration of two different classes of anti-HIV agents in the cytoplasm.

Animals↗

PubMed2001

Demonstration of downregulation of alpha-smooth muscle actin in interferon-gamma-treated myofibroblast by a novel cell-capture enzyme immunoassay.

We developed a simple method for determining the relative amount of alpha-smooth muscle actin (alphaSMA) produced in fibroblasts. The principle of the method is based on an enzyme immunoassay (EIA) for alphaSMA in microcultured fibroblasts. The optimized protocol of the assay is as follows. Human fibroblasts were cultured with transforming growth factor beta1 (TGFbeta1) in a microtiter plate and directly immobilized on the plate. The alphaSMA produced was labeled and subjected to indirect enzyme immunoassay using alkaline phosphatase, and optical density was measured. Semiquantitativeness was confirmed using various numbers of cells in which alphaSMA production was induced by treatment with TGFbeta1. The assay simply demonstrated that interferon-gamma (INF-gamma) inhibited the production of alphaSMA in an established cell line and that in primary cultured cells originated from the contractile nodule. Since the assay is simple and semi-quantitative, it is useful for elucidating the mechanism of contractile diseases and screening a large number of substances that have an inhibitory effect on the change in activity of myofibroblasts.

Actins↗

PubMed2001

Frequency of failure to isolate Shigella spp. by the direct plating technique and improvement of isolation by enrichment in selenite broth.

In order to clarify the failure to isolate Shigella spp. by direct plating, we compared frequencies of Shigella spp. isolation by direct plating and by plating after enrichment in selenite broth. A total 67 strains were isolated in this study. The strains of 38 (56.7%) were isolated only by direct plating, and 25 (37.3%) strains were isolated by both direct plating and after enrichment. Four strains (6.0%) were isolated after enrichment but not by direct plating. Since 6% of isolated Shigella spp. were not isolated by direct plating, we recommend that direct plating and additional isolations from selenite broth should be performed. The significance concerning reduction of concentration of sodium selenite in enrichment broth is discussed.

Bacteriological Techniques↗

PubMed2001

Granulomatous and cytokine responses to pulmonary Cryptococcus neoformans in two strains of rats.

The present study was undertaken to elucidate the participation of Th1 and Th2 responses in granulomatous inflammation induced by Cryptococcus neoformans using Lewis and Brown Norway rats which have Th1-polarized and Th2-polarized innate immunity, respectively. Both strains demonstrated granulomatous inflammation in the lung, and the lesions were composed mainly of mononuclear phagocytes and surrounded by lymphocytes. Lewis rats demonstrated tuberculoid epithelioid cell granulomas with a central necrosis resembling caseation, and increased transcription of Th1 relevant cytokines. On the other hand, Brown Norway rats showed mature granulomas including eosinophils with increased transcription of IL-12 without increased transcription of not only IFN-gamma and IL-2 but also Th2 cytokines such as IL-4, IL-5, and IL-10, unexpectedly. The colony-forming unit of the lung was decreased exponentially in both strains, and that of Brown Norway rats was significantly lower than that of Lewis rats 10 days after the inoculation. This indicated that Brown Norway rats demonstrated more fungicidal activity than Lewis rats in the early stage of the infection. The role of eosinophils with humoral immunity may be considered to be resistant in Brown Norway rats in addition of the function of macrophages.

Animals↗

PubMed2001

The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behçet's disease.

Behçet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behçet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behçet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3' terminal end segment encoding the 3' untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behçet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behçet's disease.

5' Flanking Region↗

PubMed2001

Targeted down-regulation of MLL-AF9 with antisense oligodeoxyribonucleotide reduces the expression of the HOXA7 and -A10 genes and induces apoptosis in a human leukemia cell line, THP-1.

The MLL gene is frequently rearranged in leukemias, and MLL chimeric proteins generated by chromosomal translocations play crucial roles in leukemogenesis. Targets of murine Mll include HOX proteins that regulate body pattern formation and hematopoiesis. However, it is not known whether or not the MLL chimeric proteins regulate the HOX gene expression in human leukemia. To address this issue, THP-1 cells, a human leukemia cell line expressing MLL-AF9, were treated with antisense oligodeoxyribonucleotide (ODN) complementary to the coding sequence of the MLL-AF9 junction. Down-regulation of the MLL-AF9 transcript was accompanied by the reduced expression of the HOXA7 and -A10 genes, but not of the HOXA2, -A4, -A5, and -A9 genes. The number of viable cells cultured with 20 microM antisense ODN for 5 days was 10-fold lower than that of the sense ODN-treated control. And the number of the annexin V-/propidium iodide- apoptotic cells in the antisense ODN-treated cells after 3 days of culture was two-fold higher than that in the control. Staining of the antisense ODN-treated cells with Hoechst 33258 showed the morphology characteristic to apoptosis. These results indicate that MLL-AF9 regulates the expression of the selected HOX genes as well as prevents the leukemic cells from apoptosis.

Apoptosis↗

PubMed2001

Production and pharmacologic modulation of the granulocyte-associated allergic responses to ovalbumin in murine skin models induced by injecting ovalbumin-specific Th1 or Th2 cells.

Because interferon-gamma, interleukin-4, and interleukin-5 have been identified at the mRNA and protein levels in the lesional skin of patients with atopic dermatitis, we investigated the roles played by granulocytes as effector cells in allergic inflammation by using two unique murine skin models. In vitro generated Th1 and Th2 cells from naïve splenocytes of antiovalbumin T cell receptor transgenic BALB/C mice were adoptively transferred with ovalbumin into the ear pinnae or air-pouches produced in the back skin of naïve, nontransgenic BALB/C mice. The injection of Th1 cells with ovalbumin induced delayed type ear swelling that peaked at 48 h, whereas that of Th2 resulted in ear swelling that peaked at a much earlier time, 24 h. Histologic study of the swollen ear skin and granulocytes recruited into the air-pouch demonstrated that, although the Th1-induced inflammation caused a neutrophil-predominant infiltrate with few eosinophils, larger numbers of eosinophils accumulated in the Th2-induced inflammation. Using these murine models, we further evaluated the effects of drugs used for the treatment of atopic diseases. The results showed that FK506 administration could effectively reduce skin inflammation induced by either Th cells. Interestingly, the neutrophil elastase inhibitor ONO-6818 efficiently inhibited Th1-induced inflammation. In contrast, a leukotriene receptor antagonist, ONO-1078, specifically suppressed Th2-induced inflammation. We also found that each ONO drug exerted direct influence on specified granulocytes, as neither affected in vitro production of relevant Th cytokines. Thus, we succeeded in developing animal skin inflammation models in which we can evaluate the contribution of protein antigen-specific Th1 or Th2 cells through the action of granulocytic effector cells.

Animals↗

PubMed2001

A rat model of hypereosinophilic syndrome.

Hypereosinophilia-occurring rats without chemical and antigen treatment have been maintained in our laboratory. The rat, Matsumoto Eosinophilia Shinshu (mes), showed hypereosinophilia at the age of 9 weeks or older and developed eosinophil-related inflammatory lesions in many organs. These lesions included: aortitis, granulomatous lesion in the mesenteric lymph node, inflammatory fibroid polyp of the stomach and pulmonary vasculitis with septal infiltration. These lesions were involved with cellular infiltration of eosinophils and macrophages, and deposition of eosinophilic crystals which immunohistologically showed major basic protein and eosinophilic peroxidase derived from eosinophilic lysosomal constituents. Although the distribution of lesions in mes is a little different from that of hypereosinophilic syndrome (HES) in humans, in that endomyocardial fibrosis appears in HES while aortitis appears in mes, mes is probably comparable with HES. The present paper describes the pathological aspects of the lesions in mes and discusses the pathogenesis of tissue injury related to eosinophilic infiltration.

Animals↗

PubMed2001

Histological diversity of vasculitic lesions in MPO-ANCA-positive autopsy cases.

To investigate the variety of histological features of vasculitic lesions in myeloperoxidase-specific antineutrophil cytoplasmic antibody (pANCA)-related vasculitis, retrospective pathological analysis was done on 13 autopsy cases, collected from 1990 to 1998 at five hospitals. These cases were classified into three groups: (i) pulmonary-renal syndrome characterized by capillaritis of lung and glomeruli with occasional small-vessel arteritis and/or phlebitis; (ii) glomerular capillaritis without pulmonary involvement associated with significant small-vessel arteritis; and (iii) extensive distribution of small-vessel arteritis with no capillary involvement. The results suggest that pANCA-related vasculitis encompasses a wide variety of vasculitic syndromes, including pulmonary-renal syndrome, microscopic polyarteritis nodosa, and classic polyarteritis nodosa. pANCA may contribute to pathogenesis in all of these cases.

Aged↗

PubMed2001

Atrial fibrillation impairs endothelial function of forearm vessels in humans.

BACKGROUND: Although there have been many studies on the effects of atrial fibrillation (AF) on cardiac function, few studies have been done on its effects on endothelial function. The present study was designed to examine the effects of AF on endothelial function in human subjects. METHODS AND RESULTS: Changes in forearm blood flow (FBF) induced by acetylcholine and nitroglycerin were measured by using plethysmography in 14 patients with lone AF, 13 patients with AF and underlying heart disease, and 12 normal control subjects. In the patients, these measurements were repeated after cardioversion. Although baseline FBF was the same in the 3 groups, acetylcholine-induced increases in FBF were significantly smaller in both patient groups than in the control group, and FBF increases were particularly depressed in AF patients with underlying heart disease. After restoration of sinus rhythm by cardioversion, FBF response to the highest dose of acetylcholine increased by 46% in patients with lone AF (n = 10) and by 90% in AF patients with underlying heart disease (n = 11). Nitroglycerin-induced vasodilatation was the same in all 3 groups and was not affected by cardioversion. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilatation is impaired by AF and improves after sinus rhythm is restored.

Acetylcholine↗

PubMed2001

MR imaging and thermography of facial angioedema: a case report.

Magnetic resonance imaging and thermography were performed in a 67-year-old man with idiopathic facial angioedema. Thermography suggested decreased heat emission in the region of the angioedema. Magnetic resonance imaging revealed diffuse high intensity in the subcutaneous interstitial tissue and dilated veins on T2-weighted images. Marked contrast enhancement was noted in the subcutaneous tissue on postcontrast T1-weighted images.

Aged↗

PubMed2001

An improved procedure of electron microscopic in situ hybridization for detecting adenovirus DNA.

Electron microscopic in situ hybridization (EM-ISH) is a useful method in determining the localization of a specific nucleic acid at the ultrastructural level. Since the EM-ISH protocol includes many steps, no standard protocol for EM-ISH is available yet. In this study, we optimized quantitatively the critical conditions with respect to embedding resin, nucleic acid labeling and hybridization reaction time, by using adenovirus-infected cells as the indicator cells. The optimal detection of an adenovirus-specific nucleic acid was obtained by overnight hybridization reaction on sections embedded in Lowicryl K4M resin. Random-primed-labeled probes improved the reactivity. At least 60% of virus particles in paracrystalline arrays was found to contain viral DNA. These arrays in adenovirus-infected cells are useful in evaluating quantitatively the efficiency of protocols of EM-ISH.

Adenoviridae↗

PubMed2001

Comparison of a new method for computer analysis with standard techniques for measuring survival rates in the rat transverse rectus abdominis musculocutaneous flap.

Many methods have been used to measure experimental flap survival in animal models. These have previously included planimetry, computer programs, and (routinely by the authors) the simple measurement of the weight of a template traced according to the dimensions of a given flap. To test the validity of their method, an alternative technique was developed by the authors' biostatiticians. Initially, in a study of rat transverse rectus abdominis musculocutaneous (TRAM) flaps, all templates were also scanned electronically to form bitmaps. Using commonly available software programs, each bitmap was colorized corresponding to viable and nonviable areas of the flaps. A summation of individual pixels by color could then be used to calculate the percentage of flap survival. A comparison of both methodologies in 64 rat TRAM flaps found that the survival rate was slightly greater overall when a computer analysis had been performed (3.1 +/- 1.7%), but this was not a significant difference (p = 0.479). Thus, the previous standard method was proven reliable, but just as precise calculations are now possible using the convenience of any personal computer.

Animals↗