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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 1,009 records · Page 56Linked to original sources

Transcatheter arterial renal and adrenal embolization with iohexol-ethanol solutions. Animal experimental study and clinical application.

RATIONALE AND OBJECTIVES: The authors compared the embolic effect of radiolucent absolute ethanol (AE) with that of a radiopaque iohexol-ethanol (IES) solution for renal ablation in dogs and for the destruction of human aldosteronomas by the technique of transcatheter arterial embolization (TAE) to test whether IES can be an alternative to AE. METHODS: The embolic agents were infused through a balloon catheter into the renal arteries of 17 dogs (9 infused with 0.3 mL/kg AE; 8 infused with IES). The immediate and parenchyma were compared between the two groups. Transcatheter arterial embolization with IES also was performed in three humans with unilateral aldosteronoma. RESULTS: The IES was visualized faintly under fluoroscopy in all dogs. There were no significant differences in embolic effects between the AE and IES. Three patients with aldosteronoma were treated successfully by TAE with IES. CONCLUSIONS: The IES can be used as a "visible ethanol" to improve the safety and ease of ethanol embolization.

Adrenal Cortex Neoplasms↗

Prospective studies on left ventricular geometric patterns and exercise tolerance in unmedicated men with borderline and mild hypertension.

OBJECTIVE: This study was designed and conducted to assess the clinical significance of left ventricular geometric patterns and physical fitness in subjects with untreated borderline and mild hypertension. METHODS: Symptom-limited maximal treadmill stress testings and echocardiographic examinations were administered to 192 previously unmedicated men. Left ventricular geometric patterns were determined by the combined criteria of left ventricular mass index and relative wall thickness. Subjects whose left ventricular mass index was < 125 g/m2 were followed up for more than 3 years. RESULTS: Normalized treadmill time was lower and pressure rate products at peak exercise were higher in patients with concentric hypertrophy than in those with normal geometry. Of the 77 patients who revealed left ventricular mass index at baseline < 125 g/m2 and who were successfully followed without medication for more than 3 years, 18 demonstrated concentric hypertrophy at the final follow-up examination. During the follow-up period, these 18 patients had significant further augmentation of concentric geometric features, significant decreases in both cardiac output and normalized treadmill time, and significant increases in casual blood pressure and total peripheral resistance compared with those at baseline. CONCLUSION: Patients with concentric hypertrophy exhibited slightly but significantly impaired levels of physical fitness and cardiac work efficiency, and the progression of concentric hypertrophy demonstrated further impairments of these conditions. Therefore, not only lowering blood pressure, but also improving left ventricular hypertrophy, cardiovascular hemodynamics, and physical fitness might be required in patients with concentric hypertrophy.

Adult↗

Involvement of platelet-derived growth factor receptor-alpha in hair canal formation.

Hair follicles develop and are maintained by multiple rounds of inductive events involving interactions among various cell types within the follicles and the adjacent mesenchyme. Although evidence suggests that several growth factors, cell adhesion molecules, and transcriptional regulators are involved in those cell-cell interactions, the molecular mechanisms regulating each pivotal step of hair follicle development, such as formation of the hair germ, root sheath, sebaceous gland, and hair canal, remain largely unknown. In this study, we established the antagonistic monoclonal antibody APA5 against platelet-derived growth factor (PDGF) receptor-alpha (PDGFR-alpha) and used it to investigate the role of PDGFR-alpha in neonatal skin development. In addition to the dermal mesenchyme, a known site of PDGFR-alpha expression, immunohistologic staining of neonatal skin detected transient expression of PDGFR-alpha in the perinatal epidermis for several days. On the other hand, ligands for PDGFR-alpha were detected in epithelial cells and sebaceous glands of hair follicles. To determine whether this contiguous expression of PDGF and PDGFR-alpha in neonatal skin plays a functional role, we injected APA5 into neonates to block the function of PDGFR-alpha. Consistent with the PDGF/PDGFR-alpha expression in the neonatal skin, two defects were induced by this procedure. First, hair canal formation in the epidermis was severely suppressed. Second, the growth of dermal connective tissues and of hair follicles of pelage hairs was suppressed. These results indicate that PDGF signals are involved in both the epidermis-follicle interaction and the dermal mesenchyme-follicle interaction required for hair canal formation and the growth of the dermal mesenchyme, respectively.

3T3 Cells↗

Immunoglobulins and their receptors on epidermal Langerhans cells in atopic dermatitis.

To elucidate the etiological role of immunoglobulin molecules on Langerhans cells (LCs) in atopic dermatitis, we conducted immuno-histochemical studies on the localization of immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA and IgM on epidermal LCs from 30 patients with atopic dermatitis (AD) and five non-atopic healthy volunteers. We also investigated the types of receptors for the immunoglobulins (Fc epsilon RI, Fc epsilon RII, Fc gamma RI, Fc gamma RII, and Fc gamma RIII) on epidermal LCs in the patients. IgE positive epidermal LCs were observed in 28 of 30 AD patients, and 46.7% of the epidermal LCs were positive for IgE. Both IgG1- and IgG2-positive epidermal LCs were observed in 70% of AD patients, and 21.8% and 28.7% of the total epidermal LCs were positive for IgG1 and IgG2, respectively. IgG3- or IgG4-positive LCs were present in only small proportions of AD patients. IgA-positive LCs were observed in 8 AD patients; our study suggested that the IgA bound on LCs was secretory IgA (S-IgA). These surface immunoglobulins were observed significantly more frequently on epidermal LCs in the involved skin of AD than in clinically uninvolved skin. No IgM-positive epidermal LCs were observed in the AD patients or healthy volunteers. In non-atopic healthy controls, no immunoglobulin-binding LCs were observed. In receptors for immunoglobulins, Fc epsilon RI and Fc gamma RII were exclusively expressed on nearly all epidermal LCs from all AD patients and all non-atopic controls. These results suggested that not only IgE but also IgG and IgA may play some etiological role in the pathogenesis of AD.

Adolescent↗

Serological study of Bartonella henselae in cat scratch disease in Japan.

It has become clear that Bartonella henselae is a common cause of cat scratch disease (CSD). The indirect fluorescence antibody (IFA) test for detection of IgG and IgM antibodies to B. henselae concerning CSD showed that 5 (50%) of 10 patients with CSD had a serum IgG antibody titer of 1:128 or more and that 2 (20%) patients had a serum IgM antibody titer of 1:20 or more. One of 7 asymptomatic members of patients' families (14%) had IgG antibody to B. henselae at a titer of 1:256. IgM antibody to B. henselae was not detected in sera from the patients' families. Both IgG and IgM antibodies to B. henselae were not detected in sera from the healthy control group. These data suggest that B. henselae may be a cause of CSD in Japan.

Adult↗

Functional difference between Thy-1-positive and Thy-1-negative gamma delta T cells induced by Escherichia coli infection in mice.

There is an increase in number of gamma delta T cells in the peritoneal cavity after intraperitoneal (i.p.) inoculation with Escherichia coli. The E. coli-induced gamma delta T cells in C3H/He mice contain a large amount of Thy-1-negative population in addition to the Thy-1-positive population. We investigated the difference between the Thy-1-positive and the Thy-1-negative gamma delta T cells. Although it was found that only up to 4% of the gamma delta T cells on day 5 after infection were in cycling phase, and that the gamma delta T cells did not proliferate by immobilized anti-T-cell receptor (TCR) gamma delta monoclonal antibody stimulation, the gamma delta T cells proliferated in the presence of interleukin-2 (IL-2) and IL-7. The Thy-1-negative gamma delta T cells showed higher proliferative response compared with the Thy-1-positive gamma delta T cells. Furthermore, the Thy-1-negative gamma delta T cells showed lower IFN-gamma mRNA expression than the Thy-1-positive gamma delta T cells. On the other hand, both the Thy-1-positive and Thy-1-negative gamma delta T cells predominantly expressed V gamma 1, V gamma 4, V gamma 5, V gamma 6 and V delta 1, and no difference of V region usage was detected between them. These results suggest that functions of Thy-1-positive gamma delta T cells differ from Thy-1-negative gamma delta T cells although Thy-1-positive and Thy-1-negative gamma delta T cells may have similar V region repertoire and, possibly, similar antigen specificity.

Animals↗

Objective evaluation of function of the lower lip reconstructed with a myocutaneous advancement flap.

Many surgical methods have been developed for reconstruction of extensive defects resulting from resection of lower lip cancer, with the aim of achieving of normal appearance and function. However, observers' subjective evaluation, which is the method usually employed, makes comparison of the outcomes of appearance and function obtained from different techniques difficult. In this paper, a speech intelligibility test and electromyography were used as objective means of evaluating the motor function of the reconstructed lower lip.

Carcinoma, Squamous Cell↗

Real-time monitoring of HCV-RNA by single tube assay kit and potential importance for predicting virological sustained response in patients with chronic hepatitis C.

In an attempt to predict virological sustained responders among patients with chronic hepatitis C after interferon therapy, HCV-RNA in serum was measured by a one tube RT-PCR assay kit using the RNA corresponding to 5 microL serum (standard assay) or 300 microL serum (enhanced-sensitivity assay). Dilution analysis revealed that sensitivity of the 'enhanced-sensitivity assay' increased by 10-100-fold when compared with a 'standard assay'. Using these assays, prospective study of interferon therapy on 38 HCV-RNA seropositive cases with chronic hepatitis (total amount 702 MU; duration of treatment 5-6 months) was performed. At the end of treatment, six were still positive and 32 became negative by the "standard assay', whereas an additional eight cases became positive (total 14 cases positive; the remaining 24 cases negative) by the 'enhanced-sensitivity assay'. Hepatitis C viral RNA state at the end of treatment remained the same 6 months later in 23 cases (61%) by a 'standard assay' and in 31 (82%) by the 'enhanced-sensitivity assay'. Of importance was that all patients (14 cases) demonstrating HCV-RNA in serum at the end of therapy, even by the "enhanced-sensitivity assay', did not show the disappearance of HCV-RNA in serum despite the long follow up. From these results, in order to improve our treatment efficacy, we should try to modify our treatment protocol to the extent that at least HCV-RNA becomes undetectable. That can be only feasible during treatment by real-time monitoring of HCV-RNA.

Adult↗

Intracorporeal lithotripsy with the Swiss Lithoclast.

BACKGROUND: In addition to currently available modalities of intracorporeal lithotripsy (ultrasonic, electrohydraulic, and laser), a new ballistic lithotriptor known as the Swiss Lithoclast has recently gained attention. This study reports our experience with the Swiss Lithoclast in the endoscopic management of urinary calculi. METHODS: A total of 51 patients with urinary calculi were treated with the Swiss Lithoclast; one patient with a renal calculus, 28 with ureteral calculi, and 22 with lower urinary tract (bladder, urethra and Kock pouch) calculi. RESULTS: The Lithoclast successfully fragmented 94% of the calculi, independent of stone composition. Complete failure of fragmentation was not encountered. In six of the 10 upper ureteral calculi, stone fragments were pushed up into the calyces. Adjunctive extracorporeal shock wave lithotripsy for residual fragments was performed in six cases. The stone-free rate at one and three months was 84% and 88%, respectively. There were no intraoperative or long-term complications directly related to the use of this device. CONCLUSION: The Swiss Lithoclast is a safe and effective means of intracorporeal lithotripsy. Although suitable for mid and lower ureteral stones, the device has a risk of stone push-up in patients with upper ureteral stones.

Adult↗

Increased matrix metalloproteinase-2 activity induced by TGF-beta 1 in duct cells of human salivary gland is associated with the development of cyst formation in vivo.

Proteolytic enzyme activity has been shown to be important for cyst formation. In this study, we constructed a cyst-like structure in vivo and analyzed molecular mechanisms involved in the development of the lesion. When SV40-immortalized duct cells of normal human salivary gland (NS-SV-DC) were treated with TGF-beta 1 at a concentration of 1 ng/ml or 5 ng/ml followed by co-inoculation with Matrigel into the backs of nude mice, they formed large cysts containing fluid when 5 ng/ml of TGF-beta 1 was used. Analysis of the fluid demonstrated high MMP activity. Immunohistochemical staining exhibited strong reactivity with anti-MMP-2 antibody in TGF-beta 1 (5 ng/ml)-treated NS-SV-DC. Northern blot analysis indicated that the expression of TGF-beta 1 and MMP-2 mRNAs in cells was greatly enhanced by treatment with 5 ng/ml TGF-beta 1. These findings suggest that the in vivo cyst formation by TGF-beta 1-treated cells is associated with continuous induction of MMP-2 activity.

Animals↗

Transepithelial fluid shift generated by osmolarity gradients in unstimulated perfused rat submandibular glands.

The effects of osmotic gradients on transepithelial water movements were examined in unstimulated perfused submandibular glands of the rat. Osmotic gradients were applied transepithelially by adding sucrose to or removing it from the perfusate. An infusion of hypotonic perfusate shifted fluid from the interstitium to the lumen (luminal fluid shift) transiently, whereas an infusion of hypertonic perfusate shifted fluid from the lumen to the interstitium (interstitial fluid shift) transiently. The amount of fluid shifted from lumen to interstitium increased as the luminal fluid osmolarity was raised or as the perfusate osmolarity was reduced. Thus, fluid movements across the salivary epithelium were shown to be simply dependent on the osmolarity difference between lumen and interstitium. To estimate the effective pore radius of the epithelium, non-electrolyte solutions (urea, dimethylurea, diethylurea, mannitol, sucrose and maltotriose) were also used as luminal solutions. The results from non-electrolyte experiments showed that the effective pore radius of the passage for non-electrolytes was slightly larger than 0.38 nm. Solutes smaller than mannitol were less effective in opposing the interstitial fluid shift, and the value of effective pore radius in this report was similar to that of the secretory water pathway that has been measured in solvent drag studies (0.4 0.45 nm). These findings suggest that the passage for non-electrolytes may be water transport pathway in salivary epithelium.

Animals↗

[Development of a detection system for Helicobacter pylori DNA in gastric juice].

A rapid and sensitive PCR-based microwell plate assay (PCR-MWP) system to detect the 16 S ribosome RNA gene of Helicobacter pylori was developed. Analytical sensitivity, evaluated with purified recombinant plasmid DNA and genomic DNA of H. pylori, was one copy of DNA per PCR. Specificity was validated with a panel of DNA from 75 kinds of microorganisms including Helicobacter showed weak positives, when 1 pg of DNA was input. Other microorganisms gave negative signals even when 100 pg of DNA was used for PCR. When compared with a Nested-PCR system to detect the urease A-subunit gene performed by a commercial reference laboratory, the results obtained (sensitivity 93.3% and specificity 73.3%) was almost equivalent. The PCR-MWP was rapid and easy for the detection of H. pylori DNA in gastric juice specimen.

DNA, Bacterial↗

Retrospective survey of chronic Q fever in Japan by using PCR to detect Coxiella burnetii DNA in paraffin-embedded clinical samples.

We used PCR to detect Coxiella burnetii DNA in paraffin-embedded tissues obtained from patients with chronic endocarditis in which the etiological agent had been unknown. On the basis of the published nucleotide sequence of the C. burnetii htpB gene, primers were chosen to produce an amplified fragment of 285 bp. A total of 60 samples from 56 patients were tested for the presence of C. burnetii DNA. Five samples from four patients were found to be positive. All of the amplified DNA fragments possessed a TthHB8I restriction site, as predicted from the published sequence of C. burnetii. In one of the four positive patients, rickettsia-like particles were found in sections of tissue stained by Gimenez's method. This is the first report of chronic Q fever in Japan.

Base Sequence↗

Structural requirements of CCK analogues to differentiate second messengers and pancreatic secretion.

We previously demonstrated that, in rat pancreatic acinar cells, the high-affinity cholecystokinin (CCK) receptor agonist JMV-180 utilizes the phospholipase A2 (PLA2) cascade to mediate Ca2+ oscillations and amylase secretion. In contrast, the low-affinity CCK receptor utilizes the phospholipase C beta 1 (PLC beta 1) pathway. We have investigated structural requirements of CCK analogues to activate different intracellular pathways. CCK analogues such as CCK-8 [Met28,31; half-maximal effective concentration (EC50) = 0.4 pM], CCK-7 (Met28,31; EC50 = 0.7 pM), and NONA (Thr28/Nle31; EC50 = 5 pM) caused a biphasic amylase secretion. Reduction of secretion occurred with high doses of these peptides (> 100 pM). In contrast, CCK-5 (Met31; EC50 = 20,000pM), JMV-180 (Nle28,31; 1,500 pM), and OPE (Nle28,31; 200 pM) caused a monophasic secretion. CCK-8, but not JMV-180, increased protein kinase C (PKC) activities. The PKC activator phorbol ester inhibited an increase in myo-inositol 1,4,5-trisphosphate levels induced by CCK-8 and abolished monophasic amylase secretion induced by OPE. CCK-8, CCK-7, and NONA caused Ca2+ oscillations (< 100 pM) or large Ca2+ transients (> 100 pM). In contrast, JMV-180 and OPE evoked Ca2+ oscillations, even in high doses. Ca(2+)-signaling modes induced by CCK-5 were intermediate types between CCK-8 and JMV-180. CCK-8- and CCK-7-stimulated Ca2+ spikes were inhibited by the PLC inhibitor U-73122, but not by the PLA2 inhibitor ONO-RS-082. The action of CCK-5 was only partially sensitive to the PLC inhibitor. In contrast, JMV-180- and OPE-stimulated Ca2+ oscillations were inhibited by the PLA2, but not by the PLC, inhibitor. NONA was sensitive to PLC and PLA2 inhibitors. Although JMV-180 differs from CCK-8 by having an Asp-2 phenylethylester, rather than an Asp-phenylalanine amide, it is unlikely that these differences in the carboxyl terminus are important in determining which second-messenger systems will be activated. This is because CCK-5 (Phe33-CONH2) causes monophasic amylase secretion and Ca2+ oscillation in a manner similar to those induced by JMV-180 (2-phenylethylester). Meanwhile NONA (Phe33-CONH2) appeared to activate PLC and PLA2 pathways. The actions of all CCK analogues were abolished by L-364,718, indicating mediation by CCK-A receptors. Therefore, depending on the agonists used, CCK-A receptor activation in pancreatic acini may result in differential involvement of second-messenger systems, Ca2+ signal transduction, and amylase secretion. On the basis of the amino acid sequence of the carboxy terminus of CCK analogues, it appears that key amino acids for this differentiation are Met28 (or Thr28) for PLC pathways and Nle28 for PLA2 pathways.

Amino Acid Sequence↗

Intraglomerular deposition of intact cross-linked fibrin in IgA nephropathy and Henoch-Schönlein purpura nephritis.

To investigate the significance of intraglomerular coagulation and fibrinolysis in IgA nephropathy (IgA-N) and Henoch-Schönlein purpura nephritis (HSPN), the distribution of intact cross-linked fibrin (XFb) modulated by plasmin activity was examined in 25 patients with IgA-N and in 12 with HSPN. In addition to the conventional method detecting fibrin-related antigen (FRA) with an antibody against fibrinogen, the enhanced intensity of immunoreactivity of cross-linked FRA (KL-FRA) using the monoclonal antibody DD3B6/22 after plasmin exposure was evaluated to assess intraglomerular deposition of intact XFb. Also, intraglomerular invasion of macrophages was detected using the monoclonal antibody KP1 against CD68. Sixteen of a total of 37 specimens (43%) showed increased intensity of XL-FRA staining after plasmin treatment which is considered to reflect the distribution of intact XFb. Increases in the intensity of XL-FRA staining were observed mainly in mesangium and partially along glomerular capillary loops and also in a few cases in the crescents. The incidence (67%) of increases in XL-FRA staining after plasmin exposure in HSPN specimens was significantly higher than that in IgA-N specimens (32%; p < 0.05). In the group positive for XL-FRA after plasmin exposure, the numbers of macrophages per glomerulus were significantly higher (n = 15; mean +/- SD = 1.6 +/- 0.9) than in the negative group (n = 6; 0.5 +/- 0.6; p < 0.01). In HSPN, the number of macrophages per glomerulus (n = 8; 1.9 +/- 1.0) was higher than that in IgA-N (n = 13; 0.9 +/- 0.9; p < 0.05). Based on these results, we conclude that XFb is often produced and distributed in intact form in the glomeruli both in IgA-N and HSPN, associated with a relatively low intraglomerular plasmin activity, and that intraglomerular coagulation may progress in accordance with macrophage infiltration, especially in HSPN.

Fibrin↗

Distinct stages of melanocyte differentiation revealed by anlaysis of nonuniform pigmentation patterns.

The injection of an antagonistic anti-murine c-kit monoclonal antibody ACK2 during mouse embryonic development produced three distinctive pigmentation patterns on the coat of the offspring. Pattern 1 consisted of pigmentation in craniofacial and caudal regions and was induced by an ACK2 injection between 9.5 and 11.5 days post coitum (dpc). In pattern 2, the entire coat was unpigmented and was induced by the injection at around 13.0 dpc. Pattern 3 consisted of pigmented patches spreading ventrolaterally from the dorsoanterior trunk regions towards the anterior and posterior directions and it was induced by ACK2 administered at 14.5-15.0 dpc. We investigated the embryological basis of these nonuniform pigmentation patterns to elucidate the process of melanoblast differentiation between lineage commitment and colonization into developing hair follicles. The results showed the following. (1) Melanocyte differentiation at the embryonic stage from 10.5 to 12.5 dpc progresses in a spatially nonuniform fashion, being faster in the craniofacial and caudal regions than in the trunk; pattern 1 reflects this. (2) Melanoblasts are activated to proliferate synchronously upon entering into the epidermis; pattern 2 correlates with this process. (3) c-kit functions as a survival signal for proliferating melanoblasts in the epidermis. (4) The melanoblasts that enter developing hair follicles can survive without a c-kit signal; pattern 3 essentially represents the hair follicles colonized by these cells. Analysis of the melanoblast distribution of ls/ls embryos that bear a loss-of-function mutation in the endothelin 3 gene suggested that endothelin 3 is required for early melanoblast differentiation before entering into the epidermis, whereas proliferation in the epidermis takes place without this molecule. Based on these data, we propose 4 distinct steps of embryonic melanocyte differentiation: (1) migration in the dermis, which requires both c-kit and endothelin 3; (2) a state before epidermal entry that is resistant to anti-c-kit mAb; (3) cell proliferation after entering the epidermal layer, which requires c-kit and endothelin receptor B but not endothelin 3 and (4) integration into developing hair follicles, which renders melanoblasts resistant to anti-c-kit mAb. Thus, melanoblast differentiation proceeds by alternately repeating c-kit -dependent and c-kit-independent stages and c-kit functions as a survival factor for the proliferating melanoblasts.

Animals↗

Identification of metabolites of KE-298, a new antirheumatic drug, and its physiological properties in rats.

To characterize the pharmacokinetic properties of a new antirheumatic drug, KE-298, the metabolic fate of [14C]labeled KE-298 in rats was investigated, focussing especially on the identification of metabolites and its physiological properties. [14C]KE-298 was rapidly and almost completely absorbed after oral administration, and was well distributed throughout the body. In plasma, only a small amount of unchanged KE-298 was detected and the major component was an active metabolite, deacetyl-KE-298, which accounted for approximately 50% of the radioactivity in the plasma. Further evidence was obtained by 1H-NMR analysis that deacetyl-KE-298 existed as ketone-thiol and thiohemiacetal forms in a tautomeric equilibrium. As the second main metabolite in plasma, S-methyl-KE-298, a methyl conjugate of deacetyl-KE-298, was detected. Neither deacetyl-KE-298-amino acid mixed disulfide nor any disulfide of the drugs was found. Though a thiol-containing drug generally remains in the body due to the formation of mixed disulfide with protein, no evidence of retained radioactivity was found in any tissues after the administration of [14C]KE-298. Further, in the ex vivo studies of plasma protein binding, the formation of drug-protein conjugate was scarcely detected. These results suggest that the metabolic pattern of deacetyl-KE-298 is different from that of common thiol-containing drugs, and that the reactivity of the thiol moiety of deacetyl-KE-298 to protein is extremely low. This property of deacetyl-KE-298 may be principally responsible for the nonaccumulation of radioactivity in the tissues after the administration of [14C]KE-298.

Animals↗