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Biomedical subjects

T Tanikawa

Publications and source records attributed to T Tanikawa.

At least 19 recordsLinked to original sources

Production of IgA monoclonal antibody against Shiga toxin binding subunits employing nasal-associated lymphoid tissue.

We established an IgA monoclonal antibody (mAb) against Shiga toxin 1 B subunits (Stx1B) from mouse nasal-associated lymphoid tissues (NALT) of BALB/c mice. We have developed an improved protocol in which cross-linked Stx1B is intranasally administered together with cholera toxin. Surface IgA-positive NALT lymphocytes from mice immunized in this manner were enriched and then fused with mouse myeloma cells to produce hybridoma cells. Hybridoma culture supernatants were examined to see if they contain IgA against Stx1B and if they can inhibit carbohydrate recognition by Stx1B. For the latter purpose, we prepared carbohydrate ligands in which globotriose is present on the poly-lysine backbone. The established IgA mAb exhibited saturable and dose-dependent binding to the immobilized Stx1B. Inversely, the binding of the carbohydrate ligands to the immobilized Stx1B was inhibited by the mAb pretreatment. Immunoblotting and SDS-PAGE analysis revealed dimeric IgA. The IgA mAb inhibited the binding of digoxigenin-conjugated Stx1B to natural ligands displayed on a Burkitt's lymphoma cell line, Ramos. These results suggested that surface IgA-positive B cells in the inductive sites of the mucosal immune system in the upper respiratory tract are a potent source for producing IgA mAb against protein antigens with weak immunogenicity such as Stx1B.

Animals↗

Synthesis and antibacterial activity of acylides (3-O-acyl-erythromycin derivatives): a novel class of macrolide antibiotics.

Introduction of an acyl group to the 3-O-position of erythromycin A derivatives instead of L-cladinose led to a novel class of macrolide antibiotics that we named "acylides". The 3-O-nitrophenylacetyl derivative TEA0777 showed significantly potent activity against not only erythromycin-susceptible Gram-positive pathogens but also inducibly macrolides-lincosamides-streptogramin B (MLS(B))-resistant Staphylococcus aureus and efflux-resistant Streptococcus pneumoniae. These results indicated that acylides have potential as next-generation macrolide antibiotics.

Animals↗

Suppression of CYP3A2 mRNA expression in the warfarin-resistant roof rat, Rattus rattus: possible involvement of cytochrome P450 in the warfarin resistance mechanism.

1. The continual use of warfarin as a rodenticide has caused the development of populations of warfarin-resistant roof rat. To study the biochemical mechanism of warfarin resistance, the mRNA expression levels of the major P450 forms in the warfarin-resistant and -susceptible roof rat liver following exposure to warfarin were quantified by competitive RT-PCR. 2. The constitutive levels of CYP2C11 and CYP3A2 mRNAs in the warfarin-resistant and -susceptible roof rat were extremely low compared with those in the STD rat. In response to warfarin administration, the CYP3A2 mRNA level in the warfarin-susceptible rat increased to about 3-fold of that before the treatment, whereas in the warfarin-resistant roof rat, CYP3A2 mRNA remained at a low level. 3. The present results suggest the possibility that reduced synthesis of CYP3A2 mRNA is involved in the warfarin-resistant mechanism in the roof rat.

Animals↗

[Prostate cancer].

Carcinoma of the prostate constitutes a major and escalating international health problem. In many developed countries prostate cancer is the most commonly diagnosed malignancy in men, and seems to overtake lung cancer as major cause of cancer mortality. In Japan mortality of the prostate cancer is relatively low, but future incidence and mortality of the prostate cancer will be dramatically increased. Risk factors of the prostate cancer were well known as Western-type lifestyle and diet. Carcinoma of the prostate are detected early by prostatic specific antigen and systematic trans-rectal ultrasonography guided prostatic needle biopsy. Once prostate cancer has been diagnosed in a patient, histologically graded, and staged as accurately as possible, clinicians are duty bound to offer the best advice about treatment options, even though the risks and benefits of competing therapies. Radical prostatectomy and radiation therapy are known as treatment of localized prostate cancer, antiandrogen therapy is known as treatment of advanced prostate cancer. Alternative approaches utilizing, for example microable inhibitors, inhibitor of growth factors and gene therapy also hold exciting promise.

Biomarkers, Tumor↗

Use of miniature ultrasonic probe system for intravesical ultrasonography for transitional cell cancer of the urinary tract.

OBJECTIVE: We describe the use of a miniature ultrasonic probe (MUP) system for intravesical ultrasonography for staging of urinary bladder and/or ureteral tumors. MATERIAL AND METHODS: Seventeen patients with bladder tumors were enrolled in this study. Probes (8 F; 15 and 20 MHz) were inserted through a channel in a 22 F rigid cystoscopy sheath. RESULTS: Using the MUP, each tumor could be scanned under simultaneous cystoscopic observation to choose the optimal probe position. However, in 4 of 17 patients optimal scanning could not be obtained because of large tumors and poor ultrasound penetration or because of tumor localization at the anterior dome which did not allow an appropriate scanning plane for staging. Of 13 evaluable patients, 5 with no interruption or folding of the low-echoic muscle layer were diagnosed as having a superficial tumor, and this was confirmed histopathologically in all but one case. All 8 cases evaluated as having invasive tumors demonstrated muscle invasion histologically. CONCLUSION: The MUP can be more easily manipulated than a conventional probe.

Adult↗

Role of pertussis toxin-sensitive G protein in metabolic vasodilation of coronary microcirculation.

We have previously demonstrated that pertussis toxin (PTX)-sensitive G protein (G(PTX)) plays a major role in coronary microvascular vasomotion during hypoperfusion. We aimed to elucidate the role of G(PTX) during increasing metabolic demand. In 18 mongrel dogs, coronary arteriolar diameters were measured by fluorescence microangiography using a floating objective. Myocardial oxygen consumption (MVO(2)) was increased by rapid left atrial pacing. In six dogs, PTX (300 ng/ml) was superfused onto the heart surface for 2 h to locally block G(PTX). In eight dogs, the vehicle (Krebs solution) was superfused in the same way. Before and after each treatment, the diameters were measured during control (130 beats/min) and rapid pacing (260 beats/min) in each group. Metabolic stimulation before and after the vehicle treatment caused 8.6 +/- 1. 8 and 16.1 +/- 3.6% dilation of coronary arterioles <100 microm in diameter (57 +/- 8 microm at control, n = 10), respectively. PTX treatment clearly abolished the dilation of arterioles (12.8 +/- 2. 5% before and 0.9 +/- 1.6% after the treatment, P < 0.001 vs. vehicle; 66 +/- 8 microm at control, n = 11) in response to metabolic stimulation. The increases in MVO(2) and coronary flow velocity were comparable between the vehicle and PTX groups. In four dogs, 8-phenyltheophylline (10 microM, superfusion for 30 min) did not affect the metabolic dilation of arterioles (15.3 +/- 2.0% before and 16.4 +/- 3.8% after treatment; 84.3 +/- 11.0 microm at control, n = 8). Thus we conclude that G(PTX) plays a major role in regulating the coronary microvascular tone during active hyperemia, and adenosine does not contribute to metabolic vasodilation via G(PTX) activation.

Animals↗

Expression of E-cadherin and catenins on testis tumor.

E-cadherin (ECD) is a homophilic Ca(2+)-dependent adhesion molecule associated with cell-to-cell interactions and normal growth. Recent reports have suggested that decrease or loss of ECD facilitates tumor progression and/or metastasis. ECD functions in a complex called an adherens junction, which includes several other proteins including alpha- and beta-catenin. In the present study, fresh-frozen sections from 32 testis cancers, 16 seminomas and 16 non-seminomatous germ cell tumors (NSGCT), were examined immunohistochemically. E-cadherin was not expressed on normal germ cells, but expressed on 3 (18.8%) of 16 seminomas and 10 (62.5%) of 16 NSGCTs, mainly on the epithelial component of teratoma cells. alpha-Catenin was detected on 0 (0%) of 13 seminomas and 4 (25%) of 16 NSGCTs. beta-Catenin was detected on 10 (71.4%) of 14 seminomas and 13 (81.2%) of 16 NSGCTs. ECD was detected significantly more frequently on NSGCTs than on seminomas. Immunoblot analysis confirmed the expression of ECD and beta-catenin in NSGCTs. Expression of ECD and catenins may reflect the degree of differentiation and provide some information on the character of the tumor.

Adult↗

Effect of diadenosine tetraphosphate (AP4A) on coronary arterial microvessels in the beating canine heart.

Diadenosine tetraphosphate (AP4A) can be released from activated platelets and the present study examined its effect on coronary arterial microvessels. The role of purinoceptors in the coronary microcirculation in vivo was also investigated. In open chest dogs, coronary arterioles were observed using a microscope with a floating objective. In Protocol 1, AP4A (1, 10, 100 and 1,000 micromol/L) was superfused onto the heart surface before and during the superfusion of 10 micromol/L of 8-phenyltheophylline (8-PT), a P1 purinoceptor blocker. In Protocol 2, AP4A (0.1, 1, 10, and 100 nmol x kg(-1) x min(-1)) was infused into the left anterior descending coronary artery before and during the superfusion of 10 micromol/L of 8-PT. In addition to 8-PT, 30 micromol/L of pyridoxalphosphate-6-azophenyl 2',4'-disulphonic acid (PPADS), a P2X purinoceptor blocker in Protocol 3, or 300 micromol/L of N(omega)-nitro-L-arginine (LNNA) in Protocol 4, was continuously superfused, and 4 doses of AP4A were cumulatively superfused as in Protocol 1. In Protocol 5, 10 micromol/L of alpha,beta-methylene ATP, an agonist of P2X purinoceptors, was superfused for 60 min. Superfused AP4A dilated arterioles in a dose-dependent manner. The magnitude of dilatation was greater in smaller arterioles (small vessel < or = 150 microm: 24.5+/-2.2% vs large vessel > 150 microm: 10.6+/-1.5% at a dose of 1,000 micromol/L, p<0.001). On the other hand, intraluminally applied AP4A also dilated arterioles, but no size dependency was shown. In the presence of 8-PT, vasodilatory responses to superfused and intraluminally applied AP4A were attenuated and the lower doses of AP4A constricted arterioles. This vasoconstrictor effect was not affected by PPADS. The vasodilatory effect of the higher doses of AP4A was almost abolished in the presence of LNNA. Alpha,beta-methylene ATP had no effect on coronary microvascular diameters. AP4A has bidirectional effects on coronary arterial microvessels: vasodilatory effects mediated by P1 purinoceptors and NO, which might be mediated by P2Y purinoceptors, and a vasoconstrictor effect, which is not mediated by P2X purinoceptors.

Adenosine Triphosphate↗

Significance of serum-soluble CD95 (Fas/APO-1) on prognosis in renal cell cancer patients.

Serum-soluble CD95 (sCD95) levels for 72 renal cell cancer patients were significantly higher than those of 17 healthy donors. Twenty-one of 72 patients had elevated (defined as more than mean of healthy donors + 2 s.d.) sCD95. The disease-specific survival rate was significantly lower in the elevated sCD95 group. Serum sCD95 level was shown to be an independent prognostic factor by univariate and multivariate analysis, indicating a possible significant role in determining treatment strategies.

Adult↗

Recurrence of IgA nephropathy 17 months after renal transplantation in the allograft transmitted thin basement membrane disease (TBMD) from donor.

Recurrence of IgA nephropathy (IgAN) following renal transplantation has been described in 40-50% of such patients and it usually has a good outcome. We present the case of a 20-yr-old woman with IgAN who developed end-stage renal failure in 1995. In November 1996, she received a kidney from a living-related donor and was treated with tacrolimus, azathioprine and steroids. Zero- and one-hour biopsies were performed, which revealed minor glomerular abnormalities in light microscopy, thin basement membrane disease (TBMD) in electron microscopy. Eight months later she developed microscopic hematuria and proteinuria; however, the graft function was normal. Renal biopsy revealed an IgAN that is thought to be due to recurrence of the original disease.

Adult↗

Adoptive immunotherapy of patients with metastatic renal cell cancer using lymphokine-activated killer cells, interleukin-2 and cyclophosphamide: long-term results.

BACKGROUND: Initial results of adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) appeared to offer promise for treating renal cell cancer (RCC). However, lower response rates were seen in subsequent trials, and the long-term results of this treatment method have not been fully reported. In this study, we examine long-term results of adoptive immunotherapy using LAK cells, IL-2, and cyclophosphamide (LAK/IL-2/CPM therapy). METHODS: We administered 10 courses of therapy to 9 patients with advanced RCC. One patient had liver and para-aortic lymph node metastases; the others had only lung metastases. The clinical effects were initially evaluated 4 weeks after therapy and follow-up was continued for periods of 43 to 76 months. RESULTS: The 4-week evaluation revealed 3 complete responses (CR), 3 partial responses (PR), 1 minor response (MR), 1 patient with no change in disease status (NC), and 2 patients whose disease progressed (PD). One CR patient remained apparently free of disease for 43 months. After tumors recurred in the lung of another CR patient further disease progression was suppressed by IL-2 administration until the patient died from other causes at 46 months. The third CR patient showed tumor recurrence in the lung and was re-treated with the same LAK/CPM/IL-2 therapy. Lung tumors decreased in size (PR), but the patient died due to brain metastasis 2 months after the second round of treatment. The 2 initial PR patients, as well as the MR and NC patients, developed regrowth or new metastatic lesions within 2 to 15 months following therapy. The 2 PD patients died 2 and 9 months after therapy. CONCLUSION: Long-term effects of LAK/IL-2/CPM therapy were not correlated with the maximal response observed 4 weeks after therapy. Although LAK/IL-2/CPM therapy appears suitable for use as induction therapy in RCC, our data suggest that long-term suppression will require surgical removal of remnant tumors or more intensive maintenance therapy.

Adult↗

Treatment of bilateral renal cell cancer and multiple lung metastasis: nephron-sparing surgery and resection of lung tumors after interleukin-2 therapy.

We report a case of bilateral renal cell cancer and multiple lung metastasis who was first treated with left radical nephrectomy and nephron-sparing surgery of the right kidney. Consecutive interleukin-2 administration achieved partial response in lung disease and residual tumors were surgically removed. The disease-free state has continued for 33 months.

Aged↗

Superior sagittal sinus thrombosis treated with combined local thrombolytic and systemic anticoagulation therapy.

We recently encountered a patient with thrombosis of the superior sagittal sinus of an idiopathic cause. The patient was treated initially with combined local thrombolytic therapy through the burr hole over the superior sagittal sinus and systemic anticoagulant therapy. Continuous ventricular drainage and hyperbaric oxygenation therapy were used to control the increased intracranial pressure. The superior sagittal sinus was successfully recanalized. Whereas the patient suffered a complication with subacute subdural haematoma, he was successfully treated with the combination of these therapies. The rationale and approach are discussed.

Anticoagulants↗

Split cannula method for accurate placement of an electrode for deep brain stimulation: technical note.

OBJECTIVE: We describe a "split cannula method" for accurate placement of a deep brain stimulation electrode. This method eliminates the risk of displacement of the electrode when withdrawing the outer guide cannula. METHOD: A separate short guide cannula is covered over the distal part of a long cannula for microrecording or macrostimulation. After confirmation of the stimulation point, the short cannula is fixed with an accessory-holding device and the long cannula is pulled out. The electrode for deep brain stimulation is inserted through the short cannula. Because this cannula is much shorter than the electrode, securing the stimulation electrode at any withdrawal stage of the outer guide cannula is always possible. RESULTS AND CONCLUSION: With this simple method, we experienced no displacement of the stimulation point during stereotactic insertion of a deep brain stimulation electrode. This method can be easily adapted to any stereotactic frame.

Brain↗