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Biomedical subjects

Y Iwaki

Publications and source records attributed to Y Iwaki.

At least 19 recordsLinked to original sources
PubMed2006

Successful living related kidney transplantation across an anti-donor HLA antibody.

In preconditioning highly sensitized kidney transplant candidates, renal allograft outcomes have been better when the serum titer for class I anti-HLA donor-specific antibody (DSA) is low in the recipient at the time of transplantation. However, the ideal level to which the titer should be lowered is still controversial. We report a primary living related kidney transplant in a 34-year-old highly sensitized woman (pretransplant panel-reactive antibody=70%) with end-stage renal disease secondary to chronic glomerulonephritis. We sought to desensitize by lowering the DSA titer specifically to 1:4 pretransplant. A standard complement-dependent cytotoxicity cross-match with her donor (sister) was repeatedly negative, although she was positive for class I antibody against her mismatched HLA antigen (A*2402) at a titer up to 1:16 by the single-antigen flowbead assay. The target DSA titer of 1:4 before transplant was achieved by 12 sessions of plasmapheresis (PP) over 7 weeks, plus two intravenous immune globulin infusions (IVIG) (500 mg/kg/infusion). The patient outcome was excellent. Neither IVIG nor PP was needed posttransplant. The serum creatinine ranged between 0.5 mg/dL and 1.2 mg/dL, and no rejection episode was documented at 28 weeks posttransplant. Therefore, we encourage the use of IVIG and PP to lower the DSA titer to at least 1:4 before kidney transplantation in highly sensitized patients. Large prospective trials are needed to establish a consensus for pretransplant risk assignment and to evaluate the need for desensitization.

Adult↗
PubMed2005

Renal biopsy donor group: the influence of glomerulosclerosis on transplant outcomes.

The UNOS donor population was examined from 1999 to 2002, and approximately 25% of the over 23,000 donors were biopsied (Bx). There was a significant trend (P < .001) of older donors, cardiovascular accident, and hypertension in the Bx group versus the non-Bx group. The percent GS was directly correlated (P < .001) to graft survival, delayed graft function, and primary nonfunction. Cox regression showed significant relative risk (RR) for >10% GS, hypertension, donors over the age of 50, and African American recipients. RR in donors with >10% GS could be ameliorated (P < .001) by choosing donors with <5 HLA-A, -B, or -DR mismatches (MM), or recipients who were nonsensitized, and/or first transplant. Risk should be managed in donors by choosing appropriate recipients and high-risk immunosuppresion protocols.

Adult↗
PubMed2005

Average P/F ratio during donor management for finding out the potential donor of lung procurement.

We investigated the potential donors from cases without lung procurement in spite of considering procurement as the donor. We reviewed 207 cases considered for lung procurement. Donors were divided into 2 groups according to whether or not their lungs were harvested: 50 did and 157 did not. We investigated their age, gender, donor management periods, blood pressure, heart rate, P/F ratio, PCO2, HCO3, positive end-expiratory pressure (PEEP), respiratory rate, abnormal findings in the chest X-ray, blood chemistries, sputum culture, and intravenous administration of steroid. Univariable or multivariable logistic regression analysis was used to predict lung harvesting by various factors. Univariable logistic regression analysis revealed maximum heart rate (HR) and respiratory rate (RR), maximum, minimum, and average P/F ratio, and abnormal findings in the chest X-ray, to be predictors to perform transplant. The maximum HR and RR of the non-harvest group are higher than those of the harvest group. Multivariable logistic regression analysis revealed average P/F ratio only to be a predictor to transplant. We divided the non-harvest group into 2 groups according to whether or not their P/F ratio was >300: 55 did (P/F 300 group) and 102 did not (P/F 299 group). Between P/F 299 group and the harvest group, univariable logistic regression analysis revealed maximum HR, maximum and minimum RR, maximum PEEP, maximum, minimum, and average P/F ratio, and abnormal findings in the chest X-ray to be predictors to transplant. Maximum HR, PEEP, and maximum and minimum RR of the P/F 299 group are higher than those of the harvest group. Maximum, minimum, and average P/F ratio of the P/F 299 group are lower than those of the harvest group. The average PCO2 of P/F 299 group is higher than that of the harvest group. The rate of abnormal findings in the chest X-ray of the P/F 299 group is higher than that of the harvest group. Multivariable logistic regression analysis revealed average P/F ratio only to be a predictor to transplant. There were no predictors between the P/F 300 group and the harvest group in both univariable and multivariable logistic regression analyses. Furthermore, there were no different factors between the P/F 300 group and the harvest group. Our study showed that 35.5% of the non-harvest group had a P/F ratio of >300 and had no difference compared with the harvest group. Our data suggest that potential donors existed in the non-harvest group and increased the number of lung procurement to 27.3% from 13.0% of all donors.

Blood Pressure↗
PubMed2004

Multiplexed analysis of polymorphisms in the HLA gene complex using bead array chips.

A novel custom bead array technology is introduced, and it is applied to multiplexed analysis of highly polymorphic human leukocyte antigen (HLA) genetic loci. Our technology combines the construction of probe libraries on color-encoded microparticles (beads) with semiconductor chip processing to produce custom-designed high-density bead array chips in large quantities. Using this novel assay format, two modes of parallel molecular typing of the HLA complex were implemented, namely direct hybridization, illustrated here for class II HLA-DR, and a novel format of on-chip polymerase-mediated primer elongation, illustrated here for class I HLA-A, HLA-B, and HLA-DR using patient and reference cell-line DNA samples. Hybridization-mediated multiplexed analysis of polymorphism method was validated with 142 samples, resulting in 100% concordance with sequence-specific oligonucleotide typing results and a concomitant average of 40% less allele ambiguity. In addition, elongation and hybridization reactions were combined to identify multiple polymorphisms on the same phase of DNA for allele identification.

HLA Antigens↗
PubMed2002

Clinical, electrophysiological, and serological overlap between Miller Fisher syndrome and acute sensory ataxic neuropathy.

We report a patient with severe sensory ataxia, areflexia, and ophthalmoplegia with preservation of limb muscle strength. Electrophysiological examinations revealed peripheral sensory nerve involvement. A serological examination showed the elevation of IgG antibodies to various b-series gangliosides as well as GT1a. These indicated that this case is an overlap between acute sensory ataxic neuropathy and Miller Fisher syndrome. Autoantibody is implicated as potential pathogenic agents in some cases of acute sensory ataxic neuropathy.

Acute Disease↗
PubMed2001

[Effect of different concentrations of tranilast on posterior capsule opacification].

PURPOSE: To evaluate the effect of different concentrations(0.5, 1.0, 2.0%) of tranilast eyedrops in preventing fibrous posterior capsule opacification (PCO) in rabbits. METHODS: Experimental phacoemulsification procedures and in-the-bag placement of intraocular lens(IOL) implant were performed. An anterior eye segment analysis system(EAS-1000, Nidek Co, Ltd) was used to evaluate the degree of PCO during 5 weeks after surgery. RESULTS: The development of PCO was significantly suppressed in the eyes treated with tranilast eyedrops from 1 week after surgery. The mean PCO density after treatment with 0.5% tranilast was 59.1 +/- 9.3 (mean deviation +/- standard error) and 57.1 +/- 8.2, while for 1.0% tranilast it was 40.1 +/- 6.8 and 46.6 +/- 8.4, and for 2.0% tranilast it was 38.5 +/- 6.0 and 37.5 +/- 5.6 (computer compatible tape, CCT) at 1 week and 5 weeks, respectively. In the control group, the mean PCO density was 89.3 +/- 10.4 and 137.4 +/- 32.8 at 1 week and 5 weeks, respectively(p < 0.05). However, no significant statistical difference was observed in any of the findings for the 3 different tranilast concentrations. CONCLUSION: These results suggest that the 0.5% tranilast eyedrops, which are already available on the market, are sufficiently effective for inhibiting PCO.

Animals↗
PubMed2000

Differentiation of responses to allergenic and irritant compounds in mouse popliteal lymph node assay.

The mouse popliteal lymph node assay (PLNA) has been proposed as an immunotoxicological test to predict allergenic chemicals. However, PLN response is also observed in association with non-specific activation induced by some irritants. We, therefore, examined the kinetics of the PLN cellularity indices of primary and secondary responses. Flow cytometric analysis was used to measure the proportions of T and B cells in PLN. Male ICR mice were subcutaneously injected with TNBS (an allergenic compound) or SDS (an irritant compound) in the left hind footpad, and with vehicle in the right one. On day 28 after first injection, mice were injected with 1/10 or 1/100 dose of the initial injection. On day 7 after first injection of TNBS, primary response reached maximal PLN cellularity index (16.5). On day 2 after second injection, secondary response reached maximal PLN cellularity index (13.1). A marked increase in proportion of B cells was observed in the PLN. On the other hand, after first injection of SDS, primary response reached maximal PLN cellularity index (2.8) on day 10, but neither secondary response nor increase in the B cell proportion were observed. These results suggest that the detection of secondary response and the flow cytometric analysis are useful in differentiating responses to allergenic and irritant compounds in the PLNA.

Allergens↗
PubMed2000

Type 1 diabetes mellitus caused by treatment with interferon-beta.

A 57-year-old man was referred to our outpatient clinic after interferon-beta (IFN-beta) treatment for 7 weeks. While IFN-beta therapy was continued in our outpatient clinic, his blood glucose level increased gradually, and he was admitted to our hospital for hyperglycemia. The patient was prescribed a 1,600-kcal diet and intensive insulin therapy was performed. GAD antibody became positive 15 months after the start of IFN therapy, and disappeared 27 months after the start of IFN therapy. Insulin secretion was depleted and the patient had HLA-DR4, B54, and DRB1*0405. This appears to be a case of type 1 diabetes mellitus induced by administration of IFN-beta alone.

Antiviral Agents↗
PubMed2000

Gene delivery to human chondrocytes by an adeno associated virus vector.

OBJECTIVE: To investigate the efficiency of gene transduction to human chondrocytes using an adeno associated virus (AAV) vector. METHODS: We transduced green fluorescent protein (GFP) gene using AAV vector to primary human chondrocytes as well as human cartilage organ cultures, in which chondrocytes are surrounded by extracellular matrix. Expression of GFP gene was analyzed at various time points after transduction by fluorescence microscopy and immunohistochemistry. RESULTS: In primary chondrocytes, the percentages of GFP positive cells were 15.9% or 16.0% on Day 1 and 95.0% or 93.7% on Day 7 after gene transduction. In cartilage organ cultures, gene delivery was observed in cells located not only in the superficial layer but also in the deep layer within the cartilage tissue. Up to 45.3+/-7.4% or 46.0+/-3.9% of chondrocytes expressed GFP for at least 28 days. CONCLUSION: AAV vector could be useful for direct gene delivery to chondrocytes in situ.

Adenoviridae↗
PubMed2000

[Poison elimination methods in acute poisoning].

This paper presents current ideas about the application of poison elimination methods in acute poisoning. The methods are divided into two groups: poison elimination before absorption; and enhancement of elimination after drug absorption. The former include washes, emesis, gastric lavage, and administration of activated charcoal and cathartics, while the latter include forced diuresis and extracorporeal toxin elimination such as hemodialysis or hemoperfusion. The indications, contraindications, techniques, and complications, associated with these elimination methods, except for extracorporeal toxin elimination, are discussed. In the treatment of poisoning, early and comprehensive poison elimination is important.

Acute Disease↗
PubMed1999

Effect of tranilast eyedrops in preventing posterior capsule opacification: preliminary report.

PURPOSE: To evaluate the effect of tranilast eyedrops in preventing fibrous opacification of the posterior lens capsule after cataract extraction and intraocular lens (IOL) implantation. SETTING: The Second Department of Ophthalmology, Toho University School of Medicine, Tokyo, and Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, Japan. METHODS: This study comprised eyes having continuous curvilinear capsulorhexis and phacoemulsification/aspiration followed by implantation of a posterior chamber IOL in the capsular bag. In this prospective, randomized, controlled, and double-masked trial, tranilast 0.5% (Rizaben) eyedrops (15 eyes) or its placebo eyedrops (20 eyes) were given 4 times a day for 3 months after surgery. An anterior eye segment analysis system (EAS 1000, Nidek Co., Ltd.) was used to evaluate the degree of fibrous posterior capsule opacification (PCO) 1 week and 1 and 3 months after surgery. RESULTS: The mean PCO density in the tranilast group was 17.1 cct +/- 4.6 (SD), 20.0 +/- 3.6 cct, and 23.0 +/- 7.7 cct (cct = computer compatible tape) at 1 week and 1 and 3 months, respectively. In the control group, it was 18.2 +/- 5.3, 30.2 +/- 7.8, and 38.4 +/- 8.0 cct, respectively. There was a significant difference in the 1 and 3 month findings between the 2 groups (P < .001). CONCLUSION: Tranilast was effective in preventing fibrous PCO at an early postoperative stage. The possible mechanisms of its effect may be prevention of collagen synthesis by minimizing transforming growth factor type beta released during lens epithelial cell metaplasia.

Aged↗
PubMed1999

Isolation of recombinant adeno-associated virus vector-cellular DNA junctions from mouse liver.

Recombinant adeno-associated virus (rAAV) vectors allow for sustained expression of transgene products from mouse liver following a single portal vein administration. Here a rAAV vector expressing human coagulation factor F.IX (hF.IX), AAV-EF1alpha-F.IX (hF.IX expression was controlled by the human elongation factor 1alpha [EF1alpha] enhancer-promoter) was injected into mice via the portal vein or tail vein, or directly into the liver parenchyma, and the forms of rAAV vector DNA extracted from the liver were analyzed. Southern blot analyses suggested that rAAV vector integrated into the host genome, forming mainly head-to-tail concatemers with occasional deletions of the inverted terminal repeats (ITRs) and their flanking sequences. To further confirm vector integration, we developed a shuttle vector system and isolated and sequenced rAAV vector-cellular DNA junctions from transduced mouse livers. Analysis of 18 junctions revealed various rearrangements, including ITR deletions and amplifications of the vector and cellular DNA sequences. The breakpoints of the vector were mostly located within the ITRs, and cellular DNA sequences were recombined with the vector genome in a nonhomologous manner. Two rAAV-targeted DNA sequences were identified as the mouse rRNA gene and the alpha1 collagen gene. These observations serve as direct evidence of rAAV integration into the host genome of mouse liver and allow us to begin to elucidate the mechanisms involved in rAAV integration into tissues in vivo.

Animals↗
PubMed1999

Mouse popliteal lymph node assay for assessment of allergic and autoimmunity-inducing potentials of low-molecular-weight drugs.

In the present collaborative study, popliteal lymph node (PLN) responses to penicillin G (an allergenic chemical), D-penicillamine (an autoimmunity-inducing chemical), and barbital (a negative reference chemical) were investigated in three different mouse strains by ten pharmaceutical companies. Two inbred mouse strains (BALB/c and A/J) and one outbred strain (ICR) were subcutaneously injected with saline solutions containing penicillin G (1.25, 2.5 and 5 mg/mouse), D-penicillamine (0.5, 1 and 2 mg/mouse), or barbital (2 mg/mouse) into one hind footpad and saline only was injected into the contralateral footpad. PLN cellularity indices were determined on day 7. In the three strains tested, the penicillin G and D-penicillamine injections resulted in approximately dose-dependent responses. In contrast, barbital failed to generate a significant PLN reaction. In the typical data from one of the participating laboratories, the PLN responses of A/J, BALB/c, and ICR to penicillin G were high, intermediate and low, respectively, while their PLN responses to D-penicillamine were all high. Some variation in PLN cellularity indices was observed among the participating laboratories, but reproducibility of the popliteal lymph node assay (PLNA) evaluation was partly confirmed. Although the appropriate selection of mouse strains and drug dosage levels has to be considered, these results suggest that the PLNA may be an appropriate screening system for prediction of the allergic or autoimmunity-inducing potentials of low-molecular-weight drugs.

Allergens↗
PubMed1999

The influence of donor age on kidney graft survival in the 1990s.

Based on analyses of the UNOS Registry data for cadaver kidney transplants performed between 1991-1999 we showed that: 1. 15-40 year old donor kidneys provided the best one-year graft survival rates. When donors were analyzed with recipients, younger (0-10) and older (70-90) donors and recipients (Table 2) had the lowest one-year graft success rates. 2. Chronic loss rate, the constant rate of graft loss between one and 5 years, showed younger donor kidneys had a significantly lower chronic loss rate compared with each older donor category. Apparently the younger donor kidneys have a resiliency and nephron reserve that provides better long-term function. However, they may have lower short-term (1-yr) graft survival rates, possibly due to their small size. 3. Black and White donor kidneys had similar one-year graft survival rates; however, in every age group, recipients of White donor kidneys had significantly better 5-year graft survival rates than Black donor kidneys. There was also a noticeably lower chronic loss rate among recipients of White than Black donor kidneys. 4. HLA-matched White donor kidneys had better one- and 5-year graft survival rates and lower chronic loss rates than HLA-mismatched kidneys. The matching effect was lost when the donor age increased beyond age 40. PRA had an effect both at one and 5 years after transplantation. The chronic loss rate was similar with high and low PRA. Therefore, PRA had a relatively short-term effect. 5. Cold ischemia time had a modest effect after 35 hours both at one and 5 years. However, the chronic loss rate was unaffected by CIT, suggesting prolonged ischemia time had a relatively short-term effect. 6. More focused attention on sensitization and lowered CIT can both have a significant effect on short-term graft survival rates. However, both matching and younger donor organs provide the best opportunity for better long-term graft success rates.

Adolescent↗
PubMed1998

Adeno-associated viral vector-mediated gene transfer of human blood coagulation factor IX into mouse liver.

Recombinant adeno-associated virus vectors (AAV) were prepared in high titer (10(12) to 10(13) particles/mL) for the expression of human factor IX after in vivo transduction of murine hepatocytes. Injection of AAV-CMV-F.IX (expression from the human cytomegalovirus IE enhancer/promoter) into the portal vein of adult mice resulted in no detectable human factor IX in plasma, but in mice injected intravenously as newborns with the same vector, expression was initially 55 to 110 ng/mL. The expression in the liver was mostly transient, and plasma levels decreased to undetectable levels within 5 weeks. However, long-term expression of human F.IX was detected by immunofluorescence staining in 0.25% of hepatocytes 8 to 10 months postinjection. The loss of expression was likely caused by suppression of the CMV promoter, because polymerase chain reaction data showed no substantial loss of vector DNA in mouse liver. A second vector in which F.IX expression was controlled by the human EF1alpha promoter was constructed and injected into the portal vein of adult C57BL/6 mice at a dose of 6.3 x 10(10) particles. This resulted in therapeutic plasma levels (200 to 320 ng/mL) for a period of at least 6 months, whereas no human F.IX was detected in plasma of mice injected with AAV-CMV-F.IX. Doses of AAV-EF1alpha-F. IX of 2.7 x 10(11) particles resulted in plasma levels of 700 to 3, 200 ng/mL. Liver-derived expression of human F.IX from the AAV-EF1alpha-F.IX vector was confirmed by immunofluorescence staining. We conclude that recombinant AAV can efficiently transduce hepatocytes and direct stable expression of an F.IX transgene in mouse liver, but sustained expression is critically dependent on the choice of promoter.

Adult↗