FK 506 abrogates induction of regulatory cells after intratracheal delivery of alloantigen.
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Biomedical subjects
Publications and source records attributed to Y Ikeda.
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The influence of tooth loss on the viability of cholinergic neurons was examined in rats. At 25th postnatal week, rats were divided into the three groups; a control group fed a solid diet, a soft diet group fed a powder diet and a molar crown-less group in which all molar crowns were removed and the powder diet was given. At 15 and 35 weeks post-treatment, the number of choline acetyltransferase (ChAT)-positive neurons in the nucleus of the diagonal band/medial septal nucleus (NDB/MS) was significantly smaller in the molar crown-less group than in the control group (P < 0.01). This was not the case in the pedunculopontine tegmental nucleus or (PPT) or in the trigeminal motor nucleus. Biochemical assay showed no statistically significant differences in choline concentrations in the hippocampus between the control and the molar crown-less group both at 15 and at 35 weeks post-treatment. Nevertheless, acetylcholine (ACh) concentration in the hippocampus of the molar crown-less group was significantly lower than that of the control group at 15 weeks post-treatment (P < 0.05). Taken together, a decrease of oral sensory information may have caused a reduction in the number of ChAT-positive neurons selectively in NDB/MS, which in turn caused a decline of ACh concentrations in the hippocampus.
The recent development of radioguided parathyroidectomy has allowed parathyroidectomy to be quickly performed by a significantly less invasive procedure. Radioguided parathyroidectomy is also likely to decrease operation time, risk of complications, hospital stay, and the overall cost of patient care, result in a smaller scar and rapid, nearly pain-free recovery, and allow local anesthesia. Despite these apparent benefits, a case-control study showed no distinct advantages of employing intraoperative sestamibi identification during parathyroidectomy.
Intraoperative quick parathyroid hormone (QPTH) assay is claimed to prevent failure during parathyroidectomy for hyperparathyroidism. The causes of operative failure have included multiglandular disease, ectopic parathyroid glands, supernumerary parathyroid glands, errors in frozen section evaluations, and missed diagnosis. A QPTH assay has been recognized as a useful method of determining whether hyperfunctioning tissues have been completely excised. However, an intraoperative QPTH assay may fail to detect the presence of double parathyroid adenomas. Use of this assay in conjunction with preoperative and intraoperative localization studies has led to the advocacy of more directed cervical procedures, such as limited, video-assisted, and endoscopic parathyroidectomy.
During the last five years, minimally invasive procedures have been adopted for the surgical treatment of hyperparathyroidism, because preoperative localization studies such as high-resolution ultrasonography and sestamibi scintigraphy, guidance by intraoperative scans, and the use of quick, intraoperative parathyroid hormone assay have improved. Endoscopic parathyroidectomy was performed by Gagner in 1996, and surgical procedures using endoscopy have been devised. The endoscopic procedures range from the "pure" endoscopic approach characterized by constant gas insufflation to video-assisted gasless techniques. We adopted the "pure" endoscopic approach, because a small incision can be made far from the neck and the cosmetic result is excellent. We report our technique with no scars in the neck region for endoscopic unilateral neck exploration with primary hyperparathyroidism and for endoscopic bilateral neck exploration with renal hyperparathyroidism.
We have developed endoscopic thyroidectomy by an anterior chest approach and an axillary approach. In this study, we evaluate the efficacy of these two types of endoscopic procedures and conventional open surgery. The degree of surgical invasiveness and the nature of patients' complaints after surgery were compared using the results of the operation and a questionnaire. The mean operating time for the endoscopic procedure was significantly longer than that for open surgery; however, there was no difference in postoperative pain in the three groups. Three months after surgery, the incidence of discomfort while swallowing in open surgery was higher than that in endoscopic surgery. All the patients who were treated using the axillary approach were satisfied with the cosmetic results. However, five patients (25%) who were treated using the anterior chest approach and 15 patients (75%; P < 0.01) who underwent open surgery complained abut the cosmetic results. The incidence of postoperative complaints after endoscopic surgery is significantly lower than that after open surgery. Patients who were treated using the axillary approach can obtain superior cosmetic results, compared with those who received other procedures.
The subject of performing prophylactic or elective modified dissections of the neck in patients with clinically occult lymph nodal metastases from thyroid cancers is controversial since metastases to lymph nodes are associated with high rates of recurrences. Biopsies of sentinel lymph nodes can be performed successfully in patients with thyroid cancers since they can be identified with dyes or 99mTc. Our preliminary findings indicate that biopsies of sentinel lymph nodes can be useful in the treatment of thyroid cancers; however, the clinical significance of identifying metastases in regional lymph nodes by this technique remains to be determined.
Since corticosteroids are indispensable hormones, partial or cortical-sparing adrenalectomies may be adopted for the surgical treatment of adrenal diseases. In this article, we describe the technique and results of these procedures. Laparoscopic partial or cortical-sparing adrenalectomy has been performed in 10 patients. Seven cases had an aldosterone-producing adenoma (APA) and three had a pheochromocytoma. Three cases with an APA and a case with a pheochromocytoma had tumors located far from the adrenal central vein, and the vein could be preserved. Four cases with an APA and two with a pheochromocytoma had tumors located close to the adrenal central vein, and it was necessary to section the central vein to resect them. All endoscopic procedures were performed successfully. There were no postoperative complications. At follow-up, adrenal 131I-adosterol scintigrams showed the preservation of remnant adrenal function in all patients. Laparoscopic partial or cortical-sparing adrenal surgery was safely performed, and adrenal function was preserved irrespective of whether the adrenal central vein could be preserved or not. We consider this to be a useful operative technique for selected cases.
More than 95% of patients with primary hyperparathyroidism have been treated with bilateral neck exploration by experienced surgeons. This procedure has been performed without employing preoperative localization tests or specialized techniques of intraoperative measurement. A renewed interest in unilateral neck exploration for primary hyperparathyroidism emerged (in three developments), in an attempt to maintain the excellent cure rate and to minimize the invasiveness of the procedure. The first development was the introduction of sestamibi scintigrams as a new preoperative localization technique and intraoperative nuclear mapping with a hand-held gamma probe. The localization of adenomas using this technique was much more accurate than that of previous localization studies, allowing unilateral procedures to become feasible. Sestamibi guidance enables parathyroidectomies to be performed much more rapidly through a significantly less invasive dissection. Secondly, the intraoperative quick parathyroid hormone assay allows the confirmation of removal of the parathyroid mass. The third development was endoscopic parathyroidectomy. Various approaches have been shown to be technically feasible, including endoscopic procedures that rely on CO2 insufflation to create a working space or video-assisted procedures in which the working space is maintained through conventional external retraction. Given the safety and high success rate of the standard exploration, the potential advantages of these new strategies include decreased operating time, local or regional anaesthesia rather then general anaesthesia, and smaller incisions.
We have prospectively evaluated the efficacy of real-time PCR-guided preemptive therapy for CMV diseases in allogeneic hematopoietic stem cell transplant recipients with grades II-IV acute GVHD. The dose of ganciclovir was adjusted according to the viral load determined by real-time polymerase chain reaction (PCR). On detecting CMV reactivation in the plasma, ganciclovir was initiated at a dose of 5 mg/kg body weight once daily, and the dose was increased to twice daily if viral load continued to increase after initiating ganciclovir. In 39 evaluable patients, CMV reactivation assessed by real-time PCR became positive in 30 (77%). One developed CMV gastroenteritis before PCR became positive. Thus the remaining 29 patients were treated preemptively with ganciclovir. The dose of ganciclovir was increased in 12 patients (41%) of preemptively treated patients for increasing viral load. CMV diseases were diagnosed in two patients (one gastroenteritis and one retinitis), and late CMV disease was diagnosed in one patient (gastritis). The treatment was generally well-tolerated, but three patients (10%) developed neutropenia (neutrophil count less than 1.0 x 10(9)/l). In conclusion, real-time PCR-guided preemptive therapy with decreased dose of ganciclovir is feasible and does not increase the frequency of CMV diseases if the dose is adjusted according to the viral load.
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Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.
The ability of human immunodeficiency virus (HIV)- and equine infectious anaemia virus (EIAV)-based vectors to transduce cell lines from a range of species was compared. Both vectors carried the vesicular stomatitis virus G (VSV-G) envelope protein and encoded an enhanced green fluorescent protein (eGFP) gene driven by a human cytomegalovirus (CMV) early promoter. Immunostaining for viral core proteins and VSV-G was used to demonstrate that the HIV and EIAV vector preparations contained similar numbers of virus particles. Various cell lines were transduced with these vectors and the transduction efficiency was estimated by measuring eGFP expression. Efficient transduction by both vectors was observed in human, hamster, pig, horse, cat and dog cell lines, although EIAV vector was about 10-fold less efficient in human, hamster and pig cells normalised to the total number of viral particles. This could be partly explained by the lower RNA genome levels per particle for EIAV as measured by real-time RT-PCR. Rodent cells appeared to be transduced inefficiently with both vectors, but when the CMV promoter was substituted with the EF1alpha promoter in the HIV vectors, the expression level increased leading to an increase in the measurable level of transduction.
BACKGROUND: Many studies have indicated that individuals with Down's syndrome (DS) show a specific deficit in short-term memory for verbal information. The aim of the present study was to investigate the influence of the length of words on verbal short-term memory in individuals with DS. METHODS: Twenty-eight children with DS and 10 control participants matched for memory span were tested on verbal serial recall and speech rate, which are thought to involve rehearsal and output speed. RESULTS: Although a significant word-length effect was observed in both groups for the recall of a larger number of items with a shorter spoken duration than for those with a longer spoken duration, the number of correct recalls in the group with DS was reduced compared to the control subjects. The results demonstrating poor short-term memory in children with DS were irrelevant to speech rate. In addition, the proportion of repetition-gained errors in serial recall was higher in children with DS than in control subjects. CONCLUSIONS: The present findings suggest that poor access to long-term lexical knowledge, rather than overt articulation speed, constrains verbal short-term memory functions in individuals with DS.
Regulation of acute-phase serum amyloid A (A-SAA) synthesis by proinflammatory cytokines and steroid hormones in human aortic smooth muscle cells (HASMCs) is distinct from that in HepG2 cells. To study the cis- and trans-activating promoter element involved in the SAA1 gene expression by HASMCs and HepG2 cells, we constructed plasmid vectors for luciferase reporter gene assay with varying lengths of SAA1 upstream regulatory region (up to 1431 bp), and examined their response to proinflammatory cytokines and/or steroid hormones. The corresponding vectors with the SAA4 upstream regulatory region served as controls. The presence of proposed transcriptional regulatory factors binding to these regions was confirmed immunohistochemically. The sequences of 1478 and 1836 bp of the SAA1 and SAA4 5'-flanking regions were determined, respectively. SAA1 promoter transcription in cultured HASMCs was upregulated not by proinflammatory cytokines, but rather by glucocorticoids. This differed from HepG2 cells, in which SAA1 promoter transcription was upregulated synergistically by proinflammatory cytokines and glucocorticoids. The promoter activity of a series of truncated SAA1 promoter constructs measured using the reporter gene assay showed that the 5'-region from -252 to -175, containing a consensus site for CCAAT/enhancer binding proteins alpha,beta (C/EBPalpha,beta), was essential for SAA1 induction in HASMCs. In HepG2 cells, the 5'-region from -119 to -79, containing a nuclear factor kappa-B (NFkappaB) consensus sequence, was essential for the induction. The functional significance of the C/EBP site as indicated by the immunohistochemical result was that in HASMCs anti-C/EBPbeta reactivity was shifted from the cytoplasm to the nuclei. We have, therefore, demonstrated that the region containing the C/EBPalpha,beta consensus binding site between the bases -252 and -175 is important for the glucocorticoid-induced SAA1 gene expression in HASMCs but not in HepG2 cells.
A 54-year-old woman developed polymyositis 6 months after allogeneic bone marrow transplantation (BMT) for acute myelogenous leukemia transformed from myelodysplasia. At the onset of myositis, the patient had oral dryness, and the histology of oral mucosa was compatible with chronic graft-versus-host disease (GVHD). Muscle biopsy revealed focal muscle necrosis with massive lymphocytic infiltration. She was diagnosed with polymyositis, and the dose of cyclosporine was increased. Three months later, a complete resolution of myositis had been obtained, and the cyclosporine was tapered off. However, 51 months after the first episode of myositis, she again noted severe myalgia and was diagnosed with a recurrence of polymyositis based on high serum creatinine kinase (CK) and the findings of magnetic resonance imaging (MRI). At that time, chronic GVHD in other organs was not present. She achieved a second remission of polymyositis with cyclosporine, and has remained in remission for 4 years. The pathogenesis of myositis can be attributed to the immunologic imbalance characteristic of the post-allogeneic BMT setting.
OBJECTIVE: To examine differences in autoantibody response and immunogenetic background between patients with systemic sclerosis (SSc) and those with other autoimmune diseases who had serum anti-Th/To antibodies. METHODS: Serum samples from 1048 Japanese patients with various autoimmune diseases were screened for anti-Th/To antibodies using RNA and protein immunoprecipitation assays. The reactivity to RNase P subunits was examined by immunoprecipitating (35)S labelled recombinant Rpp38, Rpp30, and hPop1 produced by in vitro transcription and translation. HLA-DRB1, DQB1, and DPB1 alleles were identified using a polymerase chain reaction followed by a restriction fragment length polymorphism assay. RESULTS: Serum anti-Th/To antibodies were detected in 14 of 303 patients with SSc and seven of 745 patients without SSc (4.6% v 0.9%; p=0.0003). Similar percentages of patients with and without SSc showed immunoreactivity to Rpp38 and Rpp30, but more patients with SSc than patients without SSc showed a reactivity to hPop1 (93% v 14%; p=0.002). In patients with anti-Th/To antibodies DRB1*1502 or *0802 was detected more often, and the DRB1*0405-DQB1*0401 haplotype less often in patients with SSc than in patients without SSc (79% v 14%, p=0.02, and 7% v 71%, p=0.01, respectively). CONCLUSIONS: Anti-Th/To antibodies were detected in a small proportion of autoimmune patients lacking clinical features related to SSc. A close relationship between disease expression and anti-hPop1 reactivity as well as HLA class II alleles in anti-Th/To positive patients suggests that the process of anti-Th/To antibody production may be different between patients with and those without SSc.
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