Biomedical subjects

R J Hayashi

Publications and source records attributed to R J Hayashi.

12 recordsLinked to original sources

PubMed2001

Treatment of steroid-resistant acute graft-versus-host disease with anti-thymocyte globulin.

Acute graft-versus-host disease (aGVHD) is a major cause of mortality after allogeneic stem cell transplantation. Although initial treatment with corticosteroids is effective in the majority of patients, 30--60% develop steroid resistance. Anti-thymocyte globulin (ATG) is commonly used as first-line therapy for steroid resistant (SR) aGVHD. However, data on its efficacy are limited. At two institutions we reviewed the results of treatment with ATG of 58 patients with SR aGVHD. Initial manifestations of aGVHD were treated with 2 mg/kg/day of methylprednisolone (MP). Equine ATG was administered as first-line therapy for SR aGVHD, a median of 9 days (range, 3 to 39) after initiation of MP. At the time of initiation of ATG, IBMTR severity indices B, C and D were observed in 6%, 40% and 54% of patients, respectively. Improvement was observed in 30% of patients treated with ATG. Skin disease was more likely to improve with ATG (79%), while progression of gut and liver aGVHD was observed in 40% and 66% of patients, respectively. Despite initial improvement, 52 patients (90%) died a median of 40 days after ATG therapy from progressive aGVHD and/or infection (74%), ARDS (15%), or relapse (11%). Only six patients (10%), three of whom had aGVHD limited to the skin at the time ATG was administered, are long-term survivors. We conclude that initial improvement of SR aGVHD occurs with ATG in a minority of patients, and very few patients become long-term survivors. Furthermore, this treatment is associated with a high rate of major complications.

Actuarial Analysis↗

PubMed2001

Posttransplant lymphoproliferative disease in children: correlation of histology to clinical behavior.

PURPOSE: To determine whether the morphologic features of posttransplant lymphoproliferative disease (PTLD) correlated to a response to therapy. PATIENTS AND METHODS: We reviewed our experience with PTLD in the pediatric population. We identified 32 patients with a total of 36 episodes of PTLD. The diagnosis was confirmed by tissue examination and classified according to the degree of monomorphic features of the lesion. Thirty-four of 36 episodes were managed with immunosuppression reduction, and the patients were assessed for their response to this strategy. Chemotherapy was used to treat 10 of 15 patients who had progressive disease, and their subsequent course was also analyzed. RESULTS: Sixteen of 17 (94%) patients with polymorphic morphology responded to immunosuppression reduction compared with only 5 of 17 (29%) patients with monomorphic features (P < 0.001). All of the patients with progressive disease who did not receive additional therapy died. Standard chemotherapy regimens for lymphoma were administered to 10 patients with progressive disease, with a high response rate (90%), durable remissions, and acceptable toxicity. CONCLUSIONS: We conclude that the morphologic characteristics of PTLD provide information to potentially help guide treatment strategies in the management of this disease. Standard chemotherapy regimens for malignant lymphoma appear to be a viable treatment option for patients with progressive disease, although further investigation is needed.

Adolescent↗

PubMed2001

Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging.

OBJECTIVE: MR imaging of central nervous system (CNS) malignancies falls short of a definitive evaluation. Tissue diagnosis remains the gold standard. Diffusion-tensor MR imaging measures the apparent diffusion coefficient and diffusion anisotropy of water in tissue. The purpose of this study was to test the hypothesis that the apparent diffusion coefficient may improve the MR imaging evaluation of newly diagnosed CNS neoplasms. We examined the relationship between the apparent diffusion coefficient, anisotropy, and tumor cellularity in 12 pediatric patients. MATERIALS AND METHODS: On the basis of histopathologic evaluation, tumors in this case series were segregated into three types: low-grade gliomas, embryonal tumors, and nonembryonal high-grade tumors. Mean apparent diffusion coefficient and anisotropy values obtained from the solid components of each tumor were compared with cellularity, total cellular area, and total nuclear area derived from biopsy material. RESULTS: The apparent diffusion coefficient ratio (tumor to normal brain) correlated well with tumor classification (p = 0.001). Anisotropy was decreased similarly in all tumor classifications. The absolute apparent diffusion coefficient correlated well with cellularity (p = 0.014) and total nuclear area (p = 0.005) per high-power field. The correlation between apparent diffusion coefficient and total cellular area per high-power field was not statistically significant. CONCLUSION: The apparent diffusion coefficient may be predictive of tumor classification and may be a useful tool in characterizing tumor cellularity and total nuclear area. These parameters are not available in standard MR imaging. Therefore, diffusion-tensor imaging may enhance the diagnostic process in pediatric CNS malignancies.

Adolescent↗

PubMed2000

Posttransplantation lymphoproliferative disorder in children: clinical, histopathologic, and imaging features.

Posttransplantation lymphoproliferative disorder (PTLD) is a condition in patients who receive transplants in which chronic immunosuppression leads to an unregulated expansion of lymphoid cells; the condition ranges from hyperplasia to malignant lymphoid proliferation. Risk factors affecting the incidence of PTLD include allograft type, Epstein-Barr virus infection, and immunosuppression. In this article, we review the clinical, histopathologic, and imaging features of PTLD in children. Because PTLD can affect nearly any organ system, a wide variety of clinical manifestations is possible. The heterogeneous nature of the disease is also reflected on imaging studies. The goals of imaging in patients with PTLD are to detect disease, guide biopsy, and direct appropriate follow-up imaging rather than to establish a specific diagnosis. Because the clinical and imaging manifestations of PTLD are nonspecific and are not reliably predictive of histopathologic subtype, tissue biopsy is necessary for final diagnosis.

Biopsy↗

PubMed1999

Unique CD4(+) T cells in TCR alpha chain-deficient class I MHC-restricted TCR transgenic mice: role in a superantigen-mediated disease process.

Mice carrying a transgenic TCR with targeted disruption of the TCR alpha chain (H-Y alpha(-/-)) possess CD4(+) T cells which express the transgenic TCR beta without the alpha chain. These mice developed the murine acquired immunodeficiency syndrome (MAIDS) after infection with LP-BM5 retroviruses, a process which requires CD4(+) T cells. These cells are negative for TCR delta chain and pre-TCR alpha chain expression, and thus express a unique surface receptor with the TCR beta chain as a component. The cells respond to MAIDS virus-associated superantigen and concanavalin A, but not to protein antigens such as ovalbumin. Thus, this novel surface receptor appears to play an important role in the pathogenesis of MAIDS.

Animals↗

PubMed1998

Differences between responses of naive and activated T cells to anergy induction.

T cell unresponsiveness to Ag stimulation can be induced by several means. The precise mechanism by which this process occurs remains poorly understood. Preincubating T cells with either EDCI-fixed APC or ionomycin is a proven means of inducing T cell anergy with reduced IL-2 production in response to Ag stimulation. Using T cells from mice expressing the TCR transgene DO11.10, which is specific for a peptide (323-339) derived from hen egg OVA, we demonstrate that naive cells obtained directly from the host are resistant to the anergy induction by either fixed APC or ionomycin. TCR transgenic mice also deficient in the recombination-activating gene-2 (RAG-2(-/-)), preventing the formation of T cells with endogenous TCRs, were immunized with OVA, and in vivo activated T cells with low expression of CD62 were isolated. These primed cells possess the same sensitivity to ionomycin-induced anergy as in vitro activated cell lines. This unresponsive state most profoundly affects Ag-induced IL-2 production, with IFN-gamma and IL-3 affected to a lesser degree and no effect observed on IL-4 production. Thus, T cells in vivo can be distinguished phenotypically by their susceptibility to anergic stimuli. Anergy so induced affects selected T cell functions.

Animals↗

PubMed1994

In vivo priming of two distinct antitumor effector populations: the role of MHC class I expression.

Downregulation of major histocompatibility complex (MHC) class I expression is an important mechanism by which tumors evade classical T cell-dependent immune responses. Therefore, a system was designed to evaluate parameters for active immunization against MHC class I- tumors. Mice were capable of rejecting a MHC class I- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I- tumor vaccine. This response was critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells. A strong protective response against MHC class I+ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I+ GM-CSF-secreting tumor cells. This response required CD4+ and CD8+ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression of at least one MHC class I gene. Finally, class I MHC expression on the vaccinating cells inhibited the response generated against a MHC class I- tumor challenge. These results demonstrate that the host is capable of being immunized against a tumor that has lost MHC class I expression and reveal conditions under which distinct effector cells play a role in the systemic antitumor immune response.

Animals↗

PubMed1986

Use of 20% fat emulsion in total parenteral nutrition.

Sixteen elderly postoperative patients were randomized in a crossover study comparing isocaloric volumes of 20% and 10% fat emulsions used for total parenteral nutrition (TPN). The caloric intake was maintained constant during the two 7-day periods of each infusion. The indices measured after each period were total volume of fluid administered, change in body weight, hematocrit, serum sodium, creatinine, albumin, blood urea nitrogen, glucose, inorganic phosphate, and cholesterol. The total volume of 10% isocaloric nutrient solution was significantly (p less than .05) greater than that of the 20% solution. A rise in body weight and a fall in serum indices of hydration status were observed; five patients developed clinical signs of overhydration while on the 10% solution. These changes did not occur with the 20% solution. Thus, isocaloric substitution of a 20% fat emulsion for a 10% fat emulsion with TPN prevented overhydration and hemodilution without compromising nutrient intake.

Aged↗

PubMed1985

Identification of Igh-C-linked determinants on suppressor T cell hybrids and factors specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

Hyperimmunization of BALB/c mice with concanavalin A-stimulated blasts from the Ig allotype-congenic strain, C.B20, results in the production of antibodies reactive with T cells in an allotype-restricted manner. Spleen cells from these hyperimmune BALB/c mice were used to generate a panel of hybridomas that secrete monoclonal antibodies, reactive, in an allotype-restricted manner, exclusively with T cells subpopulations, and in particular, reactive with suppressor T cell hybridomas and their secreted soluble factors. Two functional classes of antibodies were identified: those that react with single polypeptide-chain suppressor T cell factors (TsF1) and the suppressor T cell hybridomas that produce such factors, and those that react with two polypeptide-chain suppressor T cell factors (TsF2) and their corresponding suppressor T cell hybridomas. These two classes of antibody were used to isolate molecules from the membranes of the respective suppressor T cell hybrids that are functionally and structurally related to the secreted suppressor T cell factors, suggesting a receptor function for these molecules.

Animals↗

PubMed1985

Regulation of biogenic amine methyltransferases by glucocorticoids via S-adenosylmethionine and its metabolizing enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase.

This report examines the possibility that glucocorticoids control the degradation of adrenal phenylethanolamine N-methyltransferase and pineal hydroxyindole O-methyltransferase by regulating endogenous concentrations of the cosubstrate, S-adenosylmethionine, via its metabolic enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase. Assays for these latter enzymes were established and optimized in the adrenal and pineal glands. The effects of hypophysectomy and dexamethasone or ACTH treatment on these enzymes were monitored along with concomitant changes in methyltransferase activity. Hypophysectomy simultaneously decreases methionine adenosyltransferase and S-adenosylhomocysteine hydrolase activity in both tissues. Dexamethasone administration to hypophysectomized animals does not alter either methionine adenosyltransferase activity or S-adenosylhomocysteine hydrolase activity in the adrenal gland. However, it does increase S-adenosylhomocysteine hydrolase activity in the pineal gland. In contrast, ACTH administration restores both enzymes in the adrenal while being ineffective in the pineal. These results suggest that glucocorticoids may be regulating S-adenosylmethionine levels and methyltransferase activity via the metabolic enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase, but that glucocorticoid control may be both tissue- and drug-specific.

Acetylserotonin O-Methyltransferase↗

PubMed1984

Amelioration of metabolic complications of conventional total parenteral nutrition. A prospective randomized study.

The most common metabolic complications of total parenteral nutrition (TPN), glucose intolerance and abnormal liver function, can be significantly reduced when 30% of the glucose calories are replaced by fat. We gave 88 patients either conventional TPN (CON-TPN, 25% dextrose and 4.25% amino acids) or modified TPN (MOD-TPN, 15% dextrose, fat, and 5% amino acids). The treatment groups were as follows: group A, no surgery with TPN only; group B, postoperative TPN; and group C, preoperative and postoperative TPN. Serial blood samples were analyzed for glucose, albumin, triglycerides, and insulin, and for liver function values. Nine patients manifested hyperglycemia and were removed from the study; seven patients had received CON-TPN and two had received MOD-TPN. In group A, the insulin level rose 50% less with MOD-TPN. There was a 50% smaller rise in the triglyceride, SGOT, and SGPT levels in patients who received MOD-TPN. Replacing one third of the TPN glucose calories with fat leads to better glucose tolerance and fewer hepatic complications.

Female↗

PubMedDate not supplied

Short-term effects of fat emulsion on serum lipids in postoperative patients.

The effect of short-term infusion of intravenous fat on serum lipids was assessed in 23 patients who had elective cancer operations and were given 20% Intralipid for 5 days postoperatively as part of a standard total parenteral nutrition regimen. Serum lipids were measured prior to, during and after the 5-day infusion period. The percentage of cholesterol as high-density lipoproteins (HDL) fell from a mean preinfusion value of 34.7 +/- 2.8 to 27.9 +/- 2.5 (p less than 0.05), while the percentage of cholesterol as low-density lipoproteins (LDL) increased from 40.7 +/- 2.2 to 46.8 +/- 3.4 (p less than 0.05). Serum triglycerides fell significantly (p less than 0.01) from 106.2 +/- 13.7 mg/dl to 64.6 +/- 8.8 mg/dl at 3 days, being 85.3 +/- 3.7 mg/dl at 5 days. No significant change in percent cholesterol as very low-density lipoproteins (VLDL), or levels of serum total cholesterol or phospholipids occurred. Lipoprotein X was detectable in six patients after 5 days. To study triglyceride clearance 1.7 g/kg of fat emulsion was infused over 8 hr and serial blood samples obtained. Within 3 hr of stopping the fat infusion, triglyceride levels had fallen to preinfusion values.

Cholesterol↗