Association of Japanese cedar pollinosis and sensitization with HLA-DPB1 in the Japanese adolescent

Background

Allergic rhinitis (AR) is a heterogeneous disorder that significantly affects daily activity, work productivity, sleep, learning, and quality of life in all generations. Japanese cedar (JC) pollen is the most common allergen responsible for the development of AR in Japan. AR caused by JC pollen is considered to be a multifactorial inheritance disease that is caused by both environmental and genetic factors. The aim of this study was to investigate whether Human Leukocyte Antigen-DPB1 (HLA-DPB1) is associated with JC sensitization/pollinosis.

Bedside analysis of human milk for adjustable nutrition strategy

Aim: Mother's milk is optimum for preterm infants, but human milk fortifier is required at times, because some nutrients are sometimes insufficient for infant growth. It is important to measure the nutrients in breast milk at bedside so that the amount of nutrients that need to be supplemented can be determined. A human milk analyser (HMA, Miris®) is currently available. We examined if the macronutrient values measured by human milk analyser are comparable with those measured by conventional methods. We also sought to discover whether we could dilute the milk sample used for the human milk analyser measurement if the amount of milk available for testing was insufficient.
Subjects and Methods: First, the results of protein, fat and lactose content in breast milk samples obtained using the human milk analyser and conventional methods were compared. Second, we measured diluted samples and compared the values with nondiluted samples.
Results: When comparing the human milk analyser and conventional methods, all three nutrients exhibited a significantly positive correlation (p < 0.001); lactose content was reliable on the condition that it is 6–7 g/dL. The lactose content measured by the HPLC method was obtained by 3.05 × human milk analyser value − 13.4. When comparing diluted and nondiluted samples, fat and protein had expected values after dilution whereas lactose did not.
Conclusion: The human milk analyser can inform us about the amount of major nutrients in breast milk: fat, protein and lactose. However, when human milk is diluted, the lactose content measured by the human milk analyser is overestimated.     

Ischemic heart disease associated with bortezomib treatment combined with dexamethasone in a patient with multiple myeloma

A 79-year-old female patient with multiple myeloma who had no prior cardiac disease history developed an acute myocardial infarction on day 5 after receiving bortezomib and dexamethasone (BD). After treatment of coronary stenoses by stents, she received another course of BD therapy and developed angina pectoris on day 5 after the therapy. Bortezomib’s antitumor effect is due to the inhibition of proteasome activity. This inhibition may increase endothelial progenitor cell apoptosis and decrease endothelial nitric oxide synthase/nitric oxide (eNOS/NO), thus leading to coronary spasm. It is, therefore, important to carefully monitor patients being treated with bortezomib for the potential occurrence of ischemic heart disease.     

Significance of manipulating intratumor hypoxia in the effect on lung metastases in radiotherapy,with reference to its effect on the sensitivity of intratumor quiescent cells

Purpose To evaluate the effect of manipulating intratumor hypoxia during radiotherapy on lung metastasis, referring to its effect on the sensitivity of quiescent tumor cells. Materials and Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following loading with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The sensitivity of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P + Q) tumor cell population was determined from BrdU non-treated tumors. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results In the total cells, a more marked enhancement in sensitivity was observed with nicotinamide than MTH. In Q cells, MTH combination induced a more marked enhancement than nicotinamide. Both nicotinamide and MTH reduced the size of the hypoxic fraction in the two cell populations, especially nicotinamide in the total cells and MTH in Q cells. Without γ-ray irradiation, nicotinamide loading tended to decrease the number of lung metastases. With γ-ray irradiation, nicotinamide loading and MTH, especially the former, reduced the number of metastases more than γ-ray irradiation only. Conclusion Hypoxia manipulation in solid tumors has the potential to influence lung metastases. Notably, acute hypoxia-releasing nicotinamide may be promising for reducing the number of lung metastases.     

Clinical Usefulness of Determining the Rate of Thermal Clearance within Heated Tumors

Between June 1987 and June 1988, 28 patients (28 tumors) withliver, retroperitoneal, intrapelvic, or superficial tumors weretreated with hyperthermia combined with radiotherapy and/orchemotherapy. Hyperthermia was administered once or twice aweek for 30-60 min per session, up to a total of 2–11sessions, with an 8-MHz RF capacitive heating device. Bloodflow in the tumors was evaluated from the rate of thermal clearance(TCR) using the bio-heat transfer equation. The TCR was measuredin the middle of the first heating session and at the end ofthe last heating session by turning off the output power ofthe heating device. For 9 patients, contrast-enhanced CT scanswere taken and CT numbers at the centers of tumors were measuredbefore and after the entire course of hyperthermia. Changesin TCR were closely related to average tumor center temperature,changes in CT number, and tumor response. When smaller and moresuperficial tumors were treated by hyperthermia combined withradiotherapy and/or chemotherapy that consisted of many heatingsessions and during which a high average tumor center temperaturewas achieved, a better tumor response was obtained. The betterthe tumor response, the higher the local control rate became.The cause-specific survival rate of patients who achieved goodtumor responses was higher than that of patients who showedpoor tumor responses. Changes in TCR and CT number in heatedtumors were useful and important indicators of tumor responseto hyperthermia.     

Reduced Activity of Anabolizing Enzymes in 5-Fluorouracil-resistant Human Stomach Cancer Cells

The mechanism of resistance to 5-fluorouracil (5-FU) was studied with NUGC-3/5FU/L, a human stomach cancer cell line which had acquired resistance as a consequence of repeated 5-day exposures to stepwise-increasing concentrations of 5-FU in vitro . NUGC-3/5FU/L was 200-fold and over 16-fold resistant to 96-h and 1-h exposures to 5-FU, respectively. NUGC-3/5FU/L incorporated less 5-FU into RNA, indicating resistance to the RNA-directed action of 5-FU. On the other hand, NUGC-3/5FU/L also showed resistance to in situ thymidylate synthase (TS) inhibition by 5-FU. Polymerase chain reaction-single-strand conformation polymorphism analysis of TS cDNA and a FdUMP ligand binding assay showed that quantitative and qualitative alterations of TS are not responsible for this resistance. In contrast, the ability to metabolize 5-FU to its active metabolites, FUTP and FdUMP, was reduced in NUGC-3/5FU/L. We found that not only the activities of uridine phosphorylase/kinase and orotate phosphoribosyl-transferase (OPRT), but also the level of phosphoribosyl pyrophosphate, a cosubstrate for OPRT, were significantly lower in NUGC-3/5FU/L than in the parent NUGC-3. These results indicated that resistance to 5-FU in NUGC-3/5FU/L is due to reduced activities of 5-FU-anabolizing enzymes, but not to an alteration of TS. 2'-Deoxyinosine effectively enhanced TS inhibition by 5-FU in the resistant cells, thus markedly sensitizing them to 5-FU.     

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control

Purpose: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). Materials and methods: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60–66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72–74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for >2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. Results: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42–49 days was significantly higher than that of tumors with an OTT of >49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). Conclusions: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.     

Clinicl Significance of Mesangial IgM Deposits in Minimal Change Nephrotic Syndrome

The clinicopathologic features and the response to corticosteroid therapy were compared in 9 patients with minimal change nephrotic syndrome (MCNS) and diffuse mesangial IgM deposits (Group I) and in 32 of those without IgM deposits (Group II). However, serum IgM levels in Group I in both relapse and remission were significantly higher than those of Group II and controls (p<0.001). In Group I mesangial IgM deposits were diffuse in 9 (100%), mesangial C_1q was present in 4, IgA and fibrinogen were each observed in 1, respectively. Electron dense deposits in the mesangium were also present in 2 to 5 patients in Group I. No significant differences were found between the two groups in age of onset, sex ratio, laboratory data except for serum IgM level, duration before biopsy, follow-up periods, outcome, and response to steroid therapy. Our data suggest that a more severe degree of either impairment of mesangial clearance of IgM or overproduction of IgM may be involved in patients with MCNS and mesangial IgM deposits but that these patients could not be considered a distinct group of patients.