Proliferative Effect of Dextran Sulfate Sodium (DSS)-Pulsed Macrophages on T Cells from Mice with DSS-Induced Colitis and Inhibition of Effect by IgG

The authors have previously reported that homologous immunoglobulin (Ig)G reduces the occurrence of dextran sulfate sodium (DSS)-induced colitis, mainly by suppressing recruitment of immunocompetent cells into colitis lesions. However, the mechanisms of cell recruitment and of its suppression by IgG remain unclear. In addressing these questions, this study focused on the activation of T cells in the presence of macrophages. The authors found that [³H]-thymidine uptake of T cells from DSS-induced colitis mice, but not from normal mice, was significantly enhanced when cultured with DSS-pulsed macrophages. From the profile of cytokine production, it was suggested that T helper 1 (Th1)-type cells become predominant during stimulation. Addition of homologous IgG significantly suppressed T cell proliferation in a dose-dependent manner, while no suppressive effect was observed with heterologous IgG. Mouse IgG F(ab')₂, but not Fc, fragments partially mimicked the suppressive effect of whole IgG. These findings provide evidence that Th1-type cells may play an important role in the development of DSS-induced colitis and that homologous IgG exerts its protective action at least in part through the F(ab')₂ portion.     

Improvement of Transdermal Delivery of Tetragastrin by Lipophilic Modification with Fatty Acids

The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order: acetyl > butyroyl > caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids. These results suggest that chemical modification of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.     

Biopharmaceutics: Effect of Ointment Bases on Topical and Transdermal Delivery of Salicylic Acid in Rats: Evaluation by Skin Microdialysis

Microdialysis has been used to determine the concentration of salicylic acid in skin tissue and plasma periodically for 4 h to evaluate the effect of ointment bases on topical and transdermal delivery of salicylic acid. The ointment bases examined were solbase (water-soluble), poloid and white petrolatum (oleaginous), hydrophilic poloid (water in oil (w/o) type emulsion lacking water) and absorptive ointment (w/o-type emulsion containing water). The ointments (0.1 g) containing 25 μmol salicylic acid were applied for 2 h to the surface of rat skin (1 cm²) with (intact) or without the stratum corneum. For intact skin, the extent of topical delivery from different ointments, evaluated by the area under the concentration-time curve (AUC) of salicylic acid in the skin tissue (AUCskin), increased in the order solbase. white petrolatum, poloid, hydrophilic poloid. absorptive ointment. The ratio of AUC_skin (topical delivery) to the AUC of salicylic acid in plasma (AUC_plasma, transdermal delivery) varied remarkably among the different bases, the greatest ratio being observed for absorptive ointment. When the ointments were applied to skin surface without stratum corneum, AUC_skin for solbase was much higher (about 45 times that for intact skin), whereas only a small (two-fold) increase was observed for poloid and hydrophilic poloid and the increase was negligible for white petrolatum and absorptive ointment. For skin without the stratum corneum, the ratio AUC_skin/AUC_plasma for the different ointments was comparable, although the magnitudes of AUC_skin and AUC_plasma still varied substantially. The variance of AUC values arises as a result of the different rates of release of salicylic acid from the bases. These results indicate that: the topical and transdermal delivery of salicylic acid in intact skin varies substantially among different ointment bases, and the greatest topical delivery is observed for absorptive ointment; use of absorptive ointment increases the retention of salicylic acid in the stratum corneum; and the stratum corneum functions strongly as a penetration barrier for solbase, moderately for poloid and hydrophilic poloid, and less for absorptive ointment and white petrolatum.     

Blast Crisis of Chronic Myelogenous Leukemia with Tumor Formation Characterized by T-cell Features--A Case Report

We report a case of chronic myelogenous leukemia (CML) associatedwith pronounced peripheral lymphadenopathy, with the cells havingthe Philadelphia (Phl) chromosome and T-cell features. A 23-year-oldman who was diagnosed as having CML and treated with busulfanwas admitted to our hospital because of increasing hepatosplenomegalyand pronounced lymphadenopathy. An axillary lymph node biopsydisclosed that the malignant cells formed rosettes with neuraminidase-treatedsheep red blood cells (En) (95.0%) and were positive for Leu1 (91.8%). Of the cytochemical reactions, peroxidase was negativeand periodic acid-Shiff, acid -naphthyl acetate esterase andß-glucuronidase were all positive. The karyotype ofthe bone marrow cells was 46 XY Phl positive (22q–), andthat of the lymph node cells was 51 XY Phl positive +8, +9,+18, +19, +21, 22q–. He was treated with various anti-leukemicagents and irradiation. Despite such treatments, he died ofpneumonia. This is a report of a CML patients with blast crisisand tumor formation characterized by T-cell features.     

Retrosigmoid Approach in the Supine Position Using ORBEYE: A Consecutive Series of 14 Cases

One of the merits of recently introduced exoscopes, including ORBEYE, is that they are superior to a conventional microscope in terms of ergonomic features. Taking advantage of it, the retrosigmoid approach can be performed in the supine position using ORBEYE. We report a consecutive series of 14 operations through the retrosigmoid approach in the supine position using ORBEYE. Fourteen consecutive patients who underwent surgery through the retrosigmoid approach for cerebellopontine (CP) angle lesions in the supine position using ORBEYE were targeted, and surgical outcomes and complications were examined. We evaluated the posture of the operator and the surgical field during this approach compared with those using a conventional microscope. In all 14 cases, all operative procedures were accomplished only using the ORBEYE. There were no operative complications due to this approach. Using ORBEYE, even when the angle of the operative visual axis was horizontal, the operators could manipulate in a comfortable posture. They were not forced to be in an uncomfortable posture that extended their arms, as is often the case with a conventional microscope. Therefore, they could use shorter surgical instruments. As the cerebellum shifted downward with gravity even using slight retraction during this approach, the working space of the surgical field was easily secured. Through this approach, the operators can perform stable microsurgery of CP angle lesions in a comfortable posture. This approach can reduce the burden on the operator and the patient, leading to a refined surgical procedure.     

Rapid Administration of High-Dose Human Antibody Fab Fragments to Dogs: Pharmacokinetics and Toxicity

Rapid Administration of High-Dose Human Antibody Fab Fragmentsto Dogs: Pharmacokinetics and Toxicity. Keyler, D. E., Salerno,D. M., Murakami, M. M., Ruth, G., and Pentel, P. R. (1991).Fundam. Appl Toxicol 17, 83-91. The treatment of drug overdosewith drug-specific antibody fragments may require very highantibody doses. To address the feasibility of this therapy,we studied the pharmacokinetics and toxicity of high-dose humannonspecific Fab fragments in beagles. Three dogs received 5.3g/kg Fab iv over 1 hr. Because nephrotoxicity was observed,three subsequent dogs received 3.2 g/kg. The fraction of theFab dose excreted in urine (10 ± 6%%) was lower thanreported values for either high or low doses of Fab in otherspecies. The terminal serum elimination half-life (42 hr forthe higher and 48 hr for the lower dose) was also longer thanreported values for other species, due to lower renal and nonrenalFab clearance. Fab administration was tolerated without adversehemodynamic effects. One of three dogs at each dose developedtransient oliguria. All dogs developed a transient but markedincrease in the serum creatinine concentration. At 2 weeks creatinineclearance had returned to normal. Urinary protein and albuminexcretion at 2 weeks were within the normal range for dogs butwere increased over their baseline values. The histology ofall organs was normal at 3 weeks by light microscopy, and renalhistology by electron microscopy was also normal. The mechanismof Fab nephrotoxicity, not observed previously with high-doseFab in rats or lower doses of Fab in other species includingdogs, is not clear. These data suggest that further study ofthe potential toxicity of high-dose Fab, and its reversibility,is needed to assess the feasibility of treating drug overdosewith this antibody fragment The long terminal half-life of high-doseFab in the dog and its low renal clearance contrast with valuesobserved with lower doses of Fab in other species but wouldnot be expected to preclude the use of high-dose Fab for drugoverdose.     

Theophylline metabolism in acute asthma with MxA-indicated viral infection

BACKGROUND: Although viral infection might alter theophylline metabolism in acute asthma, there are some difficulties in detecting infection due to various kinds of viruses in a clinical setting. METHODS: To evaluate the usefulness of assessment of MxA protein in acute asthma exacerbated by viral infection, MxA protein expression in lymphocytes was assayed by flow cytometric analysis in whole peripheral blood in 21 children (aged 0-6 years) receiving continuous theophylline infusion for management of asthma attack. Serum theophylline levels were measured at 24 and 72 h after initiating theophylline infusion. RESULTS: At the beginning of theophylline infusion, 11 children had increased expression of MxA protein, indicating viral infected states. After 24 h continuous infusion, there were no differences in theophylline levels between MxA-negative and MxA-positive groups. After 72 h infusion, the mean theophylline level of MxA-positive children was significantly higher than that of MxA-negative children (9.7 +/- 2.2 microg/mL vs 7.3 +/- 1.6 microg/mL). The ratio of theophylline clearance at 72 h to that at 24 h in the MxA-positive group was significantly lower than that of the MxA-negative group (1.1 +/- 0.2 vs 1.4 +/- 0.1). CONCLUSIONS: Viral infection appeared to affect theophylline metabolism. Flow cytometric assay of lymphoid MxA protein expression in whole blood is an easy and useful method of evaluating viral infection in acute asthma exacerbation.     

Decreased pulmonary perfusion in hypersensitivity pneumonitis caused by Shiitake mushroom spores

Hypersensitivity pneumonitis is an occupational hazard of mushroom workers. We describe a patient with severe hypersensitivity pneumonitis caused by spores of the Shiitake mushroom ( Lentinus edodes ) who showed a marked decrease in pulmonary perfusion, as demonstrated by pulmonary scintigraphy. This patient was treated successfully with prednisolone. These results suggest that pulmonary vasculitis may be associated with patients with hypersensitivity pneumonitis, and that steroid therapy may be clinically useful in treatment.     

Preoperative Characteristics of Auditory Brainstem Response in Acoustic Neuroma with Useful Hearing: Importance as a Preliminary Investigation for Intraoperative Monitoring

We classified the results of preoperative auditory brainstem response (ABR) in 121 patients with useful hearing and considered the utility of preoperative ABR as a preliminary assessment for intraoperative monitoring. Wave V was confirmed in 113 patients and was not confirmed in 8 patients. Intraoperative ABR could not detect wave V in these 8 patients. The 8 patients without wave V were classified into two groups (flat and wave I only), and the reason why wave V could not be detected may have differed between the groups. Because high-frequency hearing was impaired in flat patients, an alternative to click stimulation may be more effective. Monitoring cochlear nerve action potential (CNAP) may be useful because CNAP could be detected in 4 of 5 wave I only patients. Useful hearing was preserved after surgery in 1 patient in the flat group and 2 patients in wave I only group. Among patients with wave V, the mean interaural latency difference of wave V was 0.88 ms in Class A (n = 57) and 1.26 ms in Class B (n = 56). Because the latency of wave V is already prolonged before surgery, to estimate delay in wave V latency during surgery probably underestimates cochlear nerve damage. Recording intraoperative ABR is indispensable to avoid cochlear nerve damage and to provide information for surgical decisions. Confirming the condition of ABR before surgery helps to solve certain problems, such as choosing to monitor the interaural latency difference of wave V, CNAP, or alternative sound-evoked ABR.