Fibrosis, portal hypertension, and hepatic volume changes induced by intra-arterial radiotherapy with 90yttrium microspheres.

PURPOSE: To identify changes in hepatic parenchymal volume, fibrosis, and induction of portal hypertension following radioembolization with glass microspheres for patients with metastatic disease to the liver. RESULTS: In our series of sequential bilobar (n = 17) treatments, a mean decrease in liver volume of 11.8% was noted. In this group, a mean splenic volume increase of 27.9% and portal vein diameter increase of 4.8% were noted. For patients receiving unilobar treatments (n = 15), mean ipsilateral lobar volume decrease of 8.9%, contralateral lobar hypertrophy of 21.2%, and a 5.4% increase in portal vein diameter were also noted. These findings were not associated with clinical toxicities. CONCLUSION: (90)Yttrium radioembolization utilizing glass microspheres in patients with liver metastases results in changes of hepatic parenchymal volume and also induced findings suggestive of fibrosis and portal hypertension. Further studies assessing the long-term effects are warranted.

Effect of cyclothiazide on spontaneous miniature excitatory postsynaptic currents in rat hippocampal pyramidal cells.

Spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded from the CA1 region of slices using the whole-cell patch-clamp technique. Cyclothiazide (0.1 mM), a complete blocker of desensitization of (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) channels, was applied to determine the changes in amplitude and kinetics of mEPSCs occurring with complete suppression of desensitization. The amplitude of mEPSC (A) was not affected significantly by cyclothiazide, but both the rise (taur) and the decay time (taud) were consistently increased (from 2.3 to 6.5 ms and from 9.9 to 22.2 ms respectively). The amplitude dependence of both taud and taur became much greater, but there was no upward shift of the best-fitting lines. The slopes of the control best-fitting lines were (+/-SD; ms/pA; n=5) 0.39+/-0.05 for taud:A and 0.12+/-0.07 for taur:A, but, in the presence of cyclothiazide, the corresponding slopes were much steeper (2.1+/-0.60 and 0.68+/-0. 21; holding potential was -50 mV and temperature 32 degreesC). These changes, which were slow to develop, suggest that cyclothiazide blocks AMPA receptor channel desensitization, whilst having no effect on the closing rate of AMPA channels. Judging by the extent of change, the speed of diffusion of glutamate in the synaptic cleft is probably similar to that in water. In conclusion, this study provides evidence that: (1) under control conditions, desensitization of AMPA channels plays a major role in shaping the time course of synaptic currents in CA1; and (2) cyclothiazide prolongs their time course solely by abolishing desensitization.

Migration of epithelium during phenytoin-dependent gingival overgrowth in mice.

A small cavity was made in the mesiopalatal area of the maxillary first molar adjacent to the gingiva. Mice were maintained on 40 mg/kg phenytoin (or on diluent for control) by daily intraperitoneal injections. After 9 weeks, light microscopic observations revealed that in experimental mice, epithelial cells migrated towards the cavity and covered it. In controls, epithelial cell migration towards the cavity did not occur. For scanning electron microscopic (SEM) studies, specimens were fixed in 4% glutaraldehyde in 0.1 M phosphate buffer, pH 7.2, for 2 hours, dehydrated, critical point dried and coated with gold. The surface of the outer gingival epithelium of experimental and of control mice showed a honeycomb arrangement of the microridges suggesting their keratinized nature. Epithelial cells lining the cavity showed well marked macroridges along their borders. Parallel microridges were observed on the upper surface of these cells suggesting that they were non-keratinized. It was concluded that the migrating epithelial cells, that covered the cavity during phenytoin-dependent gingival overgrowth, were of the non-keratinized type.

Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes.

Langerhans cells (LC) are Ia+ leukocytes that account for less than 2% of the cells in murine epidermal isolates. We purified LC by cell sorting to study their capacity to stimulate antigen-specific responses from unprimed and sensitized T cells. Sorting was performed after 12 or 72 h of epidermal culture, since our earlier work had indicated that LC became immunologically active during that time interval. At 12 and 72 h, the LC were uniformly and equally rich in the Ia glycoproteins that are recognized by helper T cells. At both time points, LC were comparable in their capacity to stimulate sensitized helper T lymphocytes, and would cluster the T cells in an antigen-dependent fashion at 4 degrees C. However, 12-h LC did not sensitize T cells, as indicated by their inactivity in stimulating the primary MLR or antibody response, and they were unable to cluster T cells in an antigen-independent fashion at 37 degrees C. The latter properties were acquired during 72 h of culture. As a result, the function of 72-h LC fully resembled that of lymphoid dendritic cells. We propose that the maturation of stimulatory function within the dendritic cell lineage represents an important control point in the induction phase of cell-mediated immunity.

Induction of immunoglobulin synthesis in corticosteroid-treated blood lymphocytes of a patient with acquired agammaglobulinemia.

Coculture experiments between lymphocytes of a 17-year-old immunodeficient male, DL, and a group of normal subjects, assaying pokeweed mitogen (PWM)-stimulated Ig secretion as a measure of B-cell function, revealed immunoregulatory abnormalities. Initial studies disclosed that DL had corticosteroid-sensitive T suppressor (Ts) cells capable of blocking Ig secretion by both HLA-identical and HLA-nonidentical cells in coculture. Cocultures of DL's peripheral blood mononuclear cells could be induced to secrete Ig in large amounts after certain maneuvers--the most informative of which involved mixing prednisolone-treated DL mononuclear cells with any normal T lymphocytes except those from DL himself. When these same experimental manipulations were performed individually, i.e., prednisolone treatment of cultured DL cells to remove Ts activity, or mixing equal numbers of normal T cells with untreated DL mononuclear cells, Ig was not produced. The data indicated that the T-cell abnormalities in DL included an excess of Ts cells and a deficiency to T helper (Th) cells. When repeat studies were performed later in the clinical course, during which interval a number of clinical interventions were attempted, it was found that the patient's cells were no longer corticosteroid sensitive and, further, they suppressed only HLA-identical cells.