Antinociceptive Effects of Morphine Were Different Between Experimental and Genetic Diabetes

This study was designed to investigate the effect of morphine on formalin-induced nociceptive responses in streptozotocin (STZ) induced-diabetic mice, noninsulin-dependent genetically diabetic db/db mice and their respective controls (ddY and +/+). In nondiabetic (ddY and +/+) mice, morphine (1–10 mg/kg, PO) dose dependently attenuated the biphasic nociceptive responses induced by SC injection of formalin to the hindpaw, demonstrating equipotency on both the first and second phases. Para-chlorophenylalanine (800 mg/kg × 2, PO) and pindolol (1 mg/kg, IP) reduced the effect of morphine on the first phase, sulpiride (10 mg/kg, IP) abolished the effect on both phases, while ketanserin (1 mg/kg, IP) had no effect. In STZ (200 mg/kg, IP)-diabetic mice, morphine weakly attenuated the nociception in comparison to control ddY mice, whereas it had comparable effects in both the first and second phases of control +/+ mice and db/db mice. The serotonergic agonist, meta-chlorophenylpiperazine (0.32–3.2 mg/kg, PO), dose dependently attenuated the biphasic nociceptive responses to formalin in both phases of diabetic mice; however, FR64822, a dopaminergic compound (0.1–10 mg/kg, PO), had little effect. We speculate that activation of both dopaminergic (DA)- and serotonergic-mediated mechanisms are potentially responsible for the effect of morphine on the first phase, while the DA-mediated effect is involved in the second phase. The DA-mediated mechanism, but not the serotonin-mediated one, appears to be altered in both STZ-diabetic and db/db mice. These results suggest that the attenuated effects of morphine might be due to a dopaminergic dysfunction in STZ mice, and that there might be other mechanisms compensating for this attenuation of dopaminergic function in db/db mice.     

Acute kindling: interstimulation interval effects and spontaneous interictal or ictal epileptiform discharges

With regard to "acute kindling" that signifies progressive changes in various epileptiform discharges produced with repeated electrical stimulations in a brief time span in acute experiments, the interstimulation interval effect was examined. Kindling developments produced respectively with 3 and 30-minute interval stimulations to the visual cortex of rabbits were compared with each other. Eventually, in kindling with a longer interstimulation interval, after-discharges induced in every trial of stimulation were often lengthened in duration more prominently than those with the shorter interstimulation interval and, furthermore, occasional slight relapses in the afterdischarge duration occurred more infrequently in the former than in the latter. These results suggest that the interstimulation interval plays an important role in the development of acute kindling, presumably in relation to postictal inhibition. In addition, spontaneous interictal or ictal epileptiform discharges occasionally arising during the 3-minute interstimulation intervals were reported. These spontaneous discharges may suggest a high epileptogenicity in acute kindling.     

Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells

CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.     

Deposition velocity of gaseous I to rice grains

Among the routes of gaseous I transfer to rice grains, direct deposition to the hull of rice plants and the subsequent transfer to brown rice and polished rice should be more critical than leaf absorption-translocation. A grain number normalized deposition velocity (Vs) is recommended as a key parameter to assess the amount of gaseous I deposited on the rough rice. This parameter is given as "iodine content per unit number of grain per unit time" divided by "iodine concentration per unit volume of the air." After the heading period the surface area of rough rice is almost constant but weight increases with time. Therefore, mass normalized deposition velocity (VD) varies with time. By introducing Vs instead of VD, the variations could be converged into narrow ranges. The contribution of gaseous I from the atmosphere to rough rice, brown rice and polished rice were estimated using Vs values obtained experimentally and gaseous I concentration in the air.     

Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated byβ protein immunostain

Summary We studied senile plaques (SP) in the cerebella of six autopsied subjects with Alzheimer-type dementia (ATD) and ten non-ATD autopsied subjects between the ages of 78 and 90. Neither SP nor amyloid angiopathy (AA) was observed in any of the non-ATD subjects. In the four of the six ATD subjects, diffuse plaques in the molecular layer were seen as ill-defined areas of fine fibrillar materials by protein immunostaining with formic acid pretreatment, the modified Bielschowsky stain, and periodic acid-methenamine silver (PAM) stain. The plaques were not visible with Bodian, Congo red, or periodic acid-Schiff stains. Compact plaques in the Purkinje cell or in the granular cell layers were found in three of the six subjects. Their amyloid core was often surrounded by areolar amyloid deposits. AA was observed in three of the six subjects. The argyrophilia of the diffuse and compact plaques, demonstrated by the modified Bielschowsky and PAM stains, became undetectable when the sections were first treated with formic acid. Such treatment made the plaques immunoreactive with protein antiserum. The findings suggested that cerebellar diffuse plaques and compact plaques consist mainly of an amyloid component, and are characteristic of ATD.     

Pathological changes induced by formaldehyde in open-ended rat tracheal implants preexposed to benzo(a)pyrene

The promotion effects of 0.1% formaldehyde (HCHO) in phosphate-buffered saline (PBS) were tested in rat tracheal implants preexposed to a minimal carcinogenic dose of 468 micrograms benzo(a)pyrene (BAP) released over one month from 865 micrograms BAP-beeswax pellets. At the time of pellet removal, the tracheas were made into open-ended, flow-through, tracheal implants (FTTI), and exposed twice/week to HCHO for 30 weeks. Morphological alterations in the FTTI were monitored biweekly by collection of exfoliated cells from the luminal washings for cytopathologic diagnosis, and periodically by sacrificing animals for histopathology. FTTI exposed to the BAP followed by 30 weeks of HCHO had extensive squamous metaplasia, a high proliferation index of 7.87 [3H]thymidine-labeled cells/mm basement membrane, and foci of moderate and marked atypia. Clear diagnosis of some of the lesions was difficult because of the acute toxic effects of the repeated exposures to HCHO. These effects were seen in the tissues as well as in the exfoliated cells, which attest to the latter as an efficient, non-destructive, method for determining the responses of the tracheas to exposure to toxic and carcinogenic agents. FTTI exposed to BAP followed by twice weekly PBS, had a mostly flattened epithelium, and a low proliferation index (0.39). FTTI exposed to beeswax pellets, followed by the HCHO had a relatively high proliferation index (4.20) in a mucociliary epithelium exhibiting some basal cell hyperplasia. Control FTTI had a normal mucociliary epithelium with a proliferation index of 1.52 [3H]thymidine labeled cells/mm basement membrane.     

Polyethylenes Having Well‐Defined Bimodal Molecular Weight Distributions Formed with Bis(phenoxy‐imine) Zr Complexes

Summary: Bis(phenoxy‐imine) Zr complexes with MAO activation can produce polyethylenes with well‐defined bimodal molecular weight distributions. Polymerization behavior indicates that minor changes in the ligand structures can have a significant effect on the modality of the resulting polyethylenes. Although there is no direct relationship between the bimodal catalytic behavior and the structure of a precatalyst complex in solution, a precatalyst complex having a methyl or methoxy group para to the phenoxy‐oxygen inclined to exhibit bimodal behavior whereas that with a pentafluorophenyl group on the imine‐nitrogen displayed unimodal behavior. Polymerization results suggest that bimodal behavior is linked to the presence of two kinds of cationic active species, which arise from different modes of ligand coordination. A qualitative correlation was found between the calculated amounts of possible cationic active species and the uni‐ and bimodal catalytic behavior. Based on the results obtained, we concluded that the bimodal polyethylenes are produced by two kinds of cationic active species having two available cis‐located sites with cis‐N, trans‐O and cis‐N, cis‐O arrangements. The results introduced herein are rare examples of the production of well‐defined bimodal polyethylenes using a single precatalyst.

Bis(phenoxy imine) Zr complexes can produce well‐defined bimodal polyethylenes.     

Expression of synaptotagmin 1 in the taste buds of rat gustatory papillae

Synapses between taste receptor cells and primary sensory afferent fibers transmit the output signal from taste buds to the central nervous system. The synaptic vesicle cycle at the synapses involves vesicle docking, priming, fusion, endocytosis, and recycling. Many kinds of synaptic vesicle proteins participate in synaptic vesicle cycles. One of these, synaptotagmin 1, binds Ca(2+) phospholipids with high affinity and plays a role in Ca(2+) regulated neurotransmitter release in the central and peripheral nervous systems. However, the expression patterns of synaptotagmin 1 in rat taste tissues have not been determined. We therefore examined the expression patterns of synaptotagmin 1 and several cell specific markers of type II and III cells in rat taste buds. RT-PCR assay showed that synaptotagmin 1 mRNA was expressed in circumvallate papillae. In fungiform, foliate, and circumvallate papillae, the antibody against synaptotagmin 1 yielded the labeling of a subset of taste bud cells and intra- and subgemmal nerve processes. Double labeled experiments showed that synaptotagmin 1 positive cells co-expressed type III cell markers, PGP 9.5, and NCAM. Intragemmal nerve processes positive for synaptotagmin 1 co-expressed PGP 9.5. Conversely, all synaptotagmin 1 expressing cells did not co-expressed type II cell markers, PLCbeta2, or gustducin. These results show that synaptotagmin 1 may play some regulatory roles in vesicle membrane fusion events with the plasma membrane at the synapses of type III cells in rat taste buds.     

Low grade malignant peripheral nerve sheath tumour: varied cytological and histological patterns

BACKGROUND: A small number of malignant peripheral nerve sheath tumours (MPNSTs) are low grade, and the nature of these low grade tumours has never been systematically assessed. AIMS: To describe the clinicopathological, immunohistochemical, and ultrastructural features of low grade MPNST and to discuss the main differential diagnoses. METHODS: Four cases of low grade MPNST were studied, including one coexistent with neurofibromatosis type 1. The tumours were analysed with respect to nuclear atypia, cellularity, nuclear enlargement, hyperchromasia, mitotic rate, and necrosis. Immunohistochemistry was performed by standard techniques, and an ultrastructural study was performed on one tumour. RESULTS: The ages of the patients ranged from 32 to 72 years (mean, 58). Two were male and two were female. Three tumours occurred in the deep tissue, including one in the retroperitoneum, and one was located in the dermal and subcutaneous tissue. The maximum diameters of the tumours ranged from 3.5 to 8.0 cm. Microscopically, all tumours showed moderate hypercellularity, an increased nuclear to cytoplasmic ratio, and hyperchromasia, but exhibited varied growth patterns, including those that were atypical neurofibroma-like, low grade fibromyxoid sarcoma-like, low grade epithelioid, and haemangiopericytoma-like. All tumours showed immunoreactivity for S-100 protein and vimentin. CONCLUSIONS: These findings suggest that careful clinical and histological evaluation, along with S-100 protein immunostaining, are essential for the accurate diagnosis of low grade MPNST.