The vigilance-promoting drug modafinil counteracts the reduction of tyrosine hydroxylase immunoreactivity and of dopamine stores in nigrostriatal dopamine neurons in the male rat after a partial transection of the dopamine pathway

We studied the ability of the vigilance-promoting drug modafinil to modulate the anterograde and retrograde changes in tyrosine hydroxylase (TH) immunoreactivity and in dopamine (DA) stores in the nigro-neostriatal DA neurons, following a partial hemitransection of this ascending DA system, using a combined morphometrical, biochemical and behavioural analysis. Modafinil was given daily i.p. in doses of 10–100 mg/kg, starting 15 min after the lesion, and the partially hemitransected rats were killed 2 weeks later. Changes in TH-immunoreactive nerve cell bodies and nerve terminals induced by the partial hemitransection were studied in the substantia nigra and neostriatum in combination with image analysis. The substantia nigra and neostriatum were also subjected to biochemical analysis of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Modafinil treatment dose-dependently (10–100 mg/kg) counteracted the hemitransection-induced disappearance of nigral TH-immunoreactive nerve cell body profiles and neostriatal TH-immunoreactive nerve terminal profiles. A 2-week treatment with 100 mg/kg of modafinil also counteracted the hemitransection-induced depletion of DA stores in the neostriatum and the ventral midbrain. Moreover, the repeated daily treatment with modafinil (100 mg/kg) protected against the hemitransection-induced disappearance of striatal 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and noradrenaline levels. Striatal DA function was analysed by studying apomorphine-induced (1 mg/kg, s.c.) ipsilateral rotational behaviour 4 and 11 days after the operation. A marked dose-dependent reduction of ipsilateral rotational behaviour was demonstrated after the daily modafinil treatment in the partially hemitransected rats. In another model involving unilateral nigral microinjections of 6-hydroxydopamine, acute (one single dose) modafinil (100 mg/kg) did not affect the contralateral rotational behaviour induced by apomorphine (0.05 mg/kg s.c.), when given 30 min before the apomorphine. Taken together, morphological, neurochemical and behavioural evidence has been obtained that anterograde and retrograde changes induced in the DA stores and TH immunoreactivity of the nigro-neostriatal DA neurons by a partial hemitransection are counteracted by modafinil in a dose dependent way with 100 mg/kg producing a significant protective action against impairment of DA transmission. The results of this study open up the possibility that modafinil may protect against the anterograde and retrograde degeneration of nigrostriatal DA neurons seen after mechanically induced injury.     

Androgenic modulation of the activity of lumbar neurons involved in the rat bulbocavernosus reflex

The bulbocavernosus (BC) reflex, produced in the BC motor nerve in response to electrical stimulation of the contralateral pudendal sensory nerve, was investigated in intact, castrated, and testosterone-treated castrated male rats under urethane anesthesia. No significant group differences in the reflex latency, sensory or motor conduction velocity, or central delay were observed. A conditioning pulse to the pudendal sensory nerve caused suppression of the averaged antidromic field potential recorded in the contralateral spinal nucleus of the bulbocavernosus (SNB) after stimulation of the SNB axons in the BC motor nerve. The suppression occurred at 6- to 35-ms intervals between shocks to pudendal sensory nerve and BC motor nerve, and was markedly smaller in castrated males than in the other two groups. In contrast, a conditioning pulse to the contralateral BC motor nerve had no effect on the SNB antidromic field potential. These results indicate that androgen modulates the efficacy of synaptic transmission onto SNB motoneurons or other neurons involved in the BC reflex.     

The course of aggressive behavior induced by a single injection of delta 9-tetrahydrocannabinol and its characteristics

Female, Wistar King A rats subjected to one day of isolated housing, during which all food was withheld for 22 hr and supplied for only 2 hr, and then given a single dose of Δ⁹-tetrahydrocannabinol (THC) markedly exhibited muricide and rod-attack behavior. This continued for 100 days after treatment as far as the animals remained in isolation. They displayed rat pup-killing behavior as well, although normal virgin female rats did not show such behavior. When the rats were transferred from isolated housing to group housing 60 days after THC treatment, rod-attack behavior disappeared completely in all rats and muricide disappeared in 13 of the 28 rats which exhibited muricide. However, when these rats were returned to isolation after a 15 day period of group housing, rod-attack behavior and muricide identical to that observed previously reappeared. It is concluded that housing condition plays a crucial role in the occurrence and maintenance of THC-induced aggression including muricide.     

Expression of Functional Molecules in Non-Hodgkin's Lymphoma

It is well known that non Hodgkin's lymphoma (NHL) cells express various antigens which are normally involved in a variety of functions. In addition, NHL is diverse in its proliferative capacity. To investigate the relation between these factors and the clinical picture, 45 cases of NHL were studied by immunohistochemistry using snap-frozen materials obtained before therapy. Reactivities with 27 monoclonal antibodies were examined and the results were correlated with clinical findings. The expression of surface μ and CAM-1 in B-NHLs and CD25 in T-NHLs were significantly associated with bone marrow involvement. B-NHLs without expression of CD21(B2) and T-NHLs with CD25 were seen more frequently in cases with a LDH value of over 500 units/ml. The positivity rate of Ki-67 on B-NHLs was correlated with serum LDH value, NHL histologic classification, and overall survival. These data indicate that immunophenotyping and determination of the proliferative capacity of NHL are of value not only for confirmation of the histopathologic classification of the tumor but also for assessment of clinical behavior.     

A novel translocation involving chromosomes 2, 9, 14, and 22 in chronic myeloid leukemia

A 46-year-old man with chronic myelogenous leukemia was found to have a new complex translocation. In chronic phase, all of the bone marrow cells had a rearrangement of a t(2;9;14;22) (p21;q34;q32;q11). Southern blot analysis of leukocyte DNA revealed rearrangement of the breakpoint cluster region (bcr) within the 5.8-Kb bcr. The patient eventually died in blast crisis 28 months later. The cytogenetic findings of bone marrow cells showed a 46,XY,t(2;9;14;22)(p21;q34;q32;qll),add(lp),del(3q) karyotype in blast crisis.     

Reduced NR2A expression and prolonged decay of NMDA receptor-mediated synaptic current in rat vagal motoneurons following axotomy

To elucidate characteristic changes in the N -methyl- d -aspartate (NMDA) receptor on neurons following axotomy, subunit expressions and functional features of the NMDA receptor were examined in the dorsal motor nucleus of vagus (DMV) of rats receiving vagal axotomy at the neck. Western blotting analysis demonstrated that the expression of NR2A decreased 2–3 days after in vivo axotomy, while expression of NR1 and NR2B, NR2C and NR2D subunits did not change significantly. To examine the functional changes, patch clamp recordings in whole-cell mode were employed on the axotomized DMV neurons identified by retrograde labelling with fluorescent dye. The amplitude ratios of ifenprodil-sensitive components of NMDA response and d , l -2-amino-5-phosphovaleric acid (APV)-sensitive evoked postsynaptic current increased after axotomy. In addition, APV-sensitive postsynaptic currents exhibited a longer decay time in identified axotomized vagal motoneurons than in control neurons. No significant differences in the current density of the NMDA response and the peak amplitude of APV-sensitive synaptic currents were observed between axotomized and intact DMV neurons. In conclusion, a decrease in NR2A expression results in the appearance of functional characteristics of the NMDA receptor predominantly containing the NR2B subunit. This might lead to a long-term increase of the susceptibility of neurons to excitotoxicity.     

The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons

During the development of the hippocampus, the action of GABA shifts from depolarizing to hyperpolarizing, and brain-derived neurotrophic factor (BDNF) has important roles in GABAergic transmission. We demonstrate that BDNF (20 ng ml⁻¹) rapidly and reversibly potentiates postsynaptic GABA_A receptor-mediated currents (by 80.5 ± 14.3 %, n = 10) in hippocampal CA1 pyramidal neurons isolated from postnatal day (P)6 rats, using nystatin-perforated patch-clamp recordings. This potentiation is caused by an elevation of intracellular Ca²⁺ that occurs in response to the activation of Trk B receptor tyrosine kinase and phospholipase C-γ. The modulation of the GABA_A responses by BDNF in hippocampal CA1 pyramidal neurons isolated from P10 rats was more diverse (from potentiating to inhibitory), and at P14, BDNF induced a long-lasting inhibition. In addition, Ca²⁺/calmodulin-dependent protein kinase 2 plays important roles in the potentiating, but not in the inhibitory effect, of BDNF on the GABA_A responses. These results suggest that changes in the intracellular signalling pathway could contribute to the developmental shift of the actions of BDNF on inhibitory systems.     

Long-term Natural Course of the Osteochondral Lesion of the Talus in a Child: A Case Report

Recent reports have described midterm natural courses of osteochondral lesion of the talus (OLT) and lack of progression of ankle osteoarthritis (OA) in adult patients. The relationship between the OLT managed with nonoperative treatment and development of OA in children remains unknown. We report the long-term course of medial OLT in a 12-year-old female who was treated nonoperatively for 10 years. Radiographically, no osteoarthritic changes were observed at the first examination. She initially returned to her basketball club after nonoperative treatment. Although daily activities were not restricted, limitation of recreational activities began to appear at 4 years of follow-up. Subsequently, plain radiographs revealed bone absorption around the osteochondral fragment and osteophyte formation at the medial gutter, then ankle OA was advanced at the final follow-up.     

Clinical diagnosis of gliomatosis cerebri by radioimages

Gliomatosis cerebri (GC) is a rare clinical entity characterized by diffuse and infiltrative overgrowth of the tumor cells. Most of the previously reported cases of GC were autopsy cases because the clinical diagnosis of GC has been difficult. The authors report four cases diagnosed clinically as GC. Cases 1 and 2 are females aged 19 and 69. Cases 3 and 4 are males aged 47 and 50. In the first three cases, CT findings were almost normal. MRI study, especially on its T2 weighted image (T2W1), clearly demonstrated the wide extent of the infiltration of the tumor cells along the white matter. The last case occurred in the pre-MRI era, but contrast enhanced CT showed a bilateral periventricular high density area accompanied by diffuse low density white matter. Three of them underwent echo-guided needle biopsy, and one underwent partial excision of the lesion. Histological diagnosis was glioblastoma in Cases 1 and 4, and anaplastic astrocytoma in Cases 2 and 3. Difficulty in the clinical diagnosis of GC has been based on the fact that traditional imaging studies, including CT, can not clearly show the extent of tumor cell infiltration. MRI study is a very sensitive imaging technique which can easily demonstrate the area infiltrated by glioma cells. So we may be able to make clinical diagnosis of GC, coupling the data from MRI study and brain biopsy. The authors expect that accumulation of clinical experiences of GC may give useful information for the investigation of "invasion", which is one of the major problems in the treatment of malignant gliomas.     

A case of round atelectasis

A case of round atelectasis was reported. The roentgenographic features of round atelectasis are "comet tail sign" and localized pleural thickening. Round atelectasis appears as a mass like lesion that often mimics a pulmonary neoplasm. Recognition of this entity will help to prevent unnecessary procedures such as thoracotomy and pulmonary resection.