The mechanism of action of tumor necrosis factor (TNF) on tumor vascularity--study using a transparent chamber

Effects of human recombinant TNF on the tumor blood vessels and on the thrombus formation were investigated in relation to its mode of antitumor action against Meth-A sarcoma transplanted in BALB/c mice. The extent of the blood vessel lesion was evaluated by using transparent chamber placed in the mouse skin. Bleeding, hyperemia and congestion were observed at 1-2h, 4-6h and 24h after TNF (1 X 10(4)U/mouse) administration, respectively. In contrast, no histological changes in the normal blood vessels were observed microscopically following TNF injection. Thrombus formation was evoked in the tumor vessels 4h after TNF injection. However, when thrombus formation was prevented by heparin, no difference was observed among antitumor action of TNF against Meth-A fibrosarcoma necrotic response and the rate of complete cure. These results suggest that the direct effects of TNF causing lesions in the tumor blood vessels plays an important role in its antitumor action.     

Alteration in the function of cerebral neurotransmitter receptors during the establishment of alcohol dependence: neurochemical aspects

Chronic alcohol treatment induces a variety of effects on the metabolism of neurotransmitters and the function of their receptors. Recent studies on alcohol dependence and/or functional tolerance to alcohol have clearly demonstrated that neurotransmitter-gated and receptor-coupled ion channels, as well as neurotransmitter receptor coupled with intracellular mediator systems, such as phosphatidylinositides and cyclic nucleotide-generating systems, are invariably suppressed during alcohol dependence. Future studies on the central actions of alcohol and on alcohol dependence should therefore be directed at the molecular changes in synaptic membrane-bound components such as neurotransmitter receptors, as well as on neurotransmitter release and relevant membrane-bound enzymes.     

Development of gamma-aminobutyric acid (GABA)ergic neurons in cerebral cortical neurons in primary culture

The developmental patterns of gamma-aminobutyric acid (GABA)ergic neurons in primary culture obtained from the neopallium of 15-day-old fetus of mouse were investigated in terms of morphological features, GABA metabolism and GABA receptor binding. Morphological investigations revealed that these cells possessed typical features of neurons and the formation of synapses was detected at 10 days after the inoculation. During neuronal growth on polylysine surfaces, GABA contents and activity of GABA transaminase (GABA-T) showed a progressive increase in the time of culture. Similarly, L-glutamic acid decarboxylase (GAD) showed a progressive elevation during neuronal development in vitro, which corresponded well with the change in immunoreactivity to anti-GAD examined immunohistochemically. In addition, the high K+-evoked release of [3H]GABA also showed an enhancement during the growth in vitro. The numbers of binding sites (Bmax) for [3H]muscimol and [3H]flunitrazepam (FLN) also showed increases with the time of incubation, although affinity (Kd) to the labeled ligands did not show any noticeable changes. Moreover, it was observed that [3H]FLN binding was enhanced by GABA even in neurons cultured for 7 days. These results indicate that cerebral cortical neurons in primary culture possess GABA biosynthesizing and degrading systems including a high-affinity uptake mechanism for GABA. The present results also indicate that these cells possess synaptic contacts as well as GABAA receptors coupled with benzodiazepine receptor from a relatively early stage of cellular development.     

Spontaneous peripelvic extravasation: reports of two cases

Spontaneous peripelvic extravasation must be distinguished from spontaneous rupture of the renal pelvis in urological emergency. The literatures revealed 42 cases of peripelvic extravasation and 35 cases of rupture of the renal pelvis in Japan. Most of them were caused by urolithiasis and malignant tumors. We report 2 cases of spontaneous peripelvic extravasation caused by urolithiasis, which were successfully treated conservatively.     

Serum lipids, lipoproteins and apolipoproteins in patients with senile dementia]

Serum lipid, lipoprotein, apolipoprotein, and sterol profiles were studied in 22 patients with senile dementia of the Alzheimer type (SDAT) and 29 patients with vascular dementia (VD). Levels of high density lipoprotein-cholesterol (HDL-C) were lower in both patients groups of SDAT and VD than in control group. Apolipoprotein AI and AII are two major proteins in HDL. In this study, apolipoprotein AI levels were normal, but apolipoprotein AII levels were lower in the patient groups, especially in the VD group, than in the control group. Lipoprotein(a) levels were higher in both patient groups, especially in the VD group. There were no differences of cholesterol, cholesterol precursors (desmosterol and lathosterol), and plant sterols (campesterol and beta-sitosterol) among the three groups. Murine apolipoprotein AII is a serum precursor of murine senile amyloid protein, and the apolipoprotein AII variant with proline-->glutamine substitution at position 5 in the serum of accelerated senescence-prone mice is identical to the murine senile amyloid fibril protein from amyloid-deposited tissues of these mice. In human SDAT and VD, the reason for the low level of apolipoprotein AII remains unclear.     

Local cerebral blood flow measured by stable xenon CT during fentanyl-diazepam anesthesia

We assessed the local cerebral blood flow (LCBF) in 40 patients under fentanyl-diazepam anesthesia. The measurement of LCBF was made using 50%–70% stable xenon with 20 min of inhalation interval and a shuttle method for computed tomography imaging. All patients were anesthetized with 5.95±1.76 μg·kg⁻¹ fentanyl and 0.22±0.07 mg·kg⁻¹ diazepam under mechanical ventilation during CBF measurement. The values and distribution of LCBF on non-affected hemisphere appeared to be unaltered by fentanyldiazepam anesthesia. We also assessed the cerebral carbon dioxide reactivity in 6 patients. The cerebral carbon dioxide reactivity, expressed as percentage change in LCBF per unit change in arterial carbon dioxide partial pressure, was 5.39±1.07, and there were no significant differences of reactivity among regions studied. In conclusion, we showed reference values of LCBF and carbon dioxide reactivity, measured by stable xenon-enhanced computed tomography, in patients under fentanyl-diazepam anesthesia. Carbon dioxide reactivity was preserved in all regions including gray matter, white matter, and basal ganglia.