Inhibitory effects of barbiturates on nicotinic acetylcholine receptors in rat central nervous system neurons

BACKGROUND: Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central and autonomic nervous systems. The authors have previously shown that depressant and convulsant barbiturates both inhibit the ganglion-type nAchRs in PC12 cells. However, the central and gangliontype receptors have different subunit composition and pharmacologic properties. In this study, the authors investigated the effects of thiopental, depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5 phenyl-5-propyl barbituric acid (MPPB) on neuronal nAChRs in the rat central nervous system to explore significance of these effects in barbiturate anesthesia. METHODS: Whole-cell currents were measured in acutely dissociated rat medial habenula (MHb) neurons by applying 10 or 100 microM nicotine in the absence or presence of thiopental 3-100 microM. Effects of R(-)- and S(+)-MPPB on the nicotine-induced current were also studied. RESULTS: Thiopental suppressed the nicotine-elicited inward current and accelerated the current decay dose-dependently at the clinical relevant concentrations. R(-)- and S(+)-MPPB both inhibited the nicotine-induced current dose-dependently without augmenting the current decay. There was no significant difference in the magnitudes of inhibition by R(-)- and S(+)-MPPB. CONCLUSIONS: Although thiopental suppressed the current mediated through native nAchRs in rat MHb neurons at the clinically relevant concentrations, the depressant and convulsant stereoisomers of MPPB both inhibited the current in the same extent. These findings are consistent with the results previously obtained in the ganglion-type receptors of PC12 cells and suggest that inhibition of nAChRs in MHb neurons is not directly relevant to the hypnotic or anticonvulsive actions of barbiturates.     

A case of giant cell tumor originating from the rib

We have experienced a case of giant cell tumor originating from the rib. A 45-year-old male was admitted to our hospital because of a mass in the left chest wall. A tumor shadow was observed in the left side of chest X ray. Chest CT, bone scintigram showed tumor originating from the left 4th rib. The tumor was suspected giant cell tumor of bone by needle biopsy examination. The tumor was completely resected with chest wall surrounding the tumor. The defect of chest wall was reconstructed with Marlex mesh and the Latissimus dorsi muscle flap. The pathological diagnosis was a giant cell tumor of bone. The patient has been well for two years and one month since surgery, with no signs of recurrence.     

Angiotensin-converting enzyme inhibitors and probucol suppress the time-dependent increase in urinary Type IV collagen excretion of Type II diabetes mellitus patients with early diabetic nephropathy

BACKGROUND: A multicenter prospective clinical trial was carried out in 9 National Hospitals in Japan to elucidate the time-dependent change in urinary Type IV collagen excretion rate of Type II diabetes mellitus (DM) patients, and to investigate whether an angiotensin-converting enzyme inhibitor (ACE-I) or probucol is effective in preventing progression of renal involvement of diabetics by evaluating urinary Type IV collagen excretion. METHODS: Normo- and microalbuminuric patients with Type II DM were recruited. Patients were assigned to either the control (n = 88), ACE-I (n = 43) or probucol (n = 37) group and treated for 24 months. Besides albumin excretion rate (AER), urinary Type IV collagen excretion rate was also measured. RESULTS: Although, AER, urinary N-acetyl-beta-D-glucosaminidase and beta2-microglobulin excretion rates in the control group did not vary over 24 months, urinary Type IV collagen excretion rate in the control group increased time-dependently (p < 0.01 vs baseline at 18 months and p < 0.005 vs baseline at 24 months). In the ACE-I and probucol groups, time-dependent increases in urinary Type IV collagen excretion rates were not observed. In the ACE-I group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 24 months (p < 0.05). In the probucol group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 6 months (p < 0.05). In the ACE-I group, AER decreased significantly compared with baseline at 18 months (p < 0.05) and at 24 months (p < 0.005). CONCLUSIONS: ACE-I has a beneficial effect and probucol may have a beneficial effect in preventing the progression of early diabetic nephropathy. Measurement of the urinary Type IV collagen excretion rate in combination with AER would be useful for the management of early renal involvement in Type II DM.     

Problems involved in endovascular embolization of intracranial aneurysms with three-dimensional Guglielmi detachable coils

We experienced nine cases of intracranial aneurysms which were treated with three-dimensional Guglielmi detachable coils (3D-GDC). 3D-GDC is useful in the construction of the initial frame for the embolization of aneurysms, but it also has certain disadvantages for achieving successful treatment. Nine patients with nine intracranial aneurysms were treated with 3D-GDC for initial framing from October, 1999 to September, 2000 at the National Cardio-Vascular Center, Japan. Angiographically complete and successful occlusion was performed in only three patients. Four patients developed parent artery stenosis due to small loops of the 3D-GDC protruding from the aneurysm. Two patients experienced incomplete occlusion because small loops of the 3D-GDC caused cells to form in the framing, and additional coils could not be inserted into some cells. 3D-GDC is useful as an initial framing coil, but we should be careful when placing additional coils into an aneurysm because we cannot predict the effect of the small loops of 3D-GDC on the embolization of aneurysms.     

Assessment of preferential Th1 or Th2 induction by low-molecular-weight compounds using a reverse transcription-polymerase chain reaction method: comparison of two mouse strains, C57BL/6 and BALB/c.

The aim of this study was to examine whether the RT-PCR method for various Th1/Th2 cytokines is appropriate for determination of response to allergens using C57BL/6 and Balb/c mice, which are known to preferentially demonstrate Th1 and Th2 responses, respectively. To this end, both strains of mice were sensitized by skin painting with the contact allergen dinitrochlorobenzene (DNCB) or the respiratory allergen trimellitic anhydride (TMA). We used the sensitizing protocol adopted by Kimber and coworkers (Toxicology 103, 63-73, 1995). At various time points after the last application, the levels of mRNA expression for Th1-type cytokines IFN-gamma, IL-18, and IL-12p40, as well as receptor IL-18R, and the Th2-type cytokine IL-4 and the receptor ST2L, in lymph nodes were measured. The results suggest that differential expression of IL-12p40 and IL-4 mRNA after 24 h allows clear discrimination between DNCB and TMA in C57BL/6 mice, more obviously than in Balb/c mice. Furthermore, to examine this method, C57BL/6 mice were exposed to OXA, DNFB, and TNCB (Th1-predominant allergens) or PA, TDI, and MDI (Th2-predominant allergens). Elevation of IL-12p40 expression was significant with the Th1 inducers, while the level of IL-4 was higher with Th2-predominant allergens. The results of the present study demonstrate, for the first time, that differential expression of IL-12p40 and IL-4 in C57BL/6 mice may be useful as a parameter for assessing influence of contact and respiratory allergens.     

Visualization of cerebrospinal fluid movement with spin labeling at MR imaging: preliminary results in normal and pathophysiologic conditions

Institutional review board approval and informed consent were obtained for this study. This study was HIPAA compliant. The purpose of this study was to visualize the movement of cerebrospinal fluid (CSF) noninvasively by using an unenhanced magnetic resonance imaging technique. A time-spatial labeling inversion pulse (SLIP) technique was applied to label, or tag, CSF in a region of interest. The tagged CSF was clearly visualized at inversion times of 1500-4500 msec after pulse labeling in both intracranial and intraspinal compartments. Noninvasive visualization of CSF movement, including bulk and turbulent flow, in normal (n = 7) and altered (n = 2) physiologic conditions was possible by using the unenhanced time-SLIP technique.     

Human papillomavirus detected in female breast carcinomas in Japan

To investigate the aetiological role of human papillomavirus (HPV) in breast cancer, we examined the presence, genotype, viral load, and physical status of HPV in 124 Japanese female patients with breast carcinoma. Human papillomavirus presence was examined by PCR using SPF10 primers, and primer sets targeting the E6 region of HPV-16, -18, and -33. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus DNA was detected in 26 (21%) breast carcinomas. The most frequently detected HPV genotype was HPV-16 (92%), followed by HPV-6 (46%), HPV-18 (12%), and HPV-33 (4%). In 11 normal epithelium specimens adjacent to 11 HPV-16-positive carcinomas, 7 were HPV-16-positive. However, none of the normal breast tissue specimens adjacent to HPV-negative breast carcinomas were HPV-positive. The real-time PCR analysis suggested the presence of integrated form of viral DNA in all HPV-16-positive samples, and estimated viral load was low with a geometric mean of 5.4 copies per 10(4) cells. In conclusion, although HPV DNA was detected in 26 (21%) breast carcinomas and, in all HPV-16-positive cases, the HPV genome was considered integrated into the host genome, their low viral loads suggest it is unlikely that integrated HPV is aetiologically involved in the development of Japanese breast carcinomas that we examined.     

Current situation and future for cytometry--leukocyte function]

There are granulocytes, monocytes and lymphocytes in the leukocyte of the peripheral blood. These leukocytes play an important part to each other for biophylaxis by forming the network. Therefore, it is important inspection to measure the number of these leukocytes and function. Recently, various reference techniques in flow cytometry have been developed for the leukocyte function. It is introduced phagocytosis for granulocyte, cytoplasmic free Calcium localization in granulocytes, lymphocyte transformation and cytoplasmic pH in lymphocytes.     

Failure of Ureteric Bud Invasion : A New Model of Renal Agenesis in Mice

FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%). Bilateral renal agenesis is lethal within 2 days after birth. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metanephric mesenchyme at around embryonic day 11, resulting in apoptosis of metanephric cells and leading to renal agenesis on the affected side. The metanephros seemed to be normal because co-culturing of the FUBI metanephros with homologous spinal cord induced differentiation of the rudiment, but co-culturing with the homologous ureteric bud frequently did not. Genetic analysis revealed that more than two genes were involved in this malformation and we mapped one of the modifier loci, fubi1, on chromosome 2, at approximately 65 cM from the centromere. In this region, there are two possible candidate genes, Wilms' tumor 1 and formin, that play important roles in kidney development. Some of formin mutants shared a similar phenotype with FUBI; however, there was no difference in the expression of formin in embryonic kidneys between FUBI and control NFS/N mice. Studies of fubi1 congenic mice indicated that interaction of two or more loci is essential for the FUBI phenotype.