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Despite substantial progress in identifying and understanding causative mutations in autosomal dominant polycystic kidney disease (ADPKD), little is known about subsequent cellular events leading to cyst formation. In prior studies we reported that Cadherin 8, a type II Cadherin, expression is sufficient to induce cyst emergence from HK-2 cells grown as tubule arrays in collagen matrix (1). However, emergent cysts did not exhibit the luminal enlargement observed in ADPKD. In this communication, we reconstitute cyst emergence with consequent cyst lumen expansion in 3D culture by stable co-expression of Cadherin 8 in combination with a constitutively active mutant of YAP1, the key effector of the HIPPO pathway. Specifically, immortalized cells derived from ADPKD cyst epithelia formed cysts with substantially larger lumen sizes when transduced with YAP1-5SA. Conversely, expression of the YAP1 inhibitor, AMOTL1, in these cells resulted in their forming cysts with smaller lumens than control cells. Our data show that cyst formation results from a sequential two-step process consisting of cyst initiation and subsequent cyst expansion. Taken together, cyst initiation induced by Cadherin 8 expression is proposed to result from decreased cell-cell adhesion while cyst expansion is driven by increased Yap1 activity.

OBJECTIVE: To study the characteristics of gut microbiota and its association with the activity of β-glucuronidase (β-GD) in neonates with hyperbilirubinemia. METHODS: A total of 50 neonates with hyperbilirubinemia who were admitted in January to December, 2018, were enrolled as the hyperbilirubinemia group, and 30 neonates without hyperbilirubinemia were enrolled as the control group. The 16S rRNA high-throughput sequencing method was used to compare gut microbiota between the two groups. The phenolphthalein-glucuronic acid substrate method was used to measure the activity of β-GD in the intestinal tract of neonates with hyperbilirubinemia before and after treatment. RESULTS: The comparison of the distribution of gut microbiota at the genus level showed a significant difference in the abundance of 52 bacteria between the hyperbilirubinemia and control groups before treatment (P < 0.05), as well as a significant difference in the abundance of 42 bacteria between the hyperbilirubinemia group on day 3 after treatment and the control group on day 3 after enrollment (P < 0.05). After treatment, the hyperbilirubinemia group had significant reductions in the content of Escherichia and Staphylococcus in the intestinal tract (P < 0.05) and the activity of β-GD in feces (P < 0.05). The activity of β-GD in feces was positively correlated with the abundance of Staphylococcus and Escherichia before and after treatment in the neonates with hyperbilirubinemia (r(s)=0.5948-0.7245, P < 0.01). CONCLUSIONS: There are differences in gut microbiota between the neonates with hyperbilirubinemia and those without hyperbilirubinemia. The activity of β-GD in feces is positively correlated with the abundance of Staphylococcus and Escherichia in neonates with hyperbilirubinemia. Gut microbiota may affect the development of neonatal hyperbilirubinemia by regulating the activity of β-GD. The determination and analysis of gut microbiota and β-GD activity may have certain clinical significance for the early assessment of the development of neonatal hyperbilirubinemia.

OBJECTIVE: To study the effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates. METHODS: The neonates with hyperbilirubinemia who were hospitalized from January to December 2018 were enrolled and randomly divided into an observation group (n=61) and a control group (n=63). The neonates in the observation group were treated with phototherapy combined with Saccharomyces boulardii, and those in the control group were treated with phototherapy combined with placebo. Treatment outcomes were compared between the two groups. Fecal samples were collected 72 hours after treatment and 16s rRNA high-throughput sequencing was used to compare the features of gut microbiota between the two groups. RESULTS: There was no significant difference in the total serum bilirubin level between the two groups before treatment (P > 0.05). At 24, 48, and 72 hours after treatment, the observation group had a significantly lower level of total serum bilirubin than the control group (P < 0.05). Compared with the control group, the observation group had a significantly lower proportion of neonates requiring phototherapy again[20% (12/61) vs 75% (47/63), P < 0.05]. Compared with the control group, the observation group had a significantly higher abundance of Bacteroides (P < 0.05) and a significantly lower abundance of Escherichia coli and Staphylococcus in the intestine at 72 hours after treatment (P < 0.05). CONCLUSIONS: In neonates with hyperbilirubinemia, phototherapy combined with Saccharomyces boulardii can effectively reduce bilirubin level and prevent the recurrence of jaundice. Saccharomyces boulardii can favour the treatment outcome by regulating the gut microbiota of neonates.

In this work, a novel material design is proposed and implemented for developing a high performance resistive-type strain sensor. Accordingly, an electrically conductive composite film of polyurethane/silver nanowires is prepared. Owing to the synergistic effects of the transparent and sunlight self-healable polyurethane matrix, low-density and thin network of welded long silver nanowires, spray-coating, and sandwich structure consisting of two polyurethane layers and a silver nanowire network interlayer, the key factors that control the robustness and responsivity of the conduction paths while contradicting each other, are united, and the long-term cyclic loading induced failure can be self-repaired under sunshine. As a result, the composite successfully integrates high transparency, sensitivity, durability, self-healability and flexibility together, exhibiting promising application potential.

Background Although increased accumulation of neutrophils has been noted in chronic rhinosinusitis (CRS), the function and regulation of neutrophils in CRS are largely unknown. IL-36 family cytokines may play an important role in neutrophilic inflammation. Objective This study sought to investigate the expression and function of IL-36 cytokines in CRS. Methods Quantitative RT-PCR, immunohistochemistry, immunofluorescence, and ELISA were used to investigate the expression of IL-36 cytokines and IL-36 receptor (IL-36R) in sinonasal mucosa. The expression of IL-36R on neutrophils in polyps and blood was measured by flow cytometry. Purified blood neutrophils were cultured to investigate the regulation of IL-36R expression. The cleavage of IL-36γ was detected by Western blotting. Dispersed nasal polyp cells were treated with IL-36γ with or without elastase inhibitor and dexamethasone. Results Neutrophil infiltration and expression of IL-36 cytokines and IL-36R were upregulated in both CRS with and without nasal polyps. IL-36γ was the most abundant isoform and mainly expressed by epithelial cells in CRS. Neutrophils were the principal IL-36R + cell type in polyps. IL-36R expression was almost absent in blood neutrophils and upregulated by IL-6, IL-1β, and Dermatophagoides pteronyssinus group 1. Elastase activity was increased in polyps and degraded full-length IL-36γ. Consistently, the levels of cleaved IL-36γ were increased in polyps. Full-length IL-36γ promoted the production of matrix metalloproteinase 9; IL-17A; and chemokine (C-X-C motif) ligands 1, 2, and 8 from dispersed nasal polyp cells, which was abolished by elastase inhibitor. The proinflammatory effect of IL-36γ was not suppressed by dexamethasone. Conclusions Increased production and activation of IL-36γ may act on neutrophils and further exaggerate neutrophilic inflammation in CRS.

Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine (P

This work evaluated the effect of air- and modified atmosphere-packaging (MAP) on the shelf life of chilled freshwater shrimp, which is widely distributed in China and Japan. Freshwater shrimp were stored in air and under modified atmosphere packaging (M1: 80% CO2/20% N2, M2: 50% CO2/50% N2, M3: 30% CO2/70% N2) at 4 ℃ for up to 12 days. Microbiological, physico-chemical, changes in degree of depression and sensory attributes were measured. The results showed that total viable counts (TVC) reached the limiting value (7.0 log CFU/g) after 4, 10, 10 and 8 days of storage under aerobic, M1, M2 and M3 packaging conditions, respectively, while the sensory values (odor) with the trend for TVC. During the storage, the total volatile basic nitrogen (TVB-N) content of chilled freshwater shrimp in MAP packaging was lower than that in air-packaging, especially the M1 and M2 Group. However, the M1 group of modified air box depression significantly higher than the others, affecting the appearance of the product. And the M1 group had the lower elasticity values in comparison with those freshwater shrimp of M2 Group. In conclusion, 50%CO2 concentration packaging prolonged the shelf-life by at least 6 days when stored at 4°C. Our results provide practical information to extend the shelf-life of chilled freshwater shrimp, which will benefit the industry by reducing unnecessary waste.

With the continuous development of internet technology, its application scope has been widely. In the field of education, it is becoming more and more mature and forming a complementary relationship with traditional education. In this paper, through t computer.NET platform architecture, we analyze the composition and running mechanism of.NET structure. Based on this we construct the exact image recognition method with block matching, which matches the martial arts action image. We use VB.NET internet technology to construct the martial arts teaching action design system, and use simulation technology to test. The results show that the system can meet the needs of martial arts teaching, and has strong practicability.

The harm of bridge deformation is serious, real time monitoring of bridge deformation is important to ensure the safe use. Over the years, the routine measuring method is unable to complete the multiple, dynamic monitoring. This paper discusses the method of multi-points instantaneous monitoring by using GPS technology, makes a great contribution to improve the technology of bridge detection, and has achieved good results.

Overhead cranes are essentially a kind of complex underactuated nonlinear mechanical systems, and it is a challenge to design an anti-swing controller for overhead cranes, hence, many people design controllers of overhead cranes ignoring the changing of the rope length and other parameters. In this study, we propose a multi-sliding mode controller to solve the problem of anti-swing and positioning controller for an overhead crane with rope length variations. This controller can provide a simultaneous trolley-position regulation, sway suppression, and load hoisting control. Also, this paper adopts a new method to decrease the chattering of the control input. Stability analysis of the proposed controller is given in the paper. The proposed controller does not rely on the accurate knowledge of overhead crane system model, and it is simple and easy to apply, and robust to disturbances. The simulation results show the good performance of the proposed controller.

With progress making in the art of industrial fields, control methods for synchronized multi-motor systems get more and more extensive applications, and there are increasingly high requirements for synchronous controllers. In this paper, a new control method for multi-axis drive systems is proposed, an adjacent-coupling algorithm based synchronization control strategy is designed, and a CMAC neural network based controller is developed. Simulation results show good performance of synchronization control accuracy, interference immunity, and convergence for the suggested synchronous controller

Compared with a traditional single-container overhead crane, the double-container overhead crane is a type of new efficient container stevedoring machinery, however, it is actually a complicated nonlinear system. In this brief, both the kinematic and dynamic characteristics concerning the double-container crane are investigated, and then an accurate dynamic model of the underactuated double-container overhead crane is established by utilizing Euler-Lagrange's method. Not only is the variation of the rope and payloads, but also some uncertainties such as mechanical frictions and air-resistance in the environment are taken into account in modeling. Simulation results show the validity of the established double-container overhead crane model.

While a variety of genetic mutations have been shown to be associated with renal cyst formation, mechanisms of renal cyst formation are largely unknown. In prior communications we described alterations in E-cadherin assembly in cultured cystic epithelial cells (Charron AJ, Nakamura S, Bacallao R, Wandinger-Ness A. J Cell Biol 149: 111–124, 2000). Using the same cell line we assayed cadherin expression by RT-PCR using primer pairs that anneal to highly conserved sequences of cadherin genes but flank informative regions of cadherins. Using this approach we found that autosomal dominant polycystic kidney disease (ADPKD) cells express cadherin 8, a neuronal cadherin with limited expression in the kidney. Immunohistochemistry confirmed cadherin 8 expression in cystic epithelia. To test the functional significance of cadherin 8 expression in renal epithelial cells, we adapted a three-dimensional collagen culture method in which HK-2 cells form tubule structures and microinjected adenovirus into the matrix space surrounding tubule structures. Adenovirus expressing cadherin 8 under the control of a tet promoter caused cyst structures to grow out of the tubules when coinjected with adenovirus expressing a tet transactivator. Microinjection of single adenovirus expressing either tet transactivator or cadherin 8 failed to cause cyst formation. When doxycycline was added to the culture, following coinjection of adenovirus, there was a dose-response reduction in cadherin 8 expression and cyst formation. Similarly, HK-2 cells transfected with Flag-tagged cadherin 8 form cysts in addition to tubular structures. HK-2 cells transfected with Flag-tagged N-cadherin do not form cysts. These data suggest that ectopic expression of cadherin 8 in renal epithelial cells is sufficient to cause the morphogenic pattern of cyst formation.

Sixty pet feeding families were obtained by random sampling in Hangzhou. The positive rate of IgG antibodies to Toxoplasma gondii in pet owners was 3.3% (4/120). The rate in males and females was 8.6% (3/35) and 1.2% (1/85) (χ2=4.207, P0.05). The positive rate in pet dogs was 13.3% (8/60). The positive rate in dogs fed with a raw-meat diet (33.3%, 4/12) were significantly higher than that of others (4.2%, 2/48) (χ2=6.123, P0.05).

Ischemic preconditioning is well known to afford protection against subsequent episodes of ischemia/reperfusion (I/R) in multiple organs, including the kidney, but the mechanisms involved are not fully understood. We proposed that ischemic preconditioning results in an altered mitochondrial proteome that confers resistance to subsequent I/R injury. We subjected rats to moderate ischemic injury and used liquid chromatography – mass spectroscopy (LC/MS) to analyze the proteome of kidney cortical mitochondria isolated following 14 days of recovery from I/R. The expression of several proteins was elevated following preconditioning, and two were selected for further analysis: Isocitrate dehydrogenase 2 (IDH2) and a member of the sulfotransferase family (SULT1A1). The effect of increased expression of these proteins was evaluated by using hydrodynamic gene delivery of plasmid vectors to overexpress each protein. Strikingly, hydrodynamic delivery of IDH2 and SULT1A1 genes attenuated the peak in serum creatinine ...

The microvascular wall is remarkably simple, consisting only of the endothelial lining, subjacent basal lamina, and underlying periendothelial cells. This study describes the characterization of a novel microvascular protein. This 80,000-molecular weight protein was predominantly associated with electron-lucent amorphous material in capillary basal laminae and therefore termed cablin (protein of the capillary basal lamina). Consistent with its immunolocalization to the microvasculature, cablin was synthesized and secreted by cultured endothelial cells and vascular smooth muscle cells. Furthermore, cablin expression was induced during neovascularization. The predicted amino acid sequence of cablin revealed a prevalence of polar amino acids. Accounting for the low yet significant homology to several α-helical proteins, these residues were best accommodated by secondary structure predictions that aligned the molecule into two large α-helical domains. The presence of the integrin-binding RGD tripeptide and a putative elastin-binding sequence suggest that this rodlike molecule is suited to cross-link cells and matrix constituents. In this capacity it could contribute to the mechanical strength or the angiogenic potential of the microvasculature.

Fragile X syndrome is recognized as the most common inherited cause of mental retardation in western countries. The prevalence of the fragile X syndrome in Asian populations is uncertain. We report a multi-institutional collaborative study of molecular screening for the fragile X syndrome from 1,127 Chinese mentally retarded (MR) individuals. We found that 2.8% of the Chinese MR population screened by DNA analysis had the fragile X full mutation. Our screening indicated that the fragile X syndrome prevalence was very close to that of Caucasian subjects. In addition, we found that 62.5% of fragile X chromosomes had a single haplotype for DXS548-FRAXAC1 (21-18 repeats) which was present in only 9.7% of controls. This unique distribution of microsatellite markers flanking the FMR1 CGG repeats suggests that the fragile X syndrome in Chinese populations, as in the Caucasian, may also be derived from founder chromosomes.

Batten disease, the juvenile form of neuronal ceroid lipofuscinosis, is a prevalent neuron degenerative disorder of childhood. A 1.02-kb genomic deletion in the Batten disease gene CLN3 has been determined to be a common mutation. We developed a PCR method to screen for this deletion and tested 43 Batten disease probands. We found 36% (31/86) of Batten disease chromosomes did not carry the 1.02-kb deletion. Of the three heterozygotes for the 1.02-kb deletion, a novel G-to-A missense mutation at nucleotide 1020 of the CLN3 cDNA sequence was found on two of the non-1.02-kb deletion chromosomes. The missense mutation resulted in a substitution of glutamic acid (E) by lysine (K) at position 295 (E295 K). The E295 K mutation causes a change in predicted local protein conformation. This glutamic acid is a highly conserved acidic amino acid, being present in human, mouse, dog and yeast, which suggests it may play an important role in the function of the Batten disease protein.

To explore the iodine level in the environment and the iodine status among the general population as well as the prevalence of thyroid nodules in Hangzhou city. Relationship between the prevalence of thyroid nodules and the policy of universal salt iodization in Hangzhou was also analyzed.Questionnaire, a 3-day weighed dietary record method, and 3 days' 24-hour dietary recall method were used to understand the iodine nutrition status and dietary intake of iodine among the general population in the city. Drinking water, edible salt and morning urine were collected to determine iodine content. All objects under survey underwent the thyroid B ultrasonic examination. Statistical analysis was done by SPSS 13.0 and SAS 9.1.(1) In total, 12 620 effective questionnaires were available, with 221 water samples, 12 730 urine samples, and 3593 salt samples collected. 12 515 objects underwent B ultrasonic examination, and 1848 received dietary investigation. (2) Water iodine level of Hangzhou was in the range of 0.20 - 5.99 µg/L, with the median level as 2.58 µg/L. (3) Average daily dietary intake of iodine for adult males in Hangzhou was 289.2 µg/d. The contribution of iodine intake from iodized salt was 74.4%. (4) The median of Hangzhou residents' urinary iodine was 178.80 µg/L, with the urinary iodine levels at 100 µg/L-, 200 µg/L-,100 µg/L, and ≥ 300 µg/L groups were 37.14%, 23.11%, 21.05%, and 18.69% respectively. Urinary iodine of pregnant women was 141.0 µg/L. (5) Incidence of thyroid nodules in females (28.6%) was higher than that of males (20.1%). The detection rate increased with age (6.4% at group 6-, 10.9% at 12-, 12.0% at 18-, 24.4% at 40-, and 38.8% at 65-); with the highest in urban area (29.8%), followed by suburbs (23.3%) and in rural area it showed the least (20.3%). Urinary iodine level was found lower among the population who had been detected with thyroid nodules (160.36 µg/L) than those among the undetected population (182.00 µg/L).Hangzhou appeared to be an area where the environmental was iodine deficient. Iodized salt was the major source of iodine intake. The iodine status among the general population seemed to be safe and suitable, but the iodine level for pregnant women was not sufficient. There was still no evidence indicating that the universal salt iodization policy in Hangzhou was associated with the prevalence of thyroid nodules.

Experiments were conducted under open-top-chambers conditions to assess the photosynthetic responses of wheat plants (Triticum aestivum L., YangMail6) to supplemental UV-B radiation (10%-10.9% higher then control group, T1) and enhanced ozone [(100 +/- 9) nmol x mol(-1), T2], separately and in combination (combination treatment, T3), making use of LCpro + Portable Photosynthesis System and DIVING-PAM Fluorometer to determine gas exchange and chlorophyll fluorescence parameters. Results indicated that P(n), G(s), T(r), P(m) and I(k) of T1, T2 and T3 treatments decreased significantly compared to CK (control group, natural air and UV-B radiant intensity condition), while there were no differences between T3 and T1 or T2 or both in major growth stages. UV-B fiercely inhibited the stomatal conductance and transpiration of plants, while T1 stimulated stomata opening and transpiration in jointing stage. Dark respiration (R(d)) of T1 was increased, while no significance difference was found between T2 and CK or T3 and CK in most stages. T1 and T2 reduced F(v)/F(m) value only in booting stage, while T3 was significant lower than CK except jointing stage. qP value declined significantly in treatments of T1, T2 and T3 as Compared to CK, with decreasing amplitude occurring in the order T3T1T2. NPQ, Y (NPQ), Y (NO) value of T1, T2 and T3 treatments increased significantly compared to CK, with maximum increasing amplitude occurring in the order T3T1T2, of which NPQ of T1 and T2 turned to decrease since filling stage, and T3 turned to decrease since flowering stage to a greater degree than T1 and T2. T1, T2 and T3 also caused significance reduction in Y (II), with reducing amplitude occurring in the order T3T1T2. Obviously, supplemental UV-B radiation and enhanced ozone caused a significant decrease in gas exchange capacity, maximum photochemical capacity and photosynthetic activity of winter wheat, and the photoprotective mechanism was damage, leading to greater proportion of excitation energy dissipated in the form of non-regulated heat and fluorescence. The photosystems of winter wheat were damaged by both excess energy and UV-B or excess energy and O3, or excess energy, UV-B and O3 together. UV-B and O3 in combination enhanced the negative effects on photo-protective mechanisms and excitation energy distribution in PS II compared to UV-B or O3 alone, while the interactive effects were less than addition.

Vinyl-functionalized periodic mesoporous organosilica materials (PMOs) with a crystal-like wall structure were synthesized, for the first time, by direct co-condensation of 1,4-bis(triethoxysilyl)benzene (BTEB) and triethoxyvinylsilane (TEVS). The synthesis approach led to high loading of vinyl functional groups and controlled regular morphologies. The resultant materials with different TEVS contents (up to 60 molar percentage) consisted of well-ordered mesopores (2.82–3.29 nm) with molecular-scale periodicity (7.6 A) in the walls, so that the high thermal stability of phenylene-bridged organosilica and versatile functionality of vinyl groups are combined. By exploring the influence of TEVS loading and the second monomer, tetraethoxysilane (TEOS), on the molecular-scale regularities, the rule of synergetic assembling of functional monosilylated TEVS and bissilylated BTEB was revealed. That is, the PMOs framework was built up only by BTEB, while TEVS was always terminally bonded to the channels surface.

To investigate the genetic diversity of Plasmodium vivax transmission-blocking vaccine candidate antigen (TBV) Pvs25, with P. vivax isolates from Hubei and Zhejiang Provinces, and to compare the genetic polymorphism of Pvs25 with that from Bangladesh.The parasite DNA used for the genetic polymorphism assay was obtained from dried filter paper blood spots. The genes were PCR amplified and the products were purified and sequenced directly.45 complete new sequences were analyzed. Only 3 nucleotide changes were found that would result in amino acid substitutions in Pvs25 in comparison with the sequence from P. vivax Sal-I strain. The measurement of nucleotide diversity (pi) was remarkably similar for the two populations, indicating that DNA sequences and deduced amino acid sequences were highly homologous among the geographically dispersed isolates or isolates from the same geographical region.The results suggest that Pvs25 has limited antigenic polymorphism, especially compared with candidate antigens expressed by hepatic and erythrocytic stage, which may support the development and application of Pvs25-based transmission-blocking vaccine in China.

Seventy-three patients have been treated with Gamma Knife radiosurgery (GKR) for pituitary adenomas. 12 had undergone surgery prior to GKR. Three had had previous radiation therapy. The prescription dose administered to the tumor margin ranged from 9 to 35 Gy. 65 patients were followed up for an average of 29 months. A slight expansion of tumor volume occurred in 3 cases. Otherwise, the tumor volume remained unchanged or decreased in the remainder. Endocrine changes were present in all except 3 cases. GKR was followed by a speedy decrease in raised serum hormone levels in the case of both growth hormone (GH)and adrenocortico-tropic hormone (ACTH). In 3 patients there was some visual deterioration associated with a slight increase in tumor volume. In 2 cases, the tumors were removed surgically. Some preliminary conclusions may be drawn. The dose required to correct an endocrinopathy may be higher than that required for control of tumor growth. The recommended prescription dose for endocrine-active adenomas may be more than 30 Gy. While clinical improvement may be noted in patients with raised serum prolactin levels (PRL), normalization of the endocrinopathy may be less readily achieved than in the case of raised GH and ACTH levels. Gamma Knife radiosurgery as a primary treatment of pituitary adenomas can be safe and effective.

From September 1994 to June 1995, eight patients with intractable parkinsonism underwent gamma thalamotomy in our hospital. All of these patients were male, with an average age of 59.3 years. The duration of the disease from initial diagnosis was 2-10 years (mean 6.8 years). All had failed or had serious side effects with antiparkinsonian medicine. Seven cases had tremor-dominant symptoms, while the other had mainly rigidity. Six cases had bilateral symptoms. Computed tomography or magnetic resonance imaging (MRI) was undertaken prior to treatment in all cases to exclude focal brain lesions. Stereotactic MRI was taken with the Leksell frame in place and both T1- and T2-weighted images were obtained. The targets were located in the area of Vim/Voa/Vop based on the Schaltenbrand atlas. In seven cases, two plugged 4-mm-collimator shots were used. The maximum dose was 160 Gy in six cases and 180 Gy in one case. In another case, a single 4-mm-collimator shot was used, and a maximum dose of 160 Gy was delivered to the target center. The border of the internal capsule was outside the 20-30% isodose line. We intended the 50% isodose line to have an oval-shaped region with the use of two shots and should correspond to the shape of Vim. Follow-up data were available for six patients (mean: 4.5 months, range: 2-9 months). Tremor disappeared in three cases and improved in the other three. In one of these six cases, the tremor disappeared just 3 days after gamma thalamotomy. Rigidity improved in four of these six cases. In only one patient, treated with a maximum dose of 180 Gy, was there any contralateral limb weakness, which developed 3 months after treatment and has been recovering gradually. Follow-up MRI T2-weighted images in this case showed that the diameter of the lesion was larger than intended and there was a region of diffuse edema in the thalamus and upper brain stem. No other complications occurred in this series.

Metorphamide (MET) elicited a potent, dose-dependent analgesia and respiratory depression in mice and rabbits. MET induced-analgesia was naloxone reversible and potentiated by bestatin. Naloxonazine, a relatively selective mu 1 blocker, at certain dosage (50 micrograms per rabbit, icv), could abolish the analgesia but not the respiratory inhibition produced by MET. Our result indicates that mu 1 receptors mediate the MET induced-analgesia but not its respiratory effect. Since MET is a mu- and kappa-ligand with very low delta activity, the MET induced respiratory depression may be mediated by mu 2 or kappa binding sites.