Anatomical considerations of the iliac crest on percutaneous endoscopic discectomy using a transforaminal approach

Background Context

Percutaneous endoscopic discectomy is a minimally invasive procedure for the surgical treatment of lumbar disc herniation (LDH). It can be performed under local anesthesia and requires a skin incision of only 8?mm, with minimal disruption of the spinal structures including ligaments and muscles. However, performing percutaneous endoscopic discectomy with a transforaminal approach (TF-PED) for the lower lumbar spine is associated with some anatomical problems, such as interference from the iliac crest. This study sought to assess the operability of TF-PED for the lower lumbar spine.

Endogenous adenosine protects CA1 neurons from kainic acid-induced neuronal cell loss in the rat hippocampus

CA3 pyramidal neurons in the rat hippocampus show selective vulnerability to the intracerebroventricular injection of kainic acid (KA). However, the mechanism of this selective neuronal vulnerability remains unclear. In this study, we examined the contribution of endogenous adenosine, a potent inhibitory neuromodulator, to the differences in the neuronal vulnerability of the hippocampus, using microtubule-associated protein (MAP)-2, phosphorylated c-Jun, and major histocompatibility complex (MHC) class II immunoreactivities as markers for neuronal cell loss, neuronal apoptosis and glial activation, respectively. Pretreatment with 8-cyclopenthyltheophylline (CPT), an A1 adenosine receptor antagonist, significantly exacerbated KA-induced neuronal cell loss in both the CA1 and CA3. Although c-Jun phosphorylation, a critical step in neuronal apoptosis, was not detected in the vehicle-injected rat hippocampus, c-Jun phosphorylation was induced in the CA3 by the injection of KA alone. Pretreatment with CPT induced c-Jun phosphorylation in both the CA1 and CA3. MHC class II antigen was also detected in the regions of c-Jun phosphorylation. Coadministration of N6-cyclopenthyladenosine (CHA), an A1 adenosine receptor agonist, attenuated the neuronal cell loss in the CA1 and CA3 with or without pretreatment with CPT. These results strongly suggest that endogenous adenosine has neuroprotective effects against excitotoxin-induced neurodegeneration in the CA1 through its A1 receptors.     

Synaptic potentials produced in jaw-closer and jaw-opener motoneurons by palatal stimulation

Summary Excitation and inhibition of temporal and digastric motoneurons (Temp. and Dig. Mns) during transient jaw closing, the so-called jaw-closing reflex, were studied in cats. Application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and it was found that mechanosensory inputs from the posterior palatal mucosa produce depolarizing potentials on the Temp. Mns responsible for jaw closure during the jaw-closing reflex. We have demonstrated that in one-third of 27 explored Temp. Mns the initial bursts of spikes were elicited before the onset of jaw closure, suggesting that these cells contribute to initiate jaw closure during the jaw-closing reflex. The remaining cells probably contributed to maintain the occlusal phase. Furthermore, it was found that mechanosensory inputs from the posterior palatal mucosa produce a hyperpolarization-depolarization sequence in the Dig. Mns responsible for the jawclosing reflex. In addition, when pressure stimulation was applied to the anterior palatal mucosa, sustained jaw opening was elicited and an increase of firing frequency of Dig. Mns occurred 40 ms before the onset of jaw opening and continued for 80 ms.     

Phenotypic expression of gastrointestinal differentiation markers in colorectal adenocarcinomas with liver metastasis

AIM: The purpose of the present study was to clarify the correlation between phenotypic expression of gastrointestinal differentiation markers and colorectal cancer behaviour, particularly invasion and hepatic metastasis. METHODS: Thirty-one cases of advanced colorectal adenocarcinoma (CRC) with liver metastasis were selected. Phenotypic patterns were evaluated immunohistochemically by means of antibodies to CD10, MUC2, and human gastric mucin (HGM). RESULTS: The incidence of MUC2 (45.2%) and HGM (16.1%) expression in CRCs with liver metastasis did not differ from non-metastatic CRCs. In contrast, the incidence of CD10 expression was significantly higher in CRCs with liver metastasis (58.1%) than in control CRCs (21.7%). Phenotypic expression in the liver metastasis carcinomas was similar to that of the primary lesions. CONCLUSIONS: The findings suggest that cases of CRC with CD10 expression are at increased risk of liver metastasis. Even if there is no liver metastasis at laparotomy for CRC, careful follow-up is recommended for CRCs with CD10 expression.     

Phenotypic classification of human CD8+ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

Phenotypic classification of human CD8(+) T cells using three cell surface markers, CD27, CD28 and CD45RA, was recently suggested to be useful for identification of naive, memory and effector CD8(+) T cells. However, it still remains unclear whether such classification precisely reflects functional classification of CD8(+) T cells. To clarify this, we characterized each CD27CD28CD45RA subset of total and human cytomegalovirus (HCMV)-specific CD8(+) T cells by analyzing the expression of perforin and two chemokine receptors, CCR5 and CCR7, as well as their function. An inverse correlation between perforin and CD27 expression was found in all four CD28CD45RA subsets. Therefore, to achieve a phenotypic classification of CD8(+) T cells that more precisely reflects their function, the CD27(+) subset was divided into CD27(low) and CD27(high) subsets based on the expression level of CD27. Functional and flow cytometric analyses of CD27CD28CD45RA subsets showed that this phenotypic classification reflects functional classification of CD8(+) T cells. HCMV-specific CD8(+) T cells from healthy HCMV-seropositive individuals were predominantly found in effector and memory/effector subsets, indicating that HCMV-specific effector CD8(+) T cells are actively induced by HCMV replication in healthy HCMV carriers. Phenotypic analyses of CD8(+) T cells using this classification will enable the characterization of antigen-specific CD8(+) T cells.     

Synthesis and characterization of homo- and co-oligomers of tetracyclo[4.4.0.12,5.17,10]dodecene-3 by cationic polymerization

Cationic homopolymerization of tetracyclo[4.4.0.1^2,5.1^7,10]dodecene-3 (TCD) and its copolymerization with styrene (St) were carried out with the catalyst system Al(C₂H₅)Cl₂/tert-butyl chloride, and the effects of temperature and TCD/St feed ratio, on polymer solubility, molecular weight and glass transition temperature (T_g) were investigated. A soluble oligomer with a molecular weight of 1000 was prepared by homopolymerization of TCD at +10°C or by copolymerization with St (>4 mol-% in the feed) at ?50°C. ¹³C NMR analysis of the TCD homo- and TCD/St copolymers revealed both 3,4- and 3,11-additions for the repeating units from TCD. A polymerization mechanism including initiation, propagation, termination (deprotonation), and further crosslinking reactions is proposed. Moreover, it was demonstrated that a TCD/St copolymer with a controlled T_g in the range of 100 to 260°C can be prepared by selecting the TCD/St composition.     

Glycemic Control and Insulin Improve Muscle Mass and Gait Speed in Type 2 Diabetes: The MUSCLES-DM Study

ObjectivesType 2 diabetes is a risk factor for sarcopenia. Evidence on the prevention of sarcopenia using blood glucose–lowering therapy is limited. We aimed to examine the relationship between changes in glycemic control and sarcopenia and the effect of antidiabetic agents against sarcopenia in patients with type 2 diabetes.DesignWe conducted an observational longitudinal study.Setting and ParticipantsIn total, 588 Japanese patients with diabetes of an ongoing multicenter study completed 1-year follow-up measurements for sarcopenia and clinical data.MethodsThe data set of the Multicenter Study for Clarifying Evidence for Sarcopenia in patients with Diabetes Mellitus (the MUSCLES-DM study) was analyzed.ResultsDuring the follow-up period, the frequency of sarcopenia marginally increased, and the means of skeletal muscle mass index (SMI), handgrip strength, and gait speed did not show any changes. However, on dividing into 5 groups depending on the degree of changes in glycated hemoglobin (HbA_1c) value, the patients with a decrease of ≥1% in HbA_1c exhibited a significant increase in SMI. Our analysis revealed similar results for gait speed but not handgrip strength. Using the multiple linear regression model, we identified that a ≥1% decrease in HbA_1c value was an independent determinant of the changes in SMI and gait speed. We also determined that insulin use at baseline was an independent factor for the changes in SMI.Conclusions and ImplicationsCorrection of poor glycemic control and use of insulin were significantly associated with the increase in skeletal muscle mass or gait speed in Japanese patients with type 2 diabetes. The current finding increases our understanding of the importance of glycemic control for the prevention of cardiovascular diseases and sarcopenia.     

A highly sensitive enzyme-linked immunosorbent assay for etoposide using β-d-galactosidase as a label

Summary A highly sensitive enzyme-linked immunosorbent assay (ELISA) for etoposide (EP) was developed, which is capable of accurately measuring as little as 40 pg EP/ml. Anti-EP sera were obtained by immunizing rabbits with EP conjugated with mercaptosuccinyl bovine serum albumin (MS.BSA) usingN-[-(4-diazophenyl)ethyl]maleimide (DPEM) as a heterobifuntional coupling agent. An enzyme marker was similarly prepared by coupling EP with -d-galactosidase (-Gal; EC 3.2.1.23) via DPEM. This ELISA was specific for EP and showed a very slight cross-reactivity with its major metabolite,cis-hydroxy acid of EP (0.91%), but none with 4-demethylepipodophyllotoxin and drugs commonly used with EP in combination chemotherapy for cancer treatment. The values for EP concentration detected by this assay were comparable with those detected by the highperformance liquid chromatography (HPLC) method. However, the ELISA was about 1,250 times more sensitive in detecting EP at lower concentrations. Using this assay, drug levels were easily determined in the blood and urine of rats for 7 h after i.v. administration of EP at a single dose of 3 mg/kg. Due to its sensitivity and specificity for EP, the ELISA should prove to be a valuable new tool for use in clinical pharmacological studies.     

High frequency of BRAFV600E mutation in acquired nevi and small congenital nevi, but low frequency of mutation in medium-sized congenital nevi

To investigate whether the frequency of the BRAF(V600E) (V-raf murine sarcoma virus oncogene homolog B1) mutation in melanocytic nevi is associated with sun exposure patterns, we examined 120 acquired melanocytic nevi excised from various anatomic sites, including glabrous skin, as well as 62 congenital nevi. We used a new mutation detection system based on the shifted termination assay, called Mutector, which was able to detect only 5% of heterozygous mutant cells within the samples. We detected the mutation in 105/120 (87.5%) acquired nevi and 43/62 (69.4%) congenital nevi. Notably, we found the mutation in 35/43 (81.4%) acquired nevi excised from glabrous skin and genitalia. These results strongly suggest that UV light is not necessarily required for the acquisition of the BRAF(V600E) mutation, and suggest that non-mutagenic effects of UV light to melanocytes may be more important in the nevogenesis. Additionally, we showed heterogeneous distribution of BRAF-mutated cells within the lesions of small congenital nevi by a combination of laser microdissection and direct sequencing. Finally, we found low frequency of BRAF(V600E) mutation (6/20, 30.0%) in medium-sized congenital nevi. Most of these nevi with wild-type BRAF had neroblastoma ras viral oncogene homolog mutations (9/14, 64.3%), suggesting different pathogenesis of medium-sized congenital nevi from acquired nevi and small congenital nevi.     

Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice

Abstract Embryonic induction of hair follicles is a fascinating model of localized morphogenesis from a simple homogeneous epithelial cell sheet. Accumulating evidence indicates that Sonic hedgehog (Shh) signaling plays a central role in hair follicle formation. We quantitated the expression levels of Shh and its receptor genes, Patched (Ptc) and Patched-2 (Ptch2), in two distinct experimental systems in which the development of hair follicles was suppressed. Shh, Ptc, and Ptch2 were induced about six- to tenfold in normal embryonic hair germs in vivo as well as in developing skin tissue maintained in organ culture. This induction was almost completely inhibited both in the developing skin tissue of ICR mice cultured with 30 ng/ml epidermal growth factor and in embryos of Tabby mutant mice (a model of hypohidrotic ectodermal dysplasia) at 14.5–15.5 days postcoitus. Expression of Shh, Ptc and Ptch2 was induced in the Tabby embryos at 16.5 days postcoitus, indicating that Shh signaling may be involved in the formation not only of the well-studied guard hair but also of the awl hair. The potential of the two biological systems for studying molecular mechanisms in hair follicle formation, particularly at an early phase including Shh signaling, is discussed. Received: 24 October 2000 / Revised: 24 March 2001 / Accepted: 11 July 2001