Tropoelastin expression by periodontal fibroblasts

Elastic system fibers are load-bearing proteins found in periodontal tissue. There are three types--oxytalan, elaunin, and elastic fibers--which differ in their relative microfibril and elastin contents. Oxytalan fibers are known to be distributed in the periodontal ligaments and gingiva, whereas elaunin and elastic fibers are present only in the gingiva. We examined gene expression and accumulation of tropoelastin in the cell-matrix layers of human gingival fibroblasts (HGF) and periodontal ligament fibroblasts (HPLF) in vitro. HGF and HPLF were cultured in MEM containing 10% newborn calf serum for 8 wks. Northern blotting and RT-PCR analyses showed that only HGF expressed mRNA encoding tropoelastin. Western blotting analysis demonstrated 77-kDa protropoelastin and 68-kDa tropoelastin only in the cell-matrix layer of HGF cultured for 8 wks. These results suggest that the different tropoelastin expression patterns reflect the difference between HGF and HPLF phenotypes.     

Effects of arousal level on the physiological responding on the Concealed Information Test

This study examined effects of arousal level on the physiological responses in a polygraph examination using the Concealed Information Test (CIT). Thirty-nine healthy college students were tested with or without evaluative observation. Electrodermal activity, blood pressure, heart rate, normalized pulse volume, and respiration were recorded. Observation elevated participants' arousal level, which was manifested in self-reports, high skin conductance level, and low normalized pulse volume (i.e., vasoconstriction). However, differential reactivity to critical and non-critical items on the physiological measures was less affected by observation. These results suggested that participants' arousal level has little effect on differential physiological reactivity on the CIT.     

Experimental incision-induced pain in human skin: effects of systemic lidocaine on flare formation and hyperalgesia

In order to try to gain a better understanding of the mechanisms of post-operative pain, this study was designed to psychophysically determine physiological and pharmacological characteristics of experimental pain induced by a 4-mm-long incision through the skin, fascia and muscle in the volar forearm of humans. In experiment 1, the subjects (n=8) were administered lidocaine systemically (a bolus injection of 2mg/kg for a period of 5 min followed by an intravenous infusion of 2mg/kg/h for another 40 min), and then the incision was made. In experiment 2, cumulative doses of lidocaine (0.5-2mg/kg) were systemically injected in the subjects (n=8) 30 min after the incision had been made, when primary and secondary hyperalgesia had fully developed. Spontaneous pain was assessed using the visual analog scale (VAS). Primary hyperalgesia was defined as mechanical pain thresholds to von Frey hair stimuli (from 7 to 151 mN) in the injured area. The area of secondary hyperalgesia to punctate mechanical stimuli was assessed using a rigid von Frey hair (151 mN). Flare formation was assessed in the first experiment using a laser doppler imager (LDI).Pain perception was maximal when the incision was made and then rapidly disappeared within 30 min after the incision had been made. Primary hyperalgesia was apparent at 15 min after the incision had been made and remained for 2 days. The incision resulted in a relatively large area of flare formation immediately after the incision had been made. The area of flare began to shrink within 15 min and was limited to a small area around the injured area at 30 min after incision. Secondary hyperalgesia was apparent at 30 min after incision and persisted for 3h after incision and then gradually disappeared over the next 3h. In experiment 1, pre-traumatic treatment with systemic lidocaine suppressed primary hyperalgesia only during the first 1h after the incision had been made. The lidocaine suppressed the development of flare formation without affecting the pain rating when the incision was made. The development of secondary hyperalgesia continued to be suppressed after completion of the lidocaine infusion.In experiment 2, post-traumatic treatment with lidocaine temporarily suppressed primary as well as secondary hyperalgesia that had fully developed; however, the primary and secondary hyperalgesia again became apparent after completion of the lidocaine administration.These findings suggest that pre-traumatic treatment with lidocaine reduces the excessive inputs from the injured peripheral nerves, thus suppressing development of flare formation and secondary hyperalgesia through peripheral and central mechanisms, respectively. Pre-traumatic treatment with lidocaine would temporarily stabilize the sensitized nerves in the injured area, but the nerves would be sensitized after completion of the administration. Post-traumatic treatment with lidocaine reduced primary and secondary hyperalgesia that had fully developed. However, the finding that the suppressive effect of lidocaine on secondary hyperalgesia was temporary suggests that the development and maintenance of secondary hyperalgesia are caused by different mechanisms.     

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis

Japanese Journal of Ophthalmology - To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. A retrospective, observational study....     

Novel multidrug therapy for children with cyclosporine-resistant or -intolerant nephrotic syndrome

An effective treatment for children with refractory nephrotic syndrome (NS), especially in those with cyclosporine (CsA)-resistant or CsA-intolerant NS, has yet to be established. Recently, the efficacy of multidrug therapy consisting of tacrolimus (Tac), mycophenolate mofetil (MMF) in combination with prednisolone (PDN) in adult patients with refractory NS has been reported. We successfully treated 14 consecutive children with refractory CsA-resistant or CsA-intolerant NS using combination therapy consisting of relatively low-dose Tac, mizoribine (MZR), which has a mechanism of action very similar to that of MMF, and PDN. There were no serious clinical toxicities. Of the 14 children, 9 with a mean age of 13.0 years had steroid-dependent NS (SDNS) and 5 with a mean age of 9.6 years had steroid-resistant NS (SRNS). All SDNS patients had minimal change disease (MCD), 4 with SRNS had focal segmental glomerulosclerosis (FSGS), and the remaining child had MCD on renal biopsy. All patients were in a prospective cohort, but were evaluated retrospectively. The mean follow-up from the initiation of multidrug therapy was 18.4 months in SDNS and 18.6 months in SRNS patients. At the last observation point, the calculated relapse rate and minimum dose of PDN required for maintenance of clinical remission after the start of multidrug therapy were significantly decreased compared with those prior to this therapy, while on CsA, in SDNS patients (0.4?±?0.5 times/year vs 2.9?±?1.5 times/year, P?=?0.0077, and 0.3?±?0.2 mg/kg on alternate days vs 0.5?±?0.2 mg/kg on alternate days, P?=?0.0184 respectively). All SDNS and two SRNS patients (40%) achieved complete remission, allowing further decreases in the minimal doses of PDN required for maintenance of clinical remission in most our patients. However, one patient with FSGS remained refractory to multidrug therapy and subsequently developed end-stage renal disease. These clinical observations, although preliminary and involving a small number of patients, suggest that multidrug therapy consisting of relatively low-dose Tac, MZR, and PDN might be effective and safe for treating children with refractory CsA-resistant or CsA-intolerant NS. However, further studies involving larger numbers of patients are needed.     

No association between dietary patterns and depressive symptoms among a community-dwelling population in Japan

Background

Patients who self-poison have high repetition and high mortality rates. Therefore, appropriate follow-up is important. The aims of the present work were to study treatment received, satisfaction with health care services, and psychiatric symptoms after hospitalization for self-poisoning.

Methods

A cohort of patients who self-poisoned (n = 867) over a period of 1 year received a questionnaire 3 months after discharge. The Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), and Generalized Self-Efficacy Scale (GSE) were used. The participation rate was 28% (n = 242); mean age, 41 years; 66% females.

Results

Although only 14% of patients were registered without follow-up referrals at discharge, 41% reported no such measures. Overall, satisfaction with treatment was fairly good, although 29% of patients waited more than 3 weeks for their first appointment. A total of 22% reported repeated self-poisoning and 17% cutting. The mean BDI and BHS scores were 23.3 and 10.1, respectively (both moderate to severe). The GSE score was 25.2. BDI score was 25.6 among patients with suicide attempts, 24.9 for appeals, and 20.1 for substance-use-related poisonings.

Conclusions

Despite plans for follow-up, many patients reported that they did not receive any. The reported frequency of psychiatric symptoms and self-harm behavior indicate that a more active follow-up is needed.     

Fibrillin-1 and fibrillin-2 are essential for formation of thick oxytalan fibers in human nonpigmented ciliary epithelial cells in vitro

The ciliary zonule, also known as Zinn's zonule, is composed of oxytalan fibers. However, the mechanism by which epithelial cells in the ciliary body form these fibers in not fully understood. We examined human nonpigmented ciliary epithelial cells to determine the appearance and amount of oxytalan fibers in terms of positivity for their major components, fibrillin-1 and fibrillin-2. Examination of fibrillin-1 and fibrillin-2 expression by immunofluorescence revealed that thin fibers positive for fibrillin-1 on Day 2 changed to thick fibers by Day 8. The fibers positive for fibrillin-2 appeared on the thick fibrillin-1-positive fibers after Day 4. Northern blot analysis revealed that the level of fibrillin-1 did not change markedly, while induction of fibrillin-2 gene was evident on Day 5. Western blot analysis showed that fibrillin-1 deposition increased gradually, while that of fibrillin-2 increased markedly from Day 5 to Day 8. Fibrillin-1 suppression did not lead to the formation of fibrillin-2-positive thick fibers, whereas fibrillin-2 suppression led to the formation of fibrillin-1-positive thin fibers, but not thick fibers. These results suggest that both fibrillin-1 and fibrillin-2 are essential for the formation of thick oxytalan fibers in the ciliary zonule and are informative for clarifying the mechanism of homeostasis of the ocular matrix.     

Femoral neck fractures in older patients: indication for osteosynthesis

 In almost all the patients over 65 years of age with intracapsular femoral neck fractures who we treated over a 2-year period, we used osteosynthesis with Ace 6.5-mm cannulated cancellous screws. We then followed them for at least 24 months. Each of the seven nondisplaced fractures healed. Of the 20 displaced fractures, 14 were rated as healed, 5 as failures, and 1 as a late segmental collapse. Among the 14 displaced fractures with an operative delay of 1 day, 12 healed, whereas only 2 of the 6 fractures with an operative delay of 2 days or more did so. Of the 12 typical fractures (with a medial spike in the head fragment), 10 healed, as did 4 of the 8 crescent or mixed-type fractures. The treatment of choice for nondisplaced fractures is osteosynthesis. Displaced fractures that occur on the day of operation or the day before should be treated with osteosynthesis if they are the typical type. The rest of the displaced fractures should be considered candidates for primary prosthetic replacement. Received: May 17, 2002 / Accepted: October 18, 2002 Offprint requests to: E. Itadera, Department of Orthopaedic Surgery, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan     

Portal vein stenosis after pancreatectomy following neoadjuvant chemoradiation therapy for pancreatic cancer

Extrahepatic portal vein (PV) stenosis has various causes, such as tumor encasement, pancreatitis and as a postsurgical complication. With regard to post-pancreaticoduodenectomy, intraoperative radiation therapy with/ without PV resection is reported to be associated with PV stenosis. However, there has been no report of PV stenosis after pancreatectomy following neoadjuvant chemoradiation therapy (NACRT). Here we report the cases of three patients with PV stenosis after pancreatectomy and PV resection following gemcitabine-based NACRT for pancreatic cancer and their successful treatment with stent placement. We have performed NACRT in 18 patients with borderline resectable pancreatic cancer since 2005. Of the 15 patients who completed NACRT, nine had undergone pancreatectomy. Combined portal resection was performed in eight of the nine patients. We report here three patients with PV stenosis, and thus the ratio of post-operative PV stenosis in patients with PV resection following NACRT is 37.5% in this series. We encountered no case of PV stenosis among 22 patients operated with PV resection for pancreatobiliary cancer without NACRT during the same period. A relationship between PV stenosis and NACRT is suspected, but further investigation is required to determine whether NACRT has relevance to PV stenosis.     

Pregnancy-associated plasma protein-A polymorphism and the risk of recurrent pregnancy loss

Pregnancy-associated plasma protein-A (PAPP-A)/insulin-like growth factor-binding protein-4 (IGFBP4) protease is a member of the metzincin family of metalloproteases, known as a sensitive biomarker of adverse pregnancy outcomes. Recently, a missense A/C (Tyr/Ser) polymorphism (dbSNP: rs7020782) in the PAPPA gene has been reported. To examine the association between recurrent pregnancy loss (RPL) and this polymorphism, a case-control study of 215 cases with two or more pregnancy losses (PLs) and 420 fertile controls was performed. Genotyping of the PAPPA polymorphism was determined by allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Sixty-nine cases (32.1%) were heterozygous and 11 cases (5.1%) were homozygous for the C allele of PAPPA; the respective figures were 127 (30.2%) and 11 (2.6%) in the controls. Women carrying the C allele had a tendency to increased risk of RPL (AA genotype [reference]; AC genotype: odds ratio [OR], 1.17; 95% confidence interval [CI], 0.82–1.68; CC genotype: OR, 2.06; 95% CI, 0.87–4.90), but it was not significant. Women with three or more PLs had a similar tendency (AA genotype [reference]; AC genotype: OR, 1.04; 95% CI, 0.66–1.64; CC genotype: OR, 2.20; 95% CI, 0.82–5.91). The risk of RPL with at least one PL after 9 weeks’ gestation significantly increased in women carrying the C allele (AA genotype [reference]; AC genotype: OR, 1.54; 95% CI, 0.95–2.49; CC genotype: OR, 2.83; 95% CI, 1.00–8.05; AC + CC genotypes: OR, 1.65; CI, 1.04–2.62). This is the first report on the PAPPA gene polymorphism in women with RPL, demonstrating some association between the investigated polymorphism and the risk of RPL.