Stimulated saliva secretion is reduced in proton pump inhibitor-resistant severe reflux esophagitis patients

Esophagus - Salivary secretion in patients with proton-pump inhibitor (PPI)-resistant severe reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth...     

Xenopus Zic3, a primary regulator both in neural and neural crest development

Xenopus Zic3 is a Xenopus homologue of mouse Zic and Drosophila pair-rule gene, odd-paired. We show here that Zic3 has significant roles both in neural and neural crest development in Xenopus embryo. Expression of Zic3 is first detected in prospective neural plate region at gastrulation. Onset of the expression was earlier than most proneural genes and followed chordin expression. The expression was induced by blockade of BMP4 signal. Overexpression of Zic3 resulted in hyperplastic neural and neural crest derived tissue. In animal cap explant, the overexpression of Zic3 induced expression of all the proneural genes and neural crest marker genes. These findings suggest that Zic3 can determine the ectodermal cell fate and promote the earliest step of neural and neural crest development.     

Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis

Intercellular cross-talk between osteoblasts and osteoclasts is important for controlling bone remolding and maintenance. However, the precise molecular mechanism by which osteoblasts regulate osteoclastogenesis is still largely unknown. Here, we show that osteoblasts can induce Ca(2+) oscillation-independent osteoclastogenesis. We found that bone marrow-derived monocyte/macrophage precursor cells (BMMs) lacking inositol 1,4,5-trisphosphate receptor type2 (IP(3)R2) did not exhibit Ca(2+) oscillation or differentiation into multinuclear osteoclasts in response to recombinant receptor activator of NF-kappaB ligand/macrophage colony-stimulating factor stimulation. IP(3)R2 knockout BMMs, however, underwent osteoclastogenesis when they were cocultured with osteoblasts or in vivo in the absence of Ca(2+) oscillation. Furthermore, we found that Ca(2+) oscillation-independent osteoclastogenesis was insensitive to FK506, a calcineurin inhibitor. Taken together, we conclude that both Ca(2+) oscillation/calcineurin-dependent and -independent signaling pathways contribute to NFATc1 activation, leading to efficient osteoclastogenesis in vivo.     

Liver sarcoidosis that presented with dysphagia

We report a case of liver sarcoidosis with dysphagia. Although akinesia of the soft palate, disappearance of the palatal reflex, and pyramidal signs indicated brainstem lesions, brain magnetic resonance imaging showed no lesion and the focus was obscure. Iritis, parotiditis, and hilar lymphadenopathy supported the diagnosis of sarcoidosis. However, lung biopsy was normal. Finally, sarcoidosis was diagnosed by liver biopsy. We speculated that microgranulomas in the brainstem that did not exhibit imaging abnormalities causing the neurological symptoms and that liver biopsy can be an effective diagnostic tool even for cases that presented with neurological signs, but no gastrointestinal symptom.     

Central Bisegmentectomy for Malignant Liver Tumors: Experience in 8 Patients

Central bisegmentectomy (CBS) of the liver is an en bloc hepatic resection of Couiaud segments 4, 5, and 8. The indications for CBS include benign and malignant tumors occupying both the left medial and right anterior segments. However, CBS has rarely been reported. Here, we investigate CBS in patients with suboptimal liver function for whom an extended lobectomy is not an optimal solution. Each case was 1 of 8 patients who underwent CBS for hepatocellular carcinoma (HCC) or colorectal cancer liver metastasis (CRLM) at the Department of Surgery, Jikei University Hospital. Indications for CBS consisted of CRLM in 3 patients and HCC in 5 patients. The median duration of operation was 552 minutes, and median blood loss was 2263 g. No postoperative nor in-hospital mortalities occurred. In this study, 1-, 2-, and 3-year disease-free survival rates were 62.5%, 12.5%, and 12.5%, respectively, and 1-, 2-, and 3-year overall survival rates were 100%, 100%, and 85.7%, respectively. CBS is advocated for central liver tumors in patients with suboptimal liver function for whom extended lobectomy could result in less than optimal remnant liver volume and function.Key words: Central bisegmentectomy, Colorectal cancer liver metastasis, Hepatocellular carcinomaCentral bisegmentectomy (CBS) of the liver is an en bloc hepatic resection of Couiaud segments 4, 5, and 8.¹ McBride and Wallace² first reported this procedure in 1972. The indications for CBS include benign and malignant tumors occupying both the left medial and right anterior segments. The traditional procedure for such tumors is extended right or left lobectomy or trisegmentectomy. Because of the possibility of conservation of remnant liver parenchymal volume, CBS may be superior to extended lobectomy or trisegmentectomy, especially for patients with low residual liver function due to viral hepatitis or adjuvant chemotherapy. However, CBS has rarely been reported. We herein report our experience with 8 patients who underwent CBS for colorectal cancer liver metastasis (CRLM) or hepatocellular carcinoma (HCC).     

Performance status scale for head and neck scores for oral cancer survivors: predictors and factors for improving quality of life

Objectives

This study aimed to determine the factors associated with long-term quality of life of oral cancer survivors.

Materials and methods

A total of 508 survivors were assessed using the performance status scale for head and neck (PSS-HN), which comprises Eating in Public (E-Public), Normalcy of Diet (N-Diet), and Understandability of Speech (U-Speech). Stepwise multiple linear regression analysis was performed.

Results

The median time between the end of treatment and participating in the survey was 38 months (range, 6–250). Overall, 57–60% of survivors achieved full performance (100 score) of each PSS-HN score, whereas 15% had moderate or severe impairment (≤ 50 score) in E-Public and N-Diet, and 4% had impairment in U-Speech. These three scores deteriorated with increasing T-stage. Age, soft tissue reconstruction, trismus, and missing occlusal contacts on the contralateral side were significantly associated with E-Public and N-Diet. Neck dissection, hard tissue reconstruction, and missing occlusal contacts bilaterally were associated with U-Speech score.

Conclusion

Older age, T4 tumor, and soft tissue reconstruction were predictors of low E-Public and N-Diet performance scores. Increasing mouth opening and maintaining optimal occlusal contacts on the contralateral side may be effective ways to improve N-Diet and E-Public performance. Maintaining optimal occlusal contacts bilaterally may be effective for improving speech performance.

Clinical relevance

Oral health care to increase optimal occlusal contacts and rehabilitation of trismus may be promising factors to improve the functional performance of oral cancer survivors.

     

Disruption of actin‐binding domain‐containing Dystonin protein causes dystonia musculorum in mice

The Dystonin gene (Dst) is responsible for dystonia musculorum (dt), an inherited mouse model of hereditary neuropathy accompanied by progressive motor symptoms such as dystonia and cerebellar ataxia. Dst‐a isoforms, which contain actin‐binding domains, are predominantly expressed in the nervous system. Although sensory neuron degeneration in the peripheral nervous system during the early postnatal stage is a well‐recognised phenotype in dt, the histological characteristics and neuronal circuits in the central nervous system responsible for motor symptoms remain unclear. To analyse the causative neuronal networks and roles of Dst isoforms, we generated novel multipurpose Dst gene trap mice, in which actin‐binding domain‐containing isoforms are disrupted. Homozygous mice showed typical dt phenotypes with sensory degeneration and progressive motor symptoms. The gene trap allele (Dst^Gt) encodes a mutant Dystonin‐LacZ fusion protein, which is detectable by X‐gal (5‐bromo‐4‐chloro‐3‐indolyl‐β‐D‐galactoside) staining. We observed wide expression of the actin‐binding domain‐containing Dystonin isoforms in the central nervous system (CNS) and peripheral nervous system. This raised the possibility that not only secondary neuronal defects in the CNS subsequent to peripheral sensory degeneration but also cell‐autonomous defects in the CNS contribute to the motor symptoms. Expression analysis of immediate early genes revealed decreased neuronal activity in the cerebellar‐thalamo‐striatal pathway in the homozygous brain, implying the involvement of this pathway in the dt phenotype. These novel Dst^Gt mice showed that a loss‐of‐function mutation in the actin‐binding domain‐containing Dystonin isoforms led to typical dt phenotypes. Furthermore, this novel multipurpose Dst^Gt allele offers a unique tool for analysing the causative neuronal networks involved in the dt phenotype.     

Infection-immunity liaison: Pathogen-driven autoimmune-mimicry (PDAIM)

Autoimmunity causes pathological conditions resulting in autoimmune diseases (ADs). Although autoimmunity is a mystery, immunological dogma suggests that autoreactive cell reactivation (ACR) breaks self-tolerance and induces autoimmunity. Thus, ACR is a royal pathway for ADs. Cumulative evidence implicates environmental factors as secondary triggers of ADs in the genetically susceptible hosts. Infection is the most likely trigger. Although several mechanisms have been proposed to explain how infectious agents trigger ADs, ACR is assumed to be an essential pathway.