Palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus: possible involvement of CD163+ M2 macrophages in two cases, and a review of published works.

BACKGROUND: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. OBJECTIVE: We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. METHODS: The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. RESULTS: Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. LIMITATIONS: This study examined only two cases; the pathogenesis of the disease remains to be clarified. CONCLUSION: PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions.

Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study.

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 0.01, r = -0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.

Evaluation of quantitative trait loci affecting intramuscular fat and reproductive traits in pigs using marker-assisted introgression.

We investigated the effects of previously identified quantitative trait loci (QTL) in an experimental backcross (BC) between Chinese Meishan pigs and commercial Duroc pigs. We performed marker-assisted introgression of two QTL for intramuscular fat (IMF) content (IMF population) and three QTL for reproductive traits (reproduction population) from a donor Meishan pig into a recipient Duroc pig. At the fourth BC generation of the IMF population and third BC generation of the reproduction population, carrier animals were selected for the production of animals homozygous for the QTL. Our previous studies have shown that the presence of a Meishan allele on the IMF QTL is associated with low IMF values, and the Meishan allele on the reproductive QTL is associated with large litters. In this study, the presence of a Duroc allele at the IMF QTL on SSC9 resulted in a 0.27% increase in IMF (additive effect = 0.27 ± 0.08), whereas the presence of a Meishan allele at the IMF QTL on SSC7 resulted in a 0.34% increase in IMF (additive effect = -0.34 ± 0.09). The presence of the Meishan allele at the IMF QTL on SSC7 thus had the opposite effect to our previous studies, that is, increased IMF. In the reproduction population, we observed no differences between the genotypes of the three QTL in regard to number of corpora lutea or litter size. Marker-assisted introgression at these QTL is thus unlikely to result in an associated increase in litter size. These results show that it is possible to introgress alleles from other breeds into a selection population using molecular markers; any unexpected results might be associated with the genetic background.

Full-layer mucosal histology in achalasia: Histological epithelial wave is characteristic in "pinstripe pattern"-positive achalasia.

BACKGROUND: Previously, the mucosal histology in achalasia has only been investigated using superficial biopsy or surgically resected esophageal specimens in end-stage cases. We investigated the histology of the full-layer mucosa in early and advanced achalasia. METHODS: Endoscopy was performed for the pinstripe pattern (PSP) (an early achalasia indicator) and dilation and thickening of the mucosa (advanced achalasia indicators). A mucosal entry site for peroral endoscopic myotomy was created using cap-fitted endoscopic mucosal resection to access the full-layer mucosa and the submucosa. KEY RESULTS: Mucosal histology was compared between 32 patients with achalasia and 15 controls. Histological esophagitis with findings of inflammatory cell infiltration and dilated intercellular spaces was observed more in patients with achalasia than in controls (87.5% vs 13.3%, P<.001; 84.4% vs 46.7%, P=.049). Muscularis mucosae (MM) atrophy and epithelial wave were only observed in achalasia (40.6% vs 0%, P=.005; 28.1% vs 0%, P=.043). Fibrosis was more common in achalasia, but without statistical significance (31.3% vs 20.0%, P=.503). In achalasia with endoscopic dilation and thickening of the mucosa, MM atrophy was observed histologically, and in cases involving endoscopic PSP, the histological epithelial wave was observed. CONCLUSIONS & INFERENCES: Histological findings of esophagitis were observed endoscopically even in early achalasia. Pinstripe pattern corresponds to the epithelial wave observed histologically in achalasia, whereas endoscopic findings in advanced achalasia correspond to MM atrophy. Appropriate management is necessary during early achalasia to prevent progression to advanced achalasia with more severe histological changes.

Ombitasvir-Paritaprevir-Ritonavir Therapy in a Kidney Transplant Recipient With Chronic Hepatitis C Virus Genotype 1 Infection: A Case Report on the Importance of Considering Drug-Drug Interactions and Monitoring Cyclosporine Levels.

A 74-year-old Japanese man with a history of chronic hepatitis C and kidney transplant (KT) was administered pegylated-interferon plus ribavirin therapy. However, this therapy was ineffective. The patient was then hospitalized to receive ombitasvir (OBV) plus paritaprevir (PTV) plus ritonavir (r) antiviral combination therapy. He tested negative for the virus after 4 weeks, and completed 12 weeks of treatment. The patient ultimately achieved a sustained virological response after the 12 weeks of treatment. Cyclosporine (CyA) trough levels, during the OBV-PTV-r therapy, reached a peak within 5 days of initiating therapy, and increases in serum creatinine and total bilirubin were also observed. However, onset of irreversible nephropathy and hepatopathy were avoided by reducing the CyA dosage. The OBV-PTV-r therapy demonstrated a sufficient antiviral effect and could be safely administered postoperatively to patients having undergone KT. When a combination therapy with interferon-free, direct-acting antivirals is used in patients post-transplantation, consideration of drug-drug interactions with and monitoring CyA are of vital importance.

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

BACKGROUND: Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. METHODS: During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. KEY RESULTS: Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. CONCLUSIONS & INFERENCES: Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium.

Mechanism in progressive lacunar infarction: a case report with magnetic resonance imaging.

BACKGROUND: The mechanism of a progressive lacunar infarction is not well understood, and changes in ischemic tissue after onset have not yet been clarified clinically. OBJECTIVE: To investigate the pathophysiological characteristics of a case of progressive lacunar infarction using diffusion-weighted and conventional magnetic resonance imaging (MRI) scans. PATIENT: A 73-year-old woman was hospitalized 18 hours after stroke onset and was diagnosed as having a lacunar infarction in the perforating territory of the left middle cerebral artery. Despite treatment, the hemiparesis worsened, with the peak on the fourth day after onset. Diffusion-weighted and conventional MRI scans provided clues to the pathogenesis. FINDINGS AND CONCLUSIONS: In the acute stage, gradual enlargement of the hyperintense lesion, reflecting fresh ischemic tissue, and neurological deterioration were observed by serial examination of diffusion-weighted MRI scans. A conventional coronal MRI scan revealed a 2-layered ischemic lesion, suggesting the involvement of perforating arteries. These findings indicated that hemodynamic impairment of the microcirculation in the perforators was the major cause of the lacunar infarction.

Antitumor effect of vesnarinone on human hepatocellular carcinoma cell lines.

Vesnarinone, a quinolinone derivative, induces apoptosis and differentiation in some tumor cell lines. We examined the antitumor effect of vesnarinone on three human hepatocellular carcinoma (HCC) cell lines. Vesnarinone suppressed the proliferation of all three HCC cell lines, but did not induce apoptosis and differentiation. Vesnarinone has also been reported to inhibit both nucleoside and nucleobase transport. Concomitant administration of vesnarinone and a de novo nucleotide synthesis inhibitor potentiated the growth-inhibitory effect of vesnarinone on HCC cells. Vesnarinone may be useful as a new biochemical modulator of anticancer agents.

Long-term haemodynamic effects of octreotide on postprandial splanchnic hyperemia in humans: a placebo-controlled echo-doppler study.

BACKGROUND: Octreotide is a potent splanchnic hypotensive somatostatin analogue effective in the treatment of acute variceal bleeding. AIM: To study the effects of octreotide on basal and postprandial splanchnic and systemic haemodynamics, and hormonal changes in humans. METHODS: Twenty-four healthy volunteers were randomized to receive a liquid meal and either octreotide (OCT, 100 microg bolus) or placebo repeatedly every 4 h for 48 h. Splanchnic (Doppler ultrasound) and systemic haemodynamics (non-invasive cardiac monitoring) were assessed for 2 h on four consecutive days: one control day and after doses 1 (0 h), 7 (24 h) and 13 (48 h). RESULTS: The maximum postprandial increases in mean blood velocity of the superior mesenteric artery (SMA-Vmean +72%), portal (PBF +52%) and total hepatic blood flow (HBF +50%) observed in the placebo group, were abolished after the first dose of octreotide (SMA-Vmean -23%, P<0.01; PBF -22%, P<0.01; HBF -21%, P<0.01). Postprandial hyperemia was restored at the end of the 48-h study period, but baseline SMA-Vmean (placebo 40+/-12, OCT 29+/-11 cm/s, P<0.05) and PBF (placebo 1200+/-971, OCT 743+/-449 mL/min, P<0.05) remained significantly lower in the octreotide group. The postprandial decrease of systemic vascular resistance and increase of cardiac index were prevented by octreotide for 48 h. CONCLUSIONS: Repeated 4-hourly bolus injections of octreotide reduce splanchnic blood flow for at least 48 h, but the prevention of food-induced splanchnic hyperemia is short-lasting.

Wild-type p53 gene-induced morphological changes and growth suppression in hepatoma cells.

The human hepatocellular carcinoma (HCC) cell line, HLF, expresses only mutant-type p53 (mt-p53), which has an amino acid substitution at the 244th residue from glycine to alanine. HLF cells were transfected with wild-type p53 (wt-p53) cDNA construct pC53-SN3, mt-p53 cDNA construct pC53-SCX [which differs by a single nucleotide, resulting in alanine instead of valine at the 143rd residue in p53 (p53-143)], or pCMV-Neo-Bam, as a control, by a liposome method. After G418 selection, three wt-p53 stable transformants (WT), four mt-p53 transformants (MT), and three control vector transformants (VT) were obtained. We analyzed the cell growth and morphological changes of these transformants under different culture conditions [fetal calf serum (FCS), 10%, 1%, and 0%]. Whereas no difference from control in the growth rate and morphology was observed under the 10% FCS conditions, serum starvation induced remarkable phenotypical changes in all three WTs, but not in the other transformant. Corresponding to these phenotypical changes, the transcriptional activity of wt-p53 was increased more than nine fold. These results indicated that serum starvation would induce wt-p53 biological function, which is tightly linked to morphological changes and growth suppression. To induce these changes, the introduction of the wt-p53 gene itself was not sufficient, and additional triggering, i.e., serum starvation, was indispensable.

Clinicopathologic features of early hepatocellular carcinoma.

BACKGROUND/AIMS: This study attempts to clarify the clinicopathologic definition of early hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: We evaluated 57 patients, with HCCs less than 3 cm in diameter, in terms of prognosis, incidence of extrahepatic metastasis, and tumor recurrence rate following treatment. RESULTS: Survival was related to both tumor number and histologic differentiation, but was not related to tumor size. Furthermore, prognosis appeared to depend on the functional reserve of the liver. The incidence of extrahepatic metastasis was related to histologic differentiation. There was no significant difference in the recurrence rates of patients with uninodular tumors in terms of tumor size. CONCLUSIONS: Our findings indicate that early HCCs measure 15 mm or less in diameter, are uninodular, and are histologically well-differentiated. Finally, the functional reserve of the liver will likely be an additional parameter that will further characterize early HCCs.

Quantitative trait loci analysis for growth and carcass traits in a Meishan x Duroc F2 resource population.

We constructed a pig F2 resource population by crossing a Meishan sow and a Duroc boar to locate economically important trait loci. The F2 generation was composed of 865 animals (450 males and 415 females) from four F1 males and 24 F1 females and was genotyped for 180 informative microsatellite markers spanning 2,263.6 cM of the whole pig genome. Results of the genome scan showed evidence for significant quantitative trait loci (<1% genomewise error rate) affecting weight at 30 d and average daily gain on Sus scrofa chromosome (SSC) 6, carcass yield on SSC 7, backfat thickness on SSC 7 and SSC X, vertebra number on SSC 1 and SSC 7, loin muscle area on SSC 1 and SSC 7, moisture on SSC 13, intramuscular fat content on SSC 7, and testicular weight on SSC 3 and SSC X. Moreover, 5% genomewise significant QTL were found for birth weight on SSC 7, average daily gain on SSC 4, carcass length on SSC 6, SSC 7, and SSC X and lightness (L value) on SSC 3. We identified 38 QTL for 28 traits at the 5% genomewise level. Of the 38 QTL, 24 QTL for 17 traits were significant at the 1% genomewise level. Analysis of marker genotypes supported the breed of origin results and provided further evidence that a suggestive QTL for circumference of cannon bone also was segregating within the Meishan parent. We identified genomic regions related with growth and meat quality traits. Fine mapping will be required for their application in introgression programs and gene cloning.

An osteometrical study of the cranium and mandible of the lesser mouse deer (Chevrotain), Tragulus javanicus.

The lesser mouse deer (Tragulus javanicus) is one of the most primitive ruminants. Skulls of lesser mouse deer were measured to evaluate their growth. The age was estimated from the eruption and attrition of molars on the mandible. A total of 95 specimens was divided into five age groups, and the growth pattern in each sex was established for some measurements. The relative growth coefficients were calculated for the head and body length and several parts of the cranium and mandible against the profile length. Sexual dimorphism could not be found on the skull in any age group except for measurements related to the upper canine. However, females showed a higher value in head and body length in the oldest group. This feature was consistent with an interpretation of mouse deer society as monogamous. Growth was more rapid in length than in width. Various statistical analyses showed that the visceral cranium related to masticatory facility was much better developed than the neurocranium. However, observations on the shape of the mandible ramus and of the premolars implied that the masticatory function was not suitable for taking roughage. This speculation agreed with previous reports on the feeding habits and digestive organs of the mouse deer.

[Bacterial cerebritis developed from purulent meningitis--serial CT and MRI study of a case].

A 54-year-old woman was admitted to our hospital because of purulent meningitis caused by Streptococcus pneumoniae during a long-term administration of prednisolone for the treatment of bronchial asthma. After admission, both antibiotics and steroids were given, which resulted in her good general and neurological condition, and the normal protein and glucose content in her cerebrospinal fluid three weeks later. However, post-contrast computerized tomography (CT) at this time showed various size of multiple irregular high-densities devoid of capsular component in the white matter of the bilateral cerebral hemisphere. MRI examination revealed that the lesions were of low intensity on the T1-weighted sequence whereas high on T2-weighted sequence. Gd-DTPA enhanced the T1-weighted images on these lesions. These findings may indicate that the lesions were at the pre-encapsulation stage of cerebritis, because the lesions were gradually reduced and disappeared after the subsequent antibiotic therapy. It is emphasized that patients with purulent meningitis under steroid therapy require careful observation for the risk of bacterial cerebritis.

[Diffusion MRI for evaluating TIA--a case of reversible ischemic injury in the territory of the deep perforators].

A 61-year-old man was admitted to our hospital because of left pure motor hemiparesis. Neuroradiological examination was performed after three hours of onset, but no apparent lesion responsible for the hemiparesis was detected by CT and MRI. Diffusion weighted MRI (DWI), however, demonstrated a high signal area with good contrast in the posterior limb of right internal capsule. This lesion was compatible with patient's clinical symptoms. Apparent diffusion coefficient (ADC) of the lesion was lower than that of normal control at the timing of admission. On the following day within 24 hours after the onset, it was revealed that both left hemiparesis and high signal area on DWI had disappeared, and the ADC on the ischemic lesion was restored to normal level. Changes in the intensity on DWI corresponded well with reversion of ischemic injury, which suggested that DWI was very useful for diagnosis of TIA.