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Malaria is still a global challenge with significant morbidity and mortality, especially in the African, South-East Asian and Latin American region. Malaria diagnosis is a crucial pillar in the control and elimination efforts, often accomplished by administration of mass-scale Rapid diagnostic tests (RDTs). The inherent limitations of RDTs-failure of detection in low transmission settings, and deletion of one of the target proteins-Histidine rich protein (HRP) are evident from multiple reports; thus necessitating the need to explore novel diagnostic tools/targets. The present study used peptide microarray to screen potential epitopes from 13 antigenic proteins (CSP, EXP1, LSA1, TRAP, AARP, AMA1, GLURP, MSP1, MSP2, MSP3, MSP4, P48/45, HAP2) of P. falciparum. Three cyclic constrained immunoreactive peptides-C6 (EXP1), A8 (MSP2), B7 (GLURP) were identified from 5,458 cyclic constrained peptides (in duplicate) against P. falciparum infected sera. Peptides (C6, A8, B7-cyclic constrained) and (G11, DSQ, NQN-corresponding linear peptides) were fairly immunoreactive towards P. falciparum-infected sera in dot-blot assay. Using indirect ELISA, cyclic constrained peptides (C6 & B7) were found to be specific to P. falciparum infected sera and further, observed to be significantly reactive towards antibodies from field-collected P. falciparum infected sera. Notably, the structural location of the epitopes defines the reactivity, observed by the preferential recognition of cyclic constrained peptides vs linear peptides and corroborated by the homology modeling analysis of selected proteins. In conclusion, the study identified three cyclic constrained immunoreactive peptides (C6, B7 & A8) from P. falciparum secretory/surface proteins and two of them (C6 & B7) were validated for their diagnostic potential with field-collected P. falciparum infected sera samples.

Accurate imaging is essential for effective treatment planning in periodontology. The aim of this ex vivo study was to investigate the accuracy of cone beam computed tomography (CBCT) and digital periapical radiographs (PA) in imaging periodontal defects. Hypotheses are: 1. That CBCT is a more accurate method than PA concerning vertical measurements of periodontal bone defects2. That CBCT itself is an accurate method to describe vertical periodontal bone loss MATERIAL AND METHODS: In this study, 117 periodontal defects from 10 human cadavers were investigated radiographically by CBCT and PA by one calibrated observer. Afterwards the vertical bone loss was measured with a periodontal probe by the same calibrated observer. Differences between radiographic and clinical measurements were calculated and analyzed. Bland-Altmann plots including 95% limits of agreement were calculated.The 95% limits of agreement ranged from 3.29 to -3.27 mm between clinical measurements and measurements in PAs, and from 2.13 to -1.97 mm in CBCTs. The mean difference between clinical and radiographic measurements was 0.0009 mm for PA and 0.0835 mm for CBCT.When comparing the clinical measurements, CBCT had a higher agreement and less deviations than PAs, and CBCT seems to be an accurate method to describe vertical periodontal bone loss.Accurate description of defects is helpful for accurate treatment planning.

In mammalian cells, the bulky DNA adducts caused by ultraviolet radiation are mainly repaired via the nucleotide excision repair (NER) pathway; some defects in this pathway lead to a genetic disorder known as xeroderma pigmentosum (XP). Ribosomal protein S3 (rpS3), a constituent of the 40S ribosomal subunit, is a multi-functional protein with various extra-ribosomal functions, including a role in the cellular stress response and DNA repair-related activities. We report that rpS3 associates with transcription factor IIH (TFIIH) via an interaction with the xeroderma pigmentosum complementation group D (XPD) protein and complements its function in the NER pathway. For optimal repair of UV-induced duplex DNA lesions, the strong helicase activity of the TFIIH complex is required for unwinding damaged DNA around the lesion. Here, we show that XP-D cells overexpressing rpS3 showed markedly increased resistance to UV radiation through XPD and rpS3 interaction. Additionally, the knockdown of rpS3 caused reduced NER efficiency in HeLa cells and the overexpression of rpS3 partially restored helicase activity of the TFIIH complex of XP-D cells in vitro. We also present data suggesting that rpS3 is involved in post-excision processing in NER, assisting TFIIH in expediting the repair process by increasing its turnover rate when DNA is damaged. We propose that rpS3 is an accessory protein of the NER pathway and its recruitment to the repair machinery augments repair efficiency upon UV damage by enhancing XPD helicase function and increasing its turnover rate.

Background Living-donor liver transplantation (LDLT) has been accepted as feasible treatment for fulminant hepatic failure (FHF), although it has generated several debatable issues. In this study, we investigated the prognostic factors predicting fatal outcome after LDLT for FHF. Methods From April 1999 to April 2011, 60 patients underwent LT for acute liver failure, including 42 patients for FHF at Samsung Medical Center, Seoul, Korea. Among 42 patients, 30 patients underwent LDLT for FHF, and the database of these patients was analyzed retrospectively to investigate the prognostic factors after LDLT for FHF. Results Among 30 patients, 7 patients (23%) died during the in-hospital period within 6 months, and 23 patients (77%) survived until recently. In univariate analyses, donor age (>35 years), graft volume (GV)/standard liver volume (SLV) ( 120 minutes), hepatic encephalopathy (grade IV), hepato-renal syndrome (HRS), and history of ventilator care were associated with fatal outcome after LDLT for FHF. In multivariate analyses, HRS, GV/SLV ( 35 years) were significantly associated with fatal outcome. Although the statistical significance was not shown in this analysis ( P = .059), hepatic encephalopathy grade IV also appears to be a risk factor predicting fatal outcome. Conclusions The survival of patients with FHF undergoing LDLT was comparable to that in published data. In this study, HRS, GV/SLV 35 years are the independent poor prognostic factors.

The treatment of choice for combined hepatocellular and cholangiocarcinoma (cHCC-CC) is surgical resection. However, the efficacy of liver transplantation is not clear. We compared the surgical outcome of hepatic resection and liver transplantation for cHCC-CC.From 1995 to 2012, 89 patients were diagnosed with cHCC-CC after hepatic resection and 8 patients diagnosed with cHCC-CC after liver transplantation. We excluded 21 patients who were American Joint Committee on Cancer Staging Stage III or IV and lost to follow-up. The outcomes were reviewed retrospectively.The poor prognostic factors in cHCC-CC patients who underwent hepatectomy were large tumor size (5 cm), small safety margin (2 cm), and low preoperative albumin level. The disease-free survival (DFS) and overall survival (OS) between the hepatectomy group (n = 68) and the liver transplant group (n = 8) was not statistically different (5-year DFS: 26.2% vs 37.5%, P = .333; 5-year OS: 42.1% vs 50%, P = .591). In the small tumor subgroup (tumor size 5 cm), the DFS and OS between the 2 surgical procedures was not different, and in the adequate resection margin subgroup (safety margin2 cm), survival was comparable.In well-selected cases with small tumor size and with preserved liver function, liver resection should be considered when complete resection is possible.

The BK nephropathy (BKN) shows a 10% prevalence among cases of kidney transplantation (KT). We assessed the incidence of BK replication in KT recipients as well as our updated screening strategy and the impact of interventions on BK virus infections.Since September 2007, our screening protocol for BK virus included examination of urine cytology or BK virus DNA real-time polymerase chain reaction (PCR) detection on postoperative days 1, 5, 9, 16, 24, 36, 48 weeks up to 1 year. IR present, we tested urine BK virus DNA PCR quantitation. We applied the updated screening protocol from August 2010. It urine BK DNA PCR quantification was above 10(7) copies/mL, we checked regularly blood the BK virus DNA PCR quantification. In addition, if the blood BK virus DNA load was above 10(4) copies/mL and the serum creatinine elevated, we was performed an allograft biopsy. Between September 2007 and December 2011, the 58 recipients who showed BK viremia were enrolled in the present study in 2 groups according to the period of screening protocol (era I, era II).The time between kidney transplantation and BK viremia detection of era II was shorter than that of era I (16 vs 29 weeks; P = .001). Viremia clearance rate at 6 months in era II was significant higher than that of era I (82% vs 36.8%; P = .001) as well as at 12 months (100% vs 61.1%, P .001) after intervention. Interestingly, viremia clearance at 12 months after intervention was 100% in era II.An updated screening protocol for BK virus allowed early detection and accurate diagnosis of BKN. Early detection of BK virus infection enabled early intervention and improved viral clearance rate.

Background: Cytosine arabinoside-based chemotherapy coupled with anthracycline is currently the first-line treatment for acute myeloid leukaemia (AML), but diverse responses to the regimen constitute obstacles to successful treatment. Therefore, outcome prediction to chemotherapy at diagnosis is believed to be a critical consideration. Methods: The mRNA expression of 12 genes closely involved in the actions of cytosine arabinoside and anthracycline was evaluated by real-time reverse transcriptase PCR (RT–PCR), in 54 diagnostic bone marrow specimens of M2-subtype AML. Results: Low expression levels of ribonucleotide reductase M2 (RRM2) and high expression levels of topoisomerase 2 beta (TOP2B) were correlated with longer survival in a univariate analysis. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005). Conclusion: Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.

We investigated the safety and efficacy of a methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) combination regimen as second-line chemotherapy for patients with advanced or metastatic transitional cell carcinoma who failed first-line gemcitabine and cisplatin (GC) chemotherapy. Thirty patients who had progressed or relapsed after GC chemotherapy as first-line treatment were enrolled in this study. The major toxicities were neutropaenia and thrombocytopaenia. A grade 3 or 4 neutropaenia occurred in 19 (63.3%) and a grade 3 or 4 thrombocytopaenia developed in nine patients (30.0%). There were no life-threatening complications during the study. The overall response was 30%. A complete response was achieved in two patients (6.7%) and a partial response in seven (23.3%). The overall disease control rate was 50%. Seven out of 16 patients who had responded previously to GC responded to M-VAC, while 2 out of 14 who had not responded to GC responded to M-VAC. The median response duration was 3.9 months and the median progression-free survival was 5.3 months. The median overall survival was 10.9 months. M-VAC showed encouraging efficacy and reversible toxicities in patients who had progressed after GC chemotherapy and, especially, M-VAC appears to be a reasonable option as a sequential treatment regimen in patients who responded previously to GC chemotherapy.

The Xpert(®) MTB/RIF assay is endorsed by the World Health Organization for the detection of rifampicin (RMP) resistant tuberculosis (TB).To evaluate Xpert for its diagnostic accuracy in detecting RMP-resistant TB and its impact on treatment outcomes.Patients with available phenotypic drug susceptibility testing (DST) results and those in whom RMP-resistant pulmonary TB was diagnosed using Xpert were evaluated. The accuracy and turnaround time (TAT) of Xpert for determining RMP-resistant TB was calculated. The TATs for treatment between patients diagnosed with RMP-resistant TB using Xpert and those diagnosed without the assay (phenotypic DST group) were compared.In 321 patients, when phenotypic DST was used as the gold standard, Xpert sensitivity and specificity for RMP resistance diagnosis was respectively 100% and 98.7%; the positive and negative predictive values were respectively 86.2% and 100%. The Xpert group had a much shorter interval from initial evaluation to commencing second-line anti-tuberculosis treatment (64 vs. 2 days, P0.001), and negative conversion of mycobacterial cultures (197 vs. 62.5 days, P0.001) than the phenotypic DST group.Xpert was accurate at diagnosing RMP resistance in this setting with an intermediate TB burden and a low level of RMP resistance. Xpert might reduce disease transmission by reducing the sputum culture conversion times for patients with RMP-resistant TB.

This study investigated the influence of a family history of diabetes on the risk of subclinical coronary atherosclerosis according to coronary computed tomography angiography (CCTA) in asymptomatic individuals.A total of 6434 consecutive asymptomatic individuals with no prior history of coronary artery disease voluntarily underwent CCTA evaluation as part of a general health examination. Coronary atherosclerotic plaque and significant coronary artery stenosis (degree of stenosis ≥50%) on CCTA were assessed. Logistic regression analysis was used to determine the association between a family history of diabetes and atherosclerotic plaque or significant coronary artery stenosis according to the degree of diabetes (normal, prediabetic and diabetic).Mean age of study participants was 53.7±7.6 years, and 4694 (73.0%) were male. A total of 1593 (24.8%) participants had a family history of diabetes in a first-degree relative. Among the study participants, 1115 (17.3%), 3122 (48.5%) and 2197 (34.1%) were categorized as diabetic, prediabetic and normal, respectively. In diabetic participants, after stepwise adjustments for clinical and laboratory variables, a family history of diabetes was significantly associated with non-calcified plaque (P0.05 for all), but did not appear to be associated with either calcified or mixed plaques or with significant coronary artery stenosis (P0.05 for all). In prediabetic and normal participants, a family history of diabetes was not associated with either atherosclerotic plaque or significant coronary artery stenosis (P0.05 for all).In asymptomatic diabetic individuals, a family history of diabetes is consistently associated with non-calcified coronary plaque after adjusting for risk factors.

ING1b is a tumor suppressor that affects transcription, cell cycle control and apoptosis. ING1b is deregulated in disease, and its activity is closely linked to that of p53. In addition to regulating protein-coding genes, we found that ING1b also influences the expression of large intergenic non-coding RNAs (lincRNAs). In particular, lincRNA-p21 was significantly induced after DNA-damage stress or by ING1b overexpression. Furthermore, lincRNA-p21 expression in response to DNA damage was significantly attenuated in cells lacking ING1b. LincRNA-p21 is also a target of p53 and can trigger apoptosis in mouse cell models. We found that this function of lincRNA-p21 is conserved in human cell models. Moreover, ING1b and p53 could function independently to influence lincRNA-p21 expression. However, their effects become more additive under conditions of stress. In particular, ING1b regulates lincRNA-p21 levels by binding to its promoter and is required for induction of lincRNA-p21 by p53. The ability of ING1b to cause apoptosis is also impaired in the absence of lincRNA-p21. Surprisingly, deletion of the ING1b plant homeodomain, which allows it to bind histones and regulate chromatin structure, did not alter regulation of lincRNA-p21. Our findings suggest that ING1b induces lincRNA-p21 expression independently of histone 3 lysine 4 trimethylation mark recognition and that lincRNA-p21 functions downstream of ING1b. Thus, regulation at the level of lincRNA-p21 may represent the point at which ING1b and p53 pathways converge to induce apoptosis under specific stress conditions.

Summary Nontuberculous mycobacteria (NTM) are ubiquitous organisms that are now seen as emerging human pathogens. NTM infections are very difficult to diagnose and treat, therefore a high index of clinical suspicion is needed for diagnosis. Cutaneous NTM infections have been primarily reported associated with previous invasive procedures. We report the case of a healthy 59-year-old woman who developed recurring abdominal skin lesions caused by Mycobacterium massiliense after she underwent noninvasive cupping therapy. We identified the pathogen using a PCR assay targeting the erm(41) gene of the bacterium. The patient was treated successfully by en bloc excision and long-term antibiotic treatment. This case shows that cutaneous infection with M. massiliense may occur in an immunocompetent person without an antecedent invasive procedure.

Using simulated noisy sequences of respiration and heart rate, we assessed the accuracy of the respiratory sinus arrhythmia transfer function (RSATF) estimation under three kinds of spontaneous breathing patterns: regular or tidal breathing, periodic breathing with apnea, and broadband breathing. Estimation employing the cross-power and autopower spectra of the simulated data produced RSATF estimates that were generally more variable than those computed with an autoregressive modeling approach. Variability and bias errors in the RSATF estimates became larger as respiratory bandwidth decreased when the breathing pattern changed from broadband to periodic to regular breathing. However, between frequencies of 0.1 and 0.3 Hz, these errors fell within 12% in all breathing patterns. Error in the RSATF estimates was only slightly increased, with reductions in data length to as low as 90 s. The results suggest the feasibility of obtaining accurate estimates of RSATF between 0.1 and 0.8 Hz from a wide variety of conditions, such as in different sleep-wake states where voluntary control of breathing is not possible and the ventilatory pattern may vary substantially.

A suburban teaching hospital in a tuberculosis (TB) prevalent area.To evaluate the proportion of pulmonary TB among patients hospitalised with suspected community-acquired pneumonia (CAP), and to develop a diagnostic index for identifying TB among these patients.TB cases confirmed using 1) sputum culture, or 2) both sputum acid-fast bacilli smear and polymerase chain reaction for Mycobacterium tuberculosis, were compared with non-tuberculous CAP by demographic, clinical, laboratory and radiographic information. Using multiple logistic regression analysis, risk factors for TB were identified. A diagnostic index was developed by summing up their simplified regression coefficients. Its performance was checked using c-statistic.TB was the second leading cause of CAP (37/528, 7.0%). Risk factors were initial symptoms7 days, serum albumin3.5 g/dl, cavitary/nodular infiltrates and upper lobe involvement (1 point for each). The c-statistic of the index was 0.856 (95%CI 0.789-0.923), and for bootstrapping samples of 1000 repetitions it was 0.856 (95%CI 0.791-0.921). For scores ≥2, sensitivity and specificity were respectively 81.1% and 75.8%.TB is one of the leading causes of CAP in TB-prevalent areas. Our diagnostic index may help clinicians identify TB immediately from CAP and initiate appropriate isolation and optimal treatment.

Introduction We studied the incidence of vesicoureteral reflux (VUR) in the graft kidney and its effect on the occurrence of urinary tract infection (UTI) and long-term graft function. Methods We performed a retrospective analysis of 64 adult kidney transplant recipients based upon voiding cystourethrography at 12 months post-transplantation. Patients underwent analysis of survival, incidence of UTIs beyond 1 year, and graft function. Results Thirty-seven male and 27 female patients in the study populations showed a mean age 42 years. VUR in the transplanted kidney at 12 months post-transplant occurred among 78.1% (50/64) of subjects: grade I ( n = 6), grade II ( n = 30), or grade III ( n = 14) reflux. Patients followed for a median 61 months (range 44–74s) showed 11 cases of UTIs in 9 subjects. There were no significant differences in clinical characteristics or incidence of, UTIs according to the presence or severity of VUR ( P = .81) or the Serum creatinine and estimated glomerular filtration rate values at 12, 36, 48, or 60 months post-transplantation. Conclusions VUR present in 78.1% of patients after kidney transplantation affected neither graft functions or graft survival. The incidence of UTI did not differ according to the presence of VUR.

We investigated the effect of the donor kidney weight (Kw) to recipient body weight (Rw)ratio (Kw/Rw) on long-term graft function. To investigate the impact of the Kw/Rw ratio on the graft function, we retrospectively collected data from 213 kidney transplant recipients at least 5 years Post-transplantations. Renal function showed a positive correlation with the Kw/Rw ratio until 5 years after transplantation (at 60 months after transplantation, R = 0.158, P = .023); however, this ratio does not affect graft survival (P = .794). We used the mixed-effect model to identify the factors that affect the estimated glomerular filtration rate (eGFR) over time. In univariate analysis, donor age, BSA, kidney weight, and Kw/Rw ratio were associated with eGFR. To identify independent factors that affect to the eGFR, multivariate analysis using a mixed model was applied. Donor age (P < .001) and Kw/Rw ratio (P < .001) were independent factors that affected the eGFR. To identify the cutoff values of the Kw/Rw ratio and donor age that affect long-term graft function, multiple testing using a mixed model was applied. The cutoff value for the Kw/Rw ratio was 3.16 (P = .0104) and the cutoff value of donor age was 44 years (P = .0001). Based on our results, we conclude that the Kw/Rw ratio and donor age are important factors for the long-term function of graft.

Successful arterial reconstruction is essential for liver transplantation. In the case of inadequate arterial inflow, an arterial conduit from the aorta using artery graft or re-establishment of arterial flow through other arteries such as the splenic artery, gastroepiploic, or sigmoid artery is considered. Herein we report our experience of 27 cases of hepatic artery reconstruction using alternative methods. The most common cause of hepatic artery reconstruction requiring alternative methods was intimal dissection for which we usually used the gastroepiploic artery. Many patients had a previous operation or transarterial chemoembolization history. Among these cases, hepatic artery reconstruction using the jejunal artery was performed for 2 cases of living donor liver transplantation due to the absence of suitable alternatives. These patients have been followed up with patent hepatic arterial flow until now. Thus, the jejunal artery can be a useful option for arterial reconstruction in living donor liver transplantation when suitable arterial inflow is absent.

The purpose of this study was to determine the changing pattern of Salmonella serotypes causing acute diarrhoea in humans in Gwangju area, Korea, during 2000-2009. A total of 596 Salmonella isolated from culture of 29,896 faecal samples of patients with acute diarrhoea were included in this study. Faecal samples were collected from local hospitals and clinics in Gwangju area during January 2000-December 2009. The mean annual frequency of isolates for the 10 years was 2.0% (range, 0.9-6.0). The isolates were serologically classified into 43 different serotypes. The 10 most common serotypes were Salmonella Enteritidis (47.9%), S. Typhimurium (20.4%), S. Braenderup (3.2%), S. Montevideo (2.9%), S. Paratyphi B (2.9%), S. London (2.3%), S. Bardo (1.7%), S. Virchow (1.7%), S. Infantis (1.5%) and S. Typhi (1.5%), accounting for 86% of all the isolates. Temporal variations were observed in the distribution of different Salmonella serotypes over the years, and only S. Enteritidis and S. Typhimurium were persistent throughout the study period. Although age specificity varied with serotypes, Salmonella was isolated most frequently from children below 5 years of age (179/596, 30.0%). A seasonal trend was apparent, and the highest rates were found in the summer months. This is the first report of the annual frequency of isolation of Salmonella serotypes, and seasonal and age-specific patterns of salmonellosis in humans in Gwangju area, Korea, over a decade-long period.

Introduction Anatomic variants of the hepatic vasculature are common, so precise preoperative donor evaluation, including variations in the vasculature, is essential. We analyzed the anatomic similarity according to the donor–recipient relationship. Methods Among the cases who underwent living donor liver transplantations from September 2008 to January 2011 we selected 104 cases with clearly defined hepatic artery and portal vein on preoperative computed tomography. They were classified according to Hiatt et al for the hepatic artery and Cheng for the portal vein. We categorized the 104 cases into three groups: parents–child (n = 40), sibling (n = 24) and no-relation (n = 40), for analysis of the concordance of the hepatic artery and portal vein. Result Anatomic variations were observed in 25% of donors and 23.1% of recipients in the hepatic artery and 6.7% of donors and 10.6% of recipients in the portal vein. There was no significant difference in the distribution of the type of hepatic vasculature. Identical anatomic variations between donors and recipients were observed in 62.5% of the parent–child; 66.7% of the sibling and 52.5% of no-related group ( P = .493) in the hepatic artery and 92.5%, 100%, and 77.5% ( P = .014) in the portal vein respectively. Conclusion There was no similarity in the anatomic variations of the hepatic artery according to the donor–recipient relationship, but a similarity in portal venous anatomy according to the donor–recipient relationship.

Primary hyperparathyroidism is the most common cause of hypercalcemia seen in the outpatient setting (Bilezikian, 1992). Skeletal involvement is evident in most patients, even in the vast majority who show no symptoms. Bone histomorphometric studies reveal that the greatest bone diminution occurs in the radial shaft, the femoral neck is intermediate, and the spine is less affected (Parisien et al., 1990). An understanding of this condition is vital for the professional nurse so that effective nursing care can be provided to those who are at risk of developing rapid bone loss and other complications of primary hyperparathyroidism. This article reviews the medical diagnosis and nursing management of primary hyperparathyroidism.

Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder (MDD). The aim of this randomised, open-label, controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms.A total of 60 MDD patients with a score above 18 on the Hamilton Anxiety Rating Scale (HARS) were randomly assigned to 8 weeks of fixed dosing treatment with mirtazapine (15-30 mg/day) and paroxetine (10-20 mg/day). Efficacy was primarily assessed with the HARS and with the 17-item Hamilton Depression Rating Scale (HDRS) at weeks 1, 2, 4 and 8 after treatment. Tolerability was assessed from adverse events.The generalised estimating equations (GEE) models showed that the rates of improvement in HDRS scores from baseline to week 8 were similar between mirtazapine and paroxetine groups. However, patients with mirtazapine exhibited earlier improvement in HARS scores at weeks 1 and 2. Week-by-week GEE models showed that these significant differences in improvement of HARS scores between the two treatment groups were detectable from the first evaluation after the treatment (week 1) and maintained through week 2. There was no difference in the overall frequency of adverse events experienced between the two treatment groups. The most common adverse event in the mirtazapine group was somnolence (n = 8), whereas that in the paroxetine group was gastrointestinal discomfort (n = 9).Mirtazapine and paroxetine were equally effective and well tolerated for the depressive symptoms in MDD patients with the high level of anxiety symptoms. Mirtazapine was, however, more effective in reducing the anxiety symptoms than paroxetine in the early weeks of treatment, suggesting that mirtazapine may have an earlier-onset action for the anxiety symptoms in MDD patients.

The purpose of this study was to evaluate the high-resolution computed tomographic (HRCT) findings of five adult patients (either immunocompromised or immunocompetent) with herpes simplex virus (HSV) pneumonia. We retrospectively assessed HRCT images of 5 patients (all male patients, age range 39-70 years; mean 62 years) with HSV pneumonia. The specific pathological findings that allowed for a definite diagnosis of HSV pneumonia included the presence of intranuclear inclusion bodies on haematoxylin and eosin staining, or positive immunohistochemical staining. High-resolution CT scans (HiSpeed Advantage or LightSpeed QX/i, GE Healthcare) using 1- or 1.25-mm collimation at 10-mm intervals without intravenous contrast medium injection were assessed, in particular for the presence and distribution of parenchymal abnormalities including ground-glass attenuation, airspace consolidation, nodules and interlobular septal thickening. In two patients, pathological specimens were obtained from open lung biopsy or bronchoscopic biopsy, and were correlated with HRCT findings. Three HRCT patterns of pulmonary abnormalities were identified in our series of HSV pneumonia: predominant areas of diffuse or multifocal ground-glass attenuation, predominant areas of multifocal peribronchial consolidations, and a mixed pattern of both. Histopathologically, areas of ground-glass attenuation seen on HRCT corresponded to diffuse alveolar damage in one patient who underwent open lung biopsy. No specific differences in HRCT findings were seen between the immunocompromised and the immunocompetent patients. In patients suspected of having an acute lower respiratory infection, whether immunocompromised or immunocompetent, a possibility of HSV pneumonia can be included in differential diagnoses when diffuse or multifocal areas of ground-glass attenuation and/or consolidations are seen on HRCT.

All-trans retinoic acid (ATRA) induces complete remission in a majority of acute promyelocytic leukaemia patients, but resistance of leukaemic cells to ATRA and its toxicity, such as hypercalcaemia, lead to a limitation of treatment. Therefore, combination therapies with differentiation-enhancing agents at non-toxic concentrations of ATRA may overcome its side effects. Here, we investigated the effect of plant-derived sesquiterpene lactone compounds and their underlying mechanisms in ATRA-induced differentiation of human leukaemia HL-60 cells.HL-60 cells were treated with four sesquiterpene lactones (helenalin, costunolide, parthenolide and sclareolide) and cell differentiation was determined by NBT reduction, Giemsa and cytofluorometric analyses. Signalling pathways were assessed by western blotting, gel-shift assay and kinase activity determinations and intracellular calcium levels were determined using a calcium-specific fluorescent probe.Helenalin, costunolide and parthenolide, but not sclareolide, increased ATRA-induced HL-60 cell differentiation into a granulocytic lineage. Signalling kinases PKC and ERK were involved in the ATRA-induced differentiation enhanced by all of the effective sesquiterpene lactones, but JNK and PI3-K were involved in the ATRA-induced differentiation enhanced by costunolide and parthenolide. Enhancement of cell differentiation closely correlated with inhibition of NF-kappaB DNA-binding activity by all three effective compounds. Importantly, enhancement of differentiation induced by 50 nM ATRA by the sesquiterpene lactones was not accompanied by elevation of basal intracellular calcium concentrations.These results indicate that plant-derived sesquiterpene lactones may enhance ATRA-mediated cell differentiation through distinct pathways.

Although radiosurgery has been found to be a safe and effective alternative treatment, seizure outcome of arteriovenous malformation (AVM) radiosurgery has not been documented in detail. We report the effect of Gamma Knife radiosurgery (GKRS) on seizures associated with AVMs and discuss the various factors that influence the prognosis.Between 1992 and 2004, 246 patients were treated with GKRS for AVMs at Kyung-Hee medical center. Forty five (17.0%) patients have non-hemorrhagic AVMs and presenting symptom was seizure. Two patients of all were excluded from this study due to loss of follow-up after radiosurgery. In this study, retrospective analysis of clinical characteristics, radiologic findings, radiosurgical seizure outcome were performed.There were 32 male and 11 female with age ranging from 10 to 74 years (mean 35 years). Type of seizure included: general tonic clonic (n = 28); focal motor or sensory (n = 7); partial complex (n = 8). The location of AVM was temporal (n = 18); frontal (n = 9); deep seated (n = 7): parietal (n = 5); occipital (n = 4). Follow-up period was from 8 months to 12 years (mean 46 months). Mean volume was 6.2 cc (2.7-20), mean marginal and maximal dosage was 19.5 (17-26) and 36.6 Gy (13-50). During follow-up after radiosurgical treatment, 23 (53.5%) of 43 patients were seizure-free, 10 (23.3%) had significant improvement, were unchanged in 8 (18.6%) and aggravated in 2 (4.6%) patients. In 33 patients, follow-up angiography or MRI was performed. Complete obliteration was achieved in 16 (49.0%) patients, partial obliteration in 13 (39.0%). Four were unchanged (12.0%). Of 33 patients with follow-up performed, 26 were followed for over 2 years. Eleven (84.6%) of 13 patients with complete obliteration were seizure-free (p0.005). Four (36.3%) of 13 with partial obliteration and unchanged remained seizure-free. Fifteen patients had experienced intractable seizure before radiosurgery. After radiosurgery, seizures disappeared in 8 (53%) patients. Seizure frequently decreased in 5 (33%) and 2 patients (14%) were unchanged but none was aggravated. Five (71%) of 7 patients with complete obliteration were seizure-free and 2 (40%) of 5 patients with partial obliteration were seizure-free.Up to now, controversy about resective surgery or radiosurgery as treatment of seizure related to AVMs still remains. In this study, we experienced that Gamma Knife radiosurgery is commonly performed to treat AVMs and can improve symptomatic seizure associated with AVMs. To clarify the mechanism of seizure control in AVMs radiosurgery is difficult, but it seems to be closely related to hemodynamic effects after radiosurgery.

This study aimed to analyse the characteristics of adrenal masses visible in the computerised tomography (CT) scans which have been also evaluated by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), and to characterise the features of 18F-FDG PET scans associated with various adrenal endocrine tumours, especially benign functional tumours. 18F-FDG PET scans of 105 patients with adrenal masses on the CT scan were analysed. Positive uptakes in the 18F-FDG PET scans were seen in 60 malignant tumours (54 metastasic lesions, six primary adrenal cancers) and seven benign tumours. The positive predictive value of 18F-FDG PET imaging to characterise an adrenal mass as a malignant tumour was 90%; the corresponding negative predictive value to rule out malignancy was also 90%. Benign adrenal tumours were smaller than that of malignant lesions (p0.05). The mean standardised uptake value max (SUVmax) of the metastatic lesions [8.4+/-6.5 (microCi/g)/microCi/kg] was significantly higher than that of the benign adrenal tumours [2.4+/-1.2 (microCi/g)/microCi/kg, p0.001]. Examination of only the primary adrenal lesions revealed that all adrenocortical carcinomas, two of three cases of pheochromocytomas, three of five neuroblastomas and two of four cases of primary aldosteronism showed positive 18F-FDG uptake. In conclusion, for patients presenting adrenal masses with a high probability of malignancy, 18F-FDG PET can be used to differentiate malignant from benign adrenal lesions. However, the 18F-FDG PET uptake did not show an always consistent pattern for endocrine tumours, which was probably due to the variability inherent in 18F-FDG uptake. This study suggests that 18F-FDG PET scanning can offer supporting data to localise and characterise adrenal tumours.

Intermediate filament (IF) nestin and small heat shock protein (sHSP) are developmentally regulated proteins. Nestin is highly expressed on proliferating neuroepithelial stem cells of the developing central nervous system (CNS). During the developmental neurulation stage, nestin is replaced by mature neuronal (neurofilament) or glial cell-specific IFs (glial fibrillary acidic protein, GFAP). Several pathologic states induce astrocytes to synthesize nestin transiently in the mature brain. However, the exact nature of the embryonic conversion from nestin to mature cytoskelton is unclear. In an attempt to define the effect of ischemic hemodynamic stress caused by cerebral arteriovenous malformation (AVM) on the brain parenchyma, we examined the synthesis and cellular distribution of sHSP and nestin in vascular elements of AVMs and in the gliotic area surrounding AVMs. Ten consecutively collected surgical specimens meeting the histological criteria for AVM were immunohistochemically stained using primary antibodies for nestin, HSP27 and alphaB-crystallin. Nestin, HSP27 and alphaB-crystallin mRNA expressions were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Nestin expression is reinduced not only in reactive astrocytes, but also in endothelial cells in the surrounding gliotic tissue of the cerebral AVM. These cells also expressed sHSP (HSP27, alphaB-crystallin) that maintain the integrity of the IF network and prevent unfolding of cellular proteins induced by various stresses. RT-PCR showed the increased expression of sHSP and nestin mRNA in the AVM specimens. These results indicate that embryonic reversion of the mature cytoskeleton to nestin and the increased expression of sHSP in response to cerebral injury are associated with increased wall tension caused by dilating AVM vessels and with the hemodynamic stress that surrounds AVMs.

Vesicouterine fistula is one of the least common types of urogenital fistula, accounting for only 1-4% of all cases. We report a case of vesicouterine fistula after vacuum delivery in a woman with a history of a previous Cesarean section. The 29-year-old woman was hospitalized due to continuous serosanguinous vaginal leakage and hematuria. Transvaginal sonography demonstrated the presence of a fistulous tract between the uterus and the bladder. Cystoscopy demonstrated a small opening in the posterior bladder wall and a cystogram revealed a fistulous tract between the posterior portion of the bladder and the uterine cavity. Since the patient could not tolerate her symptoms, we decided to close the fistulous tract surgically. The fistulous tract was excised and the bladder and uterus were closed primarily. The bladder was drained with a Foley catheter for 12 days and subsequent follow-up of the patient has demonstrated urinary continence.

1. Transcription factors such as NF-kappa B provide powerful targets for drugs to use in the treatment of cancer. In this report parthenolide (PT), a sesquiterpene lactone of herbal remedies such as feverfew (Tanacetum parthenium) with NF-kappa B inhibitory activity, markedly increased the degree of human leukaemia HL-60 cell differentiation when simultaneously combined with 5 nM 1 alpha,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)). PT by itself did not induce HL-60 cell differentiation. 2. Cytofluorometric analysis indicated that PT stimulated 1,25-(OH)(2)D(3)-induced differentiation of HL-60 cells predominantly into monocytes. 3. Pretreatment of HL-60 cells with PT before the 1,25-(OH)(2)D(3) addition also potentiated the 1,25-(OH)(2)D(3)-induced HL-60 cell differentiation in both a dose- and a time-dependent manner, in which the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-kappa B binding activity by PT. 4. In contrast, santonin, a sesquiterpene lactone without an inhibitory activity of NF-kappa B binding to the kappa B sites, did not enhance the 1,25-(OH)(2)D(3)-induced HL-60 cell differentiation. 5. In transfection experiments, PT enhanced 1,25-(OH)(2)D(3)-induced VDRE-dependent promoter activity. Furthermore, PT restored 1,25-(OH)(2)D(3)-induced VDRE-dependent promoter activity inhibited by TNF-alpha, an activator of NF-kappa B signalling pathway. 6. These results indicate that PT strongly potentiates the 1,25-(OH)(2)D(3)-induced HL-60 cell differentiation into monocytes via the inhibition of NF-kappa B activity and provide evidence that inhibition of NF-kappa B activation can be a pre-requisite to the efficient entry of promyelocytic leukaemia cells into a differentiation pathway.

The effect of silibinin, an active component of Silybum marianum, on cellular differentiation was investigated in the human promyelocytic leukemia HL-60 cell culture system. Treatment of HL-60 cells with silibinin inhibited cellular proliferation and induced cellular differentiation in a dose-dependent manner. Cytofluorometric analysis and morphologic studies indicated that silibinin induced differentiation of HL-60 cells predominantly into monocytes. Importantly, strongly synergistic induction of differentiation into monocytes was observed when silibinin was combined with 5 nM 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], a well-known differentiation inducer of HL-60 cells into the monocytic lineage. Silibinin enhanced protein kinase C (PKC) activity and increased protein levels of both PKCalpha and PKCbeta in 1,25-(OH)(2)D(3)-treated HL-60 cells. PKC and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by silibinin alone or in combination with 1,25-(OH)(2)D(3), indicating that PKC and ERK may be involved in silibinin-induced HL-60 cell differentiation.

Summary: We report the imaging findings in two patients with proliferating trichilemmal tumors. In the first patient, the tumor arose on the lower lip, a very unusual location for this type of tumor, and showed malignant transformation with metastasis to a regional lymph node. It was seen as a poorly marginated soft-tissue mass with isointense signal on T1-weighted MR images and hyperintense signal on T2-weighted images. Large areas of high signal intensity caused by necrosis were also found within the tumor on T2-weighted images. After IV administration of contrast material, the mass showed significant enhancement, with considerable portions remaining unenhanced. In the second patient, the tumor originated from a preexisting trichilemmal cyst and occurred in the hair-bearing area of the posterior part of the neck. CT scans showed a well-encapsulated cystic mass that contained multiple speckled calcifications in a wall of variable thickness. There were several foci of smooth soft-tissue elevations from the inner wall of the mass, which corresponded histologically to proliferating portions of trichilemmal cyst.

Immunogold densities for the 'classical' and 'novel' alpha chains of type IV collagen, laminin, and fibronectin are increased in the spikes in human membranous nephropathy (MN). To investigate the molecular mechanisms which underlie these changes in glomerular basement membrane (GBM) components, alpha1(IV) collagen, alpha4(IV) collagen, S-laminin, fibronectin, transforming growth factor (TGF)-beta1 and TGF-beta2 mRNA expression was examined in 12 renal biopsy specimens with MN and six renal biopsies with no detectable abnormality by RNA in situ hybridization. In controls, there were relatively low signals of alpha1(IV) collagen, alpha4(IV) collagen, S-laminin, and TGF-beta1 mRNAs, but there were no fibronectin or TGF-beta2 transcripts in glomerular cells. In MN, the number of alpha4(IV) collagen, alpha1(IV) collagen, S-laminin or TGF-beta1 mRNA-expressing cells per glomerular cross-section was significantly larger than in controls (p0.05), and fibronectin mRNA was occasionally expressed in glomerular visceral epithelial cells (GECs). No message for TGF-beta2 was seen in MN. The number of TGF-beta1 mRNA-expressing cells per glomerular cross-section significantly correlated with that of alpha1(IV) mRNA-expressing cells (p0.01). The MN patients with positivie signal for fibronectin mRNA exhibited more severe GBM thickening than those without (p0.05). These results indicate that the increased presence of GBM proteins in spikes of MN is associated with enhanced mRNA expression of these proteins. They also suggest that subepithelial deposits in MN stimulate GECs to produce TGF-beta1, which in turn could mediate the expression of GBM protein genes by GECs.

The most common high resolution CT (HRCT) findings of bronchiolitis are centrilobular nodules and branching linear structures in the secondary pulmonary lobules or areas of air trapping. These findings can be helpful in suggesting the presence of bronchiolitis. However, they are nonspecific because there are overlapping features among various kinds of bronchiolitis. Bronchiolar or peribronchiolar inflammation appears as centrilobular nodule, while bronchiolectasis filled with secretions manifests with branching linear structure on HRCT. Air trapping is secondary to bronchiolitis. Proliferative bronchiolitis with the findings of patchy areas of consolidation or ground-glass opacity can be distinguished from other bronchiolitis. Mineral dust-induced bronchiolitis and peribronchiolar lesions in sarcoidosis present with perilymphatic (centrilobular plus perilobular) micronodules in the secondary pulmonary lobule. Bronchiolitis in hypersensitivity pneumonia appears with poorly defined centrilobular nodules, associated with ground-glass opacity and air trapping.

PURPOSE: To investigate the MR findings of childhood metachromatic leukodystrophy (MLD). METHODS: Nine MR imaging studies in seven children (five girls and two boys, 10 to 32 months old) with MLD were evaluated retrospectively for the extent and progression of white matter abnormalities and the presence of contrast enhancement. RESULTS: All seven cases showed symmetric, confluent high signal intensity on T2-weighted images in the periventricular white matter and centrum semiovale. A posterior predominance of white matter abnormalities was noted in all cases. Although initially spared from demyelination in all cases, in one case, the subcortical U fibers were later involved in demyelination of follow-up MR studies. Other sites of involvement were the genu (n = 5) and splenium (n = 6) of the corpus callosum, the posterior limbs of the internal capsule (n = 5), the descending pyramidal tracts (n = 4), the claustrum (n = 4), and the cerebral white matter (n = 2); diffuse brain atrophy was seen in two cases. No enhancement of the lesion was seen on any of the five postcontrast examinations. A "tigroid" pattern, previously described in cases of Pelizaeus-Merzbacher disease, was noted in the centrum semiovale in six cases. CONCLUSION: In late-infantile MLD, demyelination is more prominent in the occipital region. In addition to demyelination of the periventricular white matter, common manifestations include a "tigroid" pattern and involvement of the corpus callosum, the internal capsule, and the corticospinal tract.

The in vitro cytotoxicity of a new platinum complex, cis-malonato [(4R, 5R)-4,5-bis(aminomethyl)-1,3-dioxolane 2- spiro 1' cyclo-pentane]platinum(II) (SKI 2054R) and cisplatin (CDDP) was evaluated against two human stomach adenocarcinoma cell lines (MKN-45 and KATO III) and a human lung adenocarcinoma cell line (PC-14). The in vitro 50% inhibitory concentration (IC50) values of SKI 2054R and CDDP against MKN-45, KATO III, and PC-14 were 1.21 and 0.51, 2.11 and 0.83, and 2.90 and 0.77 micrograms/ml, respectively. The pharma-cokinetic and ex vivo pharmacodynamic studies on SKI 2054R and CDDP were performed in beagle dogs. Equitoxic doses of SKI 2054R and CDDP (7.0 and 3.0 mg/kg, respectively) were administered i.v. bolus to beagle dose in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the two drugs declined in a biexponential fashion. The mean area under the concentration-tine curve (AUC(0)--infinity) determined for ultrafiltrable platinum derived from SKI 2054R, as an active component was 6.61 +/- 2.34 micrograms . h/ml (mean +/- S.D.), with an initial half-life of 0.26 +/- 0.14 h, a terminal half-life of 1.57 +/- 0.71 hour, a total clearance of 17.65 +/- 4.99 ml/min/kg, and a steady-state volume of distribution of 1.46 +/- 0.11 l/kg. The ex vivo antitumor activity of SKI 2054R was assessed using the ultrafiltrable plasma against MKN-45, KATO III, and PC-14 by tetrazolium-dye (MTT) assay and was compared with that of CDDP using the antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value recorded for SKI 2054R was higher than that noted for CDDP; however, statistical difference was not observed between SKI 2054R and CDDP, suggesting that the antitumor activity of SKI 2054R is comparable to that of CDDP. These results suggest that SKI 2054R is a new platinum complex which is worth being evaluated further.

Focal segmental glomerulosclerosis (FSGS) is observed in severe or atypical preeclamptic patients biopsied postpartum. To further define the structural characteristics that might be related to atypical clinical manifestations in this disorder, we analyzed the postpartum renal biopsies of eight preeclamptic patients with FSGS by morphometry and studied the structural-functional relationships. For comparison, three postpartum biopsies with primary FSGS and eight nonpregnant subjects with primary FSGS were also studied. Mesangial volume fraction was increased in the preeclamptic FSGS group being 2 times that of the pregnant or nonpregnant primary FSGS group. Mean surface density of peripheral glomerular basement membrane (PGBM) per glomerulus was markedly decreased in the preeclampsia group being 1/3 that for the pregnant or nonpregnant primary FSGS group. Volume density of cortical interstitium in the preeclamptic FSGS was smaller than that of the primary FSGS group. In preeclamptic FSGS, mesangial volume fraction correlated inversely with PGBM surface area (r = -0.84; p0.01) and with creatinine clearance (Ccr) (r = -0.63; p0.05). PGBM surface area per glomerulus in preeclamptic FSGS correlated with Ccr (r = +0.63; p0.05). Mean volume density of cortical interstitium was not related to Ccr nor with the percentage of glomeruli with FSGS in preeclamptic FSGS. These results suggest that decreased glomerular filtration function in atypical preeclampsia is linked to decreased PGBM surface area, that results from mesangial expansion and particularly from mesangial interposition.

A large meningioma in the cerebellopontine angle manifested itself as a contralateral hemifacial spasm. On computed tomographic and magnetic resonance imaging scans, the brain stem was markedly displaced and distorted by the tumor. After total removal of the meningioma, the hemifacial spasm completely disappeared.

The pharmacokinetics and ex vivo pharmacodynamics studies on cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3- dioxolane]platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP), and carboplatin (CBDCA) were performed in beagle dogs. Equitoxic doses of SKI 2053R, CDDP, and CBDCA (7.5, 2.5, and 15.0 mg/kg, respectively) were given by i.v. bolus to three beagle dogs in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the three drugs declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0--infinity) determined for ultrafiltrable platinum derived from SKI 2053R, as an active component, was 7.72 +/- 2.74 micrograms h ml-1 (mean +/- SD), with an initial half-life of 0.37 +/- 0.20 h, a terminal half-life of 2.19 +/- 0.93 h, a total clearance of 16.83 +/- 4.76 ml min-1 kg-1, and a steady-state volume of distribution of 1.57 +/- 0.30 l/kg. The ex vivo antitumor activity of SKI 2053R was assessed using the ultrafiltrable plasma against two human lung-adenocarcinoma cell lines (PC-9 and PC-14) and five stomach-adenocarcinoma cell lines (MKN-45, KATO III, SNU-1, SNU-5, and SNU-16) by tetrazolium-dye (MTT) assay and was compared with that of CDDP and CBDCA using an antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value was shown to be ranked in the following order: SKI 2053RCBDCACDDP. The mean ATI values recorded for SKI 2053R and CBDCA were significantly (P0.05) higher than that noted for CDDP; however, no statistically significant difference was observed between SKI 2053R and CBDCA, suggesting that the antitumor activity of SKI 2053R is superior to that of CDDP and is equivalent to that of CBDCA. These results suggest that SKI 2053R is a promising candidate for further development as a clinically useful anticancer drug.

The growth of a potentially antigenic tumor in an immunocompetent host is taken as an indication that the malignant cells 'escaped' the cytotoxic capacity of the immune system. An increase in our knowledge of the means by which antigens are processed and expressed allows a greater understanding of the mechanism that enables tumor cells to avoid host immunity. It provides a rationale for new, more innovative forms of treatment. Antigenic determinants are presented to cytotoxic T lymphocytes (CTLs) in the context of class I determinants, structures specified by genes within the major histocompatibility complex. Potentially antigenic tumors may express lower levels of class I determinants than surrounding non-neoplastic cells. As a consequence, the tumor-associated T cell epitopes formed by the malignant cells may go unrecognized by tumor-specific CTLs. The introduction of genes specifying class I determinants into low class I expressing tumor cells increased class I expression and restored the cells' immunogenic properties. Treatment of low class I expressing cells with interferon-gamma, or the introduction of the interferon-gamma gene into the cells resulted in an increase in the expression of class I determinants as well, and, as a consequence, recognition of the malignant cells by the immune system. Nevertheless, an immunotherapeutic strategy that stimulated a single anti-tumor effector mechanism might be unable to eliminate a heterogeneous tumor cell population. To investigate this point, mice with melanoma were treated with a mixture of interferon-gamma-secreting and IL-2-secreting cellular immunogens. The animals survived significantly longer than mice with melanoma treated with either the IL-2 or interferon-gamma-secreting immunogens alone. The complexity of the problem was illustrated by the fact that although survival was prolonged, tumor growth recurred in each instance.

✓ In order to examine the correlation between prognosis and the histological features of nuclear atypia, mitosis, endothelial proliferation, and necrosis in supratentorial adult astrocytomas, the authors reviewed 251 such cases treated at the Massachusetts General Hospital between 1972 and 1980. One point was given for the presence of each feature. The total number of features was translated into a grade as follows: none of the four features = Grade 1 (one patient), one feature = Grade 2 (36 patients), two features = Grade 3 (33 patients), and three or four features = Grade 4 (181 patients). The period of survival was significantly associated with grade, the presence or absence of each of the four histological features, patient's age, type of operation, radiation therapy, and extent of tumor (log rank, p < 0.05). The variables associated with grade were age (p < 0.001) and radiation therapy (p < 0.02). After adjustment for these variables using a Cox proportional-hazards model, the difference in overall survival time between patients in Grades 2 and 3 was not statistically significant. When comparable groups of patients were examined in terms of age or receipt of radiation therapy, the median survival times differed markedly. Patients 50 years of age or less had a median survival time of 68 months (Grade 2 tumors), 29 months (Grade 3 tumors), and 13 months (Grade 4 tumors). Patients over 50 years of age had a median survival time of 6 months (Grade 2 and 4 tumors) and 9 months (Grade 3 tumors). Those patients who had received radiation therapy had a median survival time of 68 months (Grade 2 tumors), 21 months (Grade 3 tumors), and 11 months (Grade 4 tumors). Those patients who did not receive radiation therapy had a median survival time of 1 month (Grade 2 tumors) and 2 months (Grade 3 and 4 tumors); over half of these patients died within 2 months of surgery. This grading system, originally proposed by Daumas-Duport, et al., is simple, objective, and reproducible, and correlates well with survival times. The authors recommend that astrocytomas be graded on a scale of 1 to 4, with Grade 1 reserved for the rare adult supratentorial astrocytoma with none of the four histological features.

To develop a reproducible in vivo model for the growth of human schwannomas we implanted tumor specimens from 14 different patients (13 acoustic neurinomas; 1 trigeminal schwannoma) into the subrenal capsule of 108 nude mice. In 11 experiments, the animals were implanted with only solid tumor from the surgical specimens. In two experiments, the tumor implants were made from solid tumors and cell clusters. In one experiment, the tumor implants were made from cell clusters alone. The size and neovascularization of these tumors were serially determined during a 1.5- to 3-month period. The percentages of tumors that survived or grew were 77.3% from solid tumors and 70% from cell clusters. Maximum tumor volume varied as did the time span to reach that volume. Tumor enlargement and stability correlated well with neovascularity; regressing tumor showed minimal or no neovascularity. Histological analysis of the implanted tumors showed spindle cells that are similar to the original tumor. Immunohistochemical staining for S100 demonstrated the Schwann cell nature of the implants. Analysis of genomic DNA from an acoustic neurinoma that had been implanted for 3 weeks was consistent with its human origin. There were no significant microscopic differences among groups receiving solid tumor implants or cell clusters. These studies suggest that implantation of human schwannomas into the subrenal capsule of the nude mouse is a reproducible method to study tumor growth that may be useful in testing potential therapeutic regimens or genetic modulation of schwannomas.

Cyst fluid (CF) of Taenia solium metacestode (TsM) is an important source of serodiagnostic antigens. We have investigated the molecular characteristics of the 120 kDa protein complex in TsM CF purified by fast performance liquid chromatography. The structure of the purified protein was characterized by a variety of proteomic analyses. The protein was found to consist of 2 major components of 42-46 and 22-28 kDa, and shared 3 subunits of 14, 16 and 18 kDa. The 42-46 kDa component was determined to contain 3 additional subunits of 22, 28 and 38 kDa. These 6 subunits were shown to originate from either the 14 or 18 kDa precursor. We assessed the antibody reactivity of the native protein, its individual subunits and the recombinant 14 and 18 kDa proteins, and found that the 120 kDa protein, particularly 14 and 18 kDa subunits revealed high reliability for differentiation of active and mixed stage NC from chronic NC. The subunits of the 120 kDa protein complex identified herein represent some of the low-molecular weight glycoproteins which have been described in several previous studies. Recognizing and understanding the structural and immunological relationship of these proteins will facilitate the development of new serodiagnostic assays.

From 1984 to 1988, 11 of 120 patients (9%) with motor neuron disease (MND) had paraproteins detected by serum immunofixation electrophoresis (IFE), compared with 4 (3%) by cellulose acetate gels: 1 patient had progressive spinal muscular atrophy, 5 patients had amyotrophic lateral sclerosis (ALS), and 5 patients had ALS with probable upper motor neuron signs. Four of 5 patients (80%) with cerebrospinal fluid (CSF) protein content above 75 mg/dl had paraproteins, as did 6 of 30 with values above 50 mg/dl. Four of 14 patients with cerebrospinal oligoclonal bands (OCB) also had paraproteins. Two patients with ALS, CSF protein content above 75 mg/dl, and paraproteinemia had lymphoma. We conclude the following about patients with MND: high CSF protein content (especially above 75 mg/dl) or CSF OCB makes paraproteinemia more likely; some of these patients may have lymphoma; there is an inordinately high occurrence of paraproteinemia in MND; and IFE on agarose is more sensitive than electrophoresis on cellulose acetate in detecting paraproteins. Syndromes of paraproteinemia and high CSF protein are not restricted to the lower motor neuron but qualify as “ALS” with coexisting upper motor neuron signs.

A selective subtotal cerebellar neuronal degeneration was found in a patient who died 4 1/2 months after suffering neuroleptic malignant syndrome (NMS), a rare, potentially fatal disorder associated with neuroleptic medications. It is suggested that the cerebellar neuronal degeneration in this case was due to hyperpyrexia, a cardinal clinical feature of NMS. Similar pathologic findings appear not to have been previously reported in NMS but have been described in heat-induced central nervous system (CNS) injury. The findings imply that a cerebellar syndrome might be encountered in patients who survive NMS complicated by a particularly high febrile course.

Six adults with inferior vena caval obstruction are presented. Three were the results of surgical intervention, two were secondary to large thrombi, and one was due to pressure from a large renal-cell carcinoma and adjacent nodes. All underwent a modified approach of radionuclide venography, using a moderately large volume of sodium pertechnetate. Features characteristic of inferior vena caval obstruction were demonstrated in five of the six patients, and these various features are described and discussed.