Progression of subcortical atrophy in mild Parkinson's disease and its impact on cognition.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is associated with pronounced grey matter atrophy in various brain regions. However, the association between atrophy patterns and progression from no cognitive impairment (NCI) to Parkinson's disease (PD)-MCI is not clearly known. We investigated the pattern and progression of atrophy in subcortical structures and its impact on cognition in patients with mild PD. METHODS: Sixty-five patients with mild PD with baseline and longitudinal clinical and neuropsychological assessments, and structural magnetic resonance imaging scans were studied. Movement Disorder Society Task Force criteria were used to classify patients with PD into PD-NCI (n = 54) and PD-MCI (n = 11). Based on progression over time, those who remained without cognitive impairment were classified as PD-stable (n = 42) and those who converted to MCI over 18 months were classified as PD-converters (n = 12). FreeSurfer was used to measure cortical thickness and subcortical volumes at baseline and follow-up. RESULTS: Parkinson's disease-MCI showed baseline thalamus atrophy and progressive atrophy in the thalamus, caudate, presubiculum, cornu ammonis 1 and 2-3, and significant memory and executive dysfunction compared with PD-NCI. PD-converters had greater accumbens atrophy at baseline and progressive atrophy in the thalamus, caudate and accumbens with dysfunctions in memory and executive domains. CONCLUSIONS: Progression of cognitive impairment in non-demented PD is associated with a specific pattern of subcortical atrophy. Findings from this study will allow future studies to investigate in the role of subcortical structures as a biomarker for PD dementia.

Association between white matter hyperintensity and medial temporal atrophy at various stages of Alzheimer's disease.

BACKGROUND AND PURPOSE: Whilst there is evidence implicating small vessel cerebrovascular disease in the pathogenesis of Alzheimer's disease (AD), its specific contribution to the pathophysiology of AD remains unclear. The burden of small vessel cerebrovascular disease visualized as white matter hyperintensity (WMH) and its association with medial temporal atrophy (MTA) at different stages of AD was studied. METHODS: One hundred and sixty-five cognitively normal (CN) community controls, 103 mild cognitive impairment (MCI) patients, 141 mild AD patients and 68 moderate-severe AD patients were studied. Clinical, cognitive and risk factor data were collected, and WMH and MTA were quantified by trained raters. The Jonckheere-Terpstra test for ordered alternatives was used to study the association between WMH and MTA in different stages of AD. RESULTS: The burden of total WMH increased significantly with increasing severity of AD, even after correcting for confounders. The proportion of CN, MCI, mild AD and moderate-severe AD subjects with severe burden of WMH was 6.7%, 9.7%, 28.4%, and 39.7%, respectively. A strong positive association between WMH severity and MTA was evident amongst MCI (P = 0.011) and mild AD (P = 0.003) subjects, but not in CN (P = 0.953) and moderate-severe AD subjects (P = 0.301). CONCLUSIONS: The burden of WMH increased significantly from the stage of CN to MCI to AD. The association between WMH and MTA was greatest at the stage of MCI and mild AD. This has implications on the strategy to slow the progression of AD, where measures to reduce WMH, including control of vascular risk factors, need to be optimized at the stage of MCI and mild AD.

Systemic lupus erythematosus presenting as erythema annulare centrifugum.

A case of systemic lupus erythematosus presenting as erythema annulare centrifugum involving atypical sites (face, palm and sole) and raised serum angiotensin-converting enzyme levels has been illustrated.

An Incidental Finding of Low-Grade Appendiceal Mucinous Neoplasm in a Case of Borderline Brenner Tumor of the Ovary.

The concurrent presentation of a low-grade appendiceal mucinous neoplasm (LAMN) and a borderline Brenner tumor (BT) of the ovary are exceedingly rare. Brenner tumors stand out as a particularly uncommon form, making up only around 5% of all benign epithelial tumors of the ovary. Among the ovarian Brenner, the borderline subtype is even rarer. Appendiceal neoplasm (LAMN) and right ovarian BT cannot be distinguished due to their anatomical position. LAMN is often an incidental finding and at later stages when left undiagnosed may lead to pseudomyxoma peritonei (PMP). This case describes a postmenopausal woman in her 50s experiencing abdominal pain and bloating for a week. Elevated carcinoembryonic antigen (CEA) levels and imaging suggested a potential right ovarian tumor. Interestingly, it revealed a unique combination of borderline Brenner tumor of the right ovary and low-grade appendiceal mucinous neoplasm.

Exploring the Rare Case of a Sarcomatoid Variant of Urothelial Carcinoma.

A sarcomatoid variant of urothelial carcinoma (SVUC) is an extremely rare variant, which accounts for only 0.1-0.3% of all urothelial carcinomas of the bladder. SVUC is distinguished by the presence of biphasic components; there can be morphological and/or immunohistochemical substantiation of epithelial and mesenchymal differentiation. The patients with this variant have been associated with very poor disease-specific and overall survival rates in comparison with the high-grade pure urothelial carcinoma. Being a rare entity, it usually presents at a higher grade and is related to a dismal prognosis in comparison with conventional urothelial carcinoma. Careful examination, early diagnosis, and effective treatment are the most important steps for good survival. Here, we report a 58-year-old male who presented with complaints of hematuria for one and a half months with histopathology showing features of SVUC.

An Unusual Case of CD5-Positive Extranodal Marginal Zone Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) Involving the Appendix.

Non-Hodgkin lymphoma (NHL) includes a diverse group of hematological malignancies. The common site for extranodal involvement of NHL is the gastrointestinal tract (GIT), with the stomach being the most prevalent site. The appendix is a very unusual site of involvement in NHL. This case report describes an uncommon instance of an appendicular mass in an elderly female who complained of vomiting for two weeks, as well as abdominal pain, and was radiologically suspected to have appendicular malignancy. A right hemicolectomy was done, and she was diagnosed with extranodal mucosa-associated lymphoid tissue (MALT) lymphoma involving the appendix. Postoperatively, she also developed thrombo-occlusive disease in her right lower limb, with right foot dry gangrene, for which thromboembolectomy was done. Later, a below-knee amputation was carried out. Lymphoma associated with thrombophilia is a rare presentation and not many cases have been reported in the literature. We present this case here on account of the rarity of lymphoma involving the appendix with associated thrombophilia.

Prevalence of Angiogenesis, Proliferation, and Apoptosis Markers of Cervical Cancer and Their Correlation with Clinicopathological Parameters.

The aim of the study is to investigate the expression of angiogenesis (VEGF and PDGF), angiogenesis inhibitor markers (angiostatin and endostatin), proliferation (Ki67), and apoptosis markers (p53 and p16) of cervical cancer in Indian population and to correlate them with the clinicopathological profile. It is a descriptive study of consecutive cases of cervical cancer from Saveetha Medical College and Hospital between January 2017 and December 2018. The expression of angiogenesis, angiogenesis inhibitor markers, Ki67, p53, and p16 in 60 cases of cervical sections were detected by the immunohistochemical method and analyzed with clinicopathological data. VEGF expression was positive in 16 cases (26.67%) and negative in 20 cases (33.33%). As of PDGF, 3 cases (3.33%) have shown positivity to PDGF and 33 cases have shown negativity. Angiostatin and endostatin expression was reported to be positive in 10 (16.67%) and 21 (35%) cases, respectively. Most of the cases 57 (95%) have shown both p16 and Ki67 positivity. Although p53 expression was positive in 48 cases (80%), the remaining 12 cases (20%) were p53-negative. The PDGF expression was significantly correlated to the stage of tumors. No statistically significant association was observed between angiogenesis inhibitor markers and clinicopathological parameters. A significant positive correlation was noticed between the Ki67 expression and stage of tumors.

Multiple Pigmented Seborrheic Keratosis with Sebaceous Differentiation - A Case Report.

Seborrheic keratosis is a benign lesion that is common in the trunk and head and neck regions. It shows a considerable variety of histological appearances leading to different variants. The presence of sebaceous differentiation in seborrheic keratosis is very rare and can histologically mimic benign and malignant tumors with sebaceous differentiation. We present a case of a 65-year-old male presenting with multiple nodules over the right and left sides of neck and the right preauricular region, histopathological examination of which revealed multiple pigmented seborrheic keratoses with sebaceous differentiation. This case is reported for its rare sebaceous differentiation and multiplicity along with the importance of differentiating it from a variety of benign to malignant neoplasms showing sebaceous differentiation.

A new in-vitro agglutination technique for potency estimation of antisnake venom serum (ASVS).

Traditionally the potency of ASVS is assayed quantitatively by in-vivo neutralization test for lethality in mice. A sensitive and simple in-vitro agglutination assay for the quantitative determination of Antisnake Venom Serum (ASVS) potency is reported. The method is rapid, cheap, simple, economical and above all does not require the use of experimental animals for potency assay of in process, unpurified and purified sera batches. Among in-vitro procedures, agglutination assay was favored in comparison to flocculation as the later was found to give variable results and also time consuming (high Kf value). Before application, the method was standardized and validated for choice and concentration of particulate material (latex vs. bentonite), temperature and optimum antiserum concentration. It is well known fact that venoms lose toxicity on dilution however this study demonstrated that the bentonite adsorbed venoms of the entire four snake species viz., Cobra, Krait, Russell's viper and Echis are stable even up to 30 days of storage. Among five lots each of unpurified serum, unprocessed plasma and purified sera tested, the results were found comparable with universally accepted in-vivo biological assay. The coefficient of correlation was found to be near 1.0 within 95% fiducial limits of acceptance and also significantly less variation was observed in the mean potency values and standard deviations. For all results p value was observed to be <0.01. Results indicate that in-vitro agglutination assay is suitable and can be used for potency estimation of in process as well as unpurified and purified ASVS batches.

Induction of resistance to ascites tumor in mice with MFS-180 cells treated with glutaraldehyde, lipopolysaccharide, and concanavalin A.

Immunization with MFS-180 vaccine prepared in the presence of glutaraldehyde (0.05%), lipopolysaccharide (LPS) (100 micrograms/ml), and concanavalin A (Con A) (200 micrograms/ml) could protect Swiss mice against a subsequent challenge by 1 X 10(6) MFS-180 cells. The sequence of attachment of LPS and Con A to glutaraldehyde-treated cells as found to determine the efficacy of the vaccine. LPS coupled with glutaraldehyde-treated cells before Con A could effect 100% survival, while LPS attached after Con A treatment to glutaraldehyde-treated cells showed only 60% survival. The protection was specific for syngeneic cells.

Regulation of c-jun mRNA expression by hydroxyurea in human K562 cells during erythroid differentiation.

Hydroxyurea (HU) is an antitumor agent which also induces hemoglobinization during erythroid differentiation. In addition, HU stimulates the synthesis of fetal hemoglobin in sickle cell anemia patients. To further understand its mechanism of action, we investigated the effects of HU on regulation of c-jun expression prior to the onset of erythroid differentiation of K562 cells. HU induced a dose-dependent stimulation of c-jun synthesis. The levels of c-jun mRNA was elevated 4 to 7.5-fold by HU within 2 h. This was followed by a gradual decline to the basal level by 24 h. Both nuclear run-on and actinomycin D pulse experiments strongly indicate that HU regulates c-jun mRNA expression by increasing the rate of synthesis as well as stabilizing the c-jun mRNA. In addition, the level of jun protein was elevated by 2 to 5-fold within 4 h in HU treated cells. Furthermore, concentrations of HU below 250 microM slightly increased the 5X AP-1/CAT activity. These results strongly suggest that HU induces both transcriptional and post-transcription regulation of c-jun during erythroid differentiation.

High density lipoprotein is a scavenger of superoxide anions.

Present work describes a new property of HDL to act as a scavenger of O2- free radicals in vitro. This lipoprotein prevents both enzymic and non-enzymic generation of O2- anions as evidenced by inhibition of xanthine oxidase, peroxidase, peroxidation of pyrogallol and phenazine methosulphate-NADH reaction. Ascorbate stimulated MDA formation in microsomes has been shown to be suppressed by HDL and these effects are comparable with that of BHA.

Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of superoxide anions.

Picroliv, the active principle of Picrorhiza kurrooa, and its main components which are a mixture of the iridoid glycosides, picroside-I and kutkoside, were studied in vitro as potential scavengers of oxygen free radicals. The superoxide (O2-) anions generated in a xanthine-xanthine oxidase system, as measured in terms of uric acid formed and the reduction of nitroblue tetrazolium were shown to be suppressed by picroliv, picroside-I and kutkoside. Picroliv as well as both glycosides inhibited the non-enzymic generation of O2- anions in a phenazine methosulphate NADH system. Malonaldehyde (MDA) generation in rat liver microsomes as stimulated by both the ascorbate-Fe2+ and NADPH-ADP-Fe2+ systems was shown to be inhibited by the Picroliv glycosides. Known antioxidants tocopherol (vitamin E) and butylated hydroxyanisole (BHA) were also compared with regard to their antioxidant actions in the above system. It was found that BHA afforded protection against ascorbate-Fe(2+)-induced MDA formation in microsomes but did not interfere with enzymic or non-enzymic O2- anion generation; and tocopherol inhibited lipid peroxidation in microsomes by both prooxidant systems and the generation of O2- anions in the non-enzymic system but did not interfere with xanthine oxidase activity. The present study shows that picroliv, picroside-I and kutkoside possess the properties of antioxidants which appear to be mediated through activity like that of superoxide dismutase, metal ion chelators and xanthine oxidase inhibitors.

Molecular basis of hyperlipidemia in golden hamsters during experimental infection with Ancylostoma ceylanicum (Nematoda:Strongylidae).

An infection of golden hamsters with Ancylostoma ceylanicum, a hookworm parasite, induced profound hyperlipidemia, particularly hypertriglyceridemia, and the effect was directly related to the degree of infection. A significant increase was also noticed in serum cholesterol and phospholipid levels. The appearance of lipoprotein-X, an abnormal low density lipoprotein, was detected in the serum of hookworm-infected animals. The hyperlipidemia was further characterized by an increase in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) with a concomitant decline in high density lipoproteins (HDL). Decreased lipolytic activities, especially triglyceride lipase, in hepatic tissue and induction of lipolytic activities in intestine and adipose tissues indicated mobilization of fats from adipose and jejunum with a defective removal of triglyceride-rich lipoproteins in hepatic tissues. Accumulation of lipids in liver and depletion in adipose tissue supported these results. The derangement may have a significant effect on host parasite interaction and is an important pathophysiological feature occurring during experimental ancylostomiasis.

Evaluating the use of angiotensin-converting enzyme inhibitors for older nursing home residents with chronic heart failure.

BACKGROUND: Despite their well noted therapeutic benefits for heart failure (HF), angiotensin-converting enzyme (ACE) inhibitors may be underprescribed and underdosed among older nursing home patients. OBJECTIVES: To assess the use of ACE inhibitor therapy in older (> or =70 years) nursing home residents with systolic heart failure (HF). DESIGN: A cross-sectional, retrospective analysis. SETTING: Five long-term care facilities in Providence, Rhode Island. SUBJECTS: Adults aged 70 years or older with left ventricular (LV) ejection fractions < or =40%. MEASUREMENTS: New York Heart Association (NYHA) class, comorbid diseases, and cardiac medications with logistic regression analysis to clarify their bearing on the prescription of ACE inhibitors. RESULTS: Of the 819 nursing home residents who were evaluated, 119 (24 men, 95 women) fulfilled exacting entry criteria, i.e., heart failure signs/symptoms and documented LV systolic dysfunction. Forty-one of these 119 (35%) older persons were receiving ACE inhibitor therapy, predominantly in doses (< or =50 mg captopril/day or < or =5 mg enalapril/ day) less than those of proven therapeutic efficacy. Compared with older residents not receiving ACE inhibitors, those receiving ACE inhibitors included fewer with NYHA Class I HF (0 vs 21%, P = .017), more men (58 vs 28%, P< or =.01), and more people with hypertension (61 vs 35%, P< or =.01). In contrast, diuretics were prescribed more frequently among those not receiving ACE inhibitors (83 vs 56%, P< or =.001). CONCLUSIONS: ACE inhibitors are underprescribed and underdosed among elderly nursing home patients carefully screened to include systolic HF and no contraindications to the medication. ACE inhibitors are particularly underused in those elderly with NYHA Class I HF and in those receiving diuretics.

Artificial viral envelopes containing recombinant human immunodeficiency virus (HIV) gp160.

An artificial viral envelope was constructed, resembling the human immunodeficiency virus (HIV) envelope with respect to ultrastructure, size, phospholipid profile and lipid:cholesterol ratio. Recombinant HIV surface protein gp160 was anchored in the outer surface of the envelope membrane using a double detergent dialysis. The envelopes remained physically stable for several months. Immunolabeling with anti-gp160/41 monoclonal antibody revealed surface insertion and availability of gp160 for binding. Cell fusion and cytosolic transfer of the encapsulated fluorescent marker FITC-dextran was demonstrated. Flow cytometry indicated more efficient transfer of the fluorescent marker to cells which were approximately 60% CD4+ (REX-1B), relative to cells which were only approximately 18% CD4+ (KG-1). However, plain lipid envelopes without gp160 fused very efficiently with both cell types, indicating their potential usefulness as "fusogenic liposomes". Complete artificial viral envelopes may serve as subunit vaccines, and receptor-targeted delivery systems for drugs, toxins and genetic constructs.