DNA Damage Repair in Huntington's Disease and Other Neurodegenerative Diseases.

Recent genome-wide association studies of Huntington's disease (HD) primarily highlighted genes involved in DNA damage repair mechanisms as modifiers of age at onset and disease severity, consistent with evidence that more DNA repair genes are being implicated in late age-onset neurodegenerative diseases. This provides an exciting opportunity to advance therapeutic development in HD, as these pathways have already been under intense investigation in cancer research. Also emerging are the roles of other polyglutamine disease proteins in DNA damage repair mechanisms. A potential universal trigger of oxidative DNA damage shared in these late age-onset diseases is the increase of reactive oxygen species (ROS) in human aging, defining an age-related mechanism that has defied other hypotheses of neurodegeneration. We discuss the potential commonality of DNA damage repair pathways in HD and other neurodegenerative diseases. Potential targets for therapy that may prove beneficial across many of these diseases are also identified, defining nodes in the ataxia telangiectasia-mutated (ATM) complex, mismatch repair, and poly ADP-ribose polymerases (PARPs).

An abbreviated Faecal Incontinence Quality of Life Scale for Chinese-speaking population with colorectal cancer after surgery: cultural adaptation and item reduction.

No instrument is available to assess the impact of faecal incontinence (FI) of quality of life for Chinese-speaking population. The purpose of the study was to adapt the Faecal Incontinence Quality of Life Scale (FIQL) for patients with colorectal cancer, assess the factor structure and reduce the items for brevity. A sample of 120 participants were enrolled. Internal consistency, test-retest reliability, and convergent and contrasted-groups validity were assessed. Construct validity was analysed using an exploratory and confirmatory factor analyses (CFA). The internal consistency (Cronbach's α of the total scale and four subscales = 0.98 and 0.97, 0.96, 0.92, 0.82 respectively), test-retest reliability (intraclass correlation coefficients ≥.98 for all scales with p < .001) and significant correlations of all scales with selected subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey and the Wexner scale suggested satisfactory reliability and validity. The severe FI group (with a Wexner score ≥9) scored significantly lower on the scale than the less severe FI group (with a Wexner score <9) did (p < .001). The CFA supported a two-factor structure and demonstrated an excellent model fit of the 15-item abbreviated version of the FIQL-Chinese. The FIQL-Chinese has satisfactory validity and reliability and the abbreviated version may be more practical and applicable.

Quantum spin dynamics with pairwise-tunable, long-range interactions.

We present a platform for the simulation of quantum magnetism with full control of interactions between pairs of spins at arbitrary distances in 1D and 2D lattices. In our scheme, two internal atomic states represent a pseudospin for atoms trapped within a photonic crystal waveguide (PCW). With the atomic transition frequency aligned inside a band gap of the PCW, virtual photons mediate coherent spin-spin interactions between lattice sites. To obtain full control of interaction coefficients at arbitrary atom-atom separations, ground-state energy shifts are introduced as a function of distance across the PCW. In conjunction with auxiliary pump fields, spin-exchange versus atom-atom separation can be engineered with arbitrary magnitude and phase, and arranged to introduce nontrivial Berry phases in the spin lattice, thus opening new avenues for realizing topological spin models. We illustrate the broad applicability of our scheme by explicit construction for several well-known spin models.

Superradiance for Atoms Trapped along a Photonic Crystal Waveguide.

We report observations of superradiance for atoms trapped in the near field of a photonic crystal waveguide (PCW). By fabricating the PCW with a band edge near the D(1) transition of atomic cesium, strong interaction is achieved between trapped atoms and guided-mode photons. Following short-pulse excitation, we record the decay of guided-mode emission and find a superradiant emission rate scaling as Γ̅(SR)∝N̅Γ(1D) for average atom number 0.19≲N̅≲2.6 atoms, where Γ(1D)/Γ'=1.0±0.1 is the peak single-atom radiative decay rate into the PCW guided mode, and Γ' is the radiative decay rate into all the other channels. These advances provide new tools for investigations of photon-mediated atom-atom interactions in the many-body regime.

Atom-light interactions in photonic crystals.

The integration of nanophotonics and atomic physics has been a long-sought goal that would open new frontiers for optical physics, including novel quantum transport and many-body phenomena with photon-mediated atomic interactions. Reaching this goal requires surmounting diverse challenges in nanofabrication and atomic manipulation. Here we report the development of a novel integrated optical circuit with a photonic crystal capable of both localizing and interfacing atoms with guided photons. Optical bands of a photonic crystal waveguide are aligned with selected atomic transitions. From reflection spectra measured with average atom number N=1.1+/-0.4, we infer that atoms are localized within the waveguide by optical dipole forces. The fraction of single-atom radiative decay into the waveguide is Γ1D/Γ'≃(0.32±0.08), where Γ1D is the rate of emission into the guided mode and Γ' is the decay rate into all other channels. Γ1D/Γ' is unprecedented in all current atom-photon interfaces.

Development of the hybrid Sleeping Beauty: baculovirus vector for sustained gene expression and cancer therapy.

Antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. Baculovirus is an emerging gene delivery vector but only mediates transient expression (<7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. We first constructed plasmids featuring adeno-associated virus inverted terminal repeats (AAV ITRs), oriP/Epstein-Barr virus-expressed nuclear antigen 1 (EBNA1) or Sleeping Beauty (SB) transposon and compared their efficacies in terms of persistent expression. In human embryonic kidney (HEK293) cells, AAV ITR failed to prolong the expression while oriP/EBNA1 moderately extended the expression to 35 days. In contrast, the SB system led to stable expression beyond 77 days even without antibiotic selection. Given this finding, we constructed a hybrid SB baculovirus expressing the SB transposase and harboring the transgene cassette flanked by inverted repeat/direct-repeat (IR/DR) elements recognizable by SB. The hybrid SB baculovirus efficiently transduced mammalian cells and mediated an expression duration longer than that by conventional baculoviruses, thanks to the transgene persistence and integration. The SB baculovirus (Bac-SB-T2hEA/w) expressing the antiangiogenic fusion protein comprising endostatin and angiostatin (hEA) also enabled prolonged hEA expression. With sustained hEA expression, Bac-SB-T2hEA/w repressed the angiogenesis in vivo, hindered the growth of two different tumors (prostate tumor allografts and human ovarian tumor xenografts) in mice and extended the life span of animals. These data altogether implicated the potential of the hybrid SB-baculovirus vector for prolonged hEA expression and for the treatment of multiple types of angiogenesis-dependent tumors.

Expression of sex-determining genes in human sebaceous glands and their possible role in the pathogenesis of acne.

BACKGROUND: The human skin, especially the sebaceous gland, is a steroidogenic organ similar to the gonads and adrenal cortex, possessing all the enzymes required for steroid sex-hormone synthesis and metabolism. Factors regulating cutaneous steroidogenesis associated with disease status remain largely unknown. OBJECTIVE: We hypothesized that transcription factors involved in sex formation and regulation of steroidogenesis in the classical steroidogenic organs are also expressed in the sebaceous glands. Their possible role in the pathogenesis of acne were investigated. METHODS: We used reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and Western blotting to analyse the expression of SF-1, WT-1, SRY, SOX-9 and DAX-1 mRNAs and their proteins in cultured human sebocytes and the facial skin of acne patients. RESULTS: The in situ hybridization study showed SOX-9 mRNA mainly localized in basal keratinocytes, the basal layer of the sebaceous glands and eccrine glands. Immortalized human sebaceous gland cells (SZ95) expressed mRNA for SOX-9, WT-1 and DAX-1 but not for SF-1 or SRY. The expression of DAX-1 protein was slightly inhibited by 10(-6) m oestradiol (E2) at 6 h but enhanced by 10(-6) m dihydrotestosterone (DHT) at 48 h. The facial expression of SOX-9 seemed to be higher in the acne-prone male patients, while DAX-1 was stronger in subjects without acne, although both were statistically insignificant. CONCLUSION: Our findings confirm the expression of some sex-determining genes in human sebaceous glands. Further studies on a larger patient population including the normal controls are needed to elucidate the functional significance of these transcription factors in the pathogenesis of acne.

A preliminary risk assessment of organochlorines accumulated in fish to the Indo-Pacific humpback dolphin (Sousa chinensis) in the Northwestern waters of Hong Kong.

The Indo-Pacific humpback dolphin is considered threatened due to several factors including pollution in Hong Kong and the risks due to consumption of fish tainted with polychlorinated biphenyls (PCBs) and organochlorine pesticides were assessed. Six species of fish Collichthys lucida, Pseudosciaena crocea, Johnius sp., Thryssa sp., Mugil sp. and Trichiurus sp., which comprise the main prey species of humpback dolphins were collected for analyses. Risks due to total PCBs, total TEQs, PCB 118 and the pesticides were assessed with the use of toxicity reference values as the threshold reference benchmarks. The calculated risk quotients (RQs) showed that the risks associated with organochlorines were generally low. The highest RQ was associated with total TEQs suggesting that dioxin-like PCBs may pose the highest risk to the dolphins. The HCHs, total PCBs and heptachlor had comparatively high RQs and thus they should also be the priority organochlorines that would require further investigation.

A preliminary risk assessment of trace elements accumulated in fish to the Indo-Pacific Humpback dolphin (Sousa chinensis) in the northwestern waters of Hong Kong.

In order to assess the potential risks associated with consumption of contaminated prey items to the Indo-Pacific Humpback dolphin (Sousa chinensis), fish species (Collichthys lucida, Pseudosciaena crocea, Johnius sp., Thryssa sp., Mugil sp. and Trichiurus sp.) representing the main food items of the dolphin were collected from the northwestern waters of Hong Kong, including the Sha Chau and Lung Kwu Chau Marine Park, which form the main habitat of the dolphin in Hong Kong. Within these waters, there are several potential sources of pollution including significant inputs from the Pearl River catchment, several major sewage outfalls and a series of mud pits that receive contaminated dredged sediments. Concentrations of thirteen trace elements (Ag, As, Cd, Co, Cr, Cs, Cu, Hg, Mn, Ni, Se, V, and Zn) in the fish tissue were analyzed by inductively coupled plasma mass spectrometer (ICP-MS). An assessment of the risks of adverse effects on the dolphin due to consumption of tainted fish was undertaken using two toxic reference benchmarks, namely the reference dose (RfD) and toxicity reference value (TRV). The risk quotient (RQ) calculated for each element showed that the risks from consumption of fish were generally low and within safe limits. The risks associated with arsenic, cadmium and mercury were, however, elevated. The highest calculated RQ was associated with total arsenic; however, the majority of arsenic in marine organisms tends to be in the non-toxic organic form, and the actual risk to the dolphin due to this metalloid is likely to be lower.

Exposure and time dependent DNA strand breakage in hepatopancreas of green-lipped mussels (Perna viridis) exposed to Aroclor 1254, and mixtures of B[a]P and Aroclor 1254.

Green-lipped mussels (Perna viridis) were exposed to Aroclor 1254 (0.5, 5 and 50 microgl(-1)) and a mixture of benzo[a]pyrene (B[a]P) and Aroclor 1254 (0.3+0.5 and 3+5 microgl(-1)) for 12 days. On day 0, 1, 3, 6 and 12, the levels of DNA strand breaks in the mussel hepatopancreas were monitored using an alkaline unwinding assay. The results were compared to the findings of a previous study in which the levels of DNA strand breakage in the same species were measured following exposure to various concentrations of B[a]P (0.3, 3 and 30 microgl(-1)). The results indicated that Aroclor 1254 at a concentration

Reconstruction of acquired nasolacrimal duct obstruction.

BACKGROUND: Acquired nasolacrimal duct obstruction is a common condition in patients who visit otolaryngologists and ophthalmologists. These patients often complain of epiphora and blurred vision, and sometimes they suffer from acute or chronic dacryocystitis. Other causes of acquired nasolacrimal duct obstruction include trauma, chronic inflammation, post-operative iatrogenic procedures, and tumors. Reconstruction of an acquired nasolacrimal duct obstruction provides great improvement in a patient's quality of life and satisfaction both functionally and cosmetically. In this paper, we report on surgical techniques of endonasal endoscopic dacryocystorhinostomy and traditional external dacryocystorhinostomy. A rare case of mechanical compression of the lacrimal sac by a frontal mucocele is also presented. METHODS: From 1989 through 1999, we treated 26 patients, 10 men and 16 women, with 28 cases of acquired nasolacrimal duct obstruction. Two patients had bilateral involvement. Five cases were complications of sinus surgery. Ten cases were acute dacryocystitis due to chronic nasolacrimal duct obstruction. One case of nasolacrimal duct obstruction was caused by a frontal mucocele. The remaining cases were non-specific nasolacrimal duct obstruction. Of all patients, 26 cases underwent external dacryocystorhinostomy, 1 underwent endonasal endoscopic dacryocystorhinostomy, and 1 case underwent frontal sinus dacryocystorhinostomy. RESULTS: Only 1 patient out of 28 cases that underwent surgery suffered from obstruction after external dacryocystorhinostomy for 3 months; 25 patients attained both anatomical success and clinical improvement. CONCLUSION: The success rates were high for patients undergoing either traditional external dacryocystorhinostomy or endonasal endoscopic dacryocystorhinostomy.

9-Nitrocamptothecin inhibits HIV-1 replication in human peripheral blood lymphocytes: a potential alternative for HIV-infection/AIDS therapy.

The ability of the anti-cancer drug, 9-Nitrocamptothecin (9NC), to inhibit replication of HIV-1 in clinically relevant primary lymphocytic cells was studied. Primary peripheral blood lymphocytes (PBLs) from a non-infected donor were freshly infected with HIV-1 and treated with 9NC by using three different treatment schedules. Cells were monitored for cytotoxicity by the XTT metabolic cell proliferation assay and a sensitive flow cytometric assay that was capable of measuring cell cycle changes and apoptosis. 9NC inhibited replication of HIV-1 in PBLs by greater than 95% in a dose-dependent manner as measured by the level of extracellular HIV-1 p24 release. Similar results were observed, whether 9NC was applied in a single, double, or triple dose regimen. Minimal cytotoxicity was observed for both non-infected and infected PBLs, as determined by the XTT assay. Moreover, 9NC induced apoptosis within 24 hours of drug treatment in freshly infected, but not non-infected, PBLs. The data showed that 9NC reduced replication of HIV-1 in primary human lymphocytes; thus, it indicates the potential clinical utility of this drug as an alternative or adjunct therapy for HIV-infection/AIDS.

First Report of Cactus virus X on Hylocereus undatus (Cactaceae) in Taiwan.

Hylocereus undatus Britt. & Rose (Cactaceae), commonly known as pitaya, produces edible fruits with red thorny peel and sweet white pulp containing numerous small soft seeds. In recent years, this fruit crop has become increasingly important in Taiwan. During a survey of diseases of pitaya, some plants were found with systemic mild mottling on the stems. A virus was mechanically transmitted that caused necrotic local lesions on Chenopodium amaranticolor and chlorotic lesions on C. quinoa. This virus also caused necrotic lesions with chlorotic halos on Gomphrena globosa and small chlorotic spots followed by systemic infection in Celosia argentea. Back inoculation from C. quinoa by sap transmission caused mild mottling on pitaya similar to that observed on the naturally infected plants and thus confirmed that the agent was the cause of the mottle symptom. Electron microscopic examination of negatively stained extracts from diseased plants revealed a flexuous rod-shaped virus with a length of 480 to 520 nm. Purified viral particles contained a single major protein of approximately 26 KDa as estimated by SDS polyacrylamide gel electrophoresis. In immunodiffusion tests, this virus reacted with antiserum to Cactus X virus (CVX) (ATCC #PVAS245), but did not react with antisera to Bamboo mosaic or Papaya mosaic viruses. These results establish the identity of the virus causing mottle disease on H. undatus as a strain of CVX.

9-nitrocamptothecin selectively inhibits human immunodeficiency virus type 1 replication in freshly infected parental but not 9-nitrocamptothecin-resistant U937 monocytoid cells.

We have previously reported that 9-nitrocamptothecin (9NC) inhibited human immunodeficiency type 1 (HIV-1) replication in latently HIV-1-infected T lymphocytic ACH-2 cells stimulated with the cytokine tumor necrosis factor alpha (TNF-alpha) (Moulton et al., AIDS Res Hum Retroviruses 1998;14:39). 9NC induced an accelerated apoptosis in HIV-1-infected, but not uninfected, lymphocytic cells. The present study demonstrates that 9NC selectively inhibits release of HIV-1 from freshly infected monocytoid U937 cells in a dose-response manner. Significant inhibition was achieved with concentrations of 9NC that were not toxic. In contrast, HIV-1 replication in 9NC-resistant monocytoid cells, derived from U937, was not inhibited by similar doses of 9NC. Importantly, sensitivity of HIV-1 replication to 9NC correlated with the effect of 9NC on topoisomerase I (topo I) activity. In a 9NC-sensitive subline, 9NC induced posttranslational activation of the nuclear transcription factor kappaB (NF-kappaB) after the drug treatment. This activation was neither related to selective 9NC suppression of HIV-1 replication, nor was it sufficient for the 9NC-induced toxicity in the drug-sensitive monocytoid cells. Taken together, the selective inhibition of HIV-1 replication in both lymphoid and monocytoid cells lends further credence to the potential development of 9NC as an alternative drug for treating HIV-1 infection.

Hydrops fetalis with complete heart block secondary to congenital lupus: report of one case.

Neonatal lupus erythematosus is an uncommon syndrome characterized by a congenital heart block and/or cutaneous lesion. We report a male newborn with neonatal lupus erythematosus presenting with complete heart block, cutaneous lesions, and hydrops. Transplacental passage of anti-SSA/Ro and anti-SSB/La antibodies were positive. Under the regimens of steroid for maternal systemic lupus erythematosus, perinatal anticongestive agents, and postnatal ventricular pacing with inotropic therapy, the infant died at the age of two days. The prognosis of hydrops fetalis secondary to neonatal lupus with complete heart block is usually fatal.

Effects of a urinary factor from women in early pregnancy on HIV-1, SIV and associated disease.

The effects of clinical grade crude preparations of human chorionic gonadotropin (hCG) on Kaposi's sarcoma, HIV, SIV and hematopoiesis were examined in vitro and in vivo. In contrast to previous studies, we report that the antiviral activity of hCG associated factors is not due to the native hCG heterodimer, including its purified subunits or its major degradation product, the beta-core. Using gel permeation chromatography of the clinical grade hCG and urine concentrates from pregnant women, we demonstrate that an as yet unidentified hCG associated factor (HAF) with anti-HIV, anti-SIV, anti-KS and pro-hematopoietic activities elutes as two peaks corresponding to 15-30 kDa and 2-4 kDa.

A nationwide epidemiological study of spinal cord injury in geriatric patients in Taiwan.

This prospective epidemiological survey of spinal cord injury (SCI) in Taiwan was carried out among patients attended by physicians from various medical centers and general hospitals all over Taiwan from July 1992 to June 1996. In all, 1,586 new cases of SCI were registered, representing about 70% of all possible SCI cases in Taiwan. The observed average annual incidence of SCI in Taiwan was 18.8 per million people, whereas it was 47.5 for the geriatric section. The mean age was 46.1 years with a plateau distribution after 20 years and older. Geriatric victims (297 cases, 18.7%, group II) formed a major section of SCI cases in Taiwan. Another group of younger SCI patients (15-64 years old, 1,232 cases, group I) was selected for comparison. The results showed that the male-to-female ratio, pattern of neurological deficits, and causes of injury and death of geriatric SCI patients differed significantly from those of the younger SCI group. Elderly women were exposed to a higher risk of SCI than younger women (M/F ratio 1.7:1). Falls were the leading cause of geriatric SCI, and two thirds of them occurred on level ground. Traffic accidents accounted for a third of SCI cases, half of which involved motorcycle accidents, a fifth of them pedestrians. Quadriplegia and quadriparesis occurred more frequently among elderly cases of SCI than in the younger group and a higher proportion of them died of SCI complications. Two thirds of elderly SCI patients recovered well enough after comprehensive treatment to be able to take care of themselves at home. The government should initiate programs of prevention to reduce the prevalence of geriatric SCI in Taiwan.

A nationwide epidemiological study of spinal cord injuries in Taiwan from July 1992 to June 1996.

This prospective epidemiological survey of spinal cord injury (SCI) in Taiwan was carried out by recruiting patients attended by physicians from various medical centers and general hospitals all over Taiwan from July 1992 to June 1996. A total of 6,410 cases of traumatic spinal fracture were registered among which were 1,586 new cases of SCI. The results represented 70% of the scope of SCI in Taiwan. The observed average annual incidence of SCI in Taiwan was 18.8 per million population. The mean age was 46.1 years-old with a plateau distribution for over 20 years and older. Geriatric victims are a major group of SCI in Taiwan. The male to female ratio was 3 to 1. The leading causes of SCI were traffic accidents and accidental falls. Motorcycle collisions accounted for 62% of the traffic accidents, and as most of the motorcycle riders were not helmet users, head injury became the major associated injury of SCI in Taiwan. The effectiveness of the comprehensive care system for SCI patients in Taiwan is relatively good, as reflected by the low rates of complications of SCI, the low mortality rate (6.6%) and the high percentage (67.4%) of SCI patients achieving self-care ultimately at home after rehabilitation. The analysis of person days healthy life loss and quality adjusted survival time revealed that SCI patients in Taiwan required 4 years to cope with the morbidity, and on average, could return to the main stream of life for another 30 years.

Ectopic ACTH syndrome with nocardiosis--a case report.

A 25-year-old man was admitted with chief complaints of multiple ecchymoses over face and both arms after a trivial trauma since one month before entry. Physically, he was thin without moon face, buffalo hump, or purple striae, while extensive fungus infection was present. Mild hyperglycemia, hypokalemic alkalosis were also found. Chest x-ray revealed multiple cavitary nodular lesions over bilateral lung fields. Needle biopsy from a rib lesion showed small cell carcinoma with strongly positive ACTH stain. The patient's basal cortisol level was greater than 62 micrograms/dl and failed to be suppressed by both low and high dose dexamethasone. The 24 hours urine free cortisol, 17 KS, and 17 OHCS were 8454 micrograms/24h, 49.8 mg/24h, and 50.8 mg/24h respectively. His plasma ACTH level was 725 pg/ml and remained high (1210 pg/ml) after high dose dexamethasone suppression. On the 10th day after admission, the patient's general condition got worse rapidly. Fever, dyspnea developed with progression of the lung lesions. Nocardia infection was proved. He expired three days later in spite of antibiotics and ketoconazole treatment.

Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus.

An independent strain (JI) of human herpesvirus 7 (HHV-7) was isolated from a patient with chronic fatigue syndrome (CFS). No significant association could be established by seroepidemiology between HHV-7 and CFS. HHV-7 is a T-lymphotropic virus, infecting CD4+ and CD8+ primary lymphocytes. HHV-7 can also infect SUP-T1, an immature T-cell line, with variable success. Southern blot analysis with DNA probes scanning 58.8% of the human herpesvirus 6 (HHV-6) genome and hybridizing to all HHV-6 strains tested so far revealed homology to HHV-7 with only 37.4% of the total probe length. HHV-7 contains the GGGTTA repetitive sequence, as do HHV-6 and Marek's disease chicken herpesvirus. DNA sequencing of a 186-base-pair fragment of HHV-7(JI) revealed an identity with HHV-6 and human cytomegalovirus of 57.5% and 36%, respectively. Oligonucleotide primers derived from this sequence (HV7/HV8, HV10/HV11) amplified HHV-7 DNA only and did not amplify DNA from other human herpesviruses, including 12 different HHV-6 strains. Southern blot analysis with the p43L3 probe containing the 186-base-pair HHV-7 DNA fragment hybridized to HHV-7 DNA only. The molecular divergence between human cytomegalovirus, on the one hand, and HHV-6 and HHV-7, on the other, is greater than between HHV-6 and HHV-7, which, in turn, is greater than the difference between HHV-6 strains. This study supports the classification of HHV-7 as an additional member of the human beta-herpesviruses.