Direct band-gap crossover in epitaxial monolayer boron nitride.

Hexagonal boron nitride is a large band-gap insulating material which complements the electronic and optical properties of graphene and the transition metal dichalcogenides. However, the intrinsic optical properties of monolayer boron nitride remain largely unexplored. In particular, the theoretically expected crossover to a direct-gap in the limit of the single monolayer is presently not confirmed experimentally. Here, in contrast to the technique of exfoliating few-layer 2D hexagonal boron nitride, we exploit the scalable approach of high-temperature molecular beam epitaxy to grow high-quality monolayer boron nitride on graphite substrates. We combine deep-ultraviolet photoluminescence and reflectance spectroscopy with atomic force microscopy to reveal the presence of a direct gap of energy 6.1 eV in the single atomic layers, thus confirming a crossover to direct gap in the monolayer limit.

An atomic carbon source for high temperature molecular beam epitaxy of graphene.

We report the use of a novel atomic carbon source for the molecular beam epitaxy (MBE) of graphene layers on hBN flakes and on sapphire wafers at substrate growth temperatures of ~1400 °C. The source produces a flux of predominantly atomic carbon, which diffuses through the walls of a Joule-heated tantalum tube filled with graphite powder. We demonstrate deposition of carbon on sapphire with carbon deposition rates up to 12 nm/h. Atomic force microscopy measurements reveal the formation of hexagonal moiré patterns when graphene monolayers are grown on hBN flakes. The Raman spectra of the graphene layers grown on hBN and sapphire with the sublimation carbon source and the atomic carbon source are similar, whilst the nature of the carbon aggregates is different - graphitic with the sublimation carbon source and amorphous with the atomic carbon source. At MBE growth temperatures we observe etching of the sapphire wafer surface by the flux from the atomic carbon source, which we have not observed in the MBE growth of graphene with the sublimation carbon source.

Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis.

Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1ß (IL-1ß) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E2 (PGE2) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.

Identical subchondral bone microarchitecture pattern with increased bone resorption in rheumatoid arthritis as compared to osteoarthritis.

OBJECTIVES: To analyze the differences in microarchitecture and bone remodeling of subchondral bone in femoral heads from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). DESIGNS: Peri-articular bone samples, including subchondral trabecular bone (STB) and deeper trabecular bone (DTB) were extracted from the load-bearing region of femoral heads from 20 patients with RA and 40 patients with OA during hip replacement surgery. Micro-CT, histomorphometry and backscatter scanning electron microscopy (BSEM) were performed to assess microarchitecture and bone histology parameters. RESULTS: In both RA and OA, STB showed more sclerotic microarchitecture and more active bone remodeling, compared to DTB. RA and OA showed similar microarchitecture characteristics in both STB and DTB, despite STB in RA exhibiting higher bone resorption. In addition, there was no difference in the frequency of bone cysts in STB between RA and OA. In STB, the trabecular bone surrounding subchondral bone cysts (Cys-Tb) was more sclerotic than the trabecular bone found distant to cysts (Peri-Tb), with a higher level of bone remodeling. Both Cys-Tb region and Peri-Tb region were detected to have similar microarchitectural and bone remodeling characteristics in RA and OA. CONCLUSIONS: Apart from higher bone resorption in the general subchondral bone of RA samples, the peri-articular bone exhibited similar microarchitectural and bone remodeling characteristics in RA and OA.

HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase.

Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E

Antibiotic-resistant Propionibacterium acnes among acne patients in a regional skin centre in Hong Kong.

BACKGROUND: There has been no study on antibiotic-resistant Propionibacterium acnes in Hong Kong. OBJECTIVE: We investigated the prevalence and pattern of antibiotic-resistant P. acnes and to identify any associated factors for harbouring the resistant strains. METHODS: Culture and sensitivity testing of P. acnes to commonly used antibiotics were performed. Resistance to tetracycline was defined at a minimal inhibitory concentration (MIC) of 2 µg/mL or more; erythromycin at an MIC of 0.5 µg/mL or more; clindamycin at an MIC of 0.25 µg/mL or more according to EUCAST. For breakpoints of doxycycline and minocycline, those with an MIC of 1 µg/mL or more were defined as resistant strains. RESULTS: Among the 111 specimens collected from 111 patients, 86 strains of P. acnes were recovered, one from each specimen. Twenty-five specimens had no growth. Forty-seven (54.8%) strains were found to be resistant to one or more antibiotics. Forty-six (53.5%), 18 (20.9%), 14 (16.3%), 14(16.3%) and 14 (16.3%) strains were resistant to clindamycin (CL), erythromycin (EM), tetracycline (TET), doxycycline (DOX) and minocycline (MR) respectively. Ten strains (11.6%) had cross resistance between the MLS antibiotics (erythromycin or clindamycin), one strain (1.2%) had cross resistance among the cyclines and 14 strains (16.4%) had cross resistance between the MLS and cycline antibiotics. Binary logistic regression showed an association between MLS antibiotic resistance with an increased age whereas cycline resistance was associated with the duration of treatment. CONCLUSION: Antibiotic-resistant P. acnes is prevalent in Hong Kong. Dermatologists should be more vigilant in prescribing antibiotics for acne patients.

V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption.

The vacuolar-type H(+)-ATPase (V-ATPase) proton pump is a macromolecular complex composed of at least 14 subunits organized into two functional domains, V(1) and V(0). The complex is located on the ruffled border plasma membrane of bone-resorbing osteoclasts, mediating extracellular acidification for bone demineralization during bone resorption. Genetic studies from mice to man implicate a critical role for V-ATPase subunits in osteoclast-related diseases including osteopetrosis and osteoporosis. Thus, the V-ATPase complex is a potential molecular target for the development of novel anti-resorptive agents useful for the treatment of osteolytic diseases. Here, we review the current structure and function of V-ATPase subunits, emphasizing their exquisite roles in osteoclastic function. In addition, we compare several distinct classes of V-ATPase inhibitors with specific inhibitory effects on osteoclasts. Understanding the structure-function relationship of the osteoclast V-ATPase may lead to the development of osteoclast-specific V-ATPase inhibitors that may serve as alternative therapies for the treatment of osteolytic diseases.

Evaluation of PCR for the diagnosis of dermatophytes in nail specimens from patients with suspected onychomycosis.

BACKGROUND: Conventional methods for detecting fungi in nail specimens are either nonspecific (microscopy) or insensitive (culture). Recently, PCR has been used to improve sensitivity in detecting the causative fungi in nail specimens from patients with suspected onychomycosis. AIM: To compare the detection rates of PCR with those of microscopy (with potassium hydroxide; KOH) and culture for dermatophytes in nail specimens from patients with suspected onychomycosis. METHODS: In total, 120 patients with clinically suspected onychomycosis were recruited, and using a topoisomerase II-based PCR, we compared the detection rate of dermatophytes for the three methods. RESULTS: KOH microscopy, culture and PCR respectively yielded positive rates of 35 (29.2%), 12 (10%) and 48 (40%), and negative rates of 85 (70.8%), 108 (90%) and 72 (60%). Two culture-positive specimens were not detected by PCR, but PCR picked up 38 specimens missed by culture. Of the 35 specimens that were microscopy-positive, 12 grew dermatophytes and 23 nondermatophytes. CONCLUSIONS: This study demonstrates that PCR has a higher positive and lower negative rate for detection of dermatophytes compared with KOH microscopy or culture. We suggest that PCR should be used as a complementary method for confirmation of clinically suspected dermatophytic onychomycosis.

Heterogeneous mutations of the ATP2C1 gene causing Hailey-Hailey disease in Hong Kong Chinese.

BACKGROUND: Hailey-Hailey disease (HHD) is a rare autosomal dominant dermatosis. It causes suprabasilar acantholysis leading to vesicular and crusted erosions affecting the flexures. Mutation of ATP2C1 gene encoding the human secretory pathway Ca(2+) /Mn(2+) -ATPase (hSPCA1) was identified to be the cause of this entity. OBJECTIVE: The aim of this study was to study the mutational profile of the ATP2C1 gene in Hong Kong Chinese patients with HHD. METHODS: Patients with the clinical diagnosis of HHD proven by skin biopsy were included in this study. Mutation analysis was performed in 17 Hong Kong Chinese patients with HHD. RESULTS: Ten mutations in the ATP2C1 gene were found. Six of these were novel mutations. The novel mutations included a donor splice site mutation (IVS22+1G>A); a missense mutation (c.1049A>T); two deletion mutations (c.185_188delAGTT and c.923_925delAAG); an acceptor splice site mutation (IVS21-1G>C) and an insertion mutation (c.2454dupT). CONCLUSION: The six novel mutations provide additions to the HHD mutation database. No hot-spot mutation was found and high allelic heterogeneity was demonstrated in the Hong Kong Chinese patients.

Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation.

About 10% of amyotrophic lateral sclerosis (ALS) cases are familial. We identified a five-generation Chinese family with autosomal dominant familial ALS (FALS). We performed a detailed family study, clinical and electromyographic validation, and SOD1, VEGF and CNTF mutation analyses. Forty-five living members (16 affected) were studied and DNA samples collected. Genealogical data were collected for deceased members. Based on the duration between symptom onset to ventilator dependence, they were divided into rapidly progressive (range 1-18 months, mean (SD) duration = 12.08 (+/-6.10) months, mean (SD) age of symptom onset = 39.75 (+/-9.84) years) and slowly progressive groups (>18 months; mean (SD) age of onset = 37.25 (+/-5.32) years old). We identified a heterozygous mutation of ATT to ACT of SOD1 gene at codon 149 in exon 5 resulting in substitution of isoleucine to threonine. It co-segregated with all affected members and 11 non-symptomatic members. We report a large multigenerational Chinese FALS kindred with I149T mutation in SOD1. No polymorphisms or mutations were found to date in two known modifier genes, namely, VEGF and CNTF, which were associated with heterogeneity in the phenotype within this kindred. Follow-up of the family will be helpful to explore any potential disease markers.

Myopia as a latent phenotype of a pleiotropic gene positively selected for facilitating neurocognitive development, and the effects of environmental factors in its expression.

Myopia has become an almost pandemic problem in many populations. There are compelling evidence to suggest that myopia is a hereditary condition. However, myopia would constitute a definite selection disadvantage during most stages of human evolution, which is incompatible with its moderate to high prevalence in most modern populations. The rapid upsurge of myopia over just a few decades also implies that its inheritance does not follow any of the usual patterns, and environmental factors may have an important role in precipitating its occurrence in those who are genetically predisposed. Previous studies showed that myopes were, on average, more intelligent than non-myopes, and this association had been attributed to a biological link between eye growth and brain development. We propose a pleiotropic genetic model to explain the atypical epidemiologic and inheritance pattern of myopia and its relationship with neurocognitive development. This pleiotropic gene was positively selected for its facilitation of human intelligence. The myopic component is a latent phenotype; myopia will not be expressed unless some novel external factors are encountered (i.e. a "quirk" phenomenon). Therefore, the myopic component was selectively neutral in our ancestral environment. The net gain in Darwinian fitness enables the pleiotropic gene to attain a high frequency in the human population, as reflected by our current prevalence of myopia.

Cerebrospinal fluid to serum glucose ratio in non-hypoglycorrhachic neurological conditions.

OBJECTIVE: To explore the relevance of cerebrospinal fluid to serum glucose ratio in non-hypoglycorrhachic conditions. DESIGN: Retrospective observational study. SETTING: Neurology ward, university teaching hospital, Hong Kong. PATIENTS: Adult patients with conditions unrelated to hypoglycorrhachia who underwent lumbar puncture. MAIN OUTCOME MEASURES: Cerebrospinal fluid and simultaneous serum glucose concentrations, and their ratio to each other. RESULTS: Between September 1998 and August 2003, 170 cerebrospinal fluid and serum glucose samples were collected from 138 patients. Mean cerebrospinal fluid to serum glucose ratio was 0.61 (standard deviation, 0.142; range, 0.21-1.00). With the exception of cerebrospinal fluid protein level, laboratory parameters were similar among different diseases. The glucose ratio was lower than 0.6 in 43% and lower than 0.5 in 19% of samples. Cases with a low glucose ratio appeared to have higher serum glucose concentrations (significant among groups with different glucose ratios, P<0.001). The mean glucose ratio (0.65) was also significantly higher in patients with serum glucose concentration of lower than 7.8 mmol/L compared with those with serum glucose concentration between 7.8 and 11.1 mmol/L (mean, 0.46), or higher than 11.1 mmol/L (mean, 0.46) [P<0.001]. There was a strong negative correlation between the glucose ratio and serum glucose concentration (r= -0.704, P<0.001). CONCLUSION: A lowered cerebrospinal fluid to serum glucose ratio is often seen in the absence of an appropriate disorder, especially when simultaneous serum glucose concentration is elevated. This may be explained by the saturation kinetics of glucose transportation in hyperglycaemia, and the time lag for cerebrospinal fluid and glucose to equilibrate when the blood level fluctuates.

An epidemiological study of motor neuron disease in Hong Kong.

Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.

A possible explanation for the racial difference in distribution of large-arterial cerebrovascular disease: ancestral European settlers evolved genetic resistance to atherosclerosis, but confined to the intracranial arteries.

The pattern of cerebral atherosclerosis is not the same among different races. White patients rarely have intracranial large arterial steno-occlusive disease even if their systemic arteries are extensively involved, while non-white patients frequently have their intracranial arteries affected. We postulate that during human population diversification, those who settled in Europe had acquired a stroke-suppressor genotype that increases their resistance against atherogenesis, but with protection confined to the intracranial large arteries. The contemporary affluent lifestyle accelerates the development of atherosclerosis. In the whites, it involves the whole arterial bed except the intracranial vessels. People living in non-Western countries used to have a healthier way of living. They did not develop significant atherosclerotic diseases until recently when a westernised lifestyle was adopted. Unlike the whites, their intracranial arteries will not be spared. Atherosclerosis has become a major cause of premature mortality in the modern world, and an anti-atherogenic mechanism would confer a selection advantage. With further adaptive intensification, this protection may extend to the rest of the arterial bed. As a result, future Homo sapiens will be able to tolerate an affluent lifestyle without much adverse sequel such as premature vascular death. Alternatively, if the mediator of this anti-atherogenic mechanism can be identified and applied therapeutically, we will have an ultimate mean to prevent atherosclerosis.

Wilson's disease with depression and parkinsonism.

Wilson's disease (WD) is an autosomal recessive disorder with reduced biliary excretion of copper plus impaired formation of ceruloplasmin, leading to copper accumulation in the liver, brain, kidney, and cornea. Clinical manifestations include liver damage, psychiatric symptoms, and neurological features. We report a 35-year-old woman with a history of deranged liver functions who had severe depression several years later and eventually presented with parkinsonian features. The underlying diagnosis is WD and family screening revealed WD in 2 other siblings. She could not tolerate penicillamine because of fever and leucopenia. While taking trientine hydrochloride and zinc sulphate, her parkinsonism improved and her depression remained in remission. WD should be considered in patients with unexplained liver function derangement or psychiatric symptoms. Early diagnosis and initiation of specific treatment are crucial in minimising any further cerebral and hepatic damage as well as securing possible improvement in organ functions.

Rac2 expression and mutation in human brain tumors.

BACKGROUND: Rac1 and Rac2 are interchangeable in NADPH oxidase activation. Rac1 plays an important role in regulating nuclear signalling and in the activation of transcriptional factors that regulate gene expression and cell growth. Our previous study observed mutation in effector region of Rac1 gene in brain tumors. Little is known about the expression and mutation of Rac2 in human brain tumors. METHOD: We examined the expression of Rac2 by using reverse transcriptase-polymerase chain reaction (RT-PCR) and northern blot analysis and the mutation of Rac2 gene by using DNA sequence analysis. FINDINGS: The decreased expression of Rac2 was found in 15 cases (57.7%) including 8 of 10 astrocytomas, 2 of 8 meningiomas, and 5 of 8 pituitary adenomas. Two of 13 cases with decreased expression of Rac2 had gene mutation. Only two of 26 cases had Rac2 overexpression in which no Rac2 gene mutation was found. Four of 8 cases with normal Rac2 expression had Rac2 gene mutation. The site of Rac2 gene mutation had no hot spots and was not concentrated in the effector region. CONCLUSIONS: Our results showed a low frequency of mutation and no hot spots of mutation in Rac2 gene in brain tumors, suggesting a decreased possibility of Rac2 in the brain tumorigenesis. The role of high frequency of decreased Rac2 expression in brain tumors, particularly in malignant astrocytomas, needs further investigations to be elucidated.

Bath-related headache.

Bath-related headache (BRH) is a rare primary headache syndrome. We present our experience over seven years and review all reported cases of BRH. Thirteen patients, including six from our group, are described. BRH occurred exclusively in middle-aged or elderly Oriental women (mean age 51 years, range 32-67. Hong Kong 6 cases, Taiwan 4 cases, Japan 3 cases). The typical presentation was a uniphasic cluster of severe headache recurrently triggered by bathing or other activities involving contact with water. Each attack lasted 30 min to 30 h. Onset was hyperacute, consistent with that of thunderclap headache. Reversible multisegmental cerebral vasoconstriction was found in two patients. No underlying secondary causes were identified. Response to acute treatment was generally unsatisfactory, but headache could be prevented by avoiding the specific trigger(s). BRH runs a self-limiting course; all patients remitted within three months after onset. Nimodipine may shorten the duration of illness.

A prevalence study of epilepsy in Hong Kong.

OBJECTIVES: To examine epidemiological data on epilepsy for the Hong Kong west region. DESIGN. Descriptive study. SETTING: Epilepsy clinic, university teaching hospital, Hong Kong. PATIENTS AND METHODS: The epilepsy clinic of Queen Mary Hospital manages the majority of adult patients (aged 15 years or older) with chronic seizure disorders resident in the Hong Kong west area with an adult population of 475,900. All patients underwent electroencephalography examination and each subject was independently assessed by two epileptologists for diagnosis and classified according to the International League Against Epilepsy recommendations. RESULTS: Seven hundred and thirty-six patients (female, 42.9%; male, 57.1%; mean age, 40.8 years; standard deviation, 13.6 years) with epilepsy were enrolled in the study. The prevalence rate of active epilepsy in the population 15 years or older was estimated at 1.54 per 1000 on 1 January 2002. Two hundred and eighty-five (38.7%) patients had idiopathic epilepsy syndromes, 100 (13.6%) had cryptogenic epilepsy, and 285 (38.7%) had a remote symptomatic aetiology. Seizure type was partial in 408 (55.4%) patients and generalised in 285 (38.7%). Thirty-one (4.2%) patients had a positive family history. Idiopathic generalised epilepsy syndromes described as common in the literature, such as juvenile myoclonic epilepsy and childhood absence epilepsy, were infrequently seen at 0.68% and 0.95% of cases, respectively. CONCLUSIONS: This study provides baseline data for epilepsy service development and research in Hong Kong. The prevalence rate of active epilepsy in this Chinese, adult population was low compared with that reported in other developed countries. Further population-based epidemiological research is indicated to confirm the prevalence of seizure disorders in this locality.