Magnetoelastic Effects in Doubly Clamped Electroplated Co77Fe23 Microbeam Resonators.

Magnetostrictive Co77Fe23 films are fully suspended to produce free-standing, clamped-clamped, microbeam resonators. A negative or positive shift in the resonant frequency is observed for magnetic fields applied parallel or perpendicular to the length of the beam, respectively, confirming the magnetoelastic nature of the shift. Notably, the resonance shifts linearly with higher-bias fields oriented perpendicular to the beam's length. Domain imaging elucidates the distinction in the reversal processes along the easy and hard axes. Together, these results suggest that through modification of the magnetic anisotropy, the frequency shift and angular dependence can be tuned, producing highly magnetic-field-sensitive resonators.

Determination of the exchange constant of Tb0.3Dy0.7Fe2 by broadband ferromagnetic resonance spectroscopy.

We present measurements of the exchange stiffness D and the exchange constant A of a sputtered 80 nm Tb0.3Dy0.7Fe2 film. Using a broadband ferromagnetic resonance setup in a wide frequency range from 10 GHz to 50 GHz, multiple perpendicular standing spin-wave resonances were observed with the external static magnetic field applied in-plane. The field corresponding to the strongest resonance peak at each frequency is used to determine the effective magnetization, the g-factor and the Gilbert damping. Furthermore, the dependence of spin-wave mode on field-position is observed for several frequencies. The analysis of spin-wave resonance spectra at multiple frequencies allows precise determination of the exchange stiffness D = (2.79 ± 0.02) × 10-17 T · m2 for an 80 nm thick film. From this value, we calculated the exchange constant A = (9.1 ± 0.1) pJ · m-1.

Implementation of Two-Dimensional Polycrystalline Grains in Object Oriented Micromagnetic Framework.

In response to the growing need for a more accurate micromagnetic model to understand switching phenomenon in nanoscale magnets, we developed the capability to simulate two-dimensional polycrystalline grains using the Object Oriented Micromagnetic Framework (OOMMF). This addition allows users full flexibility in determining the magnetocrystalline anisotropy and axe in each grain as well as the inter- and intragranular exchange coupling strength.

A straightforward specimen holder modification for remnant magnetic-field measurement in TEM.

We report a simple means to modify an analytic sample holder to perform ambient Hall probe measurements of the sample area inside a transmission electron microscope (TEM). These measurements are important in the case of electron microscopy studies involving magnetic materials. We characterize the magnetic field of the JEOL 2100F-LM, a microscope dedicated in design to perform magnetic imaging, and also of the JEOL 3000F FEG-TEM operated in Lorentz mode. In the case of the 3000F, we measure vertical remnant field about 300 Oe due to the objective lens of the microscope. In the case of the 2100F, design of the objective lens reduces the remnant field to about 4 Oe. We characterize the field along two orthogonal directions, and spatial characteristics of the field profile are made for both microscopes during all stages of specimen entry into the column. In the case of the 2100F, we additionally measure the field conditions as a function of objective lens excitation, which is important for in situ magnetization experiments. Finally, we provide experimental results illustrating the importance of these measurements.

Congenital hypertrophy of the retinal pigment epithelium and APC mutations in Chinese with familial adenomatous polyposis.

Mutations in the adenomatous polyposis coli gene (APC) often cause both congenital hypertrophy of the retinal pigment epithelium (CHRPE) and familial adenomatous polyposis (FAP). To investigate the relationship between APC mutations, CHRPE and FAP, all FAP patients at the Prince of Wales Hospital, Hong Kong, were asked to participate in a study. Ten Chinese patients from 6 kindreds and their family members volunteered, along with 12 healthy control subjects selected among hospital visitors and staff. All were examined for dilated fundus by indirect ophthalmoscopy. Mutations in APC coding exons were detected by sequencing. In one FAP patient, a novel A insertion at codon 1023 was detected. Three previously reported mutations were detected in 6 FAP patients: a deletion of ACAAA at codon 1061, and 2 truncating point substitutions at codons 216 and 283. In 3 FAP patients, no APC mutation was found, suggesting that mutations in APC coding regions are not the sole cause of FAP or CHRPE. A total of 64 CHRPE lesions were found in FAP patients and some relatives with and without APC mutations. Contrary to most reports, APC mutations before exon 9 did cause CHRPE lesions, albeit relatively few.

Selection of patients for laparoscopic repair of perforated peptic ulcer.

BACKGROUND: Although randomized and non-randomized studies have evaluated the safety of laparoscopic repair for perforated peptic ulcer, no definite guidelines have been published on selection of patients for laparoscopic repair. This cohort study aimed to define patients who may not benefit from laparoscopic techniques. METHODS: The data from 374 consecutive patients with perforated peptic ulcer treated by simple repair were collected prospectively and analysed. RESULTS: From January 1992 to December 1998, 219 patients were treated by open suture repair, 109 by laparoscopic sutureless (fibrin glue) repair and 46 by laparoscopic suture repair. The overall leak rate after laparoscopic suture and sutureless repair was 6 and 16 per cent respectively. Leakage was noted to be associated with a significantly higher rate of wound infection, intra-abdominal abscess formation, prolonged ileus (P < 0.001) and longer hospital stay (11 versus 5 days; P < 0.001). Multivariate analysis demonstrated that Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission predicted the likelihood of a leak after laparoscopic fibrin glue repair (P = 0.006). CONCLUSION: APACHE II score may be a useful index for selecting patients for laparoscopic fibrin glue repair.

Effects of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in an experimental model of cirrhosis.

BACKGROUND: Hepatic blood inflow occlusion during hepatectomy may influence postoperative liver regeneration. The aim of this study was to investigate the influence of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in thioacetamide-induced cirrhotic rats. METHODS: Forty-three cirrhotic Wistar-Furth rats were randomly assigned to three groups. Rats in group 1 underwent 64 per cent hepatectomy alone, those in group 2 were subjected to 15 min hepatic blood inflow occlusion followed by 64 per cent hepatectomy, and animals in group 3 were subjected to 30 min inflow occlusion followed by 64 per cent hepatectomy. Liver function, 5-bromo-2'-deoxyuridine (BrdU) labelling index and percentage of initial liver weight on days 1, 2 and 7 posthepatectomy were assessed. RESULTS: Rats in groups 1 and 2 had a significantly higher serum albumin level and a markedly lower alanine aminotransferase level than animals in group 3 on day 1 posthepatectomy (P < 0.05). There was no significant difference in the serum level of total bilirubin of the three groups on days 1, 2 and 7. The BrdU labelling index was significantly higher in groups 1 and 2 than in group 3 animals on day 1 posthepatectomy (P < 0.01 and P < 0.05 respectively). Percentages of initial liver weight were similar in groups 1, 2 and 3 on days 1, 2 and 7 after hepatectomy. CONCLUSION: Hepatic blood inflow occlusion for up to 30 min suppressed DNA synthesis and hepatocyte proliferation at an early posthepatectomy stage and consequently delayed recovery of liver function in cirrhotic rats. However, it did not affect restoration of liver mass or survival after 64 per cent hepatectomy.

Methamphetamine-induced oxidative stress in cultured mouse astrocytes.

Methamphetamine (METH) is a monoaminergic toxin that destroys dopamine terminals and causes astrogliosis in vivo. Oxidative stress has been shown to play an important role in the toxic effects of METH. In the present study, we sought to determine whether astrocytes are involved in METH-induced oxidative stress. Reactive oxygen species (ROS), ATP, and change in mitochondria membrane potential (delta psi(m)) were examined in cultured striatal, mesencephalic, and cortical astrocytes after 4 to 48 h of 4 mM METH treatment. Results showed that only striatal and mesencephalic astrocytes showed a significant increase in ROS formation from 8 and 12 h, respectively. At 48 h treatment, there was a 55 and 53% increase in ROS content in striatal and mesencephalic astrocytes, respectively, whereas cortical astrocytes showed only a 25% (not significant) increase. JC-1, a delta psi(m)-sensitive dye, showed a decrease in delta psi(m) at 8 h treatment for striatal and mesencephalic astrocytes and at 12 h for cortical astrocytes. Astrocytes from all three regions showed a similar pattern of initial increase followed by a decrease in ATP content, with striatal astrocytes resulting in a maximum depletion (39% of control value) at 48 h treatment. These findings showed that METH treatment resulted in the formation of ROS in the order of striatal > mesencephalic > cortical astrocytes. Although the formation of ROS did not severely interfere with ATP production, a depolarization of mitochondria was observed. The present study suggested that astrocytes may be an important element governing the selective vulnerability to the striatum to METH-induced oxidative stress.

A comprehensive karyotypic study on human hepatocellular carcinoma by spectral karyotyping.

The current paucity of cytogenetic information on hepatocellular carcinoma (HCC) reflects the difficulties in culturing hepatocytes in vitro. Here, we report on the successful culture of 15 HCC cases. Chromosome aneuploidy ranging from a near-diploid to hyperhexaploid karyotype was found, but their complete karyotypic interpretations were hampered by the presence of many unidentifiable rearrangements. Spectral karyotyping (SKY) was used to elucidate structural changes in these HCC samples and 3 liver cancer cell lines (PLC/PRF/5, Hep3B, and HepG2). Frequent structural abnormalities were found on chromosomes 1 (13 of 15 cases; 3 of 3 cell lines), 8 (10 of 15 cases; 2 of 3 cell lines), 17 (9 of 15 cases; 3 of 3 cell lines), and 19 (9 of 15 cases; 1 of 3 cell lines). In particular, the chromosome regions 1p13-q21, 8p12-q21, 17p11-q12, 17q22, and 19p10-q13.1 were involved in multiple rearrangements. SKY analysis also suggested several previously undescribed breakpoints in HCC. These breakpoints, predominantly pericentromeric, clustered around the chromosome bands 2q33-q34, 3p13-q12, 4p14-q12, 5p10-q11, 7p12-q11, 10q10-q11, 11q10, 11q13-q21, 12q10-q13, 12q22-q23, 13q10-q14, 15q10, 16q10-q13, 18p11-q11, 20p11-q13.1, 21q10, and 22q10. When tumor sizes were compared, a significantly higher number of structural abnormalities was found in tumors larger than 4 cm (P =.007). Rearrangements such as t(1;8), t(1;11), t(1;19), and t(17;21) that were identified in both primary tumors and cell lines might represent markers that reflect proliferative advantages. Although SKY analysis did not indicate consistent translocations, it suggested nonrandom breakpoints, predominantly in the pericentromeric region, on a number of chromosomes. These breakpoint clusters may thus prove to be more important in the liver carcinogenesis and targets for further molecular investigations.

Genomic aberrations in human hepatocellular carcinomas of differing etiologies.

We sought to assess whether genetic abnormalities in hepatocellular carcinoma differed in geographic locations associated with different risk factors. Comparative genomic hybridization (CGH) was applied to the genome-wide chromosomal analysis in 83 tumor samples from four different geographic origins. Samples were obtained from regions that differed in aflatoxin exposure: China (Hong Kong with low aflatoxin exposure and Shanghai with moderate aflatoxin exposure), Japan, and the United States (negligible aflatoxin exposure). Cases from Hong Kong and Shanghai were all hepatitis B virus (HBV) related, those from Japan were hepatitis C virus related, and those from the United States were HBV negative. In parallel, the mutational pattern of the whole p53 gene (exons 1-11) was also investigated in these cases. CGH revealed a complex pattern of chromosomal gains and losses, with the commonest aberration in each geographic location being chromosome 1q copy number gain (38-60%). Shanghai cases displayed the highest number of total aberrations per sample, with significant copy losses on 4q (75%), 8p (70%), and 16q (65%). Hepatitis C virus-related samples from Japan had a characteristically high incidence of 11q13 gain. p53 mutation(s) was detected in 23% of Hong Kong cases, 40% of Shanghai, 31% of Japan, but only 6% of the United States cases. The "aflatoxin-associated" codon 249 mutation was, however, identified only in samples from China (13% Hong Kong and 20% Shanghai). This finding, together with the highly aberrant pattern of genetic changes detected in the Shanghai series, is suggestive of the genotoxic effects of aflatoxin being more broadly based. It is also likely that there is a synergistic effect of HBV infection and high aflatoxin exposure in promoting hepatocellular carcinoma development. It appears from our CGH study that individual risk factors are indeed associated with distinct genetic aberrations, although changes in 1q gain appear common to all.

A comprehensive karyotypic analysis on a newly developed hepatocellular carcinoma cell line, HKCI-1, by spectral karyotyping and comparative genomic hybridization.

A continuously growing human hepatocellular carcinoma (HCC) cell line was established from a Chinese male, carrier of the hepatitis B virus (HBV). This cell line, designated HKCI-1, grows as an adhering monolayer of polygonal epithelial cells that embody one or more nuclei. HKCI-1 secretes alpha-fetoprotein but shows no evidence of HBV carriage. Conventional banding analysis of the short-term cultured primary tumor and the propagated HKCI-1 revealed a chromosome modal number of near-triploidy. It was, however, impossible to derive their complete karyotype due to the complex nature of chromosomal rearrangements and many marker chromosomes of uncertain origin. Spectral karyotyping (SKY) is a newly developed molecular cytogenetic technique that allows the unprecedented discernment of chromosomal abnormalities. Spectral karyotyping analysis on HKCI-1 and the primary tumor elucidated all aberrant chromosomes and revealed complex karyograms. Recurring aberrations detected in both primary tumor and HKCI-1 included der(X)t(X;11)(q10;p10), der(1)t(1;10)(q10;?pq), der(4)t(4;16)(p10;q10), i(5p), del(5)(q13), der(7)t(7;21)(q32q10::q10), der(8)t(8;17)(q10;p10), and der(9)t(9;22)(q34;?pq). Comparative genomic hybridization (CGH) was employed to monitor the culture evolution in vitro. Genomic imbalances in HKCI-1 involved chromosomal losses on 4q, 5q13-qter, 8p, 9pter-q33, 10q, 11q, 13q, 16q, 17q12-qter, and 22, and low-level gains on 6pter-q22, 7p, 8q, 9q34, 10p, 11p, 12, 17pter-q11.2, 18, 19, 20, 21, and Y. High-level amplifications were also detected on 5pter-q12, 7q11.2-qter, and Xq. The corresponding CGH finding on the primary tumor indicated similar imbalances. TP53 mutational analysis showed that both HKCI-1 and the primary tumor had the aflatoxin-associated mutation in codon 249 and an additional TP53 polymorphism in codon 72. Our present study demonstrates the value of combined SKY and CGH study in defining complex rearrangements and identifying cryptic translocations, and provides a comprehensive analysis on the chromosomal abnormalities in HKCI-1.

Congenital hypertrophy of the retinal pigment epithelium and APC mutations in two Chinese families with familial adenomatous polyposis.

PURPOSE: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) exists almost exclusively among familial adenomatous polyposis (FAP) patients with adenomatous polyposis coli (APC) mutations between codon 413 in exon 9 and codon 1387 in exon 15. We investigated the locality of APC mutations in relationship to the occurrence of CHRPE in two Chinese families with FAP. METHODS: Genomic DNA of available members of two unrelated Chinese FAP families was investigated for sequence alteration in the APC gene by polymerase chain reaction and direct sequencing. All subjects were examined by binocular indirect ophthalmoscopy (BIO) for CHRPE. RESULTS: A mutation in exon 6, Arg216Stop, was identified in one patient with FAP and CHRPE. An Arg283Stop mutation in exon 8 was found in 5 members in another family; 4 of them had FAP and all had small hypopigmented white lesions, probably a new type of CHRPE. CONCLUSIONS: We found two mutations, Arg216Stop and Arg283Stop, upstream of codon 413 in FAP patients presenting with CHRPE. Arg283Stop has not previously been reported in such patients. A large-scale study on CHRPE and APC mutations in Chinese FAP patients is required to affirm their inter-relationships and the significance of the hypopigmented white lesions.

Cephalometric morphology of Chinese with Class II division 1 malocclusion.

AIM: To investigate the craniofacial pattern of southern Chinese children with Class II Division 1 malocclusion and to compare with Chinese population norms and Caucasians with Class II Division 1 malocclusions. MATERIALS: Lateral cephalograms obtained from 105 Chinese subjects with Class II Division 1 malocclusion. RESULTS: There were no significant sex differences and subsequently the data were pooled. Except for the maxillary plane angle and the angle of the lower incisor relative to the mandibular plane, all of the selected dental-skeletal angular measurements showed significant differences between Chinese with Class II Division 1 malocclusion and Chinese norms. CONCLUSION: Compared with Caucasians, Chinese with Class II Division 1 malocclusion have more prognathic maxillas, less retrusive mandibles, flatter chins, steeper mandibular plane angles and more proclined maxillary incisors.

Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis.

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prevalent in Southeast Asia. Although the etiological factors associated are now well recognized, the interactions between individual factors and the molecular mechanisms by which they lead to cancer remain unclear. Cytogenetic analysis on HCC has been limited because of poor hepatocyte growth in vitro. The recently developed technique of comparative genomic hybridization (CGH), however, permits screening of the entire genome without the need of cell culture. CGH was applied to the study of genomic aberrations in 67 surgically resected samples of HCC, 3 of adenomatous hyperplasia (AH), and 12 of nontumorous cirrhotic liver surrounding the tumors. All samples were from patients of a racially and etiologically homogeneous population in Southern China, where chronic hepatitis B virus infection is the main etiological factor. CGH analysis of the HCC samples revealed frequent copy number gain of 1q (48/67 cases, 72%), 8q (32/67 cases, 48%), 17q (20/67 cases, 30%), and 20q (25/67 cases, 37%) and common losses on 4q (29/67 cases, 43%), 8p (25/67 cases, 37%), 13q (25/67 cases, 37%), and 16q (20/67 cases, 30%). Our finding of a high incidence of 1q gain strongly suggested this aberration was associated with the development of HCC. Genomic abnormalities were detected in 1 of the 3 AH specimens but absent in all 12 cirrhotic tissues surrounding the tumor. Clinical staging classified 3/67 HCC cases as T1, 53 cases as T2, and 11 cases as T3. No significant difference in the pattern of genomic imbalances was detected between stages T2 and T3. A significant copy number loss of 4q11-q23 was, however, identified in those tumors larger than 3 cm in diameter. Of particular interest was the identification of 8q copy number gain in all 12 cases of HCC that arose in a noncirrhotic liver, compared with only 20/55 cases in HCC arising in a cirrhotic liver. We suggest that 8q over-representation is likely associated with a growth advantage and proliferative stimulation that have encouraged malignant changes in the noncirrhotic human liver.

A selective regional response of cultured astrocytes to methamphetamine.

Methamphetamine (METH) has long-lasting neurotoxic effects on the dopamine and forebrain serotonin systems. It was reported that METH would induce the release of glutamate within the striatum and that it also caused astrogliosis. The mechanisms of this release and subsequent neurotoxicity are not well defined. The aim of this study was to examine the response of cultured astrocytes after METH-induced injury. Astrocytes were cultured from neonatal C57B1/6 mice brains. Cells were obtained from the mesencephalon, striatum and cortex in order to examine any regional differences. Cells were treated with 4mM METH for 4, 8, 12, 24 and 48 hr. Lactate dehydrogenase (LDH) levels were used as a measure of cell viability. At various time points, Western blot analyses were performed to study the change in GFAP and vimentin (markers for astrogliosis) levels. Change in glutamine synthase (GS), the enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia in astrocytes, was also examined. The results showed that METH caused marked astrogliosis in striatal and mesencephalic astrocytes. Cells were transformed from protoplasmic (inactive) to fibrous (reactive) form after 48 hr treatment. There were also large amounts of vacuoles present in the cytoplasm of these cells. LDH results showed that there was only slight increase in enzyme levels after 48 hr treatment suggesting that the astrogliosis observed was not due to the decrease in cell viability. The amount of GS were depleted more rapidly in striatal astrocytes (50% of control by 8 hr treatment) followed by mesencephalic astrocytes (reaching 10% of control by 48 hr treatment). Cortical astrocytes showed only a 48% depletion by 48 hr treatment, indicating that they are more resistant to METH-induced toxicity. The rapid depletion of GS obtained in striatal and mesencephalic astrocytes suggested that astrocytes of the dopaminergic system are more sensitive to METH-induced injury. This may be due to the direct effects of METH-induced oxidative stress on the mitochondria of these cells resulting in GS depletion and astrogliosis.