Enhanced expression of nidogen 1 around the nest of basal cell carcinoma compared with that around squamous cell carcinoma.

Basal cell carcinoma (BCC) is a malignant skin tumor originating from cells of the epidermal basal layer and adnexal epithelium, especially in sun-exposed areas. Unlike squamous cell carcinoma (SCC), BCC has a propensity to grow only locally possibly due to differences in the surrounding microenvironment including the basement membrane (BM) and stroma. To investigate the components constituting the BM and surrounding connective tissue in BCC and SCC, we analyzed the expression of BM proteins, nidogen 1 (NID1) and type IV collagen (COL4). We compared the immunohistochemical expressions of NID1 and COL4 among tumor specimens from BCC, SCC and its precancerous condition, actinic keratosis (AK), (n = 5 each condition). The expressions of NID1 and COL4 were both decreased around the tumor nest of SCC. In contrast, the expressions of both NID1 and COL4 around the nest of BCC were much higher than in the peri-lesional normal skin not only at the BM, but also in the surrounding stromal tissue. Our findings imply that the surrounding stromal cells of BCC, but not SCC or AK, excessively produce NID1 and COL4, which may be involved in preventing BCC cells from destroying the BM and invading the dermis.

Long-term weight-change slope, weight fluctuation and risk of type 2 diabetes mellitus in middle-aged Japanese men and women: findings of Aichi Workers' Cohort Study.

OBJECTIVE: This study aims to investigate the association of long-term weight-change slopes, weight fluctuation and the risk of type 2 diabetes mellitus (T2DM) in middle-aged Japanese men and women. METHODS: A total of 4234 participants of Aichi Workers' Cohort Study who were aged 35-66 years and free of diabetes in 2002 were followed through 2014. Past body weights at the ages of 20, 25, 30, 40 years, and 5 years before baseline as well as measured body weight at baseline were regressed on the ages. Slope and root-mean-square-error of the regression line were obtained and used to represent the weight changes and the weight fluctuation, respectively. The associations of the weight-change slopes and the weight fluctuation with incident T2DM were estimated by Cox proportional hazards models. RESULTS: During the median follow-up of 12.2 years, 400 incident cases of T2DM were documented. After adjustment for baseline overweight and other lifestyle covariates, the weight-change slopes were significantly associated with higher incidence of T2DM (hazard ratio (HR): 1.80, 95% confident interval (CI): 1.17-2.77 for men; and HR: 2.78, 95% CI: 1.07-7.23 for women), while the weight fluctuation was not (HR: 1.08, 95% CI: 1.00-1.18 for men and HR: 1.02, 95% CI: 0.84-1.25 for women). CONCLUSIONS: Regardless of the presence of overweight, the long-term weight-change slopes were significantly associated with the increased risk of T2DM; however, the weight fluctuation was not associated with the risk of T2DM in middle-aged Japanese men and women.

Depression but not anxiety predicts recurrent cerebrovascular events.

OBJECTIVES: Depression and anxiety after stroke occur frequently and have been suggested to have negative influence on functional outcomes. However, the effect of emotional symptoms on stroke recurrence is uncertain. The aim of this study was to define the effect of emotional symptoms on recurrent cerebrovascular events in patients with ischemic stroke. MATERIALS AND METHODS: This was a hospital-based cohort study including patients with ischemic stroke who participated in a Community Stroke Care Program that provided secondary stroke prevention strategies during 6 months transition period after discharge. We examined the association between depression and anxiety and the risk of recurrent cerebrovascular events using logistic regression model. Depression and anxiety were defined as a score of 7 or more in Hospital Anxiety and Depression Scale at 2 weeks after discharge. Recurrent cerebrovascular events comprised any recurrent stroke and transient ischemic attack (TIA) occurring during 6 months after discharge. RESULTS: Among 182 patients, 29 (15.9%) were depressed and 41 (22.5%) had anxiety symptoms. During the follow-up period, 9 patients experienced recurrent cerebrovascular events (5 of stroke and 4 of TIA). Depression was associated with recurrent cerebrovascular events at 6 months after adjustment for age, sex, and stroke severity (OR 5.22, 95% CI 1.08-25.12; P = 0.04), whereas anxiety was not (OR 0.98, 95% CI 0.2-4.92; P = 0.982). CONCLUSIONS: Depression occurring early after stroke was associated with the increased risk of recurrent cerebrovascular events in ischemic stroke survivors. Care plan to detect and manage depression should be implemented to prevent recurrent stroke.

Prediction of 10-year vascular risk in patients with diabetes: the AD-ON risk score.

AIMS: To formulate a combined cardiovascular risk score in diabetes that could be useful both to physicians and healthcare funders. METHODS: Data were derived from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE-ON) study, a randomized controlled trial (mean duration 5 years) with a post-randomization follow-up (mean 4.9 years), that included 11 140 high-risk patients with diabetes. The outcome analysed was the occurrence of either fatal or non-fatal macrovascular or renal disease. A Cox regression model was used to determine weightings in the risk score. The resultant score was recalibrated to each of three major global regions, as covered by the ADVANCE-ON study. RESULTS: Over a median of 9.9 years, 1145 patients experienced at least one component of the combined outcome event. The resultant score, the AD-ON risk score, incorporated 13 demographic or clinical variables. Its discrimination was modest [c-statistic = 0.668 (95% confidence interval 0.651, 0.685)] but its calibration was excellent (predicted and observed risks coincided well, within disparate global regions). In terms of the integrated discrimination improvement index, its performance was marginally superior, over a 10-year risk horizon, to existing risk scores in clinical use, from a restricted version of the same data, for macrovascular and renal disease separately. CONCLUSIONS: The AD-ON risk score has advantages over the existing vascular risk scores in diabetes that used data from the original ADVANCE trial, which treat macrovascular and renal diseases separately. These advantages include its simplicity of use and global application.

Association between eating rate and obesity: a systematic review and meta-analysis.

BACKGROUND: The association between eating rate and obesity has recently been reported. However, the findings remain inconclusive. OBJECTIVES: We undertook a systematic review with a meta-analysis of published epidemiological studies to provide a reliable close estimate of the association between eating rate and obesity. METHODS: A comprehensive search of MEDLINE, EMBASE and CINAHL was conducted to identify studies that reported quantitative estimates for indices of obesity based on the category of eating rate. Interventional studies or studies conducted using children as subjects were excluded. Two independent researchers extracted the data. A summary estimate was calculated using a random-effects model, and subgroup analyses were conducted to identify sources of heterogeneity. RESULTS: Data from 23 published studies were eligible for inclusion. The mean difference in body mass indices (BMIs) between individuals who ate quickly and those who ate slowly was 1.78 kg m(-2) (95% confidence interval (CI), 1.53-2.04 kg m(-2)). The pooled odds ratio of eating quickly on the presence of obesity was 2.15 (95% CI, 1.84-2.51). There was evidence of significant quantitative heterogeneity in the magnitudes of the association across studies (I2=78.4%, P-value for heterogeneity <0.001 for BMI, I2=71.9%, P-value for heterogeneity <0.001 for obesity), which may be partially explained by differences in the type of study population (a weaker association was observed for BMI in diabetic patients). CONCLUSIONS: Eating quickly is positively associated with excess body weight. Further studies are warranted to determine whether interventions to slow the speed of eating are effective for weight control.

Magnesium intake decreases Type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama Study.

AIMS: Early studies have shown that magnesium intake decreases the risk of Type 2 diabetes, but the results are still inconsistent. We prospectively examined the association between magnesium intake and incidence of Type 2 diabetes in a general Japanese population. METHODS: A total of 1999 subjects without diabetes aged 40-79 years who underwent a 75-g oral glucose tolerance test were followed up prospectively for a mean of 15.6 years. RESULTS: During the follow-up, 417 subjects developed Type 2 diabetes. The age- and sex-adjusted incidence of Type 2 diabetes significantly decreased with increasing magnesium intake quartile levels (≤ 148.5, 148.6-171.5, 171.6-195.5 and ≥ 195.6 mg/day, P for trend = 0.01). In multivariate analyses, after adjusting for comprehensive risk factors and other dietary factors, the hazard ratio of Type 2 diabetes was 0.67 (95% CI 0.49-0.92; P = 0.01) in the third quartile and 0.63 (95% CI 0.44-0.90; P = 0.01) in the highest quartile compared with the first quartile. In addition, the risk of Type 2 diabetes was 14% lower (P = 0.04) for a 1-sd increment of log-transformed magnesium intake in the multivariate-adjusted model. In stratified analysis, there were statistically significant interactions between magnesium intake and levels of homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein or alcohol intake on the risk of Type 2 diabetes (all P < 0.05). CONCLUSIONS: Our findings suggest that increased magnesium intake was a significant protective factor for the incidence of Type 2 diabetes in the general Japanese population, especially among subjects with insulin resistance, low-grade inflammation and a drinking habit.

Impact of eating rate on obesity and cardiovascular risk factors according to glucose tolerance status: the Fukuoka Diabetes Registry and the Hisayama Study.

AIMS/HYPOTHESIS: Medical nutrition therapy plays a critical role in the prevention and treatment of type 2 diabetes. However, appropriate measures of eating behaviours, such as eating rate, have not yet been clearly established. The aim of the present study was to examine the associations among eating rate, obesity and cardiovascular risk factors. METHODS: A total of 7,275 Japanese individuals aged ≥40 years who had normal fasting glucose levels, impaired fasting glucose or diabetes were divided into four groups according to self-reported eating rate: slow, medium, relatively fast and very fast. The associations between eating rate and various cardiovascular risk factors were investigated cross-sectionally. RESULTS: The proportions of participants who were obese or who had elevated waist circumference levels increased progressively with increases in eating rate (p for trend <0.001), regardless of glucose tolerance status. These associations remained significant after adjustment for potential confounders, namely, age, sex, total energy intake, dietary fibre intake, current smoking, current drinking and regular exercise (p for trend <0.001). Blood pressure and lipid levels also tended to increase in association with eating rate. HbA(1c) rose significantly as eating rate increased, even after multivariate adjustment, including BMI, in diabetic patients on insulin therapy (p = 0.02), whereas fasting plasma glucose did not increase significantly. CONCLUSIONS/INTERPRETATION: Our findings suggest that eating rate is associated with obesity and other cardiovascular risk factors and therefore may be a modifiable risk factor in the management of cardiovascular risk factors and diabetes.

Cut-off values of fasting and post-load plasma glucose and HbA1c for predicting Type 2 diabetes in community-dwelling Japanese subjects: the Hisayama Study.

AIMS: We examined the optimal cut-off values of fasting plasma glucose, 2-h post-load glucose and HbA(1c) for predicting Type 2 diabetes in community-dwelling Japanese subjects. METHODS: A total of 1982 subjects without diabetes aged 40-79 years who underwent a 75-g oral glucose tolerance test were followed prospectively for 14 years by annual health examination. RESULTS: During the follow-up, 295 subjects developed Type 2 diabetes. Compared with the first decile, the crude hazard ratio for incident Type 2 diabetes was significantly higher in the fifth fasting plasma glucose decile [5.4-5.4 mmol/l (97-98 mg/dl)] or higher, in the seventh 2-h post-load glucose decile [6.9-7.2 mmol/l (124-131 mg/dl)] or higher, and in the fifth HbA(1c) decile [34-36 mmol/mol (5.3-5.4%)] or higher. These associations remained substantially unchanged even after adjustment for confounding factors. The receiver operating characteristic curve analysis showed that the optimal cut-off values for predicting Type 2 diabetes were 5.6 mmol/l (101 mg/dl) for fasting plasma glucose, 6.9 mmol/l (124 mg/dl) for 2-h post-load glucose and 37 mmol/mol (5.5%) for HbA(1c). In a stratified analysis, the cut-off values were approximately 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), and these values were unchanged over BMI quartile levels, whereas the 2-h post-load glucose cut-off values declined with decreasing BMI levels. CONCLUSIONS: Our findings suggest that the cut-off value for predicting Type 2 diabetes in the Japanese population is 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), while the 2-h post-load glucose cut-off value is lower than the diagnostic criterion for impaired glucose tolerance.

Two risk score models for predicting incident Type 2 diabetes in Japan.

AIMS: Risk scoring methods are effective for identifying persons at high risk of Type 2 diabetes mellitus, but such approaches have not yet been established in Japan. METHODS: A total of 1935 subjects of a derivation cohort were followed up for 14 years from 1988 and 1147 subjects of a validation cohort independent of the derivation cohort were followed up for 5 years from 2002. Risk scores were estimated based on the coefficients (ß) of Cox proportional hazards model in the derivation cohort and were verified in the validation cohort. RESULTS: In the derivation cohort, the non-invasive risk model was established using significant risk factors; namely, age, sex, family history of diabetes, abdominal circumference, body mass index, hypertension, regular exercise and current smoking. We also created another scoring risk model by adding fasting plasma glucose levels to the non-invasive model (plus-fasting plasma glucose model). The area under the curve of the non-invasive model was 0.700 and it increased significantly to 0.772 (P < 0.001) in the plus-fasting plasma glucose model. The ability of the non-invasive model to predict Type 2 diabetes was comparable with that of impaired glucose tolerance, and the plus-fasting plasma glucose model was superior to it. The cumulative incidence of Type 2 diabetes was significantly increased with elevating quintiles of the sum scores of both models in the validation cohort (P for trend < 0.001). CONCLUSIONS: We developed two practical risk score models for easily identifying individuals at high risk of incident Type 2 diabetes without an oral glucose tolerance test in the Japanese population.

Glucose tolerance status and risk of dementia in the community: the Hisayama study.

OBJECTIVE: We investigated the association between glucose tolerance status defined by a 75-g oral glucose tolerance test (OGTT) and the development of dementia. METHODS: A total of 1,017 community-dwelling dementia-free subjects aged ≥60 years who underwent the OGTT were followed up for 15 years. Outcome measure was clinically diagnosed dementia. RESULTS: The age- and sex-adjusted incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) were significantly higher in subjects with diabetes than in those with normal glucose tolerance. These associations remained robust even after adjustment for confounding factors for all-cause dementia and AD, but not for VaD (all-cause dementia: adjusted hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.19 to 2.53, p = 0.004; AD: adjusted HR = 2.05, 95% CI = 1.18 to 3.57, p = 0.01; VaD: adjusted HR = 1.82, 95% CI = 0.89 to 3.71, p = 0.09). Moreover, the risks of developing all-cause dementia, AD, and VaD significantly increased with elevated 2-hour postload glucose (PG) levels even after adjustment for covariates, but no such associations were observed for fasting plasma glucose (FPG) levels: compared with those with 2-hour PG levels of <6.7 mmol/L, the multivariable-adjusted HRs of all-cause dementia and AD significantly increased in subjects with 2-hour PG levels of 7.8 to 11.0 mmol/L or over, and the risk of VaD was significantly higher in subjects with levels of ≥11.1 mmol/L. CONCLUSIONS: Our findings suggest that diabetes is a significant risk factor for all-cause dementia, AD, and probably VaD. Moreover, 2-hour PG levels, but not FPG levels, are closely associated with increased risk of all-cause dementia, AD, and VaD.

Association of Alzheimer disease pathology with abnormal lipid metabolism: the Hisayama Study.

OBJECTIVE: The relationship between lipid profiles and Alzheimer disease (AD) pathology at the population level is unclear. We searched for evidence of AD-related pathologic risk of abnormal lipid metabolism. METHODS: This study included brain specimens from a series of 147 autopsies performed between 1998 and 2003 of residents in Hisayama town, Japan (76 men and 71 women), who underwent clinical examinations in 1988. Lipid profiles, such as total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDLC), were measured in 1988. Low-density lipoprotein cholesterol (LDLC) was calculated using the Friedewald formula. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines (CERAD) and neurofibrillary tangles (NFTs) were assessed according to Braak stage. Associations between each lipid profile and AD pathology were examined by analysis of covariance and logistic regression analyses. RESULTS: Adjusted means of TC, LDLC, TC/HDLC, LDLC/HDLC, and non-HDLC (defined as TC-HDLC) were significantly higher in subjects with NPs, even in sparse to moderate stages (CERAD = 1 or 2), compared to subjects without NPs in multivariate models including APOE ε4 carrier and other confounding factors. The subjects in the highest quartiles of these lipid profiles had significantly higher risks of NPs compared to subjects in the lower respective quartiles, which may suggest a threshold effect. Conversely, there was no relationship between any lipid profile and NFTs. CONCLUSION: The results of this study suggest that dyslipidemia increases the risk of plaque-type pathology.

Delayed adverse reactions to iodinated radiographic contrast media after coronary angiography: a search for possible risk factors.

OBJECTIVE: The incidence of and risk factors for delayed adverse events (DAEs) that appear from 1 h to 7 days after injection of radiographic contrast media were investigated in patients who had undergone coronary angiography (CAG). METHODS: DAEs were monitored by questionnaire in 155 patients who received iomeprol. Isosorbide dinitrate was injected in every case. Risk factors for DAEs were analysed by a logistic regression model. RESULTS: Of 118 patients who returned questionnaires, 54 complained of DAEs, although no severe or fatal reactions occurred. Erythema, rash and nausea were frequent events. Female gender, total dose of isosorbide dinitrate <2 mg, and execution of acetylcholine provocation test were found to be the major risk factors, and the incidence of DAEs increased as the number of risk factors increased. CONCLUSION: Care should be taken when CAG is performed on female patients who undergo acetylcholine provocation tests and receive low-dose nitric oxide donor injections.

Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner.

We have recently established a cancer-reactive human monoclonal antibody, GAH, with a positive ratio of over 90% against stomach cancer. GAH was formulated as polyethyleneglycol (PEG)-modified immunoliposomal doxorubicin (DXR) (ILD) and its efficacy was examined against gastrointestinal human cancers. In in vitro studies, a comparison of ILD with PEG-modified liposomal DXR (LD) demonstrated that ILD had dose-dependent cytotoxicity for GAH-reactive B37 cancer cells, but not LD. In concordance with this result, microscopic observations showed that ILD was bound to and GAH-dependently internalised by B37 cells. In in vivo studies, ILD exhibited significantly greater antitumour activity on cancer xenograft models than LD or free DXR. The relation between efficacy and antigen density was examined on 10 xenograft models bearing cancer cells with varying GAH reactivity. Immunoliposomal doxorubicin therapeutic activity correlated with the antigen density, with a minimum number being required. Also, ILD revealed strong antitumour activity on cancers with low sensitivity to DXR or LD, suggesting that ILD overcame the DXR resistance of antigen-positive cancer cells. Thus, these results show that GAH endows liposomes with targeting activity, resulting in strong efficacy against gastrointestinal cancers.

An extended cavity femtosecond Cr:LiSAF laser pumped by low cost diode lasers.

We describe an extended cavity femtosecond Cr:LiSAF laser pumped by inexpensive single spatial mode diodes. Using a multi-pass cavity (MPC) to lower the repetition rate and a saturable Bragg reflector (SBR) for mode-locking, pulse energies of 0.75 nJ at a repetition rate of 8.6 MHz are achieved with durations of 39 fs and bandwidths of 20 nm in a prismless configuration. Pulse energies of 0.66 nJ at a repetition rate of 8.4 MHz with durations of 43 fs and bandwidths of 18.5 nm are generated using prisms for dispersion compensation. This laser offers performance approaching that of standard Ti:sapphire lasers at a fraction of the cost.

Lipid-mediated gene transfection of intercellular adhesion molecule-1 suppresses the peritoneal metastasis of gastric carcinoma.

We have previously reported that a decreased expression level of ICAM-1 in cancer cells frequently led to the development of lymph node metastasis, and suggested that ICAM-1 gene transfection may inhibit lymph node metastasis. In the present study, we investigated whether ICAM-1 gene therapy for the peritoneal metastasis of gastric carcinoma is useful as a new immuno-gene therapy. ICAM-1 gene was transfected into a gastric cancer cell line, OCUM-2MD3 (2MD3), which has a high metastatic ability to the peritoneum. A transfectant cancer cell line, 2MD3/ICAM-1, had high ICAM-1 expression on the cell surface. The adhesion and cytotoxicity abilities of peripheral blood mononuclear cells were significantly increased against 2MD3/ICAM-1 cells in comparison with 2MD3 cells. Mice inoculated with 2MD3/ICAM-1 cells in the peritoneal cavity had a significantly better survival rate than those inoculated with 2MD3 cells (log-rank test, p<0.05). Histologic findings revealed that more mononuclear cells existed around the metastatic nodules in 2MD3/ICAM-1. Although gastric carcinoma frequently causes peritoneal metastasis, no useful therapy for the metastasis of gastric carcinoma has been developed. These findings revealed that ICAM-1 gene transfection to cancer cells could be a useful immuno-gene therapy for the peritoneal metastasis of gastric carcinoma.

Establishment and characterization of OCUT-1, an undifferentiated thyroid cancer cell line expressing high level of telomerase.

BACKGROUND & OBJECTIVES: Undifferentiated thyroid cancer is one of the most aggressive human malignancies, and the prognoses that have been reported are extremely poor. A number of studies have described the clinicopathologic features of this tumor and analyzed its biologic background to explain the extraordinarily aggressive nature of the tumor. Still the mechanism of cellular aggressiveness in undifferentiated thyroid cancer is not yet fully understood. METHODS: We established and characterized an undifferentiated thyroid cancer cell line, OCUT-1, derived from the surgical specimen obtained from a 74-year-old Japanese woman with advanced undifferentiated thyroid cancer. RESULTS: The cell line had already maintained over 100 passages and was stably cultured for more than a year. The cell line was observed to maintain not only its morphologic similarity to the primary cancer cells, but also its aggressive nature, including high proliferative activity, numerous genetic abnormalities, and cytokine production. Further, we have demonstrated the expression of telomerase activity in the cell, which could represent one of the responsible mechanisms for the cellular aggressiveness of this type of tumor. CONCLUSIONS: This cell line might be useful for further study concerning the correlation between telomerase activation and disease progression or anaplastic change in thyroid cancer.

Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils.

Nd2 is a monoclonal antibody against pancreatic cancer. We have previously reported that human/mouse chimeric antibody Nd2 (c-Nd2) can induce antibody-dependent cell-mediated cytotoxicity (ADCC) with peripheral blood mononuclear cells (PBMs) as effectors. In this study, we investigated whether c-Nd2 can induce ADCC with poly-morphonuclear neutrophils (PMNs) as effector cells and the effects of granulocyte-colony stimulating factor (G-CSF) in enhancing this cytotoxicity. Cytotoxicities for pancreatic cancer cell line, SW1990 were dose-dependently increased by c-Nd2 during co-culture with PMNs and these cytotoxicities were significantly suppressed by the addition of neutralizing antibodies against CD16, which is Fcgamma receptor expressed on PMN membranes. PMNs treated with G-CSF significantly enhanced in vitro ADCC activity against SW1990 induced by c-Nd2. The in vivo growth of subcutaneously transplanted SW1990 tumor in nude mouse was significantly inhibited by i.p. administration of c-Nd2 compared to control (non-specific IgG1). In addition, this inhibitory effect was enhanced by the combination of c-Nd2 and G-CSF. Immunohistochemical study with anti-mouse neutrophil elastase antibody demonstrated strong infiltrations of PMNs into and around the transplanted tumor, treated with c-Nd2 and G-CSF. These results suggest that PMNs play an important role in c-Nd2 inducing ADCC and that combination immunotherapy of c-Nd2 with G-CSF may have clinical applications in the treatment of patients with pancreatic cancer by enhancing ADCC.

A novel spermatogenesis-related factor-1 gene expressed in maturing rat testis.

A rat gene with testis-specific expression coinciding with spermatogenesis was cloned by differential display. This spermatogenesis-related factor-1 (SRF-1) gene was not expressed in other organs. Testicular expression was detected from 5 weeks of age and increased up to 15 weeks; this level of expression was maintained for 63 weeks. The 750-bp cloned gene was coded for an open reading frame of 202 amino acids. According to in situ hybridization at 7 weeks, this gene was expressed mainly in spermatocyte. The gene product may function as a molecular motor in meiosis, as the deduced amino acid sequence showed partial homology with kinesin-related proteins. The action of this gene and its product with respect to division of reproductive cells requires further investigation.

Generation of highly repetitive optical pulses based on intracavity four-wave Raman mixing.

An extremely long train of highly repetitive pulse (17 THz) is obtained by the rotational four-wave Raman mixing of molecular hydrogen in a resonator using a computer simulation. This highly repetitive pulse can be obtained only when the laser wavelength and the resonator are adjusted to specified values. This pulse train has potential for use in ultrafast data communication because of the accurately determined repetition rate or even as a frequency standard, since the frequencies of the emission lines can be stabilized and locked to the above values.