The Saccharomyces cerevisiae Fin1 protein forms cell cycle-specific filaments between spindle pole bodies

The FIN1 gene from the yeast Saccharomyces cerevisiae encodes a basic protein with putative coiled-coil regions. Here we show that in large-budded cells a green fluorescent protein-Fin1 fusion protein is visible as a filament between the two spindle pole bodies. In resting cells the protein is undetectable, and in small-budded cells it is localized in the nucleus. During late mitosis it localizes on the spindle pole bodies. Filaments of cyano fluorescent protein-tagged Fin1 colocalize with filaments of green fluorescent protein-tagged Tub1 only in large-budded cells. By electron and atomic force microscopy we showed that purified recombinant Fin1p self-assembles into filaments with a diameter of approximately 10 nm. Our results indicate that the Fin1 protein forms a cell cycle-specific filament, additional to the microtubules, between the spindle pole bodies of dividing yeast cells.     

局部应用水杨酸治疗家族性圆柱瘤的疗效评估

背景：家族性圆柱瘤是一类罕见的遗传病，是皮肤附属器产生的赘生物。近来发现圆柱瘤抑制基因的丢失引起一种具有抗凋亡活性的转录因子NF-kB的激活。这可能解释圆柱瘤的增长失调。在细胞水平的试验中，水杨酸能阻止圆柱瘤抑制基因丢失引起的NF-kB活化，提示水杨酸可能是圆柱瘤的有效疗法。目的：评价局部应用水杨酸治疗家族性圆柱瘤的效果。方法：来自4个不同圆柱瘤家系的5例患者局部应用水杨酸治疗2次／d，随后1次／d。临床反应用连续的肿瘤测量来确定。结果：5例患者共有17个圆柱瘤：12个为目标损害，5个为对照损害。圆柱瘤的大小M=1．0cm（极差0．6～2．8）。12个圆柱瘤中2个完全消退。另外8个皮损有一些反应，但未达到局部消退的标准。对照皮损保持稳定或增大。结论：水杨酸治疗圆柱瘤耐受性好，是一种新的有效疗法。     

Sugar malabsorption in healthy neonates estimated by breath hydrogen.

Carbohydrate malabsorption in 110 healthy, term neonates was studied by estimating expired hydrogen (H2) before and after a feed on day 6 or 7. Carbohydrate malabsorption was assumed to be present if the infant excreted > 20 parts per million (ppm) H2. The frequency of carbohydrate malabsorption in 49 breast-fed infants was 25% (n = 12), in 35 infants fed a 7.5% lactose formula it was 31% (n = 11), in 26 infants fed a formula containing 1% lactose and 7.3% maltodextrin it was 15% (n = 4). These differences in frequency were not significant. Peak H2 concentration of the malabsorbers in each group, indicating the degree of carbohydrate malabsorption, was 64, 52, and 32 ppm respectively. The degree of carbohydrate malabsorption did not differ significantly between the breast-fed and the high lactose formula groups, but both groups differed from the low lactose group. H2 excretion was studied for 5 months in an exclusively breast-fed infant. In the first 2 months high concentrations were found and the infant produced 3-5 stools a day. In the next 3 months however, most H2 estimations were normal and only 1-2 stools a week were passed. With the introduction of solids, daily bowel movements promptly reoccurred. Frequency of carbohydrate malabsorption in newborn infants is fairly high and is primarily related to the lactose intake. The frequency and degree of carbohydrate malabsorption were comparable in breast-fed infants and in infants fed on a high lactose formula; this differs from results previously reported.     

Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine,bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial

Background:

Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma.

Methods:

In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated.

Results:

The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log₁₀CEC hazard ratio (HR) 0.41, 95% CI 0.18–0.91) and 6 weeks (log₁₀CEC HR 0.16, 95% CI 0.05–0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS.

Conclusion:

CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.     

Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Craniofacial, craniocervical, and pharyngeal morphology in bilateral cleft lip and palate and obstructive sleep apnea patients.

OBJECTIVE: The aim of this study was to analyze craniofacial, craniocervical, and pharyngeal morphology in surgically treated bilateral cleft lip and palate (BCLP) men, untreated men with obstructive sleep apnea (OSA), and a reference group of men. SUBJECTS AND METHODS: Lateral cephalograms were obtained of 27 male BCLP patients (mean age 29.0 +/- 8.3 years), 27 untreated male OSA patients (mean age 38.6 +/- 5.3 years), and 27 male controls serving as a reference group (mean age 30.8 +/- 9.2 years). Tracings were made, and 26 variables representing craniofacial, craniocervical, and pharyngeal dimensions were obtained using Viewbox 3.1.1.6. software. The groups were compared using a one-way analysis of variance. RESULTS: Craniofacial, craniocervical, and pharyngeal morphology of BCLP and OSA patients was similar except for a significantly more retrusive maxilla in the BCLP group. Compared to the reference group, the BCLP and OSA groups had significantly larger craniocervical angulations, smaller depth of the oropharynx at the tip of the velum, and a more inferiorly positioned hyoid bone. Significantly larger vertical dimensions were found in the BCLP group compared to the reference group. CONCLUSIONS: Craniofacial, craniocervical, and pharyngeal morphology of BCLP and OSA patients demonstrate substantial similarities except for a significantly more retrusive maxilla in the BCLP group. It is suggested that airway obstruction and postural adaptation to the obstruction may possibly be related to the aberrant craniofacial, craniocervical, and pharyngeal morphology in OSA and in BCLP patients.     

Pregnancy and severe aplastic anaemia: causal relation or coincidence?

The relationship between aplastic anaemia (AA) and pregnancy remains uncertain. To assess whether an association between pregnancy and severe aplastic anaemia (SAA) exists, we compared the frequency of pregnancy in 35 young women with newly diagnosed SAA with the expected frequency in the general population. The observed pregnancy rate in the SAA group was 3–6%. This percentage approximates the expected pregnancy rate of 4.4% in the general population and is not compatible with a strong association between pregnancy and SAA.     

Satisfaction with treatment outcome in bilateral cleft lip and palate patients

The aim of this case-controlled study was to assess satisfaction with facial appearance and function, and health-related quality of life (HRQL) in bilateral cleft lip and palate patients (BCLP). The study sample was composed of adult BCLP subjects and controls matched for age, gender and socioeconomic status. Outcome measures included a self-administered questionnaire evaluating satisfaction with facial appearance, function and HRQL. Bivariate statistics were computed to analyse the association between BCLP status and outcome measures. Forty-three treated adult BCLP patients (mean age 28.2 years, SD 7.8) were compared to 43 controls without clefts (mean age 28.5 years, SD 8.0). Quantitative and qualitative assessment revealed that BCLP patients were significantly less satisfied with the appearance of the upper lip, the nose and nasal breathing. Additionally, satisfaction with facial appearance correlated positively with HRQL. For speech, hearing and drinking, quantitative scores did not differ between BCLP and controls, while qualitative assessment revealed that BCLP patients had considerable problems and concerns with these functions. This study underlines the importance of qualitative assessment of patient satisfaction with treatment outcome to identify individual problems and concerns not revealed by quantitative measures alone.     

Effect of an intraoral retrusion plate on maxillary arch dimensions in complete bilateral cleft lip and palate patients.

OBJECTIVE: The aim of this study was to analyze maxillary arch dimensions in patients with complete bilateral cleft lip and palate treated with an intraoral retrusion plate prior to lip closure. PATIENTS: The effects of the intraoral retrusion plate were evaluated on serially obtained maxillary casts of 14 patients with complete bilateral cleft lip and palate. RESULTS: The Student's t test for dependent observations showed a significant decrease in distance between the premaxilla and the cleft lateral segments during active treatment. This decrease correlated with an increase in deviation of the premaxilla in relation to the vomer. For each millimeter decrease in distance between the premaxilla and the cleft lateral segments, an average increase in deviation of 4.0 degrees was found. Left and right cleft widths decreased significantly, premaxillary width increased significantly, and transverse dimensions did not change significantly. CONCLUSION: From this study it can be concluded that active presurgical treatment with an intraoral retrusion plate induces a significant decrease in distance between the premaxilla and the lateral segments. This decrease is frequently accompanied by an increase in deviation of the premaxilla relative to the vomer.