Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.

Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.

Occupational Stress and MMPI-2 Profile of Workers in Some Plants Undergoing Labor Dispute / 대한산업의학회지

OBJECTIVES: To identify changes in relationships with superiors or colleagues at work and family members and social networks at home, based on occupational stress and psychological characteristics in during the process of restructuring some plants undergoing a long-term labor dispute. METHODS: This study invested 213 workers involved in a long-term labor dispute using the KOSS (Korean Occupational Stress Scale) and the MMPI-2 (Minnesota Multiphasic Personality Inventory) and questionnaires. The KOSS and MMPI-2 scores in accordance with aggressiveness of trade union activity and changes in human relationships were compared. In addition, the odds ratio of whether there were differences in health behavior (perception of health status, smoking, alcohol abuse, medical treatment) and the absenteeism rate was calculated by logistic regression analysis. RESULTS: For members of the aggressiveness of trade union activity group, the rate at which the relationship between superiors or colleagues deteriorated was high, as was the total KOSS score, occupational system and lack of reward score of KOSS subclass. The depression subclass score of MMPI-2 was generally high, while the score of hypochondriasis, hysteria, psychopathic deviate, hypomania was high, and social introversion was low in the active group. In cases in which there were high score of psychopathic deviate, hypomania and paranoia, there were also signs of negative health behavior. CONCLUSIONS: Occupational stress caused by a long-term labor dispute, accompanied with depression can result in an aggressive, hostile and vulnerable personalities and have a negative impact on health behavior.

Relationship between Occupational Stress-Emotional Labor and Musculoskeletal Symptoms and Experience of Absence or Early Leave in Some Civil Affairs Officials / 대한산업의학회지

OBJECTIVES: The objectives of this study are to identify the relationship between the Korean occupational stress scale (KOSS) and emotional labor, and to study the association between emotional labor and musculoskeletal symptoms, absence or early leave due to physical problems among civil affairs officials. METHODS: 391 public workers who provide social insurance service were analyzed. A structured self-reported questionnaire was used to assess sociodemographics, job stress, emotional labor, musculoskeletal symptoms and the experience of absence or early leave due to physical problems. For a comprehensive understanding of the relationship among these factors, multiple logistic regression analysis was used. RESULTS: The Pearson coefficient was 0.409 between the job demand of KOSS and the emotional labor score. The odds ratio of musculoskeletal symptoms is 2.32(95% CI: 1.17~4.61), 2.48(95% CI: 1.15~5.33) in the groups of moderate and, high emotional labor score, respectively, compared to the low score group. On the other hand, the odds ratio of the experience of absence or early leave due to physical problems is 2.43(95% CI: 1.24~4.76) and, 3.08(95% CI: 1.44~6.57) in the same groups. CONCLUSIONS: Emotional labor acts as a factor of job demand of KOSS, and has an effect on musculoskeletal symptoms and absence or early leave among civil affairs officials.

Radiological Flattening of Lumbar Lordosis and Related Factors in Some Korean Farmers / 대한산업의학회지

OBJECTIVES: To determine if agricultural work is related to radiological flattening of lumbar lordosis, and to identify the relationship between of back pain and flat back in selected Korean farmers. METHODS: Between June 2006 and July 2008, 414 farmers, 155 (37.4%) males and 259 (62.6%) females participated in this study. We collected data on hazardous agricultural work postures and other factors from interviews, surveys, and x-ray views of lateral lumbar. The operational definition of a flat back was below -1 SD of lordotic angle, with a normal distribution between L1 and S1 level. Logistic regression analysis was conducted to evaluate the relationship between flat back and hazardous working posture ratio, sex, the severity of back pain. RESULTS: Mean lordotic angle was 42.9+/-15.7degrees. Flat back had a higher prevalence in the females (24.7%) than the males (5.8%). The odds ratio of flat back risk is 3.30 (95% CI: 1.46~7.46) in the females compared to the males, 1.31 (95% CI: 0.61~2.79), 4.11 (95% CI: 1.77~9.55) in the group of hazardous working posture ratio compared to the low risk group, 2.78 (95% CI: 1.27~6.07), 5.74 (95% CI: 2.27~14.49) in the group of L4-L5 disc space narrowing compared to normal group, 3.06 (95% CI: 1.27~7.31), 5.45 (95% CI: 1.70~17.46) in the group of lumbar spine compression fracture compared to no fracture. Odds ratio of severe back pain is 2.29 (95% CI: 1.12~4.72) in the group of flat back compared to normal group. CONCLUSIONS: Hazardous agricultural working postures, such as 'low- lifting, pulling, pushing work and high- squatting posture work' are associated with flat back. Low back pain is significantly associated with flat back group in female farmers.

Lichen Sclerosus et Atrophicus of the Glans and Prepuce of the Penis - A Case Report - / 대한피부과학회지

LSA of the glans and prepuce of the penis is uncommon. It usually appears as whitish plaques and macules and can progress to orificial narrowing, phimosis and carcinorna. The case presented herein showed distinct papules and nodules on the glans and inner side of the prepuce instead of usual flattened patches. The patient, 24 years old man, was seen first seven months after his initial notice of the illness and has been observed by the authors four years thereafter. For the first year the papuloncdules on the glans were hard in consistence and the glans itself was being contracting, From the third year, the hard papulonodules began to resolve but resulted in greatly contracted glans penis. To observe the diagncsic histopathological finding repeated biopsies were needed.

A Case of Pemphigus Vulgaris / 대한피부과학회지

Pemphigus vulgaris is serious mucocutaneous bullous disease and is rarely reported in this country. The authors had observed a patient with pemphigus vulgaris from its early stage to the autopsy, including a total of five admissions. The patient had satisfactorily responded to low doses of prednisolone (60mg/day) initially and high doses (up to 180mg/day) later, but the patient died unexpectedly during admission. Autopsy finding revealed extensive soft tissue abscesses in both gluteofemoral regions from which Pseudomonas aeruginosa was cultured.

Bowen's Disease Associated with cutaneous Horn and Squamous Cell Carcinoma / 대한피부과학회지

Bowen's disease is intraepidermal squamous cell carcinoma involving skin and certain mucocutaneous junctions. The disease usually persues a slow relatively benign course but may progress to invasive squamous cell carcinoma. The present case, 67-years-old male, showed multiple dark brownish somewhat elevated horny lesions on the trunk and extremities including both palms. Some of the lesions had the appearance of small horns. Multiple biopsy specimens revealed typical histological findings of Bowen's disease or frank invasive squamous cell carcinoma. according to the each biopsy site. Authors treated all the lesions with surgical avulsion and electrodesiccation with curettage under general anestthesia and subsequent topical 5-FU ointment application.