Israel Medical Association Journal

We describe a unique E3, the F-box protein, Ufo1, of yeast. Ufo1 recruits the mating switch endonuclease, Ho, to the SCF complex for ubiquitylation. In addition to the F-box and WD40 protein-protein interaction domains found in all F-box proteins, Ufo1 has a unique domain comprising multiple copies of the ubiquitin-interacting motif. Ufo1 interacts with the UbL-UbA protein, Ddi1, via its UIMs[1], and this is required for turnover of SCF ^Ufo1 complexes. This is a novel function for an UbL-UbA protein. Deletion of the genomic UFO1 UIMs is lethal and our data indicate that Ufo1ΔUIM acts as a dominant negative leading to inhibition of the SCF pathway of substrate degradation and to cell cycle arrest. Furthermore, we found that Ddi1 is required for the final stages of degradation of Ho endonuclease. In the absence of Ddi1, Ho does not form a complex with the 19S RP and is stabilized. Stabilization of Ho leads to perturbation of the cell cycle and to the formation of multi-budded cells. Our experiments uncover a novel role for the ubiquitin-proteasome system in maintenance of genome stability.

Objectives: To determine the prevalence of different pathogens in patients presenting to our sexually transmitted disease clinic with hematospermia.

Methods: Between January 1999 and January 2000, 16 patients presented to our STD[1] clinic with hematospermia after other non-infectious pathologies had been excluded by a referring physician. After obtaining informed consent, subjects completed a questionnaire addressing symptoms and sexual behavior. First void urine samples, as well as genitourinary and serum specimens were tested for Chlamydia trachomatis, Ureaplasma urealyticum and Herpes simplex virus. Standard bacterial cultures were also performed.

Results: Laboratory testing detected a pathogen in 12 of the 16 males presenting with hematospermia. The sexually transmitted pathogens detected were Herpes simplex virus in 5 patients (42%), Chlamydia trachomatis in 4 (33%), Enterococcus fecalis in 2 (17%), and Ureaplasma urealyticum in 1 (8%). In all cases in which a pathogen was identified, the appropriate antimicrobial agent was administered. Symptoms resolved for each patient following antimicrobial therapy. During a 1 year follow-up, all 12 patients remained free of disease.

Conclusions: Recent advances in microbiologic diagnostic techniques have facilitated the detection of pathogens in patients with hematospermia, thereby enhancing the efficacy of treatment.

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[1] STD = sexually transmitted disease

Background: A major psychological sequel of terrorist attacks is post-traumatic stress disorder. The relation between certain psychological factors specific to terrorist attacks (e.g., perceived control attributed to oneself/to the military, anticipated duration of terrorism) and PTSD[1] symptoms have not been examined.

Objective: To examine the prevalence, correlates and moderators of PTSD-like symptoms following terrorist attacks in Israel.

Methods: Soon after a long wave of terrorist attacks in Israel in 2002, a convenience sample of 149 Israelis from five cities was assessed for terrorist attack exposure, perceived control, control attributed to the government/military, anticipated duration of the terrorism wave (predictability), and frequency of listening to the news. PTSD-like symptoms were assessed with a brief self-report scale.

Results: We found that 15.4% of the sample was directly exposed to a terrorist attack and 36.5% knew someone close who had been exposed to an attack. “Clinically significant” PTSD-like symptoms were reported by 10.1% of the sample. Correlates of PTSD-like symptoms were: perceived control in men, government control, and education in women (all inversely correlated to PTSD symptoms), and news-listening frequency in women (positively correlated to PTSD symptoms). PTSD-like symptoms were attenuated by the ability to predict the duration of the terrorism wave only in citizens exposed to an attack, and by perceived government control only among citizens listening infrequently to the news.

Conclusions: This study revealed that approximately 10% of Israelis in our sample had relatively frequent PTSD-like symptoms. Correlates of PTSD-like symptoms differed between men and women, and moderator effects were found. These findings reveal additional moderators that may have implications for treating PTSD following terrorist attacks.

Background: Increased levels of high density lipoprotein (over 60 mg/dl) are considered to be a risk factor for ischemic heart disease. However, some patients with high HDL[1] still develop cardiovascular diseases.

Objective: To find out why patients with very high HDL still suffer from cardiovascular diseases.

Methods: We analyzed several risk factors, such as increased lipid peroxidation, hyperhomeocysteinemia and increased release of inflammatory molecules that could be related to the development of vascular disease in patients with high serum HDL levels. Patients with HDL cholesterol levels above 75 mg/dl were selected for this study and were separated into two groups based on the presence of atherosclerotic vascular disease, i.e., those with vascular disease (patients) and those without (controls).

Results: Plasma isolated from the patient group exhibited significantly increased lipid peroxidation by 21% and decreased total antioxidant status by 17%, but there were no differences regarding their serum or their paraoxonase activity. Moreover, both groups exhibited similar levels of serum C-reactive protein, fibrinogen and homocysteine, enabling us to eliminate these risk factors in the etiology of cardiovascular disease in the patient group.

Conclusion: Increased oxidative stress could be one of the factors leading to cardiovascular diseases in patients with high serum HDL levels.

Background: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer.

Objective: To evaluate the presence and prognostic value of MUC1 and Met-HGF/SF in the axillary drainage of these patients.

Methods: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-hepatocyte growth factor/scatter factor and b-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status.

Results: RT-PCR[1] assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF[2] in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.02 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05).

Conclusion: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.

Background: Non-gonococcal urethritis is the most common clinical diagnosis for men seeking care at sexually transmitted disease clinics.

Objective: To identify the pathogens involved in NGU[1] among males attending an Israeli STD clinic.

Methods: During 19 months spanning September 1996 to July 1998 we investigated a cohort of 238 male patients attending the Bnai Zion Medical Center STD[2] clinic with a clinical presentation of urethritis. Intraurethral swab specimens were tested for Neisseria gonorrhea, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis by culture and for herpes simplex virus by antigen detection. First voiding urine for Chlamydia trachomatis was done by polymerase chain reaction. The specific seropositivities of HSV[3] types 1 and 2 were tested by enzyme-linked immunosorbent assay.

Results: From among 238 males with dysuria or urethral discharge an etiology for urethritis was found for 71 (29.8%). N. gonorrhea was recovered in only three men (4.2%). In the remaining 68 NGU patients C. trachomatis (35/68, 51.5%) and U. urealyticum (31/68, 45.6%) were the most common infecting and co-infecting pathogens (P < 0.0001). M. hominis and T. vaginalis were found in 9/68 (13.2%), and 1 patient, respectively. HSV was recovered from the urethra in 7/68 males (10.3%) – 3 with HSV-1, 2 with HSV-2, and 2 were seronegative for HSV. None of these males had genital lesions. Although a single etiologic agent was identified in 45/68 infected men (66.2%), co-infection was common: 2 organisms in 15 (22%) and 3 organisms in 8 (11.8%).

Conclusion: C. trachomatis and U. urealyticum were the most common infecting and co-infecting pathogens in this cohort of men with NGU. Unrecognized genital HSV infections are common in males attending our STD clinic and symptomatic shedding of HSV occurs without genital lesions. Still, the microbial etiology in this group remains unclear in many patients despite careful microbiologic evaluation.

Background: Menopause affects women's health and well-being, but their knowledge of proper care and maintenance is uncertain.

Objective: To assess the attitude and approach of the healthy, low risk, postmenopausal population in Israel to personal healthcare and menopause.

Methods: The study population comprised 500 menopausal women attending community outpatient primary care clinics. All women completed a 20-item questionnaire covering personal healthcare habits, lifestyle, knowledge about menopause, and attitude and approach to menopause and use of hormone replacement therapy.

Results: The patients' mean body mass index was 25.8 ± 4.1 kg/m²; more than half the women were overweight, 28% percent engaged in regular sports activity, nd 11.2% smoked; 74% had a positive attitude towards their age; 60% underwent yearly screening mammography; 74% have had Pap smear and 86% had lipid profile measurements during the last year; self-examination of the breast was regularly performed by only 49%. HRT[1] is currently being used by 27% and had been used in the past by another 16%. The primary reasons for stopping therapy were irregular bleeding in 38% and apparent ineffectiveness in 35%. There was a positive significant correlation between level of education and both undergoing regular medical screening and engaging in regular sports activity. HRT current utilization was negatively associated with age and being a housewife.

Conclusions: A relatively high percentage of the study population safeguards its health and regularly uses HRT. We believe that stronger efforts are needed in Israel to promote good healthcare habits and positive attitudes toward menopause and HRT use.

Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.

Background: A mass influx of immigrants from the former Soviet Union to western countries and Israel followed the demise of the Soviet Bloc at the beginning of the 1990s. It was expected that these immigrants would have a higher morbidity and mortality rate similar to that in Russia.

Objectives: To measure and compare self-reported diseases, subjective health and health services utilization of a representative sample of veteran Israeli Jews and immigrants from the former USSR.

Methods: A cross-sectional survey of Israeli adults was performed by telephone interviews. The survey included 793 Israeli Jews, of whom 124 were immigrants from the former USSR who arrived in Israel after 1989 (response rate 52%).

Results: The immigrants reported a higher rate of diseases and sub-optimal health after adjustment for other variables. However, no excess in health services utilization was reported. A time trend of reporting sub-optimal subjective health was observed: the longer the immigrants spent in Israel the more their reporting patterns resembled those of immigrants who arrived in Israel before 1970. Those who arrived after 1994 more frequently reported having a chronic disease.

Conclusions: Acculturation seems to have been the main effect on the immigrants' health, together with a healthy migrant effect at the beginning of the 1990s. The immigrants' health was worse in the later years of the immigration wave, partially reflecting the poor state of health in Russia compared to Israel.
 

Background: Urinary incontinence in older women is common. Its characteristics and impact on quality of life is not well established since these women are usually reluctant to tell their healthcare providers about the problem.

Objective: To determine the characteristics of urinary incontinence in women and the manner in which it affects patients quality of life.

Methods: Twenty family physicians were requested to distribute a questionnaire to the first 25 consecutive women aged 30 to 75 years who visited their clinic for any reason. The questionnaire covered general health issues, symptoms of urinary incontinence, and quality of life.

Results: A total of 418 women, mean age 50.0 ± 11.8 years, completed the questionnaire (84% response rate). Of these, 148 (36%) reported having episodes of urinary incontinence. Urinary incontinence was found to be associated with older age, menopause, obesity and coexisting chronic disorders. Sixty percent of the women with urinary incon­tinence found it to be a disturbing symptom, and 44% reported that it had a detrimental effect on their quality of life. Only 32% of the affected women had sought medical advice, half of them from their family physician. Treatment was recommended to 66% of those who sought help, and in about two-thirds of these it brought some measure of relief.

Conclusions: Urinary incontinence is a common com­plaint among women attending primary care clinics, but it does not receive appropriate attention, Though it often adversely affects quality of life, only a small proportion of women seek medical advice. Family physicians should raise the issue as a part of the routine general health check-up.
 

Background: Israel lacks a systematic surveillance of sports injuries, and knowledge of risk factors and specific patterns of injury is inadequate. In order to promote prevention of sports-related injuries, the magnitude of the problem must first be identified and the incidence and severity of sports injuries described.

Objective: To conduct a survey on previous sports injuries among a sample of Israeli athletes.

Methods: A convenience sample of Israeli amateur athletes participating in the 1997 15th Maccabiah Games was randomly selected. The study group answered an anonymous self-administered questionnaire that included sociodemographic data, and information regarding their sports activity and sports-related injuries that had occurred during the previous 2 years.

Results: The study group, aged 12-3 years (median age 21), comprised 301 consenting athletes in 28 different sports. Of these athletes 56.1% reported having had at least one injury. Most injuries (75.6%) involved the upper and lower extremities, and 37.8% of the injured sportsmen had received medical attention from a physician. Half of the athletes participated in contact sports - both collision and limited impact. This group had a much greater proportion of reported injuries in all age groups.

Conclusion: Surveillance of sports injuries should be expanded in order to develop appropriate prevention programs in Israel.