Incidence and prevalence of psoriasis in Israel between 2011 and 2017.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease associated with a heavy burden of morbidity, disability and cost. The occurrence of the disease in Israel has not been previously investigated. OBJECTIVES: To provide standardized estimates of trends in psoriasis incidence, prevalence and mortality among patients in Israel between 2011 and 2017. METHODS: Using electronic health records from Clalit Health Services, the largest nationwide public health provider in Israel, we conducted a population-based study investigating trends in the annual incidence and prevalence of psoriasis between the years 2011 and 2017. We report age- and sex-adjusted rates, using the standard European population as a reference. RESULTS: We identified 71 094 incident psoriasis cases. The mean (SD) age of onset was 42.4 (21.0) years with a bimodal distribution, peaking in the early '30s and early '60s. Late-onset psoriasis, occurring after 40 years of age, accounted for 51.1% of incident cases. The annual psoriasis incidence rate was constant throughout the study period (280/100 000 person-years). Psoriasis prevalence rose from 2.5% in 2011 to 3.8% in 2017. CONCLUSIONS: Psoriasis prevalence is increasing in Israel, although its incidence is stable. Clinicians and policymakers should plan to address the growing demands in the clinical, economic and societal burden of psoriasis.

Chronic Traumatic Sagittal Band Injury with Extensor Tendon Dislocation: Report of a Case and New Surgical Technique.

Chronic sagittal band injury with tendon dislocation of the extensor digitorum communis in the hand often requires operative stabilization. Various surgical techniques have been reported to repair and reconstruct the sagittal band. Nonetheless, most of the techniques are technically demanding and require donor graft. In this case report, we report a novel surgical technique to centralize and stabilize the tendon by reattaching the radial sagittal band with anchor sutures. The advantages of this new technique are simple, no donor morbidity and stable repair to restore the normal biomechanics of the tendon. The patient was able to return to work in three months and no recurrent dislocation was noted at review two years after surgery.

Function of the 'direct' and 'indirect' pathways of the basal ganglia motor loop: evidence from reciprocal aiming movements in Parkinson's disease.

The purpose of this study was to test the validity of a neural-network model of the basal ganglia developed by Bischoff and colleagues (A. Bischoff, Modeling the basal ganglia in the control of arm movements (Doctoral dissertation, University of Southern California, 1998). Dissertation Abstr. Int. 59-08B (1998) 3924, 0208; A. Bischoff, M.A. Arbib, Modeling the role of basal ganglia and supplementary motor areas in sequential arm movements, Abstr. Soc. Neurosci. 23 (1997) 466; A. Bischoff, M.A. Arbib, C.J. Winstein, Modeling the role of the basal ganglia in reciprocal aiming task, Proceedings of the Fourth Annual Joint Symposium on Neural Computation, University of Southern California, Los Angeles, 7, 1997, pp. 20-27), and to examine the effects of levodopa on aiming movement performance. Findings confirm the model predictions for repetitive aiming movements. Individuals with late stage Parkinson's disease demonstrated longer movement times and longer pauses between aiming sequences compared to controls. Levodopa only slightly improved bradykinesia but not akinesia in these patients.

Development of a highly sensitive quantitative competitive PCR assay for the detection of murine cytomegalovirus DNA.

Viral persistence and molecular latency are characteristic of infection by the human cytomegalovirus (HCMV). Using the murine cytomegalovirus (MCMV) as a model for human infection, a quantitative-competitive polymerase chain reaction (QC-PCR) assay was developed to detect and quantify MCMV-DNA in the salivary glands of infected mice. The QC-PCR detected high numbers of MCMV DNA copies in the absence of infectious virus. By comparing the DNA content and the results obtained from a standard semiquantitative plaque assay, it is concluded that 1 plaque-forming unit (pfu) is the equivalent of approximately 1500 viral genomes. By day 42-post infection (pi) 4x10(3) copies of DNA/1 mg tissue were sufficient to reactivate infectious virions after cyclophosphamide immunosupression. By day 90 pi, however, when the DNA load was decreased to <1.2x10(2), reactivation was not observed. These results indicate that viral reactivation will occur when the number of infectious DNA copies is equivalent about 2-3 pfu. This quantitative test may therefore help to detect CMV and the risk of reactivation in immunosupressed patients.

Characterization of a brain-specific nuclear LIM domain protein (FHL1B) which is an alternatively spliced variant of FHL1.

We have amplified and sequenced a novel, alternatively spliced variant of a human gene coding for the four-and-a-half LIM domain protein 1 (FHL1). This gene is located at chromosome Xq27 and the spliced variant is named FHL1B. The ORF of FHL1B cDNA codes for a LIM-only protein that possesses a zinc finger and three tandem repeats of LIM domains at the N-terminus with an active bipartite nuclear localization signal (NLS) motif and a possible RBP-J binding region at the C-terminus. FHL1B and FHL1 have the same N-terminal three-and-a-half LIM domains but different C-terminal protein sequences, due to the presence of an additional alternative exon 4b in FHL1B causing a frame-shift in the 3'coding region. RT-PCR results revealed that the expression of FHL1 is not restricted in skeletal muscle and heart, but is widely distributed in other tissues, including brain, placenta, lung, liver, kidney and pancreas, albeit as a low abundance transcript. In contrast, FHL1B is specifically expressed in brain. The C-terminal alternative region in FHL1B is sufficient to localize FHL1B in the nucleus of mammalian cell. FHL1B is probably related to neural differentiation and certain fragile X syndrome.

Acylated ascorbate stimulates collagen synthesis in cultured human foreskin fibroblasts at lower doses than does ascorbic acid.

Acylated derivatives of ascorbic acid were found to be active in a number of biochemical and physiological processes. In the present study we investigated the effects of 6-O-palmitoyl ascorbate on collagen synthesis by cultured foreskin human fibroblasts. Our observations indicate a marked stimulatory effect on collagen synthesis by 6-O-palmitoyl ascorbate in the concentration range of 5-20 microM, while the synthesis stimulated by ascorbic acid was maximal at concentrations of 20-100 microM. Cells treated with 10 microM palmitoyl ascorbate for 36 h exhibited a production of collagen threefold greater than those in the presence of 10 microM ascorbic acid, and it was about the same as in cells treated with 100 microM ascorbic acid. By 48 h differences were not significant. Acylated ascorbate impaired vitality of the treated fibroblasts at concentrations exceeding 20 microM in media supplemented with 0.5% FCS. However, most of the cytotoxic effect was neutralized by FCS at a concentration of 10%. The resistance of acylated ascorbate against oxidative degradation as well as the role of free radicals in the modulation of collagen synthesis by ascorbic acid and by its derivatives is discussed.

Dynamics of an ultrasonic transducer used for wire bonding.

The vibration displacement distributions along a transducer used in ultrasonic wire bonding were measured using a heterodyne interferometer, and many nodes and anti-nodes were found. A mechanical finite element method (FEM) was used to compute the resonant frequencies and vibration mode shapes. The displacement distributions of the dominant 2nd axial mode agreed well with the measured values. Undesirable nonaxial modes, including the higher order flexural and torsional modes, also were excited at frequencies very close to the working frequency (2nd axial mode) of the transducer. Hence, the measured displacements were the resultant of all the allowable modes being excited. However, the excitation of these nonaxial modes were small enough not to affect the formation of consistent and high quality wire bonds. Results of the present study were used to determine a suitable location for installing a piezoelectric sensor to monitor the bond quality.

Molecular cloning, nucleotide sequencing, and expression of genes encoding alcohol dehydrogenases from the thermophile Thermoanaerobacter brockii and the mesophile Clostridium beijerinckii.

Proteins play a pivotal role in thermophily. Comparing the molecular properties of homologous proteins from thermophilic and mesophilic bacteria is important for understanding the mechanisms of microbial adaptation to extreme environments. The thermophile Thermoanaerobacter (Thermoanaerobium) brockii and the mesophile Clostridium beijerinckii contain an NADP(H)-linked, zinc-containing secondary alcohol dehydrogenase (TBADH and CBADH) showing a similarly broad substrate range. The structural genes encoding the TBADH and the CBADH were cloned, sequenced, and highly expressed in Escherichia coli. The coding sequences of the TB adh and the CB adh genes are, respectively, 1056 and 1053 nucleotides long. The TB adh gene encoded an amino acid sequence identical to that of the purified TBADH. Alignment of the deduced amino acid sequences of the TB and CB adh genes showed a 76% identity and a 86% similarity, and the two genes had a similar preference for codons with A or T in the third position. Multiple sequence alignment of ADHs from different sources revealed that two (Cys-46 and His-67) of the three ligands for the catalytic Zn atom of the horse-liver ADH are preserved in TBADH and CBADH. Both the TBADH and CBADH were homotetramers. The substrate specificities and thermostabilities of the TBADH and CBADH expressed inE. coli were identical to those of the enzymes isolated from T. brockii and C. beijerinckii, respectively. A comparison of the amino acid composition of the two ADHs suggests that the presence of eight additional proline residues in TBADH than in CBADH and the exchange of hydrophilic and large hydrophobic residues in CBADH for the small hydrophobic amino acids Pro, Ala, and Val in TBADH might contribute to the higher thermostability of the T. brockii enzyme.

Sensory-motor control in the ipsilesional upper extremity after stroke.

There is substantial evidence to indicate that sensory-motor control of the ipsilesional upper extremity (UE) in adults after unilateral stroke is abnormal. Some of the sensory-motor deficits differ as a function of the side of the cerebral lesion. Rapid movements of the ipsilesional UE that require precise timing and sequencing are more affected in individuals with lesions in the left hemisphere. In contrast, ipsilesional movements that have constrained spatial requirements are more affected in those with lesions in the right hemisphere. Ipsilesional UE coordination of discrete tasks may be normal, but the coordination of continuous tasks is affected in adults with left stroke. Sensation in the ipsilesional UE appears to be unaffected, or minimally affected after stroke. Strength deficits have been demonstrated in the ipsilesional UE, but primarily in those with right sided lesions. Ipsilesional performance deficits are revealed in clinical tests of function that use time to completion as the measure of success. Ipsilesional performance deficits may reflect motor control deficits that are masked on the contralateral side by hemiplegia and hemisensory loss. Interventions that focus on specific motor control deficits, such as speed of sensory-motor processing, through practice with the ipsilesional UE, may result in functional improvements in both limbs.

Treatment of murine cytomegalovirus salivary-gland infection by combined therapy with ganciclovir and thymic humoral factor gamma 2.

An optimal therapeutic regimen against primary CMV salivary-gland infection has not yet been developed. We used a murine CMV (MCMV) model system to assess the ability of combined thymic humoral factor THF-gamma 2 immunotherapy and ganciclovir (GCV) antiviral chemotherapy to eliminate detectable viral DNA from salivary glands of infected animals. Mice in different experimental groups were inoculated intraperitoneally with MCMV, treated, and then sacrificed either 2 weeks or 3 months later. To amplify and detect MCMV DNA in infected salivary-gland tissue, we developed a sensitive polymerase chain reaction (PCR) using a glycoprotein B gene primer pair that amplifies a 356 bp segment. During the acute phase of the infection, the detection of high titers of infectious virus in the salivary glands correlated with a strong PCR amplification signal. Although active virions could not be recovered from untreated animals 3 months after viral inoculation, the PCR assay detected a latent MCMV genome. Treatment with either GCV alone or THF-gamma 2 alone had little or no effect on the presence of MCMV DNA. By contrast, combined treatment with THF-gamma 2 and GCV significantly reduced the amount of salivary-gland MCMV DNA to below the limit of PCR detection. The results presented here, and experimental data from previous MCMV research in our laboratories, imply that elimination of the virus from the salivary glands could be due in part to THF-gamma 2 restoration of the various MCMV-suppressed, cell mediated immune-responses. Combining THF-gamma 2 immunotherapy and GCV antiviral chemotherapy may be an important step toward an effective therapeutic regimen that has the potential to prevent the establishment of viral latency ensuing from primary MCMV salivary-gland infection.

Expression of the gene for the receptor of gonadotropin-releasing hormone in the rat mammary gland.

Recent findings have demonstrated that the GnRH gene is expressed in the mammary gland of pregnant and lactating rats but not of virgin rats. Indeed, significant concentrations of biologically active GnRH have been found in milk of human, cow, sheep and rat. We have, therefore, looked for expression of the GnRH receptor in the rat mammary gland. By reverse transcription (RT)-PCR amplification, we have demonstrated the presence of GnRH receptor mRNA in mammary gland samples derived from virgin, pregnant and lactating rats. The GnRH receptor transcript cloned from the mammary gland was sequenced and found to have an identical coding region to the one cloned from the pituitary gland. In addition, we have found that the mammary gland, as the pituitary gland, contains at least two transcripts having the same coding region but different 5' non-coding regions. Binding studies, however, could demonstrate only low-affinity binding sites. These results, therefore, suggest that the regulation of the GnRH receptor occurs posttranscriptionally rather than at the level of transcription.

Novel therapeutic strategies against cytomegalovirus infection.

Murine CMV (MCMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV (HCMV) infection. MCMV causes T cell immune impairment in the infected mice, manifested by suppressed responses to T cell mitogens and a profound reduction of Con A induced IL-2 production. Thymic humoral factor (THF-gamma 2) is an octapeptide which was first isolated from calf thymus, characterized and chemically synthesized. This peptide has been shown to have immunoregulatory effects in various systems. Systemic treatment of MCMV-infected mice with THF-gamma 2 resulted in the enhancement of protective efficacy of MCMV immune spleen cells and the reconstitution of mitogenic responses and IL-2 secretion.

The gene for the neuropeptide gonadotropin-releasing hormone is expressed in the mammary gland of lactating rats.

The high concentration of gonadotropin-releasing hormone (GnRH) in milk of several species implies that the mammary gland is either a site of synthesis for this neuropeptide or that it is efficiently concentrated from plasma by this organ. By PCR amplification of mammary gland cDNA, we have demonstrated expression of the mRNA for GnRH. The GnRH mRNA was present in the mammary gland of pregnant and lactating rats but not of virgin rats, implying that expression of the GnRH gene is activated during pregnancy, probably by prolactin. In contrast, actin mRNA was evident in all the preparations of mammary glands. Since GnRH is also known to be synthesized by the placenta, it is likely that the placenta and the mammary gland are complementary units by which the mother exercises control over the development and the metabolism of the infant during pregnancy as well as after parturition. In addition, GnRH synthesized by the mammary gland may also affect the mother by a paracrine and/or an endocrine mechanism.

Thymic humoral factor, THF-gamma 2, enhances immunotherapy of murine cytomegalovirus (MCMV) infection by both CD4+ and CD8+ immune T cells.

Infection of mice with murine cytomegalovirus (CMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV. The contribution of the different spleen cell subsets in conferring curative immunocytotherapy to fatally MCMV-infected immunosuppressed mice was assessed using adoptive immunotherapy. It was found that the efficacy of passively transferred immune spleen cells is dose dependent and that the therapeutic effect can be enhanced considerably by treating donor mice with thymic humoral factor (THF-gamma 2). Polymerase chain reaction (PCR) of the donor spleen population was negative, indicating that no MCMV-DNA was transferred with the immune cells. Analysis of the donor mice after THF-gamma 2 treatment showed increased levels of CMV-neutralizing antibodies, while enhancement of natural killer (NK) activity was transient and lasted only during the early phase of the infection. FACS analysis demonstrated that treatment with THF-gamma 2 restored the size of both cell subsets CD4+ and CD8+ that were decreased following MCMV infection. It is shown that both CD4+ and CD8+ T-cell subsets participate in controlling the development of the fatal disease in MCMV-infected immunosuppressed recipients. It is suggested that the enhancement of the immunocompetence of both populations of spleen cells from treated donors is mediated in part by the restoration of Interleukin-2 (IL-2) production by THF-gamma 2.

Involvement of a C/EBP-like protein in the acquisition of responsiveness to glucocorticoid hormones during chick neural retina development.

The glucocorticoid receptor in chicken embryonic neural retina is expressed early in ontogeny, yet the tissue's response to the glucocorticoid hormone, i.e., induction of glutamine synthetase (GS), develops later, only during week 2 of ontogeny. Transient transfection of embryonic day 7 (E7) retinal cells, which are nonresponsive to glucocorticoids, with chimeric plasmids containing the chloramphenicol acetyltransferase reporter gene under the control of glucocorticoid-responsive promoters demonstrated that GR in E7 cells is a functional transactivating factor. We show that the limiting transcription factor that controls the developmental acquisition of responsiveness to glucocorticoids is similar to a CCAAT enhancer-binding protein (C/EBP). This protein recognizes a sequence in the promoter of the chick GS gene, which is required for eliciting the glucocorticoid response. Retinal C/EBP-like protein was not detected in the glucocorticoid-nonresponsive (E7) proliferating glioblasts but was found to be present in the glucocorticoid-responsive (E12) postmitotic cells. Premature expression of C/EBP in the nonresponsive E7 cells by transfection was shown to enhance the developmental acquisition of responsiveness to the glucocorticoid hormone, as deduced from the level of GS inducibility.

Meniscectomy operation as a surgical treatment for internal derangement of the temporomandibular joint in our department.

This paper describes the surgical treatment of six patients with internal derangement of the temporomandibular joint (nine joints). Meniscectomy was performed on all the patients, because severely advanced cases in which the articular disk could not be preserved or replaced were chosen. Our surgical technique and the results of short-term follow up are presented. Indications of meniscectomy and the criteria for postoperative evaluation are also described. The postoperative outcomes were assessed as "good" for seven joints in five patients and as "acceptable" for two joints in one patient.

Evidence that 5 S intermediate state in glucocorticoid receptor transformation contains hsp90 in addition to the steroid-binding protein.

Previous studies have shown that the exposure of molybdate-stabilized nontransformed glucocorticoid receptor (GR) of the chick embryonic neural retina to 0.4 M KCl dissociated the 9.5 S complex to a 5 S GR complex, which is an intermediate state in GR transformation. The present study was designed to characterize the 5 S GR complex. It shows that molybdate-stabilized nontransformed 9.5 S GR complex and 5 S GR interact with monoclonal antibodies (MAb) directed against 90 kDa heat shock protein (hsp90), as evidenced by the increase in the sedimentation velocity of these GR-complexes. Electrofocusing of the partially purified molybdate-stabilized nontransformed GR, prepared from [32P]-labeled neural retinas, and of the 5 S GR (derived from molybdate-stabilized preparation) showed that nontransformed GR complex, which has an apparent pI (pI') value of 5.0 +/- 0.2, and 5 S GR, which was resolved in a major peak with a pI' value of 5.8, are phosphorylated. Partially purified 5 S GR, cleared of molybdate and exposed to 25 degrees C, was resolved by electrofocusing into two phosphorylated fractions, one with a pI' value of 6.5, representing the monomeric GR form and the other with a pI' value of 5.1, apparently representing the acidic hsp90. The dissociation of hsp90 from the molybdate-cleared 5 S heterodimer seems to account for the decrease in the negative net charge of 5 S GR from pI' 6.5. Monomeric GR, derived from a molybdate-cleared, partially purified GR preparation, by the exposure to 25 degrees C, did not retain glucocorticoid-binding activity. Molybdate-stabilized 5 S GR was apparently re-assembled into the oligomeric nontransformed state when the salt concentration was reduced. This phenomenon was evident under the low-salt conditions of electrofocusing, by the shift in pI' value of GR from 5.8 to 5.0; and in glycerol density gradients containing 0.15 M KCl, by the shift in the sedimentation of the GR complex from 5 S to 9.5 S.

Mitochondrial protein synthesis may be involved in long-term memory formation.

The hypothesis that two qualitatively different stages of cerebral protein synthesis (PS) are required for the formation of long-term memory (LTM) for an active-avoidance task was investigated in rats. Cytoplasmic PS was inhibited with anisomycin (ANI-5.0 mg subcutaneously). When ANI was injected at 15 min pre- and 30 min posttraining, so that cerebral PS was inhibited by 90% for 2 hours starting just before training. LTM formation was prevented. When ANI was given after training, it was not effective. Mitochondrial PS was inhibited with chloramphenicol (CAP-1.5 mg intracisternally). Inhibition occurred 40 min after the injection. CAP interfered with LTM formation only when injected between 15 and 55 min after training. From these data it was concluded that two stages of PS are required for the formation of LTM. The first one takes place in the cytoplasm, starts with the commencement of training and is independent of newly synthesized mRNA. The second stage takes place in mitochondria starting approximately 25 min after training and is dependent upon newly formed mRNA.