Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells

Caveolin-1 is an essential structural constituent of caveolae that has been implicated in mitogenic signaling and oncogenesis. Caveolin-1 is down-regulated in oncogene-transformed and tumor-derived cells. Antisense suppression of caveolin-1 or expression of a dominant negative form are sufficient for inducing cellular transformation. Expression of recombinant caveolin-1 inhibits anchorage-independent growth in cancer cells. The present study was designed to determine whether this is caused by inhibition of cancer cell survival or cell proliferation, and to test if another important property of cancer cells, i.e. matrix invasion, is modulated by expression of caveolin. Utilizing MCF-7 human breast adenocarcinoma cells stably transfected with caveolin-1 (MCF-7/Cav1), we demonstrate that caveolin-1 expression decreases MCF-7 cell proliferation rate and markedly reduces their capacity to form colonies in soft agar. The loss of anchorage-independent growth is not associated with stimulation of anoikis; in fact, MCF-7/Cav1 cells exhibit increased survival after detachment as compared with MCF-7 cells, indicating that in these cells caveolin-1 inhibits anoikis. Analysis of matrix metalloprotease release and matrix invasion revealed that expression of caveolin-1 inhibits also these important metastasis-related phenomena. Plating MCF-7 cells on a laminin matrix resulted in activation of ERK1/2, which was dramatically inhibited in MCF-7/Cav1 cells. We conclude that high expression level of caveolin-1 in human breast cancer cells exerts a negative modulatory effect on anchorage-independent growth by inhibiting cell proliferation even though matrix-independent cell survival is enhanced. Caveolin-1 expression inhibits also matrix invasion and blocks laminin-dependent activation of ERK1/2. The inhibitory effect of caveolin-1 on these transformation-dependent processes supports the hypothesis that caveolin-1 acts as a tumor suppressor protein which may impose major phenotypic changes when expressed in human cancer cells.     

Regression of skeletal changes in type 1 Gaucher disease with enzyme replacement therapy

 A 9-year-old patient presented with an acute onset of pain of the right femur showing destructive changes with periosteal elevation mimicking osteomyelitis. Technetium-99m sulfur colloid (^99mTc SC) marrow scan revealed lack of uptake in the right femoral head and the entire shaft of the right femur. Eight months following enzyme replacement therapy, radiography showed almost complete reconstitution of the femoral shaft, and ^99mTc SC marrow scan uptake returned to normal.     

Constancy of relative body weight in children

The height and weight records of 404 schoolchildren at age 6 to 7 and at age 13 to 14 were analysed. Relative weight (i.e.% of ideal weight for height) of a child tended to change little over this period of 7 to 8 years of rapid growth. The correlation coefficient of relative weight for the group at the two ages was 0·81. In only 6% of the children did relative weight change more than 20% in either direction.This stability of relative body weight, despite the variations in environmental factors during school years, emphasizes the dominant role of genetic factors in the monitoring of body weight.     

A copper-based intrauterine device with gold or platinum core: and studies

The use of copper intrauterine contraceptive devices is currently limited to 2–3 years, mainly due to wire fragmentation, which was observed as early as after 8 months of use. In the resulting search for a long-lasting device, two new systems of duplex wire, with gold and platinum cores electrolytically coated with copper, were devised and studied. Initially, duplex wires and controls were exposed to physiological solution. Copper dissolution rate, and corrosion morphology were studied by weight-loss measurements and optical metallography. Similar systems were then surgically implanted in rat uteri for varying periods up to 26 weeks. Electron microanalysis of corrosion products in addition to weight-loss measurements and metallography was performed.The results showed that a uniform and ductile copper coating is obtainable by electroplating on gold and platinum wires. The rate of copper dissolution is similar to that of solid copper wire. No dissolution of gold and platinum in the controls or coated wires was detected by weight loss, metallography or atomic absorption measurements.Microanalysis of the deposits and corrosion products on the wires in the uterine environment showed the presence of compounds containing sulphur, chlorine, calcium and copper.The results of this study suggest that supplementing IUDs with copper-coated gold or platinum wires may result in significant prolongation of the life-span of the device by preventing uncontrolled loss of copper caused by wire fragmentation.     

Comparison of health care services for career soldiers throughout the world

Health care systems operate differently in every country and are products of historical and political factors. We compared health care systems for career soldiers in various countries with those of the Israel Defense Forces. Questionnaires requesting data regarding military health care services provided in their countries were sent to military attaches serving in Israel. The countries for which data were gathered include Argentina, Brazil, Chile, China, England, France, Finland, Germany, Hungary, Israel, Poland, Romania, Spain, and the United States. In most countries, career soldiers receive better health care services than civilians, especially in countries with military rule or under military threat.     

The hot skull sign on bone scans of obese patients resulting from disparate soft tissue attenuation

We have frequently observed diffusely increased skull activity on bone scans of obese patients, who do not have evidence of metabolic or metastatic bone disease. Skull activity of 25 obese patients were compared to that of age and sex-matched nonobese 25 patients visually and quantitatively. The results clearly indicated that diffusely increased skull activity is significantly more common on bone scans of obese patients because of disparate attenuation of overlying soft tissues. This knowledge will help obviate the need for additional radiologic and/or laboratory tests in search of other conditions associated with hot skull, ie, Paget's disease and metabolic bone disorders such as renal osteodystrophy and primary hyperparathyroidism.     

Biochemical subtyping of amyloid in formalin-fixed tissue samples confirms and supplements immunohistologic data

The systemic amyloidoses are a heterogeneous group of congophilic fibrillar protein deposition diseases that should be subtyped chemically by immunohistologic methods. Biochemical methods sometimes are required to confirm or identify the amyloid type in unfixed or informalin-fixed tissue samples. We report the results of formic acid extraction and immunochemical and biochemical characterization of deposits informalin-fixed tissue samples from 10 cases of amyloidosis and 3 from nonamyloid monoclonal immunoglobulin light chain deposition disease. The results in 11 of 13 cases demonstrated concordance with the previous immunohistochemical and/or biochemical data obtained in unfixed tissue samples from the same specimens, and in 2 of 13, the protein deposits that previously could not be classified by standard immunohistochemical methods were identified by amino acid sequence. An additional new finding of constant-region rather than variable-region fragments as the major constituent protein in 1 case of lambda light chain amyloidosis demonstrated the value of the method and its importance for future applications.     

The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa

Usher syndrome is a frequent cause of the combination of deafness and blindness due to retinitis pigmentosa (RP). Five genes are known to underlie different forms of Usher syndrome type I (USH1). In the Ashkenazi Jewish population, the R245X mutation of the PCDH15 gene may be the most common cause of USH1 (Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RK, Willner JP, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB N Engl J Med 348: 1664-1670, 2003). To estimate what percentage of Ashkenazi Jewish children born with profound hearing loss will develop RP due to R245X, we examined the prevalence of the R245X PCDH15 mutation and its carrier rate among Ashkenazi Jews in Israel. Among probands diagnosed with nonsyndromic hearing loss not due to mutations of connexin 26 (GJB2) and/or connexin 30 (GJB6), and below the age of 10, 2 of 20 (10%) were homozygous for the R245X mutation. Among older nonsyndromic deaf individuals, no homozygotes were detected, although one individual was heterozygous for R245X. The carrier rate of the R245X mutation among the normal hearing Ashkenazi population in Israel was estimated at 1%. Ashkenazi Jewish children with profound prelingual hearing loss should be evaluated for the R245X PCDH15 mutation and undergo ophthalmologic evaluation to determine whether they will develop RP. Rehabilitation can then begin before loss of vision. Early use of cochlear implants in such cases may rescue these individuals from a dual neurosensory deficit.