Emulsion polymerization of vinyl acetate: safe optimization of a hazardous complex process.

Fast and exothermic discontinuous emulsion polymerization processes are particularly difficult to optimize from both safety and productivity point of view because of the occurrence of side undesired reactions (e.g. chain transfer to monomer, backbiting, propagation of tertiary radicals, termination by disproportion, etc.) and the hazards of boiling phenomena and stable foam formation under atmospheric pressure. Moreover, the relevant number of loading, heating and cooling steps, required before starting the monomer addition (that is, the desired reaction), makes a strict product quality reproducibility very difficult to obtain. Under these operating conditions, it is necessary to employ a suitable combined theoretical and experimental procedure able to detect the optimum process dosing time at both the laboratory and the industrial scale. In this work, it is shown how to use the topological criterion theory together with proper adiabatic calorimeter and RC1 experimental data to safely optimize the synthesis of polyvinyl acetate through the radical emulsion polymerization of vinyl acetate by the means of an indirectly cooled isoperibolic semibatch reactor.

A normative study of a shorter version of Raven's progressive matrices 1938.

A shorter four-set (A, B, C, D) version of Raven's progressive matrices 1938 (PM38) has gained increasing use in neuropsychological assessment. No normative data spanning across a wide age range are, however, available. This study collected norms for the shorter version of PM38, established an inferential cut-off value and derived equivalent scores in a sample of 248 individuals from 20 to 89 years of age, evenly distributed across sex, age and education levels. Results showed significant effects of age and education but no effect of sex on performance. These normative data will complement existing norms for other tests, will increase the wealth of neuropsychological tools for which normative data are available for the Italian population, and may be useful in the early detection of individuals at risk of developing dementia.

46,XX male: clinical, hormonal/genetic findings.

The clinical genetics and hormonal status of the 46,XX male is well determined. This is a rare condition that affects one out 20,000 male births. This study evaluates 5 infertile patients with no abnormalities in sex definition in whom we noted variants in their phenotype, like small penis, hypospadias, cryptorchidism, flat scrotum, and in some of them small testis. Only one patient had gynecomastia; all patients were azoospermics. Otherwise, serum FSH levels were elevated in only 3 patients and LH in 2. Serum levels of testosterone were low in 3 cases. Karyotype was 46,XX without evidence of mosaicism. PCR of genomic DNA studied revealed only the presence of SRY gene. DNA material in the Y chromosome was similar in all patients, but this did not correlate with the phenotype findings and hormonal levels in all of them. Testing new chromosomal markers should be of great value in the definition of clinical difference.

47,XYY karyotype and normal SRY in a patient with a female phenotype.

A rare case of a female patient with a 47,XYY karyotype is described. She had normal female external genitalia, bilateral testes, rudimentary Fallopian tubes and no uterus. Molecular analysis revealed a normal SRY encoding sequence. The possible events in the etiology of this sex reversal entity are discussed.

Molecular analysis of p53 tumor-suppressor gene and microsatellites in preneoplastic and neoplastic lesions of the colon and esophagus.

Mutations in exons 4-8 of the p53 gene by the PCR-SSCP analysis in preneoplastic and neoplastic lesions of the colon (n=11) and esophagus (n=18) were screened. p53 overexpression by immunohistochemistry in 11 colonic lesions and 13 microsatellites, in all the patients (n=29), were also studied. A positive result concordancy between the three techniques was found in 1 adenoma and 2 adenocarcinomas of the colon, each with loss of heterozygocity of microsatellites. Metaplastic lesions of esophagus showed biallelic mutations and low frequency of microsatellite alterations. The relationship between genetic alterations in p53, microsatellites and type of colon and esophageal lesions is discussed.

Association of Turner's syndrome and Swyer's syndrome in the same family.

We report two phenotypically and genetically different diseases in the same family. One patient presented with Turner phenotype as a result of chromosomal mosaicism 45,X/46,X, inv(X)(q21;q24) (30%/70%). Her father's sister showed 46,XY female gonadal dysgenesis (Swyer's syndrome) as a result of a point mutation in the SRY gene on her Y chromosome. DNA sequencing revealed a G-->C transversion (nucleotide position 693) resulting in a change from glycine95 to arginine (G95R). Here we report for the first time an association of Turner's syndrome and Swyer's syndrome in the same family.

PCR analysis of Y-chromosome sequences in a 45,X male patient and a review of the literature.

The 45,X karyotype is usually associated with Turner syndrome, while male phenotype is exceptional. The authors report a 45,X male patient with normal external genitalia and sex behavior, but who was azoospermic. He had a normally developed musculature and pilose distribution, testicular volume of 15 mL and no gynecomastia but clinical stigmata of Turner syndrome (short stature, short neck and 4th metacarpal bones) and azoospermia. Hormonal plasma levels of testosterone, estradiol, prolactin, and gonadotrophins were within the normal range as was the response of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (30 and 60 min) after 100 microg iv of LH-RH administration. Testicular biopsy could not be performed. Karyotype was 45,X without evidence of mosaicism. Polymerase chain reaction of genomnic DNA studied with 12 different sequences of Y chromosome revealed only the presence of SRY gene (testis determining factor). It is possible that SRY/autosomal translocation had occurred in this patient. The study of 45,X male should be of great value in elucidating the complex mechanisms involved in normal male sex differentiation.

A novel E153X point mutation in the androgen receptor gene in a patient with complete androgen insensitivity syndrome.

AIM: To study a 46, XY newborn patient with a phenotype suggestive of an androgen insensitivity syndrome to confirm an anomaly in the AR gene. METHODS: Genomic DNA from leukocytes was isolated in order to analyze SRY gene by PCR and sequencing of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal precursors from the testis was performed in order to study testosterone production and response to hCG stimulation in culture. RESULTS: Surgical exploration disclosed two testes, no Wolffian structures and important Müllerian derivatives. The SRY gene was present in peripheral blood leukocytes. Sequencing of the AR gene evidenced a previously unreported G to T transversion in exon 1 that changed the normal glutamine 153 codon to a stop codon. Interstitial cell cultures produced sizable amounts of testosterone and were responsive to hCG stimulation. CONCLUSION: This E153X nonsense point mutation has not been described previously in cases of AIS, and could lead to the synthesis of a short truncated (153 vs 919 residues) non functional AR probably responsible for the phenotype of complete androgen insensitivity syndrome (CAIS).

Absence of mutations in the p53 tumor suppressor gene in non-invasive Cushing adenomas.

A lot of evidence supports the existence of a monoclonal origin for pituitary tumors, and several genetic alterations have already been confirmed as necessary or sufficient for unrestrained cellular growth and pituitary function. The p53 gene, a known tumor-suppressor gene (TSG), encodes a protein that exerts antiproliferative effects such as cell-growth arrest and apoptosis in response to several types of stimuli. In fact, several human cancers are believed to be caused by p53 mutations. In the case of pituitary tumors, p53 protein accumulation has been described in ACTH-secreting pituitary adenomas. Since increased amounts of the p53 protein are often related to mutations of its gene, we decided to explore the existence of p53 mutations in the tumor tissues of 9 patients bearing non-invasive corticotropinomas, excised by the transphenoidal route. We screened mutations in exons 5 to 8 of the p53 gene by the PCR-SSCP analysis. We were not able to find any mutation in the exons investigated. Our results are in close accordance with those obtained previously for other types of pituitary tumors.

Randomised, double-blind, placebo-controlled study of pivagabine in neurasthenia.

One hundred and eighteen patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), participated in a randomised, double-blind, placebo-controlled trial of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg). Pivagabine 1800 mg/d was administered orally for four weeks. At the end of the trial, active medication was significantly superior to placebo on the Clinical Global Impression (CGI) improvement of illness scale. In addition, pivagabine treatment reduced the physical and mental fatigability of patients, and increased their sense of well-being.

Molecular analysis of sex determination in sex-reversed and true hermaphroditism.

The SRY (sex region of Y) gene determines testis formation but not all cases of sex reversal in humans can be explained by alterations in this gene. We studied one 46,XY female, four 46,XX males, and nine true hermaphrodites (TH): three with an XY and six with an XX chromosomal constitution. The SRY gene was identified in the XX males and the TH with a Y chromosome but was not demonstrated in the XY female and the six XX TH. The Y-heterochromatin region was also identified in one 46,XX male, indicating a low grade mosaicism undetected by cytogenetics. The amplification of the amelogenin gene showed the presence of a 977-bp band that belongs to the short arm of chromosome X in all patients but the absence of a 780-bp band of the short arm of chromosome Y in three 46,XX males and in all the 46,XX TH. These studies demonstrate that the molecular study of sex-reversed patients and TH will help to understand the complex mechanisms of sex determination. The SRY gene is involved but other genes on the X chromosome and autosomes still remain to be studied.

Molecular analysis of sex determination in sex-reversed and true hermaphroditism

The SRY (sex region of Y) gene determines testis formation but not all cases of sex reversal in humans can be explained by alterations in this gene. We studied on 46,XY female, four 46,XX males, and nine true hermaphrodites (TH): three with an XY and six with an XX chromosomal constitution. The SRY gene was identified in the XX males and the TH with a Y chromosome but was not demonstrated in the XY female and the six XX TH. The Y-heterochromatin region was also identified in one 46,XX male, indicating a low grade mosaicism undetected by cytogenetics. The amplification of the amelogenin gene showed the presence of a 977-bp band that belongs to the short arm of chromosome X in all patients but the absence of a 780-bp band of the short arm of chromosome Y in three 46,XX males and in all the 46,XX TH. These studies demonstrate that the molecular study of sex-reversed patients and TH will help to understand the complex mechanisms of sex determination. The SRY gene is involved but other genes on the X chromosome and autosomes still remain to be studied.

Brief clinical report: interstitial deletion of the long arm of chromosome 4, del(4)(q28-->q31.3).

Interstitial deletions of the long arm of chromosome 4 are rare. Different breakpoints are involved. Only one of the patients had a very similar deletion to that of the present case. Both had low birth weight at term; weight, length and head circumference less than the third centile; epicanthic folds; apparently low-set abnormal ears; broad nasal bridge; micrognathia; hypoplastic nails; delayed psychomotor development; and mild mental retardation.

[Molecular sex determination. Significance in the diagnosis of gonadal pathologies]. / La determinación sexual a nivel molecular. Implicancia en el diagnóstico de patologías gonadales.

Sex differentiation follows two steps: sex determination where gender follows from the development of the embryonic gonads such as testes or ovaries and sex differentiation leading to the formation of internal and external genitalia. In man, testis determination is dependent on SRY gene (sex region of Y) on the short arm of Y chromosome (Yp11.3). It has an open reading frame that encodes a 220 aa protein with a 80 aa motif related to HMG box. These sequences have been shown to mediate DNA binding. Recently, a DSS locus (Dosage Sensitive Sex-Reversal) has been isolated on Xp21. This gene could be involved in ovaric determination. Moreover, it has been shown that SRY gene expression activates a regulatory pathway that leads to the expression of MIS (Mullerian Inhibiting Substance). Finally, the molecular genetic techniques have provided the tools for the analysis of these genes in patients with gonadal dysgenesis. The information obtained together with phenotype and cytogenetic data has established important correlations of diagnosic value.

La determinación sexual a nivel molecular. Implicancia en el diagnóstico de patologías gonadales. / [Molecular sex determination. Significance in the diagnosis of gonadal pathologies]

Sex differentiation follows two steps: sex determination where gender follows from the development of the embryonic gonads such as testes or ovaries and sex differentiation leading to the formation of internal and external genitalia. In man, testis determination is dependent on SRY gene (sex region of Y) on the short arm of Y chromosome (Yp11.3). It has an open reading frame that encodes a 220 aa protein with a 80 aa motif related to HMG box. These sequences have been shown to mediate DNA binding. Recently, a DSS locus (Dosage Sensitive Sex-Reversal) has been isolated on Xp21. This gene could be involved in ovaric determination. Moreover, it has been shown that SRY gene expression activates a regulatory pathway that leads to the expression of MIS (Mullerian Inhibiting Substance). Finally, the molecular genetic techniques have provided the tools for the analysis of these genes in patients with gonadal dysgenesis. The information obtained together with phenotype and cytogenetic data has established important correlations of diagnosic value.

Molecular genetics of hereditary thyroid diseases due to a defect in the thyroglobulin or thyroperoxidase synthesis.

1. Hereditary goiter and the various degrees of thyroid hypofunction are the result of structural changes in the thyroglobulin (Tg) or thyroperoxidase (TPO) proteins, the inability to couple iodotyrosines or defective iodination, impairing or substantially altering the synthesis of T4 and T3. 2. The first mutations in the Tg and TPO genes responsible for human cases of dyshormonogenesis have been described. The mutation in two siblings with hereditary goiter and marked impairment of Tg synthesis was a cytosine to thymine transition creating a stop codon at position 1510. The point mutation is removed by the preferential accumulation of a 171-nt deleted Tg mRNA. In another subject, molecular studies revealed that exon 4 was missing from the major Tg transcript due to a cytosine to guanine transversion at position minus 3 in the acceptor splice site of intron 3. 3. Genomic DNA studies identified a duplication of a 4-base sequence in the eighth exon of the TPO gene. Interestingly, besides abolishing the enzymatic activity by disrupting the reading frame of the messenger RNA and introducing stop codons, the GGCC duplication also unmasks a cryptic acceptor splice site in exon 9. 4. In conclusion, the identification of different molecular defects provided evidence that hereditary goiter associated with abnormal Tg or TPO synthesis is caused by heterogeneous genetic alterations.

Molecular genetics of hereditary thyroid disease due to a defect in the thyroglobulin or thyroperoxidase synthesis

1. Hereditary goiter and the various degrees of thyroid hypofunction are the result of structural changes in the thyroglobulin (Tg) or thyroperoxidase (TPO) proteins, the inability to couple iodotyrosines or defective iodination, impairing or substantially altering the synthesis of T4 and T3. 2. The first nmutations in the Tg and TPO genes responsable for human cases of dys-hormonogenesis have been described. The mutation in two siblings with hereditary goiter and marked impairment of Tg synthesis was a cytosine to thymine transition creating a stop codon at postion 1510. The point mutation is removed by the preferential accumulation of a 171-nt deleted Tg mRNA. In another subject, molecular studies revealed that exon 4 was missing from the major Tg transcript due to a cytosine to guanine transversion at postion minus 3 in the acceptor splice site of intron 3. 3. Genomic DNA studies identified a duplication of a 4-base sequence in the eight exon of the TPO gene. Interestingly, besides abolishing the enzymatic activity by disrupting the reading frame of the messenger RNA and introducing stop codons, the GGCC duplication also unmasks a cryptic acceptor splice site in exon 9. 4. In conclusion, the identification of different molecular defects provied evidence that hereditary goiter associated with abnormal Tg or TPO synthesis is caused by heterogeneous genetic alterations