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Prader-Willi syndrome (PWS) is a neurogenetic disorder that results from the absence of a normal paternal contribution to the 15q11-13 region. The clinical manifestations of PWS are a transient severe hypotonia in the newborn period, with mental retardation, hypogonadism and obesity observed later in development. Five transcripts with exclusive expression from the paternal allele have been isolated, but none of these has been shown to be involved in PWS. In this study, we report the isolation and characterization of NDN, a new human imprinted gene. NDN is exclusively expressed from the paternal allele in the tissues analysed and is located in the PWS region. It encodes a putative protein homologous to the mouse brain-specific NECDIN protein, NDN; as in mouse, expression in brain is restricted to post-mitotic neurons. NDN displays several characteristics of an imprinted locus, including allelic DNA methylation and asynchronous DNA replication. A complete lack of NDN expression in PWS brain and fibroblasts indicates that the gene is expressed exclusively from the paternal allele in these tissues and suggests a possible role of this new gene in PWS.

Epidemiology and natural history of cervical and endometrial carcinomas are not identical. So, the part of surgery in their prevention is different. For cervical carcinoma, mass screening and prevention allowed reduction of rates of incidence and mortality. Surgery concerns such intra-epithelial neoplasias. All the procedures, either destructive, either ablative, expose to failures as recurrence of intra-epithelial neoplasia and more as invasive carcinoma. For high grade epidermoid intra-epithelial neoplasia, conisation is the best of ablative procedures to set up an accurate pathologic diagnosis and consequently to determine adequate therapy: conservative by conisation, total hysterectomy or extended hysterectomy and lymphadenectomy. For in situ adenocarcinoma, removal of the whole cervix or total hysterectomy appears in numerous circumstances more safety. For endometrial carcinoma, there is no efficacious screening nor secondary prevention procedure available. Natural history, specially pre-invasive disease, is not well known. Atypical hyperplasia is a real pre-invasive disease and evolve to invasive carcinoma in 25%, and no more than 25% of this lesions regress under progestative therapy. Destructive procedures, biopsy-curettage and even endometrectomy under hysteroscopy don't realise and efficacious treatment of atypical hyperplasia and prevention of carcinoma. Total hysterectomy is the only one true prevention of endometrial carcinoma after failure of progestative therapy for patients who desire be pregnant, in first place for women who don't.

From October 1989 to September 1994 six resections of the bowel were performed for colorectal endometriosis. Five of, the patients, with a mean age of 32 years, presented clinical features. In all cases, colonoscopy showed a normal mucosa. All patients treated by hormonetherapy relapsed. The resection was segmental with immediate end-to-end anastomosis in 5 cases and partial in 1 case. In three cases, endometriosis of the genital tract was associated and treated during the initial laparotomy. One low rectosigmoid anastomosis fistulised. Rectosigmoid endometriosis accounts for 70% of bowel localisations and genital endometriosis is associated in 80% of cases. Deep and clinical rectosigmoid endometriosis does not respond to hormonetherapy and requires bowel resection. The pelvis should be explored and genital tract endometriosis treated. Postoperative hormonetherapy should be considered after initial surgery.

From October 1989 to September 1994, we performed six intestinal resections for rectal and sigmoidal endometriosis. The average age of the patients was 32 years old, and most had symptoms. In all cases coloscopy showed a normal mucosa. Patients had successfully been treated with hormones previously, but had relapsed when the treatment was stopped. Bowel resection was segmental, with immediate end to end anastomosis in five patients, and partial in one patient. Genital endometriosis was diagnosed in three cases and was then treated during the same procedure. A low colorectal anastomosis was complicated by a fistula, but no recurrence was observed after surgical treatment. Intestinal endometriosis tract is in 70% of cases located on the rectosigmoid. An association with genital endometriosis tract is observed in 80% of the cases. Deep rectosigmoidal endometriosis with symptoms is resistant to hormonal therapy and necessitates a surgical treatment by intestinal resection. The pelvis has always to be explored, with full evaluation and surgical treatment of genital endometriosis when necessary. Appendicular endometriosis should be removed surgically. Postoperative treatment can be additionally prescribed in cases of genital endometriosis and for leftover digestive location.

A cDNA sequencing project was initiated with the aim of isolating and mapping new genes expressed during early human development. A human embryo cDNA library was constructed, and a prescreening procedure was used to select cDNAs corresponding to poorly transcribed genes. Partial sequences were generated from one or both ends of 231 cDNA clones, and sequence comparison with genetic databases revealed that 28% were already annotated genes, 42% matched with partial sequences expressed sequence tags that had already been detected, 3% contained no insert, 5% were highly similar to sequences from other species, and 23% of the cDNAs appeared to be unknown in genetic databases. All new sequences were deposited in public genetic databases, and most of the corresponding cDNAs were regionally mapped on human chromosome bands using both fluorescence and radioactive in situ hybridization. Several cDNAs colocalized with critical regions of the genome regarding mapped disorders, thus providing candidate genes for human genetic diseases.

Background: A phase I or II trial was conducted to assess the toxicity and the efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and teniposide in patients with poor prognosis ovarian carcinoma., Methods: Thirty-seven patients were scheduled to receive tandem high dose therapy combining ifosfamide 7500 to 11250 mg/m2, carboplatin 875 ot 1000 mg/m2 and teniposide 750 to 1000 mg/m2, followed by autologous bone marrow transplantation (ABMT). Eight patients were refractory to the platin-based regimen, 7 were treated in chemosensitive relapse, and 22 in partial or complete response (PR/CR) were treated. Sixty-six cycles were administered. Sixteen patients were evaluated for response., Results: The overall response rate was 56% (CR rate: 12%). Toxic effects consisted of mainly renal toxicity, esophagitis, and enterocolitis. Three patients died of therapy-related complications. Since the time of ABMT, the median overall survival (OS) duration of the whole population was 18 months and the survival rate was 14% at 60 months. For the 22 patients treated after PR or CR, the median OS duration was 24 months and the survival rate was 32% at 60 months. Tandem high dose therapy with ABMT was unable to circumvent resistance to conventional chemotherapy or to prolong the duration of survival for patients treated in chemosensitive relapse. For patients treated after CR or PR, the survival results were similar to that achieved with conventional therapy., Conclusions: Prospective, randomized studies, including patients only after CR or with minimal residual disease, are urgently required to evaluate the activity of high dose therapy in the treatment of advanced ovarian carcinoma.

We have isolated the human homologue if the TGF beta-stimulated clone 22 gene from a human embryo cDNA library. This gene maps to the q14 region of chromosome 13. Its deduced amino acid sequence is almost 99% identical to that of mouse or rat proteins and includes a putative leucine zipper motif. An abundant major transcript of 1.8 kb and in some instances an additional 5 kb transcript were detected by Northern blotting of several human tissues. The TSC-22 protein has been shown to be well conserved across evolution as evidenced by the existence of a Drosophila homologue. These observations prompt discussion on the strong conservation of TSC-22 during evolution but also on its general function as a primary response gene expressed either when stimulated by several different factors during early human development, or in the adult in response to inducing differentiation signals.

Blind deep venous puncture is an invasive procedure with risks of serious complications compromising the availability of veins for future punctures or endangering the patient's life. We designed a new hand-held pulsed Doppler probe for coaxial guidance of the puncture needle and a dedicated pulsed Doppler device displaying the depth of the measurement volume. We used this technique prospectively in two independent centers (the nephrology department and the intensive care unit) involving senior as well as junior staff members. Either the non-Doppler or the Doppler method were randomly selected for subclavian vein catheterization in 100 patients and for internal jugular vein catheterization in 30 patients. The success rate on the first attempt was 86.2% for the non-Doppler method versus 96.8% for the Doppler method (p = 0.03). The failure rate of the non-Doppler method used by junior staff members was 9.2%, reduced to 1.5% (p = 0.05) by secondary use of the Doppler method and/or help from a senior staff member (rescue procedure). Pulsed Doppler guidance reduced significantly the failure rate of venous punctures especially when used by seniors or by juniors after a training period.

A glycoprotein expressed in exocrine pancreas (where it has been called lithostathine) and endocrine pancreas (where it has been called the regeneration protein) is encoded by a gene (REG) which maps to 2p12. A REG-related sequence (REGL) is also located in 2p12 and expressed in the pancreas. Here we describe the physical mapping of these genes within a 100-kb genomic region. A YAC clone was converted into an ordered cosmid contig. We constructed a restriction map of the cosmid contig and localized the loci corresponding to the genes. A third REG-related sequence also maps to this region. Although this sequence was previously described as a pseudogene, we show here that it is also expressed in the pancreas.

We have determined the nucleotide sequence of regl a human genomic DNA fragment homologous to the reg gene which is expressed in the exocrine pancreas and regenerating islets. Sequence comparisons of reg and regl suggested similar exon-intron organisation. Based on this assumption, specific oligonucleotides for regl exons were used to demonstrate expression of the regl gene in pancreas and liver. The proteins encoded by reg and regl comprise 166 amino acids and differ by 22 amino acids only.

The pancreatic stone protein (lithostathine) secreted by the exocrine pancreas is an inhibitor of CaCO3 crystal growth. This protein, which is also present in endocrine pancreas, has also been called the regeneration protein (reg). Here we report the mapping of the REG gene to chromosome 2 using the polymerase chain reaction for the specific amplification of human reg sequences in rodent/human somatic cell hybrid DNA. A regional assignment has been made by in situ hybridization to metaphase chromosomes using two different fluorescently labelled genomic probes corresponding to the REG gene and a related gene REGL. Both probes hybridized to chromosome 2p12 suggesting the tandem organization of these genes.

Forty-two women with "bulky" squamous cell carcinoma of the uterine cervix, larger than 5 cm, were treated between 1982 and 1988. The median follow-up was 5 years (from 37 to 106 months). The age range was from 25 to 77 years (mean: 49). There were 14 stage Ib, 5 stage IIa, and 23 stage IIb operable patients. Forty grays were delivered at mid-plane of the pelvis (23 fractions in 31 days) using the four-field technique (6-18 MV). External beam radiation therapy was followed by 20 Gy of intracavitary radiation therapy. Forty-eight days later total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) and bilateral pelvic lymphadenectomy were performed. The 3- and 5-year disease-free survival was 83 and 81%, respectively. The 5-year locoregional control rate was 83%. Thirteen patients suffered from mild to severe complications (31%) but there were only two long-term (5%) complications.

The distribution of the human ribosomal gene repeat within human Sertoli cell nucleoli was investigated with the help of DNA-DNA in situ hybridization at the light and electron microscopic level. Probes from both the transcribed part of the gene repeat and the "non-transcribed" spacer were found to hybridize predominantly to the dense fibrillar component of nucleoli. It therefore can be concluded that the dense fibrillar component of nucleoli is the major site of the intranucleolar location of the ribosomal DNA. This holds true not only for the dense fibrillar component adjacent to fibrillar centers, but also for the dense fibrillar component remote from the fibrillar centers.

From 1966 to 1984, 417 female patients were operated for genital prolapse in the department of surgical gynecology of the Salpêtrière Hospital (Pr Blondon's department). The results of the surgical treatment were studied in the posterior perineum from an anatomical (rectocele) and functional point of view (indiced rectal disorders). This study allows drawing several conclusions: when the context leads to deciding to operate the prolapse through an abdominal approach, it is desirable, in order to reduce the risk of postoperative rectocele, to systematically insert a posterior prosthetic band, which will be tethered as low as possible on the posterior aspect of the vaginal (after a sufficiently low extensive rectovaginal cleaving). The Orr-Loygue rectopexy must remain indicated for rectal prolapse, even more so as it is associated with incontinence. Since this procedure often causes constipation of even more complex exoneration disorders, it must be reserved for prolapse associated to a large rectocele (type IV) or an invalidating dyschezia.

The authors report 256 male genital examinations to determine papillomavirus lesions (HPV) in men whose female partners presented HPV cervical lesions. 46 p. cent of the examinations performed with a colposcope were abnormal. Histologically, anomalies are present in 62 p. cent of the samples and, overall, 39 p. cent of the men presented, most of the time, infraclinical lesions. Knowing that males are probably safe from malignant degeneration, it is most likely that the treatment of male lesions decreases the frequency of recurrences in women and represent a factor in limiting the extension of the epidemic. The approach of the couple in consultation is discussed.

Endometrial cancer has become one of the most frequent female cancers, second only to breast cancer. It must be looked for in women presenting several high risk factors for endometrial cancer, the common denominator of which is absolute or relative hyperoestrogenism. Hysteroscopy and guided biopsy are the most reliable techniques for the diagnosis of endometrial cancer and its precursors. These techniques must be used in symptomatic patients and in asymptomatic but high risk women whose selection remains controverted as regards the mass detection method.

Subclinical vulvar lesions have been studied using the magnifying colposcope after 5% acetic acid application in 65 women with H.P.V. related cervical lesions and/or cervical intraepithelial neoplasms. Different vulvoscopic patterns are described: micropapillae (51%), diffuse acetowhite reaction (18%), papules (13%) and leukoplakia (11%). A normal appearance was found in 7% of the cases. Histological diagnosis is far different: normal histological appearance or minimal histological changes are noted in 57% of the biopsy specimens, flat condylomas of the vulva in 38% and vulvar intraepithelial neoplasms (V.I.N.) in 15%. The most frequent clinical aspects, i.e., acetowhite reaction and micropapillae are seldom related to V.I.N. The significance of these H.P.V. histologically-related vulvar lesions is still difficult to assess. Unlike cervical intraepithelial neoplasms, the malignant potential of V.I.N. remains uncertain. The risk of progression to invasive cancer in young women is low, probably less than 5%. On the other hand, vulvae may harbour H.P.V. able to influence subsequent recurrences of dysplasias of the cervix. Further studies are needed, especially Southern blot hybridization of vulvar biopsy specimens, to determine whether these histological abnormalities definitely harbour viruses and need subsequent treatment.

At the Institut Curie in Paris 452 invasive breast cancers (T1 and T2 less than 3 cm in diameter) were managed conservatively. The patients were treated by "conservative" surgery with or without axillary dissection. All received radiotherapy postoperatively. The 5-year survival without evidence of disease was 86% (249 cases). The survival at 10 years was 77% (93 cases). These statistics are comparable to those obtained by total mastectomy with axillary clearance. The local recurrence rate was 14.5%, most of these patients being "curable" by radical surgery. There was evidence of isolated axillary node metastases in only 2% of the patients. Radiotherapy is therefore effective in treating subclinical node invasion which was observed in 30% of axillary specimens. The cosmetic results were satisfactory in 80% and complications were rare. Follow-up of these patients is difficult and must be rigorous including clinical examination and mammography and, in case of doubt, cytology by aspiration or "Tru-cut" biopsy. The authors conclude that this conservative method, in addition to its cosmetic and emotional advantages, allows us to treat with as much security as radical surgery, the early cancers of the breast (T1 and T2 less than 3 cm in diameter), with no clinically suspicious node metastases.

About 80% of patients with breast cancer ultimately die of metastatic disease at 20 years. Distant metastases are more important as a cause of death than local or regional relapses. It is for this reason that adjuvant chemotherapy is necessary, especially in young patients and those with extensive disease. Initial chemotherapy preceding any local or regional treatment is justified on the grounds that both surgery and anaesthesia lead to immunodepression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials by Nissen-Meyer, Bonadonna and Cooper (1-3). In the present study 145 patients, including 67 with inflammatory breast cancer (IBC), were treated with 4-6 weeks of Velbe, thiotepa, methotrexate, fluorouracil and prednisone, with Adriblastin added for patients with IBC, T greater than 7 cm, or N2, N3. Because of tumour regression of greater than 50% observed in 80% of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium), resulting in complete remission in all these cases. Maintenance treatment with the same drugs was prescribed for 6-18 months depending on the initial stage. Tumour regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest being 42 months. Overall survival at 2 years for IBC is 90%, with a disease-free survival of 80%. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.

Primary chemotherapy in carcinoma of the breast is justified by the high risk of distant metastases, immunodepression related to surgery and the experimental studies and clinical trials of Nissen-Meyer in 1967, and Fisher in 1968. Chemotherapy was associated with loco-regional Patey-type surgery (20 patients) or radiotherapy with cobalt and irridium (43 patients) in 63 cases of breast cancer, 33 of which were T4 or in exarcerbation. Initial chemotherapy comprised 3 to 6 infusions of Velbe, Thiotepa, Methotrexate, 5-Fluoro-uracil, prednisone plus adriamycine in the severe forms. Over 50 p. 100 tumour regression was observed in 80 p. 100 of patients without major toxicity reactions. In all cases of radiotherapy alone, the tumour disappeared completely in the two months after the end of radiotherapy. Only one of the 63 patients relapsed at the 8th month and she died. The follow-up period now ranges from 3 to 29 months (average 12 months). These results are encouraging but only a larger series will allow definite conclusions to be drawn.

The author, who in 1955 had published a thesis on the remote results of the treatment of bone cysts on children and teenagers, decided to go back to that subject 30 years later. He was able to gather 203 observations (mostly from Paris Hospitals) followed up for at least 2 years (some of them for more than 30 years) and in 15 of those cases no treatment had been undergone. The pathogenesis of the bone cyst is still unknown, but there are obvious connections between the cystic socket and the vascular metaphysis. Rigault and Padovani had the opportunity to observe, during some injections of contrasting preparation in the humeral cysts that the liquid went quickly into the auxiliary venous system. The bone cysts appear in the spongy tissue of bone metaphysis in full movement. The author thinks that the cystic sockets are made by the gathering of osteolytic bubbles and that the protrusions inside the bone are nothing, but the former limits of those bubbles. The evolution does not always follow the classical pattern and one can often observe--in particular in the humeral localisation--lytic outbreaks on a cyst which growth seemed stationary or on the way of recovery. Those outbreaks with specific evolution bring about either an extension of the socket or the appearance of a new geode. The recovery (total or partial) usually comes after septation of the cavity. It is only at the end of the growth that one can be sure of the stabilization of the remaining lesions. As for the spontaneous disappearance of the cavity, it can take years. Considering the ever encouraging evolution of the bone cysts, one must always be very careful in judging the efficacy of the different treatments that are recommended. The different traumatisms (fractures, surgery or corticoids) bring forth perturbations in the bone socket, according to a pattern that we do not know well. The result is often paradoxical: one bone cyst which was apparently stabilized will awake and spread; another, partially cured after a surgery will have to wait for a fracture of the remaining cavity to disappear completely; other bone cysts which the injections of corticoids have failed to cure will recover after a curettage or vice-versa. Every method, included the bone resections used in some localisations (fibula) can fail.(ABSTRACT TRUNCATED AT 400 WORDS)

We have analyzed mRNA transcripts from beta-globin genes carrying a homozygous point mutation at the 5' splicing site of the first intron, using a method allowing in vivo analysis of mRNA transcripts. As expected, this mutation decreases normal splicing of mRNA when cryptic splicing are utilized. We have observed that, in reticulocytes, most mature mRNA transcribed from beta-globin genes derives from specific sites of abnormal splicing. Our results differ from those previously obtained using mutant beta-globin genes introduced in cultured cells and indicate a preferential processing of the abnormal globin mRNA species in red cell precursors.

Combined treatment modality was applied in 51 consecutive patients with locally advanced breast carcinoma between December 1982 and December 1984. The treatment was started with 4 cycles of chemotherapy with combination of adriamycin, vincristine, 5-fluorouracil and cyclophosphamide. This was followed by high-energy radiotherapy (45 Gy to the breast and lymphatic areas), with or without surgery. After radiotherapy, the response rate was 76%: 39/51 (complete response 39%: 20/51). Twenty-nine patients (57%) were treated conservatively (20 treated by radiotherapy alone and 9 treated by tumorectomy with axillary dissection followed by interstitial implantation). For 22 patients (43%), the mastectomy with axillary dissection was necessary. The three year overall survival rate and disease free survival rate were 88, and 86%. Local recurrences occurred in one patient (2%). The toxicity with this combined treatment regime was low. The cosmetic results were acceptable when a conservative treatment was proposed.

Over a period of 16 years, 92 patients presenting recurrent genital prolapse, following one or several surgical interventions, were operated on via the abdominal route with the insertion of prosthetic material. The current technique used consists of promonto-fixation of the cervix using 2 Mersylene* bands, combined in the majority of cases with a retropubic colopopexy. The anatomical failure rate was 9.2% after a mean follow up of 6.7 years. Morbidity associated with this surgical technique was low: no septic or occlusive complications were noted. This technique provides a satisfactory and long lasting solution, both anatomically and functionally, to the delicate surgical problem of recurrent genital prolapse.

Thyroglobulin (Tgb) mRNA content was studied in human thyroid tissues using liquid hybridization and in situ hybridization. Liquid hybridization revealed no differences in mRNA content, except in the case of colloid adenoma in which a lower amount of Tgb mRNA was found. Conditions for quantitative in situ hybridization of [3H]DNA complementary to the mRNA of Tgb are described. In situ hybridization allowed correlation of the morpho-functional state of the follicles and their content of Tgb mRNA.

The human thyroglobulin gene was mapped by in situ hybridization whereby a 3H-labeled recombinant plasmid DNA containing a fragment of 2.3 kilobases of human thyroglobulin gene was hybridized to human chromosome preparations. A high proportion (25%) of hybridized metaphases exhibited silver grains at the distal portion of the long arm of chromosome 8. Analysis of the grain position at this site indicated that the chromosomal localization of the human thyroglobulin gene was 8q242-8q243.

Excision of intestinal implants in association with ovarian conservative surgery appears to be a safe procedure in most cases of intestinal endometriosis. Newer surgical techniques (selective laser vaporisation of abnormal tissue), advances in medical therapy (danazol, LH-RH agonists) and earlier diagnosis before obstructive phenomena, might allow conservative medical or surgical management before the development of major complications.

One case of cystosarcoma phyllodes is reported. Histologically, the neoplasm was composed of two elements: benign epithelial cells and malignant stromal cells. The stromal cells, spindle shaped, grow in solid sheets or in sparcely cellular, myxomatous and alcianophilic areas. Scanning electron microscopy demonstrates a mucous secretion, showing porelike openings and mucous droplets on the surface of tumoral cells.By transmission electron microscopy, sarcomatous cells look like very polymorphous. Secretory cells (showing dilated granular endoplasmic reticulum and abundant lysosomes) are mixed with primitive mesenchymal cells and with intermediate, myoepithelial cells. The myoid origin of these cells is demonstrated by the bundless of myofilaments terminated in marginal plaques on the plasma membrane, the numerous pinocytic vesicles and basal lamina investing irregularly the cells. Histoenzymology corroborates these findings, disclosing a high activity of alkaline phosphatase. Discovery of ambiguous myoepithelial cells associated with undifferentiated cells, likewise reported in epitheliomas, is of a great histogenetic interest. It suggests development of mammary neoplasm from stem cells coming under local of general influences, unknown today, but perhaps responsible of epithelial or conjunctive differentiation. The presence of a contralateral carcinoma in our case is consistent with this hypothesis.

In order to sublocalize NCAM, ETS1, and the anonymous DNA fragment D11S29 within 11q23, in situ hybridization was performed on pachytene bivalents. Analysis of the grain distribution within the band 11q23 indicated that the chromosomal sublocalization of both NCAM and D11S29 was in 11q23.1, whereas ETS1 was found to be localized in 11q23.3. These results clearly demonstrate the usefulness of in situ hybridization applied to pachytene bivalents to obtain accurate gene sublocalization.

The spatial relationships of acrocentric chromosomes were studied during prophase I of meiosis in human oocytes and spermatocytes by using cytogenetic techniques, electron microscopy, and in situ hybridization. Ultrastructural investigations revealed an ordered arrangement of nucleolar bivalents at the zygotene and pachytene stages. The end of the bivalent corresponding to the cytological satellite was consistently attached to the nuclear envelope. The fibrillar center of the nucleolus always contained rDNA chromatin fibers emanating from the secondary constriction region. Association of ribosomal genes from two bivalents in the same fibrillar center was frequently observed. Ultrastructural studies demonstrated the close proximity of chromatids in the short arm region of the involved nonhomologous acrocentrics. A breakage/reunion model based on our data can explain the formation of all observed types of Robertsonian translocations: monocentrics and dicentrics with or without rDNA.

Thyroglobulin is a large-size iodoglycoprotein specific to thyroid tissue and is the substrate for the synthesis of thyroid hormones, thyroxine and 3,5,3'-triiodothyronine. Recent studies, which greatly benefited from recombinant DNA methodologies, improved the knowledge of several structural features of this dimeric protein and permitted insights into some structure-function relationships. Analysis-function of the primary structure of the human thyroglobulin monomer revealed several main characteristics: 1) 3 types of internal homologies; 2) extensive homology with the bovine thyroglobulin monomer and known partial sequences in the thyroglobulins of other mammalian species; 3) significant homologies with 2 other non-thyroid proteins (acetylcholinesterase and the invariant chain of the Ia class II histocompatibility antigen); 4) a terminal localization of the hormonogenic sites at both ends of the monomer. Current studies aim at determining conformational characteristics, understanding the molecular mechanisms of thyroid hormone formation and unraveling those interactions which in the thyroid cell and the thyroid follicle will permit this large pro-hormone to synthesize and release a few small thyroid hormone molecules. A more precise knowledge of this molecule in higher vertebrates and during evolution would impart valuable information concerning thyroid pathology, since thyroglobulin has been implicated in some genetic and in autoimmune thyroid diseases.

Excellent results lasting for at least 10 years were obtained in a series of 316 cases of genital prolapse operated upon through an abdominal approach in the Broca Center, Paris. Major sling-type operations, the source of multiple particularly urinary complications, have now been replaced by surgery usually involving a combination of the following: fixation to the promontory through the anterior ligament, an inter-vesicogenital Tergal triangle, a posterior perineorrhaphy, and sometimes an inter-rectovaginal triangle and/or a rectopexy. Rare septic complications resulted from opening of a viscus with subsequent spondylodiscitis requiring removal of the prosthesis. Acute intestinal obstruction is now rarely observed as a result of performing a subtotal hysterectomy, which enables effective peritonization to be conducted. The use of prosthetic material appears to provide durable anatomical results of good quality.

Congenital absence of the vagina is the second cause of primary amenorrhea. Among 93 cases treated between 1956 and 1981, vulvar morphology was normal in only 37%. Partial bilateral absence of uterus was more frequent than total or than major asymmetric absence. 8 patients had a functional uterus. Ovaries were nearly always normal except in 5 cases of male hermaphroditism. Genetic abnormalities were exceptional. 30% patients had congenital abnormalities of urinary tract, especially when the uterus malformation was important and/or asymmetric. Unilateral renal absence was most common abnormality. 56 patients were treated by recto-vesical cleavage, without skin grafts with more than 90% anatomical and functional good results. 21 patients had been treated by Frank non operative method. Ileal and sigmoid plasties were performed five times. In absence of functional uterus, treatment of congenital absence of vagina must be simple. Frank method's when vulvar is normal; Recto-vesical cleavage, on the others cases.

Pelvic lymphadenectomy for genital cancer can lead to numerous complications, particularly lymphoceles. Two types of drainage were compared in a series of 86 patients treated by enlarged lymphadeno-colpohysterectomy. In the first group (n = 66), hermetic peritonization with aspiration drainage was performed and in the second group (n = 20), non-peritonization combined with omentoplasty was practiced. Lymphoceles developed in 23% of patients in group I, requiring 7.7% of recovery operations (5 cases). Lymphoceles did not occur in group 2. Qualities of reabsorption of peritoneum and omentum are discussed. Their combined use to avoid lymphocele complications is of benefit, particularly in patients receiving preoperative pelvic radiotherapy.

About 80 per cent of patients with breast cancer ultimately die of metastatic disease in the following twenty years. Distant metastases are more important as cause of death than loco-regional relapses, it is why adjuvant chemotherapy is necessary, especially in young patients and in those with extensive disease. Initial chemotherapy preceding any locoregional treatment is justified on the basis that both surgery and anesthesia lead to immuno-depression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials of Nissen-Meyer, Bonadonna and Cooper. We have treated 145 patients, including 67 with inflammatory breast cancer (IBC), with 4 to 6 weeks of Velbe, Thiotepa, Methotrexate Fluorouracil and Prednisone with Adriblastine added for those patients with IBC or T greater than 7 cm, or N2 N3. Because of tumor regression of more than 50 per cent observed in 80 per cent of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium) and are in a complete remission in all these cases after curietherapy. Maintenance treatment with the same drugs was prescribed for 6 to 18 months depending on the initial staging. Tumor regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest one being 42 months. The overall survival at 2 years for IBC, is 90 per cent with a disease-free survival of 80 per cent. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.

In a series of 29 HIV-seropositive women (mean age 27.4 years; 75.9 per cent acquired HIV by intravenous drug abuse) observed over a 2 years' period, we were able to determine the main epidemiological characteristics of cervico-vaginal and vulvar lesions caused by human papillomavirus (HPV). More than 58 per cent of cervico-vaginal smears showed cytological evidence of HPV infection (koilocytosis), and 6 cervical biopsies showed histological abnormalities (from CIN I to invasive carcinoma). Condyloma acuminata was found in 38 per cent of the cases, always associated with cervical HPV lesions. Systematic colposcopy of the whole female genital tract frequently detected multifocal HPV infection. HIV-seropositive women constitute a high-risk group for cervico-vaginal and vulvar HPV infection. They clearly need close supervision with frequent cervical smears and, preferably, colposcopy and biopsy for early detection and eradication of genital dysplasias and viral lesions.

Human thyroglobulin mRNA was isolated from Graves' goitres by size selection of total poly(A)-rich RNA in a sucrose gradient. It sedimented at 33 S, as in other mammalian species, and showed a single component of approximately 8500 bases by gel electrophoresis. cDNA was synthesized from the 33-S RNA by using reverse transcriptase in the presence of human placenta ribonuclease inhibitor and in conditions allowing the formation of long transcripts. The latter was made double-stranded using reverse transcriptase and blunt-ended with nuclease S1. After tailing with dCTP and terminal transferase, the double-stranded cDNA was annealed to pBR322 DNA that had been cleaved at the endonuclease PstI site and tailed with dGTP. The resulting plasmids were used to transform Escherichia coli C600 cells and four cloned recombinants were selected. Each plasmid DNA was shown to contain a sequence complementary to human thyroglobulin mRNA by hybridization with a labeled 33-S mRNA, visualization of cDNA . mRNA hybrids by electron microscopy and filter hybridization selection of mRNA directing the synthesis of immunologically related thyroglobulin peptides in the reticulocyte lysate. The four inserted DNA sequences were 1400 - 1800 base pairs long, two of them showing an homologous sequence of 1100 base pairs. Together, the four cloned DNA fragments represented 63% of the 8500 bases of human thyroglobulin mRNA.

Bologna's operation to relieve stress incontinence in patients with large cystoceles uses two vaginal strips to form a subcervical sling. Of 60 patients treated in this way, urodynamic exploration was performed preoperatively in 83% and postoperatively in 50%, while 42% underwent lateral retention and pressure cystography. All patients presented at least a stage II cystocele and hysteroptosis, 47% a patent and 93% a potential stress incontinence and 40% a sphincter incompetence. Anatomic results were excellent: 77% of total relief and 23% improvement in the cystoceles. Of greatest interest was efficacy against urinary incontinence: all patent stress incontinences were cured; none occurred after correction of cystocele, and only two cases of potential incontinence due to anatomic failure were observed. These good clinical results could be correlated with postoperative urodynamic exploration findings: the lack of persistent dysuria was related to the correction or even hypercorrection of the transmission anomaly without alteration of sphincter function. Paradoxically, images of pressure cystography showed elevation of the bladder neck in relation to symphysis pubis to be limited in extent. In 26% of cases the neck was in fact below this limit. These findings raise the question of the mechanism of re-establishment of pressure transmission. Because of the simplicity of technic of Bologna's operation, its low morbidity and it very great reliability with respect to urinary results, this method is now practised routinely in cases of prolapse with marked cystocele and patent or potential stress incontinence, even in the presence of major sphincter incompetence.