Murine B7-2, an alternative CTLA4 counter-receptor that costimulates T cell proliferation and interleukin 2 production.

The B7-1 molecule, expressed on antigen presenting cells (APC), provides a crucial costimulatory signal for T cell activation. Recent studies demonstrate the existence of alternative, non-B7-1 CTLA4 counter-receptors in mice and humans. Here, we describe the molecular cloning and demonstrate costimulatory function of the murine B7-2 (mB7-2) gene. Murine B7-2 cDNA encodes a member of the Ig supergene family that binds CTLA4-Ig and stains with the GL1 but not anti-mB7-1 mAb. Murine B7-2 costimulates the proliferation and interleukin 2 production of CD4+ T cells and this costimulation can be inhibited by either CTLA4-Ig or GL1 mAb. Identification of the B7-2 molecule will permit further manipulation of the B7:CD28/CTLA4 costimulatory pathway which has been shown to be involved in the prevention of tolerance, induction of tumor immunity, and most recently, in the pathogenesis of autoimmunity.

Rapid axonal transport of sulfated mucopolysaccharide proteins.

When sulfur-35-labeled sodium sulfate is injected intraocularly in the goldfish, labeled sulfated mucopolysaccharides rapidly appear in the contra-lateral optic tectum of the brain, demonstrating the axonal flow of sulfated mucopolysaccharides. The transport rate is the same as that observed for proteins labeled after intraocular injection of tritiated proline. Treatment of the sulfur-35-labeled material with precipitants and enzymes reveals the presence of substances with properties similar to those of heparan sulfate (the major component) and chondroitin sulfate. Dermatan sulfate was not detected.

The association between heavy metals, endometriosis and uterine myomas among premenopausal women: National Health and Nutrition Examination Survey 1999-2002.

BACKGROUND: It has been hypothesized that exposure to exogenous estrogens may be associated with endometriosis and uterine myomas. We sought to investigate the association between heavy metals which have been shown to be hormonally active and these disorders using data from the National Health and Nutrition Examination Survey, 1999-2002. METHODS: Women aged 20-49 years who had data on metals and the outcomes of interest, were premenopausal and neither pregnant nor breastfeeding were eligible (n = 1425). Lead, cadmium and mercury were measured in whole blood. Diagnosis of outcomes was based upon self-report. Logistic regression was used to examine the association between tertiles of heavy metals and disease adjusting for age, race/ethnicity, use of birth control pills prior to diagnosis and smoking status at diagnosis. RESULTS: A dose-response association between cadmium and endometriosis was observed [tertile 2 versus 1: adjusted odds ratio (OR) = 1.94, 95% confidence interval (CI): 0.73-5.18; tertile 3 versus 1: adjusted OR = 3.39, 95% CI 1.37-8.40]. This association persisted in subanalyses: (i) limiting analysis to women diagnosed in the past 10 years and (ii) limiting analysis to women diagnosed since last pregnancy, although limited by sample size. CONCLUSIONS: These results must be interpreted with caution given the cross-sectional study design. The observed association between cadmium and endometriosis deserves further investigation in properly designed studies.

The vestibular end organs: morphological and physiological diversity of afferents.

Vestibular-nerve fibers, even those innervating a single end organ, have been found to differ in their branching patterns within the neuroepithelium. They also vary in their responses to head movements and to activation of efferent fibers, and in the central pathways to which they contribute. These results are enabling plausible inferences to be made about the peripheral mechanisms determining the discharge properties of physiologically distinguishable afferents, and about the contributions the different afferents make to the overall functioning of the vestibular system.

The single helix in protein L is largely disrupted at the rate-limiting step in folding.

To investigate the role of helix formation in the folding of protein L, a 62 residue alpha/beta protein, we studied the consequences of both single and multiple mutations in the helix on the kinetics of folding. A triple mutant with 11 additional carbon atoms in core residues in the amino-terminal portion of the helix folded substantially faster than wild type, suggesting that hydrophobic association with residues elsewhere in the protein occurs at the rate-limiting step in folding. However, helix-destabilizing mutations had little effect on the rate of folding; in particular, a triple glycine substitution on the solvent-exposed side of the helix increased the unfolding rate 56-fold while reducing the folding rate less than threefold. Thus, in contrast to the predictions of models of folding involving the coalescence of well-formed secondary structure elements, the single helix in protein L appears to be largely disrupted at the rate-limiting step in folding and unfolding.

Menopause used to be considered normal.

Mishell's Textbook of Infertility, Contraception, and Reproductive Endocrinology. Fourth Edition Edited by Rogerio A. Lobo, Daniel R. Mishell, Jr, Richard J. Paulson and Donna Shoupe. Malden, MA, Blackwell Science, 1997, $175.00 (884 pages), ISBN 0-86542-385-7.

A regional ultrastructural analysis of the cellular and synaptic architecture in the chinchilla cristae ampullares.

The chinchilla crista ampullaris was studied in 10 samples, each containing 32 consecutive ultrathin sections of the entire neuroepithelium. Dissector methods were used to estimate the incidence of various synaptic features, and results were confirmed in completely reconstructed hair cells. There are large regional variations in cellular and synaptic architecture. Type I and type II hair cells are shorter, broader, and less densely packed in the central zone than in the intermediate and peripheral zones. Complex calyx endings are most common centrally. On average, there are 15-20 ribbon synapses and 25-30 calyceal invaginations in each type I hair cell. Synapses and invaginations are most numerous centrally. Central type II hair cells receive considerably fewer afferent boutons than do peripheral type II hair cells, but have similar numbers of ribbon synapses. The numbers are similar because central type II hair cells make more synapses with the outer faces of calyx endings and with individual afferent boutons. Most afferent boutons get one ribbon synapse. Boutons without ribbon synapses were only found peripherally, and boutons getting multiple synapses were most frequent centrally. Throughout the neuroepithelium, there is an average of three to four efferent boutons on each type II hair cell and calyx ending. Reciprocal synapses are rare. Most synaptic ribbons in type I hair cells are spherules; those in type II hair cells can be spherical or elongated and are particularly heterogeneous centrally. Consistent with the proposal that the crista is concentrically organized, the intermediate and peripheral zones are each similar in their cellular and synaptic architecture near the base and near the planum. An especially differentiated subzone may exist in the middle of the central zone.

Transmission between the type I hair cell and its calyx ending.

The long, uninterrupted apposition between the type I hair cell and the calyx ending has implications for the intercellular communication between these structures. Conventional synaptic transmission will be compromised unless the impedance of the ending is made relatively high. The apposition also creates the possibility of ephaptic transmission between the hair cell and the ending. Ephaptic transmission from the hair cell to the outer face of the calyx ending is too weak to make more than a minor contribution to sensory coding. Basolateral currents associated with hair-cell transduction can result in a substantial accumulation of K+ ions in the intercellular space. The accumulation can alter conventional transmission by depolarizing the hair cell and can alter afferent firing by depolarizing the ending. Reasons were presented suggesting that K+ accumulation may play an essential role in transduction involving type I hair cells, including the linearization of input-output relations and an increase in the maximal rate of discharge.

Intrauterine pregnancy following endometrial ablation.

BACKGROUND: Only five pregnancies have been reported after endometrial ablation by resectoscopic endometrial resection, for a rate of 0.7% on the basis of three series. CASE: Endometrial ablation was performed using a roller-ball electrode on a 37-year-old woman who had menorrhagia and dysmenorrhea. She subsequently conceived but experienced a missed abortion. CONCLUSION: Pregnancy is a rare occurrence following endometrial ablation. The effect of endometrial ablation on pregnancy outcome is unknown.

A randomized comparison of gasless laparoscopy and CO2 pneumoperitoneum.

OBJECTIVE: To determine if the theoretic advantages of gasless laparoscopy are realized in direct comparison to laparoscopy with pneumoperitoneum. METHODS: Fifty-seven patients undergoing laparoscopic surgery chose to participate in this trial and were randomized after the induction of general anesthesia. Twenty-nine of the 57 patients were randomized to the pneumoperitoneum group. Of the 28 patients in the gasless group, six were converted to pneumoperitoneum because of inadequate exposure. The adequacy of exposure and ease of surgery were assessed with a subjective score, and the times to exposure and for incision closure were recorded. Various anesthetic factors were measured. Patients completed an analog pain score in the recovery area and for the first 5 postoperative days. Analgesic and antiemetic use also was recorded, as was the number of days to return to normal activity. RESULTS: Times to achieve exposure and close incisions were longer, and exposure and ease of surgery were worse in the gasless group. Patients in the gasless group had lower diastolic blood pressure, minute ventilation, peak inspiratory pressures, and end tidal pCO2. There were no differences in body temperature, systolic blood pressure or heart rate, postoperative pain scores, analgesic or antiemetic use, or times to hospital discharge or return to activity between the groups. CONCLUSION: Performing laparoscopy using the Laparolift device compromised surgical exposure and thus increased technical difficulty. Patients realized no benefits from its use in terms of postoperative discomfort or return to activity. Eliminating the pneumoperitoneum allowed lower minute ventilation and peak inspiratory pressures, and end tidal pCO2 was lower. Although the concept of gasless laparoscopy holds appeal, the current prototype is not well-suited for infertility procedures.

In vitro development and implantation rates of fresh and cryopreserved sibling zygotes.

OBJECTIVE: To compare the developmental potential of cryopreserved human zygotes after thawing to sibling zygotes that were transferred without cryopreservation. METHODS: Retrospective analysis of embryo data and pregnancy outcome for all in vitro fertilization (IVF) patients who had sufficient zygotes to allow fresh embryo transfer and cryopreservation of additional sibling zygotes for later use. RESULTS: Zygotes survived cryopreservation at a high rate (87%). After thawing, cryopreserved zygotes developed at rates similar to those of fresh zygotes. Pregnancy occurred at similar rates after replacement of fresh embryos (27.9%) or replacement of cryopreserved-thawed zygote-derived embryos (24.3%). CONCLUSIONS: Human embryos can be cryopreserved at the pronuclear zygote stage with little loss of developmental potential. Cryopreservation allowed a reduction in the number of embryos transferred during an IVF retrieval cycle, thereby reducing the occurrence of multiple pregnancy. The total cumulative pregnancy rate per retrieval cycle doubled when pregnancies from cryopreserved-thawed zygotes were added to those originating from fresh zygotes.

Follicle size and implantation of embryos from in vitro fertilization.

OBJECTIVE: To determine the effect of increased follicle size at the time of hCG administration on the outcome of in vitro fertilization (IVF). METHODS: Fifty women immediately before 50 immediately after a protocol change were reviewed retrospectively. The criterion for hCG administration was changed from a leading follicle size of at least 17 mm to one of at least 20 mm (average of two dimensions). Changes in follicle size and number, oocytes recovered, fertilization rate, embryo development, implantation rate, and pregnancy rate were examined. Women over 40 years of age, those undergoing intracytoplasmic sperm injection, and those whose stimulation did not include GnRH agonists were excluded. RESULTS: The number of large follicles increased, but peak estradiol concentrations and number of oocytes recovered did not differ when hCG was administered at a follicular size of at least 20 mm. The numbers of oocytes fertilized, embryos replaced, and embryos cryopreserved were not statistically different. The percentage of cleaved fertilized oocytes was greater and the degree of embryo fragmentation smaller when hCG was administered at an increased follicular size. The implantation rate was higher and clinical and ongoing pregnancy rates tended to be higher when hCG was administered at a larger follicle size. CONCLUSION: The administration of hCG at a larger follicle size appears to have a beneficial effect on the outcome of IVF. Embryo quality-as reflected by decreased fragmentation, increased cleavage, and increased implantation rate-appears to be improved when hCG is delayed until two or more follicles reach at least 20 mm in diameter.

An evaluation of the Gore-Tex surgical membrane for the prevention of postoperative peritoneal adhesions.

The Gore-Tex surgical membrane, expanded polytetrafluoroethylene, has been used as a pericardial graft with minimal adhesion formation reported. The purpose of this study was to assess its efficacy as a barrier method for diminishing postoperative peritoneal adhesions in an animal model. Fifteen New Zealand white rabbits underwent laparotomy, with scrape and cut lesions created bilaterally on the uterine body and horns, respectively. On one side, the lesions were covered with the graft using 7-0 Gore-Tex suture; the contralateral side served as an internal control. After four weeks, the adhesions were graded and mean adhesion scores were calculated. The Gore-Tex score was 4.1 times higher than the control for scrape lesions and 1.9 times higher for cut lesions, but the difference was not statistically significant in either case. Overall, the Gore-Tex mean adhesion score was 2.3 times higher than the control, a statistically significant difference. The Gore-Tex surgical membrane did not appear to be an effective adjuvant for postoperative adhesion prophylaxis in this animal model.

Recurrent osseous metaplasia of the cervix after loop electrosurgical excision.

BACKGROUND: Osseous metaplasia of the uterus is a rare pathologic entity usually affecting the endometrial cavity without cervical extension. It has been reported after abortion, in cases of chronic endometritis, and as a result of metabolic disorders as hypervitaminosis D, hyperparathyroidism, hypercalcemia, and hyperphosphatemia. CASE: A woman developed osseous metaplasia of the cervix shortly after loop electrosurgical excision procedure (LEEP) for severe cervical dysplasia. Normal transvaginal ultrasonograms before the LEEP, and failure to detect osseous metaplasia after histologic review of the tissue obtained from that procedure indicate that the osseous metaplasia had been induced by the LEEP. The heterotopic bone formation rapidly recurred after initial removal. Her serum calcium, phosphorus, and vitamin D levels were normal. CONCLUSION: LEEP may result in healing with metaplastic bone formation.

Markedly elevated maternal serum alpha-fetoprotein associated with a normal fetus and choriocarcinoma of the placenta.

Determination of maternal serum alpha-fetoprotein (MSAFP) has become an important screening test for a variety of fetal and maternal abnormalities. A 33-year-old multiparous white woman had a markedly elevated MSAFP level (140 multiples of the median). Extensive antepartum work-up for fetal anomalies, fetal-maternal transfusion, or maternal etiology revealed no explanation. The patient subsequently delivered a healthy male infant. Pathologic examination of the placenta demonstrated a small, discrete area of choriocarcinoma. Computed tomography showed a solitary pulmonary metastasis. Because the patient did not desire future pregnancies, a total abdominal hysterectomy was performed, followed by four courses of EMA-CO chemotherapy. Her serum hCG levels subsequently became undetectable. Choriocarcinoma of the placenta must be considered in the differential diagnosis of an otherwise unexplained elevated MSAFP level.

Hysterectomy in Veterans Affairs Medical Centers.

OBJECTIVE: To examine the indications and surgical morbidity for women veterans who underwent hysterectomies in Department of Veterans Affairs Medical Centers (VAs). METHODS: Data on hysterectomies performed in VAs from 1991 to 1997 were abstracted from a surgical quality improvement program. RESULTS: Records of 1722 women who had hysterectomies in VAs over 6 years were examined. Women were predominately white (62%) and their average age was 42.5 years. Operations included abdominal (74%), vaginal (22%), and laparoscopic-assisted (4%) methods. The most common indications for surgery included uterine leiomyomas (31%), abnormal uterine bleeding (14%), and endometriosis (11%). Indications differed by race (P <.01); nonwhite women were most likely to have surgery for leiomyoma (51%), whereas white women had hysterectomies for leiomyomas (19%), abnormal bleeding (15%), endometriosis (13%), and genital prolapse (11%). The mean postoperative stay was significantly longer for abdominal hysterectomies (4.51 days) than either vaginal or laparoscopic-assisted hysterectomies (2.92 and 2.21 days, respectively; P <.001). The overall complication rate within 30 days was 9%, and the most frequent complication was urinary tract infection (3.3%). CONCLUSION: Women who underwent hysterectomies in VAs had low complication rates, comparable to hysterectomy complication rates in the United States generally.

Microsurgical fallopian tube transposition with subsequent term pregnancy.

A case is described in which a patient with a non-communicating left unicornuate uterus and surgically absent left tube and ovary delivered at term after a microsurgical anastomosis of the right fallopian tube and left cornua. Pregnancy rates with this type of procedure have been reported to be comparable to ipsilateral tubal anastomosis. Tubal transposition should be considered as an alternative option to IVF-ET in selected patients.

Effect of diethylstilbestrol on reproductive function.

OBJECTIVE: To review the effects of in utero exposure to diethylstilbestrol (DES) on müllerian development and subsequent reproductive function. DESIGN: The literature on DES and reproductive function was reviewed and summary data are presented. The studies were identified through the computerized MEDLINE database and a manual search of relevant bibliographies. RESULT(S): In utero exposure to DES resulted in reduced fertility and increased rates of ectopic pregnancy, spontaneous abortion, and preterm delivery. CONCLUSION(S): An understanding of the reproductive performance of women who were exposed to DES in utero is useful for counseling these patients regarding their risks and treatment options.

Robotic-assisted laparoscopic microsurgical tubal anastomosis: a human pilot study.

OBJECTIVE: To evaluate the feasibility and safety of a robotic device to perform a laparoscopic tubal anastomosis. DESIGN: Prospective pilot study. SETTING: Tertiary care medical center. PATIENT(S): Ten patients with previous tubal ligations underwent laparoscopic tubal ligation reversal using a robotic suturing device. INTERVENTION(S): Tubal surgery was performed with a robotic system. A two-layered closure was used for all tubes. Four stitches of 8-0 polygalactin sutures were used for each layer. MAIN OUTCOME MEASURE(S): Tubal patency; secondary measures were pregnancy rates, complications, and operative time. RESULT(S): The procedure was completed successfully in all 10 patients. No patient required conversion to an open procedure. The mean time (+/-SD) required to complete the anastomosis of both tubes was 159 +/- 33.8 minutes. Chromotubation at the end of the procedure showed patency in all tubes anastomosed. A postoperative hysterosalpingogram 6 weeks after surgery demonstrated patency in 17 of the 19 (89%) tubes anastomosed. There have been five pregnancies so far. There were no complications. CONCLUSION(S): Robotic technology can be used safely to create laparoscopic microsurgical anastomoses with adequate patency rates. Robotic technology has the potential to make laparoscopic microsuturing easier.