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PubMedDate not supplied

Intrauterine insemination for cervical and male factor without superovulation.

Intrauterine insemination (IUI) has been used for the treatment of various causes of infertility, including unexplained infertility, male factor, and cervical factor. Some centers frequently use superovulation combined with IUI. The study presented herein attempted to evaluate the efficacy of IUI without superovulation in cases where all causes of infertility other than cervical or male factors have been eliminated. However, in the case of poor or absent cervical mucus, the use of controlled ovarian hyperstimulation (COH) may obscure the actual importance of the IUI, since it is possible that the poor cervical mucus is related to poor timing, inadequate follicular maturation, or low estradiol levels, which if corrected will obviate the need for IUI. In this study IUI was targeted for 36-40 h following the sera luteinizing hormone surge. A total of 108 patients were enrolled in this study: 47 with male factor, 61 with cervical factor. Patients were followed for a maximum of three cycles unless a pregnancy occurred within 3 months of treatment. Comparison of pregnancy rates (PRs) were based on diagnosis. The cumulative PRs per cycle for each of the three cycles studied were as follows: cervical factor--19.7, 36.8, and 36.8%; male factor--12.8, 29.3, and 38.3%. Thus, PRs were comparable for both groups after three treatment cycles. These data demonstrate that IUI is an effective therapy for cervical and/or male factor, even without superovulation.

Adult↗

PubMedDate not supplied

A case-matched control study of intrahepatoarterial chemotherapy in combination with or without regional hyperthermia for treatment of primary and metastatic hepatic tumours.

The efficacy of the combined application of intrahepatoarterial (IHA) chemotherapy and regional hyperthermia for the treatment of unresectable hepatic tumours was studied in a case-matched, retrospective control study. Well-matched pairs of patients with the same or similar background factors, who had been treated with IHA chemotherapy plus hyperthermia (group A; n = 32) and with IHA chemotherapy alone (group B; n = 32) were included in this study. In group A, partial responses (PRs) were found in 2 of 8, 4 of 8, and 5 of 16 patients with hepatocellular carcinoma, metastatic gastric cancer, and metastatic colorectal cancer, respectively. In group B, PRs were found in 1 of 8, 3 of 8, and 5 of 16 patients with those diseases, respectively. Overall, PRs were found in 12 (37%) and 9 (28%) of 32 patients in groups A and B, respectively; progressive disease was found in 6 (19%) in group A and in 12 (38%) in group B. These results indicate that this combination therapy is of therapeutic benefit in the treatment of unresectable hepatic tumours.

Antineoplastic Agents↗

PubMed1985

The effects of ACTH on the renin-aldosterone system in normotensive man.

The present study examined the effects of low dose ACTH administration (0.1 mg/day for 2 days) on plasma renin concentration, (PRC), activity (PRA) and substrate (PRS), cortisol and aldosterone in man. Six healthy male volunteers on a diet calculated to contain 150 mmol Na/day received an infusion of 5% dextrose (6 ml/h) for 24 hours, then ACTH (Synacthen, Ciba-Geigy) was added to the infusion at the rate of 100 micrograms per day, for 48 h. Blood samples were taken four hourly for determination of plasma cortisol, aldosterone, PRC, PRA and PRS. There was a highly significant increase in plasma cortisol and aldosterone concentrations during ACTH infusion compared with dextrose infusion, but no significant increase in active or inactive PRC, PRA or PRS. In a separate study of 15 healthy male volunteers, dexamethasone (1 mg at 2300 h) suppressed plasma cortisol but had no effect on PRC. These results do not support the view that stimulation of aldosterone by ACTH is mediated through the renin angiotensin system.

Adrenocorticotropic Hormone↗

PubMed2006

Progesterone and estrogen receptors: opposing prognostic indicators in meningiomas.

OBJECT: The preponderance of progesterone receptors (PRs) and the scarcity of estrogen receptors (ERs) in meningiomas are well known. The expression of PRs may relate to tumor grade and recurrence. Cytogenetic abnormalities are associated with aggressive behavior, recurrence, and progression. In this study, the authors focus on the prognostic implications of hormone receptors in meningiomas to help determine the clinical and biological aggressiveness of tumors and their correlations with cytogenetic abnormalities. METHODS: Two hundred thirty-nine patients with meningiomas were separated into three groups. Group 1 (PR-positive group) comprised patients whose meningiomas displayed expression of PRs alone. Group 2 (receptor-negative group) included patients whose lesions did not have receptors for either progesterone or estrogen. Group 3 (ER-positive group) included patients whose tumors displayed expression of ERs. Clinical and histological findings, proliferative indices, tumor recurrence, and cytogenetic findings were analyzed by performing the Fisher exact test. Compared with the receptor-negative (Group 2) and ER-positive (Group 3) groups, the PR-positive group (Group 1) had a statistically significant lower proliferative index and a smaller number of patients in whom there were aggressive histopathological findings or changes in karyotype. In Groups 1, 2, and 3, the percentages of cases with aggressive histopathological findings were 10, 31, and 33%, respectively; the percentages of cases with chromosomal abnormalities were 50, 84, and 86%, respectively; and the percentages of cases in which there initially was no residual tumor but recurrence was documented were 5, 30, and 27%, respectively. A statistically significant increase in the involvement of chromosomes 14 and 22 was identified in receptor-negative and ER-positive de novo meningiomas, when compared with the PR-positive group. Abnormalities on chromosome 19 were statistically significantly higher in receptor-negative meningiomas than in PR-positive tumors. CONCLUSIONS: The expression of the PR alone in meningiomas signals a favorable clinical and biological outcome. A lack of receptors or the presence of ERs in meningiomas correlates with an accumulation of qualitative and quantitative karyotype abnormalities, a higher proportional involvement of chromosomes 14 and 22 in de novo tumors, and an increasing potential for aggressive clinical behavior, progression, and recurrence of these lesions. Sex hormone receptor status should routinely be studied for its prognostic value, especially in female patients, and should be taken into account in tumor grading. The initial receptor status of a tumor may change in progression or recurrence of tumor.

Adult↗

PubMed2026

Genetic and Lifestyle Factors Influence High 1-Hour Plasma Glucose, a Predictor of Type 2 Diabetes Mellitus.

BACKGRUOUND: High 1-hour plasma glucose (1-h PG) level has been proposed by the International Diabetes Federation to identify high-risk individuals and diagnose type 2 diabetes mellitus (T2DM). In a longitudinal cohort, we examined T2DM risk, β-cell function, and the effects of genetic and lifestyle factors on high 1-h PG. METHODS: We analyzed 7,464 participants without T2D at baseline from a community-based prospective cohort in Korea, who underwent biennial 2-h 75-g oral glucose tolerance tests over 14 years. Incident T2D risk were assessed across 1-h PG groups: < 155, 155-208, and ≥ 209 mg/dL. In 6,588 participants with at least two 1-h PG measurements, we analyzed 1-h PG trajectories by T2D polygenic risk score (PRS; low, 1st quintile; intermediate, 2nd-4th quintiles; high, 5th quintile) and lifestyle, assessed using Life's Essential 8. RESULTS: Compared to the <155 mg/dL group, hazard ratios for T2DM were 3.34 (95% confidence interval [CI], 2.99 to 3.74; P<0.001) for 155-208 mg/dL, and 6.81 (95% CI, 5.81 to 7.98; P<0.001) for ≥209 mg/dL. Both groups had lower baseline disposition index compared to the <155 mg/dL group (57.3% and 72.7%, respectively; both P<0.001). Higher T2DM PRS was associated with elevated baseline 1-h PG (low: 131 mg/dL, intermediate: 141 mg/dL, high: 151 mg/dL) and faster increase in 1-h PG (1.36 vs. 1.85 vs. 2.21 mg/dL/year; all P<0.001). Importantly, healthy lifestyle attenuated the rate of increase across all PRS groups. CONCLUSION: High 1-h PG predicts T2DM risk and is associated with β-cell dysfunction. The 1-h PG level is influenced by genetic risk and can be modified with a healthy lifestyle.

Humans↗

PubMed2000

Estrogen and progesterone receptors in non-small cell lung cancer in 248 consecutive patients who underwent surgical resection.

CONTEXT: Different authors have reported estrogen receptor (ER) expression between 0% and 96.8% and progesterone receptor (PR) expression between 21.8% and 34.7%. OBJECTIVE: To examine the discrepancies in the literature regarding the expression of ERs and PRs in non-small cell lung cancer. DESIGN: Retrospective analysis. SETTING: A referral tertiary care center. PATIENTS: We reviewed 248 consecutive cases of stage I and II non-small cell lung cancers. METHODS AND RESULTS: Sections of formalin-fixed and paraffin-embedded tumor tissue were stained with ER and PR monoclonal antibodies using the avidin-biotin complex detection system with antigen retrieval. Men represented 66.1% of the patients, and women represented 33.9%. Large cell (undifferentiated) carcinoma constituted 10.4% of the entire population; squamous cell carcinoma, 39.1%; adenocarcinoma, 33.0%; and bronchoalveolar carcinoma, 17.3%. Patients with stage I disease represented 77.0% of the population. In this patient population, we found no nuclear or cytoplasmic expression of either ERs or PRs (95% confidence interval, 0%-1.2%). CONCLUSIONS: The absence of expression of ERs and PRs differs from previous articles, which use a variety of techniques, impairing a meaningful comparison of data. In addition, the presence of ER and PR expression in a lung carcinoma is supportive of a nonpulmonary primary tumor metastatic to the lung. The absence of their expression in non-small cell lung cancer does not support a role of these transcription factors in initiating and maintaining this neoplastic process.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2002

Implications of the HIV/AIDS Prevention Research Synthesis Project for the efforts of state, territorial, and local health departments.

State, territorial and local health departments have responsibility for all three of the HIV/AIDS Prevention Research Synthesis (PRS) project's intervention categories: behavioral, social, and policy. These health departments may be aided by the PRS project in a number of ways. These ways include the provision of information on scientifically proven interventions; the determination of sociodemographic categories underrepresented in research; the promotion of consistent methodologies and standards for reporting findings; and the fostering of greater engagement with HIV prevention research among program staff. Further development of the PRS project can enhance and expand these benefits, although the project must be sure to keep practical applications in mind.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Estrogen and progesterone receptors in neoplastic and non-neoplastic thyroid lesions.

The pathogenesis of thyroid cancer is complex. Iodium deficiency, genetic factors, sex, older age, irradiation in childhood, thyroid growth stimulating antibodies and epithelial growth factor possibly affect its development. Recent reports, also epidemiological, have shown that differentiated thyroid cancer (papillary, follicular, oxyphillic) is dependent on sex hormones, especially estrogens. This has prompted research into the presence of estrogens and progesterone, as well as androgen receptors (ER, PR and AR) in normal and neoplastic thyreocytes and estradiol content in thyroid tissue. The results of these investigations imply that thyroid cancers are estrogen-dependent. There is, however, no agreement in reports about correlation between tumor malignancy and ER, PR and AR expression. In this study 72 thyroid glands have been examined using immunohistochemical assays with ERs and PRs antibodies. Positive staining was demonstrated mainly in differentiated thyroid cancer nuclei (17 ERs positive and 2 PRs positive). There was no expression of antibodies in non-neoplastic cells or in adjacent tissues. The nuclei of 3 oxyphillic and 4 follicular adenomas were also ERs positive. On the other hand nuclei of 5 follicular adenomas were PRs positive. These results are in agreement with most available data. It seems, however, that the material so far examined by the investigators is too small. Furthermore, because of using various methods the results cannot be compared. Further studies are necessary to reveal if there is any true influence of sex hormones on the development of thyroid lesions and if the detection of sex hormone receptors may help in choosing adequate therapy.

Adenoma↗

PubMed2002

Evidence that exclusive use of Follistim may produce better pregnancy results than the use of Gonal-F following in vitro fertilization (IVF) - embryo transfer (ET).

PURPOSE: To evaluate whether the equal mixture of human menopausal gonadotropin (hMG) to recombinant (r) follicle stimulating hormone (FSH) for controlled ovarian hyperstimulation (COH) adversely affects outcome following in vitro fertilization (IVF). Furthermore, to determine if the specific rFSH preparation used has any differing effects on outcome. METHODS: Retrospective study of women using the luteal phase leuprolide acetate-gonadotropin COH regimen. Outcome measures included clinical and viable pregnancy rates (PRs) and implantation rates. RESULTS: The clinical and viable PRs and implantation rates were significantly lower in the group receiving exclusively Gonal-F. Addition of hMG to the treatment protocol not only did not lower the PRs further, but in fact seemed to obviate the adverse effect of Gonal-F. CONCLUSION: Since exclusive use of Gonal-F did not adversely affect fertilization rates or quality of embryos we suspect its exclusive use in some way makes the uterine environment less receptive.

Adult↗

PubMed2003

[Clinical features and treatment of polypous rhinosinusitis combined with allergic diseases].

140 patients of ENT-clinic and 484 patients of immunological clinic with nasal and paranasal polyposis were examined to characterize clinical features and therapeutic policy in polypous rhinosinusitis (PRS) in various allergic pathology. PRS was frequently associated with allergic diseases (allergic rhinitis, bronchial asthma, aspirin intolerance, atopic dermatitis, asthmatic triad). This allows considering PRS as a particular manifestation of general allergic pathology. Therapeutic policy consists in selection of basic therapy of the underlying (allergic) disease, management of chronic infection, adequate examination of the patients and individual selection of drugs in preoperative preparation and postoperative management of patients.

Adolescent↗

PubMed2003

[Corrosion of titanium in presence of dental amalgams and fluorides].

AIM: The aim of this study was to evaluate the behaviour of titanium (Ti) in precipitant condition, and more precisely the resistance against corrosion of Ti in presence of fluorides and the electrochemical interaction between Ti- amalgam couples in fluorinated solution. METHODS: The experimental test was made with the use of an electrochemical cell. The following materials were tested: commercially pure Ti and 2 types of amalgams, the Persistalloy (Prs) and the IQC. Palladium (IQC.P). The free corrosion potential of Ti and the amalgams, the polarization curves of both amalgams and the corrosion current of the Ti-amalgam couples in the measurements were performed in 3 different electrolytic solutions: Ringer solution, fluorinated neutral Ringer solution and acid fluorinated solution. The three corrosive media are described. RESULTS: The results showed that Ti could be damaged by the presence of fluorides with an acid pH: Ti potential becomes more negative in acid fluorinated solution. The corrosion currents between Ti and amalgam couples were considered: the amalgams underwent anodic oxidation in neutral Ringer, but a reversal phenomenon occurred in the fluorinated acid solution: Ti was damaged and the amalgams both Prs and IQC.P became the cathodic partner of the couple. In neutral fluorinated solution the IQC.P amalgam induced a significantly higher corrosion of Ti, when compared to the Prs one. CONCLUSION: Results clearly show the dependence of the Ti corrosion behaviour on the pH and composition of the solution and that the outcome of the damage is affected by the composition of other metals.

Chemical Phenomena↗

PubMed1992

KTP/532 laser laparoscopy in the treatment of endometriosis-associated infertility.

OBJECTIVE: To determine the clinical effectiveness of the KTP/532 laser in treating endometriosis-associated infertility and to analyze the impact of additional infertility factors on outcome. DESIGN: Prospective cohort analysis of 74 consecutive patients followed up to 24 months after surgery. SETTING: Tertiary institutional infertility clinic. MAIN OUTCOME MEASURES: Cumulative pregnancy rates (PRs), monthly fecundity rates, monthly probability of pregnancy, crude PRs, and cure rates. RESULTS: Thirty-eight percent (28) of patients conceived with a mean +/- SE time to conception of 7.2 +/- 0.8 months. The cure rates were 74% for the total patient sample, 51% for stage I, 69% for stage II, and 64% for stage III disease. Patients who had a cervical factor (P = 0.05), who underwent intrauterine insemination (P = 0.03), who received human menopausal gonadotropin (P = 0.03), or who had additional infertility factors (P = 0.02) had significantly lower crude PRs. The presence of additional infertility factors (P less than 0.02) and intrafimbrial adhesions (P less than 0.01) had a significant impact on cure rates. In the absence of additional factors, 60% (12) of patients with stage I and II conceived. When additional factors were excluded, the overall cure rate was 80%. CONCLUSION: The results indicate that the KTP/532 laser is an effective tool for the treatment of endometriosis-related infertility. The high prevalence of subtle adhesions may lend further impetus to operative laparoscopy for stage I and II disease. Additional infertility factors may adversely affect outcome.

Adult↗

PubMedDate not supplied

Factors influencing patient survival and renal function outcome in pulmonary-renal syndrome associated with ANCA (+) vasculitis: a single-center experience.

Small vessel vasculitides, usually associated with positive antineutrophil cytoplasmic antibodies (ANCA(+)) can cause pulmonary-renal syndrome (PRS). Data from 22 patients, (19 males), aged 28-76 yrs (mean 55), with PRS were analyzed retrospectively. Renal function was estimated at presentation, 1 month after treatment initiation and at the end of follow-up (mean 4.4 +/- 3.3 yrs). Thirteen out of 22 patients had PR3 (+) ANCA and 9/22 patients had MPO (+) ANCA. Mean serum creatinine (Cr) at diagnosis was 6.6 +/- 4.4 mg/dL (M +/- SD) and proteinuria 1.6 +/- 1.4 g/24 hr (M +/- SD). During the 1st month of treatment with corticosteroids and cyclophosphamide, renal function improved in 12 patients (54.5%) (serum Cr from 8.5 +/- 4.5 to 4.3 +/- 2.3 mg/dL, p=0.001) remaining stable thereafter, and renal function deteriorated in nine patients (41%) (serum Cr from 4.1 +/- 3 to 6.5 +/- 2.9 mg/dL, p=0.03); one patient (4.5%) died because of sepsis. At the end of the study, 11/22 patients (50%) had died, eight patients of these (73%) because of respiratory failure, three patients (13.6%) reached end-stage renal disease (ESRD), five patients (36.4%) remained stable, but with impaired renal function and finally three patients (13.6%) improved, achieving almost normal renal function. In multiple regression analysis, factors contributing to final serum Cr were: dialysis dependency at the time of diagnosis p=0.01, initial proteinuria p<0.0001, and percentage of cellular crescents p=0.003. Main differences between PR3 and MPO (+) patients were the chest CT findings (bilateral nodules in PR3 (+) and "ground glass" or fibrosis in MPO (+) patients) and the renal function improvement rate after treatment initiation (rapid decline in serum Cr in PR3 (+) patients). In conclusion, PRS with ANCA (+) is associated with increased mortality. If renal function improves during the 1st month of treatment, it usually remains stable thereafter. The presence of PR3-ANCA is associated with an early response to treatment, while MPO-ANCA vasculits seems to necessitate prolonged treatment.

Adrenal Cortex Hormones↗

PubMed2006

[Bronchial obstruction reversibility test in the assessment of COPD severity--controversies].

UNLABELLED: The GOLD and ERS/ATS guidelines recommend the post-bronchodilator FEV1 (% predicted) to define the severity of chronic obstructive pulmonary disease (COPD). Yet in various publications authors analyze the pre-bronchodilator value or do not clearly state which value was used when the bronchial reversibility test was performed. The guidelines established by the Polish Respiratory Society (PRS) do not specify if performing the reversibility test is necessary to estimate the COPD severity and suggest a reversibility test evaluation which differs from that in the ERS/ ATS and GOLD recommendations. AIM: to assess the changes in the degree of severity of COPD in the classification based upon the pre- and post-bronchodilator FEV1 and to compare the interpretation of the reversibility test as suggested by GOLD and ATS/ ERS and the PRS. METHODS: 145 COPD patients (67F, 78M, mean age 67.5+/-8.9 yrs) with a negative bronchial obstruction reversibility test (salbutamol 400 microg) were enrolled to the study. For each patient the degree of COPD severity using the pre- and postbronchodilator FEV1 was established. The pre- and post-bronchodilator classifications were compared. Differences in the interpretation of the reversibility test according to the GOLD and ATS/ ERS and the Polish guidelines were analyzed. RESULTS: In 22 subjects (15.2%) the degree of disease severity changed after salbutamol. The changes were most frequent in the group of severe and very severe COPD (77.3% of changes). In 1 patient (0.7%) post-bronchodilator severity was greater than before salbutamol intake. In 7 patients (4.8%) the post-bronchodilator FEV1/FVC exceeded 70%, thus excluding the diagnosis of COPD. Of all the 145 negative (according to the ATS/ ERS and GOLD criteria) reversibility tests in 24 cases (16.6%) the test was positive when the criteria recommended by PRS were applied. CONCLUSIONS: the bronchial obstruction reversibility test is essential in the diagnosis and assessment of severity of COPD. Despite poor obstruction reversibility in this disease the use of pre-bronchodilator FEV1 in the assessment of COPD severity may be misleading and is an obstacle in the comparative analysis of studies in the domain of this disease. Differences in the guidelines for the management of COPD may also hinder comparative studies and influence epidemiologic data.

Aged↗

PubMed2006

Evaluation of the effect of endometriosis on oocyte quality and endometrial environment by comparison of donor and recipient outcomes following embryo transfer in a shared oocyte program.

PURPOSE: To determine whether endometriosis has an effect on the uterine environment vs the oocyte itself. METHODS: A retrospective study comparing pregnancy outcome of infertile donors sharing oocytes with donor egg recipients according to whether the donor or recipient had endometriosis or not was carried out. RESULTS: There were 26 transfers from donors with endometriosis vs 144 in donors without endometriosis. The clinical and viable PRs and implantation rates were 42.9%, 38.1%, and 29.4% for the endometriosis group vs 60.9%, 51.9%, and 33.2%, respectively, for donors without endometriosis (p = NS). The clinical and viable PRs and implantation rates for donors with endometriosis per ET was 41.2%, 35.3%, and 20.4% vs 50.4%, 48.0% and 28.4% for donors without endometriosis, respectively (p = NS). CONCLUSIONS: Though no significant differences were found in donors with or without endometriosis in any parameters, there did appear to be a trend for lower PRs and implantation rates in women undergoing controlled ovarian hyperstimulation.

Adult↗

PubMed1992

In vitro fertilization in unstimulated cycles: the University of Southern California experience.

OBJECTIVE: To describe the clinical experience of our center with in vitro fertilization (IVF) in unstimulated cycles and to provide a comparison to stimulated cycles. DESIGN: Spontaneous ovulatory cycles were triggered with human chorionic gonadotropin in the midcycle, and 78 aspirations for IVF were performed, with the remainder of the IVF cycle proceeding in a standard manner. SETTING: The IVF program of the University of Southern California and the California Medical Center, Los Angeles, California. PATIENTS: Spontaneously ovulatory women (n = 46) with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor. INTERVENTIONS: Human chorionic gonadotropin administration in midcycle, follicle aspiration, IVF, and embryo transfer. MAIN OUTCOME MEASURES: Embryo implantation and pregnancy. RESULTS: Seventy-eight follicle aspirations resulted in 11 clinical (14%) and 9 ongoing (12%) pregnancies. The per embryo implantation rate was 13% clinical and 11% ongoing. There was no decrease in per cycle pregnancy rates (PRs) for up to three unstimulated cycles. CONCLUSIONS: Unstimulated IVF is a viable alternative to stimulated cycles with PRs approximately one half those of stimulated cycles. It is reasonable to offer patients up to three cycles of unstimulated IVF without expecting a decrease in PRs.

Chorionic Gonadotropin↗

PubMed1991

[The results of pylorus-preserving resection of the stomach].

The functional results of pylorus-preserving resection of a stomach (PRS) in 68 patients with gastric ulcer disease were studied. According to the data of gastroscintigraphy and hepatoscintigraphy, it was established that number of patients with decreased motor-evacuatory function (MEF) of the stomach reduced from 31% before the operation to 11% at the long-term period after PRS. Duodenogastric reflux was noted in 10% of the patients as compared with 47% before the operation. MEF of the stomach normalized within 3-6 mos after the operation. Acid-producing function of the stomach after PRS steadily decreased until the development of a hypoacidic state. Basal pH of gastric, body at the long-term period was 3.39 +/- 0.59. An excellent and good result according to Visick scale was noted in 67 (98.5%) patients, a satisfactory one--in 1 (1.5%).

Follow-Up Studies↗

PubMed1990

Comparison of the crystal structures and intersubunit interactions of human immunodeficiency and Rous sarcoma virus proteases.

The crystal structures of the proteases (PRs) encoded by the Rous sarcoma virus (RSV) and the human immunodeficiency virus (HIV) have been compared. The crystallographic monomer of HIV PR superimposes on the two crystallographically independent subunits of the RSV PR dimer with root mean square deviations of 1.45 and 1.55 A for 86 and 88 common C alpha atoms, respectively. There is a conserved structural core consisting of seven beta-strands forming two perpendicular layers, a helix, and the amino- and carboxyl-terminal beta-strands. PRs from related retroviruses fold into similar structures with surface turns of variable length between the beta-strands. Both HIV and RSV PR dimers have significant subunit-subunit interactions in three regions: the "firemen's grip" at the active site; the salt bridges involving Arg8, Asp29, and Arg87 of HIV PR; and the termini of the two subunits, which form a four-stranded antiparallel beta-sheet. The specific interactions of the termini differ in the two PRs. The carboxyl termini, residues 96-99 of HIV PR and residues 119-124 of RSV PR, contribute approximately 50% of the intersubunit ionic and hydrogen bond interactions and approximately 45% of the buried surface area involved in dimer formation. This information may be useful in the design of site-directed mutations or inhibitors of dimer formation.

Amino Acid Sequence↗