Protein-protein interactions form the proteinaceous network, which plays a central role in numerous processes in the cell. This review highlights the main structures, properties of contact surfaces, and forces involved in protein-protein interactions. The properties of protein contact surfaces depend on their functions. The characteristics of contact surfaces of short-lived protein complexes share some similarities with the active sites of enzymes. The contact surfaces of permanent complexes resemble domain contacts or the protein core. It is reasonable to consider protein-protein complex formation as a continuation of protein folding. The contact surfaces of the protein complexes have unique structure and properties, so they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations have been undertaken to find or design small molecules that block protein dimerization or protein(peptide)-receptor interaction, or on the other hand, induce protein dimerization.

Animals↗

PubMedDate not supplied

Prosodic abilities in children with specific language impairment.

The purpose of this study was to compare the receptive and expressive prosodic abilities of specifically language-impaired children to those of a matched group of control normal-language children. Each subject group consisted of ten 4-year-olds, ten 5-year-olds and ten 6-year-olds. Subjects were administered two instruments which were designed for this purpose: the prosody imitation task and the emotion identification task. In the prosody imitation task subjects were required to imitate ten sentences with different linguistic and affective intonation contours. The emotion identification task required subjects to identify recordings of emotionally intoned sentences. Language-impaired children performed significantly less accurately on the imitation task but did not differ from normal-language children on the emotion identification task. Age was found to be a highly significant factor. On both tasks children performed better with increasing age. Results are discussed in reference to the developmental relationship between the child's learning of language and prosodic cues.

Affect↗

PubMedDate not supplied

Time lost from work among women choosing medical or surgical abortions.

This was a prospective cohort questionnaire study to compare the loss of ability to work in 62 women having medical and 69 having surgical abortions. Outcomes included the number of days lost from work outside the home and inside the home before and after the abortion appointment. The mean total loss from work inside the home was 10.1 days for the surgical group and 5.3 days for the medical group (P <.05). The mean total loss from work outside the home was not significant at 4.0 days for the surgical group and 2.5 days for the medical group.

Abortion, Legal↗

PubMedDate not supplied

Universal screening for domestic violence in abortion.

The purpose of this study was to evaluate the policy of universal screening for domestic violence in an abortion clinic. Compliance with the policy was low, because only 254 of 499 women seen were asked the screening questions: 58% of Caucasians, 40% of East Asians, and 37% of South Asians were screened (P =.003). Of the 254 women asked about abuse, 38 said they had been abused in the past 12 months, giving a prevalence rate of domestic violence similar to that of the general population. Screening for domestic violence in women presenting for abortion is challenging, but feasible.

Abortion, Induced↗

PubMedDate not supplied

Assessment of stereopsis in rhesus monkeys using visual evoked potentials.

Rhesus monkeys can have deficiencies in stereo vision, making it necessary to screen monkey subjects intended for single cell studies of stereo-based depth processing. We measured VEPs in two monkeys using a dynamic random-dot display in which a stereo-defined checkerboard reversed in depth. Monkeys fixated upon a small dot during stimulus presentation. One monkey showed clear evoked potentials in response to changes in disparity that were similar to those obtained in human subjects, using an identical stimulus paradigm. Controls with presentations of the monocular stimulus sequences (in which no depth reversal can be perceived) yielded no or much weaker VEPs. In the other animal, however, there was no difference in evoked potential between the two conditions. These electrophysiological findings closely match the performance of these same two subjects in a disparity discrimination task in which they were previously trained. We conclude that VEPs using this type of stimulus display can be used to screen monkeys for single cell or behavioral studies of stereopsis.

Animals↗

PubMedDate not supplied

Discovery, development and characterization of agents active against the AIDS virus.

Despite major efforts by academic and pharmaceutical research teams, no definitive prevention or cure of AIDS has been achieved. Nevertheless, this research has yielded important information on how HIV replicates and causes disease. Moreover, several inhibitors, targeted at different steps in the life cycle of HIV, have been discovered, some of which have been licensed or are being studied in the clinic. One of the major obstacles towards more effective drugs or a vaccine, is the extraordinary variability in HIV strains which occur in different parts of the world over time, and in patients. The driving force behind these numerous variants is the combination of an error-prone reverse transcriptase, a viral enzyme transcribing the viral RNA genome into DNA on the one hand and the human immune system on the other hand. This puts a constant selection pressure on the HIV population leading to the emergence of escape mutants. It therefore poses an additional challenge on the discovery and development of HIV inhibitors. A research strategy should therefore encompass the following steps: (i) the identification of new lead compounds targeted at known or unknown steps in the HIV replicative cycle, (ii) the characterization and validation of their molecular targets with emphasis on the potential for lead optimization and the likelihood of resistance development, (iii) the study of combination strategies, and (iv) clinical evaluation and validation of the aforementioned concepts.

Antiviral Agents↗

PubMedDate not supplied

Quality of life assessment after Nissen fundoplication.

The aim of this study was to evaluate the quality of life of 31 patients presenting with gastroesophageal reflux (GORD) and operated on by Nissen fundoplication. The series consisted of 23 men and 8 women; the median age was 39 years (range 22-65) and the median follow-up 36 months (range 18-74). We used a new questionnaire: the Gastrointestinal Quality of Life Index (GIQLI) that includes 36 items and uses a five-graded Likert scale (from 0 to 4) giving a maximum score of 144. This score includes five dimensions: symptoms, emotions, vitality, social relations and medical treatment. The pre- and postoperative GIQLI scores observed in the Nissen group and the score of a control group of 110 healthy patients were compared with each other. The preoperative score (71 +/- 21) was greatly impaired compared to the score (123 +/- 13) of the control group (p < 0.0001). The postoperative score (109 +/- 21) increased significantly (p < 0.0001) but remained statistically inferior to the score of the control group (p < 0.005). The analysis of the dimensions showed that the postoperative score of the symptoms was lower in the Nissen group: 56 +/- 9 versus 66 +/- 6 in the control group (p < 0.0005) whereas no statistical difference was found for the four other dimensions. This lower symptoms score was not due to recurrence of GORD symptoms but to the occurrence of flatulence and to the persistence of gurgling noises and gas bloating. In conclusion, the quality of life of the patients requiring surgery for gastroesophageal reflux was greatly impaired, it largely improved after Nissen fundoplication but did not reach the level of healthy patients because of unrelated GORD gastrointestinal symptoms.

Adolescent↗

PubMedDate not supplied

[Expression of the Mycobacterium tuberculosis cytochrome CYP51 gene in Escherichia coli].

Mycobacterium tuberculosis sterol 14 alpha-demethylase CYP51 is currently considered a promising target for a new generation of antitubercular drugs. Similarly to eucaryotic sterol 14 alpha-demethylases, candidate selective inhibitors of M. tuberculosis CYP51 belong to azoles, the N-substituted derivatives of imidazole and triazole. We have constructed a highly effective system for heterologous expression of MT CYP51 in E. coli. The recombinant protein was purified by metalloaffinity chromatography for primary in vitro screening of novel antitubercular azole compounds for their high affinity to the molecular target. Yield of the purified recombinant MT CYP51 was about 1.5 micromoles of the purified native protein per 1 l of E. coli cell culture. The recombinant protein interacted with ketoconazole with a Kd of 7.7 microM. MT CYP51 produced by our system for heterologous expression in E. coli may be used for initial testing of novel antimycobacterial azole drugs.

Amino Acid Sequence↗

PubMedDate not supplied

A new concept of long-term donor heart preservation: nucleoside transport inhibition.

Myocardial ischemia results in a breakdown of adenosine triphosphate (ATP), which is associated with an accumulation of its catabolites adenosine and inosine. Adenosine is a potent but ineffective cardioprotective agent because it is rapidly transported to the endothelium and irreversibly catabolized. With the use of specific nucleoside transport inhibition (NTI), however, endogenous adenosine may accumulate at its site of production, and its further breakdown and washout on reperfusion is prevented. In this study we tested this concept and assessed the effect of NTI drug administration on 24 hours' preservation of donor hearts for transplantation. Twelve dogs were randomly allocated to two groups. In the first group (group 1, n = 6) the hearts were arrested with a cold hyperkalemic cardioplegic solution, excised and stored for 24 hours at 0.5 degrees C. After 24 hours the hearts were transplanted orthotopically. In group 2 (n = 6) the same procedure was followed, but a specific NTI agent was added to the cardioplegic solution (1 mg/L) and administered intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). Despite maximal positive inotropic support, none of the control animals (group 1) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiogenic shock occurred in all animals. In group 2 all hearts could be weaned from cardiopulmonary bypass and were hemodynamically stable without positive inotropic support. Serial transmural left ventricular biopsies revealed in group 1 moderate catabolism of ATP during cold storage. On reperfusion a further decline of the ATP content was seen, and the accumulated nucleosides were washed out.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMedDate not supplied

Prospective analysis of 192 consecutive cholecystectomies: a comparative study between laparoscopy and laparotomy.

The hospital records of all the patients who underwent cholecystectomy because of specific biliary symptoms, between October 1990 and March 1993, were prospectively analyzed. The series consisted of 192 patients (159 women and 33 men), the mean age was 56 years and the mean body mass index was 26. Indication for surgery was uncomplicated gallstones in 113, common bile duct stones in 28 and cholecystitis in 51 patients. In those groups, respectively 94 (83%), 16 (57%) and 23 (45%) patients had a laparoscopic cholecystectomy. In total, laparoscopic cholecystectomy was successfully performed in 127 (95%) of the 133 patients in whom it was attempted. When compared with laparotomy, laparoscopic cholecystectomy was associated with shorter operative time: 88 +/- 41 min. (Mean +/- SD) versus 132 +/- 64 min. (p < 0,001), shorter postoperative hospital stay: 5 +/- 3 days versus 13 +/- 7 days (p < 0.001) and reduced cost of hospitalization: 103.301 +/- 51.062 BF versus 186.931 +/- 113.651 BF (p < 0.001). We noted an equivalent perioperative morbidity incidence in the two groups. The advantages of laparoscopy compared to laparotomy were recorded whatever the indication for cholecystectomy was. Therefore, with the increasing experience of surgeons and the improving quality of laparoscopic instruments, we think that laparoscopy can be considered for all patients requiring cholecystectomy.

Adult↗