Electron-pair excitations and the molecular Coulomb continuum.

Electron-pair excitations in the molecular hydrogen continuum are described by quantizing rotations of the momentum plane of the electron pair about the pair's relative momentum. A heliumlike description of the molecular photodouble ionization is thus extended to higher angular momenta of the electron pair. A simple three-state superposition is found to account surprisingly well for recent observations of noncoplanar electron-pair, molecular-axis angular distributions.

Fully differential cross sections for photo-double-ionization of D2.

We report the first kinematically complete study of the four-body fragmentation of the D2 molecule following absorption of a single photon. For equal energy sharing of the two electrons and a photon energy of 75.5 eV, we observed the relaxation of one of the selection rules valid for He photo-double-ionization and a strong dependence of the electron angular distribution on the orientation of the molecular axis. This effect is reproduced by a model in which a pair of photoionization amplitudes is introduced for the light polarization parallel and perpendicular to the molecular axis.

Reaction imaging with interferometry.

We analyze scattering into a double-slit interferometer with target-fragment recoil detection as a monitor of quantum correlation and entanglement in few-body reaction amplitudes. We thus investigate two-slit interference with which-way information as an enhancement to modern reaction-fragment detection. We briefly consider charged-particle scattering with recoil-ion detection from the point of view of quantum information.

Identification and characterization of a Plasmodium falciparum RNA polymerase gene with similarity to mitochondrial RNA polymerases.

Nearly all mitochondrial RNA polymerase genes identified to date are encoded in the nucleus and have similarities to T3 and T7 bacteriophage RNA polymerases. Some chloroplast genes are also transcribed by T3/T7 phage-like RNA polymerases, raising the possibility that the apicomplexan parasites, which have both a mitochondrion and a plastid, might have two such genes. As part of an investigation of Plasmodium falciparum organelle transcription, we initiated a search for T3/T7 bacteriophage-like RNA polymerase genes. We employed degenerate primers based on highly conserved plant, animal and fungal mitochondrial RNA polymerase sequences to amplify corresponding P. falciparum sequences by polymerase chain reaction (PCR). Less well-conserved flanking sequences were obtained by inverse PCR. The resulting sequence predicts a 1503 amino acid open reading frame with similarity to other T3/T7 phage-like RNA polymerases. Essential amino acids that have been identified in T7 mutant analyses are conserved in the P. falciparum RNA polymerase gene. Comparison of the sequence with preliminary data from the P. falciparum genome sequencing project revealed strain heterogeneity within two regions of the gene. The amino-terminal predicted amino acid sequence of the RNA polymerase gene has similarities to mitochondrial targeting sequences. Taken together, these points suggest that we have identified the P. falciparum mitochondrial RNA polymerase gene.

Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity.

Malaria continues to represent a very serious health problem in the tropics. The current methods of clinical treatment are showing deficiencies due to the increased incidence of resistance in the parasite. In the present paper we report the design, synthesis, and evaluation of potential antimalarial agents against a novel target, protein farnesyltransferase. We show that the most potent compounds are active against Plasmodium falciparum in vitro at submicromolar concentrations.

Analysis of targeting sequences demonstrates that trafficking to the Toxoplasma gondii plastid branches off the secretory system.

Apicomplexan parasites possess a plastid-like organelle called the apicoplast. Most proteins in the Toxoplasma gondii apicoplast are encoded in the nucleus and imported post-translationally. T. gondii apicoplast proteins often have a long N-terminal extension that directs the protein to the apicoplast. It can be modeled as a bipartite targeting sequence that contains a signal sequence and a plastid transit peptide. We identified two nuclearly encoded predicted plastid proteins and made fusions with green fluorescent protein to study protein domains required for apicoplast targeting. The N-terminal 42 amino acids of the apicoplast ribosomal protein S9 directs secretion of green fluorescent protein, indicating that targeting to the apicoplast proceeds through the secretory system. Large sections of the S9 predicted transit sequence can be deleted with no apparent impact on the ability to direct green fluorescent protein to the apicoplast. The predicted transit peptide domain of the S9 targeting sequence directs protein to the mitochondrion in vivo. The transit peptide can also direct import of green fluorescent protein into chloroplasts in vitro. These data substantiate the model that protein targeting to the apicoplast involves two distinct mechanisms: the first involving the secretory system and the second sharing features with typical chloroplast protein import.

Mechanisms of anterior cruciate ligament injury.

This study examined the mechanisms of anterior cruciate ligament (ACL) injury. In the first part of the study, using a comprehensive, standardized questionnaire, 89 athletes (100 knees) were interviewed about the events surrounding their ACL injury. A noncontact mechanism was reported in 71 (72%) knees and a contact injury in 28 (28%) knees; one patient was unsure if there was any contact. Most of the injuries were sustained at footstrike with the knee close to full extension. Noncontact mechanisms were classified as sudden deceleration prior to a change of direction or landing motion, while contact injuries occurred as a result of valgus collapse of the knee. Hamstring flexibility parameters revealed a statistically higher level of laxity in the injured athletes compared with a matched group of 28 controls. In the second part of the study, videotapes of 27 separate ACL disruptions were reviewed and confirmed that most noncontact injuries occur with the knee close to extension during a sharp deceleration or landing maneuver. Because the knee is in a position to allow the extensor mechanism to strain the ACL and maximum, eccentric muscle force conditions usually apply, the quadriceps may play an important role in ACL disruption. Passive protection of the ACL by the hamstring muscles may be reduced in patients with above-average flexibility.

Determination of drug susceptibility and DNA fingerprint patterns of clinical isolates of Mycobacterium tuberculosis from Kampala, Uganda.

OBJECTIVE: To ascertain the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis in Kampala, Uganda. SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital, Kampala, Uganda and Case Western Reserve University, Cleveland, Ohio, USA and McClellan Memorial Veterans Hospital, Little Rock, Arkansas, USA. METHODS: Using a radiometric BACTEC 460 TB system, susceptibility of 215 M. tuberculosis isolates from previously untreated patients from Kampala, Uganda (age range, 17-48 years, mean, 28 years; 56% males and 69% human immunodeficiency virus (HIV)-seropositive) was determined for isoniazid, rifampin, streptomycin and ethambutol. Isolates from 73 patients, selected on the basis of geographical location, were tested for strain diversity or relatedness using the IS6110 DNA fingerprinting technique. RESULTS: Resistance rates were as follows: isoniazid, 7.9% streptomycin, 6.1% rifampin, 1.4% and ethambutol 0.9%. Twelve per cent of the strains were resistant to at least one of the first line drugs tested and 4.7% were multiply resistant. There were no significant differences in resistance rates between patients with and without HIV infection. Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical RFLP patterns were found out of the 73 isolates tested (8.2%). Each cluster contained two isolates. Three (4.1%) isolates had less than seven copies of IS6110. CONCLUSION: This study shows that in Uganda initial drug resistance rates to anti-tuberculosis agents are low and similar to other sub-Saharan African countries and that multiple strains of M. tuberculosis have been transmitted within the community.

PIP: This study was undertaken to determine the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis (TB) in Kampala, Uganda. Using a radiometric BACTEC 460 TB system, 215 M. tuberculosis isolates from previously untreated patients (aged 17-48 years, mean age = 28 years; 56% males and 69% HIV-seropositive) were analyzed for susceptibility to isoniazid, rifampin, streptomycin, and ethambutol. Isolates from 73 patients were examined for strain diversity or relatedness using the insertional sequence 6110 (IS6110) DNA fingerprinting technique. The study revealed the following drug resistance rates: isoniazid, 7.9%; streptomycin, 6.1%; rifampin, 1.4%; and ethambutol, 0.9%. Resistance to at least one of the first line drugs tested were developed by 12% of the strains, while 4.7% showed multiple resistance. However, no significant differences in resistance rates were found between patients with and without HIV infection. Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical patterns were found out of the 73 isolates tested (8.2%). Each cluster contained two isolates, and three isolates had less than 7 copies of IS6110. These findings suggest that initial drug resistance to anti-tuberculosis agents in this region is low and similar to other countries in sub-Saharan Africa and that multiple strains of M. tuberculosis have been transmitted within the community.

Mitochondrial genome diversity in parasites.

Mitochondrial genomes have been sequenced from a wide variety of organisms, including an increasing number of parasites. They maintain some characteristics in common across the spectrum of life-a common core of genes related to mitochondrial respiration being most prominent-but have also developed a great diversity of gene content, organisation, and expression machineries. The characteristics of mitochondrial genomes vary widely among the different groups of protozoan parasites, from the minute genomes of the apicomplexans to amoebae with 20 times as many genes. Kinetoplastid protozoa have a similar number of genes to metazoans, but the details of gene organisation and expression in kinetoplastids require extraordinary mechanisms. Mitochondrial genes in nematodes and trematodes appear quite sedate in comparison, but a closer look shows a strong tendency to unusual tRNA structure and alternative initiation codons among these groups. Mitochondrial genes are increasingly coming into play as aids to phylogenetic and epidemiologic analyses, and mitochondrial functions are being recognised as potential drug targets. In addition, examination of mitochondrial genomes is producing further insights into the diversity of the wide-ranging group of organisms comprising the general category of parasites.

Autogenous tendon graft substitution for absent knee joint meniscus: a pilot study.

The purpose of this pilot study was to explore the potential of an autogenous tendon graft to substitute for an absent human knee joint meniscus. Based on the results of animal studies and human reports, it was hypothesized that autogenous tendon tissue would substitute for human knee joint meniscus: maintain mechanical integrity, convert to fibrocartilage, preserve the joint compartment, and provide symptomatic relief for the patient. Five patients, 2 men and 3 women, average age 41 years, had surgical absence of the lateral meniscus, genu valgum, and severe degenerative arthritis of the lateral compartment, but a stable knee. All patients were offered alternative treatments: do nothing, medication, arthroscopic debridement, osteotomy, and knee replacement. The operations were performed by arthroscopy. An accompanying arthroscopic debridement procedure was performed in the same compartment. In 4 cases, the donor graft was the semitendinosus tendon. In 1, the patellar tendon was used because the semitendinosus had been previously used in an anterior cruciate ligament reconstruction. Four of the 5 patients had a second-look arthroscopy and biopsy between 9 and 24 months. There was partial physical integrity to the tendon graft. The tendon graft did not completely convert to fibrocartilage. The joint surface was not preserved. Only 1 patient had minimal clinical improvement; the others were not improved. No patient was made worse. One patient had a total knee replacement 1 year later. Another had a knee fusion after 4 years. All other patients are considering future reconstructive surgery. The autogenous tendon graft as used in this pilot study was not successful as a substitute for an absent meniscus. The hypothesis was not realized. The observations from this pilot study should be helpful in future study protocol design.

Transcriptional mapping and RNA processing of the Plasmodium falciparum mitochondrial mRNAs.

The mitochondrial genome of Plasmodium falciparum encodes three protein coding genes and highly fragmented rRNAs. The genome is polycistronically transcribed and, since gene-size transcripts are much more abundant than the polycistronic transcripts, the latter are presumably cleaved to produce the smaller, mature mRNAs and rRNAs. Mapping the transcripts of the P. falciparum mitochondrial protein coding genes shows that the 3' end of each gene directly abuts the 5' end of the gene located immediately downstream. The 5' ends of the protein coding genes are also closely apposed to adjacent genes, with one directly abutting a gene on the same DNA strand and two others separated by just 13 nt from an rDNA fragment encoded on the opposite strand. These mapping data are consistent with production of the mRNAs by cleavage from a polycistronic precursor transcript. Further processing of the mRNAs comes from addition of oligo(A) tails. Unexpectedly, the presence and length of such tails varies in a gene-specific fashion. In this regard, polyadenylation of the P. falciparum mitochondrial mRNAs is more similar to that seen for the P. falciparum mitochondrial rRNAs than that of mitochondrial mRNAs in other organisms.

The fragmented mitochondrial ribosomal RNAs of Plasmodium falciparum have short A tails.

The mitochondrial genome of Plasmodium falciparum encodes highly fragmented rRNAs. Twenty small RNAs which are putative rRNA fragments have been found and 15 of them have been identified as corresponding to specific regions of rRNA sequence. To investigate the possible interactions between the fragmented rRNAs in the ribosome, we have mapped the ends of many of the small transcripts using primer extension and RNase protection analysis. Results obtained from these studies revealed that some of the rRNA transcripts were longer than the sequences which encode them. To investigate these size discrepancies, we performed 3' RACE PCR analysis and RNase H mapping. These analyses revealed non-encoded oligo(A) tails on some but not all of these small rRNAs. The approximate length of the oligo(A) tail appears to be transcript-specific, with some rRNAs consistently showing longer oligo(A) tails than others. The oligoadenylation of the rRNAs may provide a buffer zone against 3' exonucleolytic attack, thereby preserving the encoded sequences necessary for secondary structure interactions in the ribosome.

Shoulder injuries from alpine skiing and snowboarding. Aetiology, treatment and prevention.

There has been a decrease in the overall injury rate and the rate of lower extremity injuries for alpine skiing, with a resultant increase in the ratio of upper extremity to lower extremity injuries. Upper extremity injuries account for 20 to 35% of all injuries during alpine skiing and nearly 50% of all injuries during snowboarding. The most common upper extremity injuries during skiing are sprain of the thumb metacarpal-phalangeal joint ulnar collateral ligament, and the most common in snowboarding is wrist fracture. Shoulder injuries from skiing and snowboarding have been less well characterised. With the increased ratio of upper to lower extremity injuries during alpine skiing and the boom in popularity of snowboarding, shoulder injuries will be seen with increasing frequency by those who care for alpine sport injuries. Shoulder injuries account for 4 to 11% of all alpine skiing injuries and 22 to 41% of upper extremity injuries. The rate of shoulder injuries during alpine skiing is 0.2 to 0.5 injuries per thousand skier-days. During snowboarding, shoulder injuries account for 8 to 16% of all injuries and 20 to 34% of upper extremity injuries. Falls are the most common mechanism of shoulder injury, in addition to pole planting during skiing and aerial manoeuvres during snowboarding. Common shoulder injuries during skiing and snowboarding are glenohumeral instability, rotator cuff strains, acromioclavicular separations and clavicle fractures. Less common shoulder injuries include greater tuberosity fractures, trapezius strains, proximal humerus fractures, biceps strains, glenoid fractures, scapula fractures, humeral head fractures, sterno-clavicular separations, acromion fractures and biceps tendon dislocation. Prevention of shoulder injuries during skiing and snowboarding may be possible through interventions in education and technique, conditioning and equipment and environment.

Anterior cruciate ligament reconstruction. Bone-patella tendon-bone versus semitendinosus anatomic reconstruction.

In this article, the long term (2-10 years; mean, 4.8 years) followup results of two reconstructive procedures for the anterior cruciate ligament are compared. The bone-patella tendon-bone (with interference fit fixation) was performed on 69 knees, and the semitendinosus anatomic reconstruction was performed on 68 knees, in a population of 76 men and 52 women (age range, 15-60 years; average, 31 years). The patients in the two groups showed no difference in subjective results or activity level and no significant difference to manual testing. The semitendinosus procedure group had a slightly higher KT manual maximum failure rate than the patella tendon group (17% versus 11%). Arthrometric stability did not show deterioration, but patient satisfaction decreased in those patients who had meniscectomies. Both procedures showed satisfactory results during the long term followup. However, if the secondary restraints are compromised, the stiffer bone-patella tendon-bone construct is preferred for reconstruction of the chronic anterior cruciate ligament deficient knee.

Identification of additional rRNA fragments encoded by the Plasmodium falciparum 6 kb element.

Sequences similar to mitochondrial large and small subunit rRNAs are found as small scattered fragments on a tandemly reiterated 6 kb element in the human malaria parasite Plasmodium falciparum. The rDNA sequences previously identified include strongly conserved portions of rRNA, suggesting that fragmented rRNAs derived from them are able to associate into functional ribosomes. However, sequences corresponding to other expected rRNA regions were not found. We here report that 10 of the 13 previously described rDNA regions have abundant small transcripts. An additional 10 transcripts were found from regions not previously known to contain genes. Five of the latter have been identified as rRNA fragments, including those corresponding to the 5'end and 790 loop sequences of small subunit rRNA and the sarcin/ ricin loop of large subunit rRNA. Demonstration that most of the previously described rDNA regions have abundant transcripts and the identification of new transcripts with other portions of conventional rRNAs provide support for the hypothesis that these small transcripts comprise functional rRNAs.

Meniscal fixation with an absorbable staple. An experimental study in dogs.

An absorbable staple for meniscal fixation was developed and evaluated in an in vivo canine study. The staple consisted of two rigid barbed legs, made of a copolymer of polyglycolic acid and polylactic acid, connected by a flexible suture made of the same absorbable material. The staple was developed for arthroscopic use, eliminating the risk of nerve or vascular injuries associated with suture fixation. Eighty-two mongrel dogs underwent meniscal repair in this study, which was performed in two sequential parts. An incision was made in the medial meniscus at the peripheral third and was fixed with either the staple or with a single 3-0 PDS suture. The animals from the first part of the study, in which the biocompatibility of a prototype staple design, was evaluated were sacrificed at 3 days, 2 weeks, 6 weeks, 3 months, and 9 months. Those from the second part of the study, in which an improved staple design of the same material, was evaluated were sacrificed at 6 weeks, 4 months, and 1 year. The operated menisci were either examined histologically or were mechanically tested for tensile strength. Absorption of the staple began by 3 months and was almost complete by 1 year. Mechanically, the staple provided greater tensile strength augmentation of the meniscus than suture fixation for up to 4 months. In the long term, there was no difference between the staple and suture in enhancement of healing.

The Plasmodium falciparum 6 kb element is polycistronically transcribed.

The Plasmodium falciparum 6 kb element encodes three protein coding genes and highly fragmented large and small subunit rRNAs; its gene content makes it the probable mitochondrial genome. Many of the genes are encoded so close to each other that there is insufficient room for specific promoters upstream of each gene. RNase protection analysis of two rRNA fragments whose genes are adjacent provided evidence for a polycistronic transcript containing sequences from both, as well as separate small RNAs. To evaluate the possibility of further polycistronic transcription, several sets of oligonucleotide primers located in different regions of the 6 kb element were employed to amplify cDNAs. These analyses have revealed the existence of 6 kb element transcripts as long as 5.9 kb. Both mRNA and rRNA sequences are included on these putative precursor transcripts. Since these types of RNA are known to have different patterns of abundance changes during the erythrocytic portion of the parasite life cycle, RNA stability is presumably an important feature in regulating mitochondrial transcript abundance.

Shoulder injuries during alpine skiing.

We retrospectively reviewed alpine skiing injuries at a destination ski resort during three seasons to characterize the incidence and types of shoulder injuries. A total of 3451 injuries in 3247 patients were reviewed. The overall injury rate was 4.44 injuries per 1000 skier-days. Injuries to the upper extremity represented 29.1% (N = 1004) of all alpine ski injuries. Injuries involving the shoulder complex (393 injuries in 350 patients) accounted for 39.1% of upper extremity injuries and 11.4% of all alpine skiing injuries. The rate of shoulder injury was 0.51 injuries per 1000 skier-days. Patients with shoulder injuries had a mean age of 35.4 years, and the male-to-female ratio of these patients was 3:1. Falls represented the most common mechanism of shoulder injury (93.9%) in addition to collisions with skiers (2.8%), pole planning (2.3%), and collisions with trees (1%). The most common shoulder injuries were rotator cuff strains (24.2%), anterior glenohumeral dislocations or subluxations (21.6%), acromioclavicular separations (19.6%), and clavicle fractures (10.9%). Less common shoulder injuries included greater tuberosity fractures (6.9%), trapezius muscle strains (6.4%), proximal humeral fractures (3.3%), biceps tendon strains (2.3%), glenoid fractures (1.5%), scapular fractures (1%), humeral head fractures (1%), sternoclavicular separations (0.5%), an acromial fracture (0.3%), a posterior glenohumeral dislocation (0.3%), and a biceps tendon dislocation (0.3%).

A surgical algorithm for treatment of cystic degeneration of the Meniscus.

Cystic degeneration of the meniscus is not uncommon. Recent reports suggest that most (or all) meniscal cysts are associated with a meniscal tear, and that the treatment of choice is arthroscopic partial meniscectomy with cyst decompression. This report describes a case of a symptomatic lateral meniscal cyst that was suspected clinically and confirmed by magnetic resonance imaging, but was not associated with a meniscal tear at arthroscopy. Open cyst extirpation and peripheral meniscal repair were performed to maximize preservation of meniscal tissue. A clinical algorithm is presented for management of meniscal cysts.