The genome of the simian and human malaria parasite Plasmodium knowlesi.

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.

Determination of charge and molecular weight of rigid-rod polyelectrolytes.

Rod-like polyelectrolytes are an interesting model system because their persistence length is independent of the ionic strength and pH of the surrounding medium and they permit the investigation of polyelectrolytes in the absence of conformational degrees of freedom. In this work, rigid-rod poly(aramide) polyelectrolytes were synthesized by the Higashi method. Electrophoresis NMR spectroscopy in conjunction with diffusion NMR spectroscopy has been applied to determine the effective charge of the polymer. The charge was determined from the balance between the force in the electric field and the hydrodynamic friction in the steady-state electrophoretic motion. Because only organic counterions were present, and were identified in the proton NMR spectra, the counterions were investigated as well, and the fraction of condensed counterions was determined directly. From the effective charge per molecule and the knowledge of the fraction of condensed counterions, the total charge per molecule was determined. Finally, from the total charge, the number of repeat units and thus the molecular weight were inferred.

What the genome sequence is revealing about trypanosome antigenic variation.

African trypanosomes evade humoral immunity through antigenic variation, whereby they switch expression of the gene encoding their VSG (variant surface glycoprotein) coat. Switching proceeds by duplication of silent VSG genes into a transcriptionally active locus. The genome project has revealed that most of the silent archive consists of hundreds of subtelomeric VSG tandem arrays, and that most of these are not functional genes. Precedent suggests that they can contribute combinatorially to the formation of expressed, functional genes through segmental gene conversion. These findings from the genome project have major implications for evolution of the VSG archive and for transmission of the parasite in the field.

In vitro translation in a cell-free system from Trypanosoma brucei yields glycosylated and glycosylphosphatidylinositol-anchored proteins.

African trypanosomes escape many cellular and unspecific immune reactions by the expression of a protective barrier formed from a repertoire of several hundred genes encoding immunologically distinct variant surface glycoproteins (VSGs). All mature VSGs are glycosylphosphatidylionositol-anchored and N-glycosylated. To study trypanosome-specific post-translational modifications of VSG, a cell-free system capable of in vitro translation, translocation into the rough endoplasmic reticulum, N-glycosylation and glycosylphosphatidylinositol-anchor addition was established using lysates of the bloodstream form of Trypanosoma brucei. Monitoring protein synthesis by [35S]methionine incorporation, labeled protein bands were readily detected by fluorography following SDS/PAGE. Appearance of these bands increased during a time-course of 45 min and was sensitive to cycloheximide but not chloramphenicol treatment. Efficiency of this system, in terms of incorporation of radiolabeled amino acids into newly formed proteins, is similar to reticulocyte lysates. The system does not, however, allow initiation of protein synthesis. Depending on the clone used, immunoprecipitation revealed one or two newly formed VSG bands. Upon digestion with N-glycosidase F these bands resulted in a single band of a lower apparent molecular mass, indicating that newly synthesized VSG underwent translocation and glycosylation in the cell-free system. Biotinylation of VSG and a combination of precipitation with immobilized avidin and detection of VSG using antibodies specific for clones and cross-reacting determinants revealed that newly formed VSG contained the glycosylphosphatidylinositol anchor.

[Postnatal skeletal and body weight in beagles]. / Das postnatale Wachstum des Skeletts und der Körpermasse beim Beagle.

Growth of beagles is described on the basis of body weight and 14 bone measures. Eighteen male and 19 female dogs were investigated at 14 different ages from birth to the 13th month of life. Characteristics of the growth curves were evaluated using the modified Janoschek growth curve. For the classification into dwarfish, low, normal, big and gigantic growth, the growth curves are presented with percentiles. The arithmetic means and standard deviations for both sexes are presented in tables. Additionally, the degrees of maturity at birth (relative proportion of final weight or bone measure), the point of inflection for the growth curve, the times to grow to 50 and 95% of the final measures, and the asymptotic measures are also presented in tables. Sex differences in growth for the body weight and bone measures are discussed. Growth differences between large and small dog breeds are considered. The conclusion is drawn that the feeding of dogs has to be adapted to the growth course.

[Anesthesiological care of female patients with cerebrovascular aneurysms in pregnancy]. / Anästhesiologische Betreuung von Patientinnen mit Hirngefässaneurysmen in der Schwangerschaft.

This is a report on a patient who suffered subarachnoid haemorrhage from an aneurysm of the a. cerebri media during the 28th week of pregnancy. The aneurysm was clipped under neuroleptanalgesia. Besides monitoring of heart rate, blood pressure and central venous pressure as well as the treatment parameters including end-expiratory CO2, the foetal heart rate was deduced by Doppler sonography. She was hyperventilated intraoperatively with a paCO2 of 3.8-4.1 kPa. During the actual aneurysm surgery, artificial hypotension by 20 mmHg to b.p. values around 100/160 mmHg was initiated by means of nitroglycerin. It is evident from the literature compiled on this occasion that it is mandatory to monitor foetal heart rate during controlled hypotension in pregnancy. Sodium nitroprusside should not be used to initiate artificial hypotension during pregnancy, since it may result in toxic cyanide levels in the foetus. As usual in neurosurgery, hyperventilation can be performed also during pregnancy, since placental blood flow decreases only if the CO2 concentration drops to a very low level.

[Amniocentesis in the 2d trimenon: comparison of 2 technics]. / Amniozentese im zweiten Trimenon: Vergleich zweier Techniken.

The results of 1245 amniocenteses performed by the "free hand needle" technique and ultrasonic control are discussed. The use of ultrasonic control showed a much lower incidence of blood-stained amnionic fluid as well as a decreased number of repeated punctures of the amnion. The abortion rate was almost the same in both groups. According to our experience ultrasonic controlled puncture seems to be more reliable in terms of safety and success.

[Neurofibromatosis and pregnancy]. / Neurofibromatose und Schwangerschaft.

A case of neurofibromatosis (Recklinghausen's disease) in pregnancy in a 29-year-old patient is reported. The woman has had two uncomplicated pregnancies and deliveries. The lesions of the neurofibromatosis did not change during the course of the pregnancy. However, based on the few published cases it is necessary to pay attention to hypertension or an exacerbation of the neurofibromatosis.

[Immunoglobulin substitution in the treatment of neonatal septicemia]. / Immunglobulinsubstitution bei der Behandlung der neonatalen Sepsis.

The therapeutic effect of a polyvalent immunoglobulin preparation for intravenous use was tested in 82 newborns with bacterial infections. 35 of the children had neonatal sepsis, whereas in the other 47 bacteremia was not detectable. Treatment consisted either of antibiotics only or of antibiotics combined wih immunoglobulin SRK on an alternating basis for the first six days. Immunoglobulin substitution was tolerated without complications. In the group of infants with neonatal sepsis, two of 20 (10%) who were substituted with immunoglobulin and four of 15 (26%) who received no immunoglobulin died. Likewise, in the group of patients without detectable bacteremia, two of 21 on immunoglobulin substitution (10%) and four of the 26 who were not substituted (15%) died. The low mortality observed in the present study was attributed to efforts at early diagnosis and conventional early treatment on the one hand, and to immunoglobulin substitution on the other. To detect possible late sequelae of immunoglobulin therapy, particularly in hypogammaglobulinemic premature newborns, clinical and immunological investigations were performed in the septic patient group at the age of one to four years. There were no indications that administration of immunoglobulins during the neonatal period might have had an adverse effect on psychomotor and somatic development or on the immunological maturation of the infants.

[The influence of general operation risks on the indications for operations for gynaecological cancers (author's transl)]. / Der Einfluss allgemeiner Operationsrisiken auf die Operationsindikationen gynäkologischer Karzinome.

The increase of high general operative risks in women presenting for gynaecological operations suggested the investigation of the influence of these risks on the choice of treatment of gynaecologic cancers appropriate for the stage. The primary treatment of 426 gynaecologic and breast cancers of the year 1977 is reviewed. There were 53 endometrial carcinomas, 29 ovarian carcinomas, 185 breast cancers, 142 carcinomas of the cervix and pre-invasive carcinoma of the cervix. There were 17 other carcinomas. 354 patients were selected for operative treatment. 72 patients were selected for primary radiotherapy. A considerable number of patients (40-60%) were selected for treatment appropriate for the stage of the cancer by a system of diagnosis of risks, classifications of risks, evaluation of risks and pre-operative treatment of operative risks. The choice of the cancer treatment appropriate to the stage is not influenced by single risks but by the sum of the general operative risks. Typical mistakes in evaluation of operative risks versus indications for the operations are described in case reports. The reports include avoidable and unavoided risks.

[The preventive treatment of general risks prior to gynaecological operations (author's transl)]. / Präventive Therapie allgemeiner Risiken vor gynäkologischen Oerationen.

The operative treatment of high risk patients is of increasing importance in gynaecology. The preoperative preventive treatment of latent general problems is an important tool in the prevention of intraoperative and postoperative complications. The experience of the department for gynaecology in Hanover, Germany, during 1976 is reported. Among 1583 major operations 158 were carried out on patients in the risk class III. Guidelines are described for the preventive treatment of cardiac, bronchopulmonary, hypertensive and diabetic risks. The importance of obesity and advanced age is discussed in our cases.

Uterine hemodynamics and fetal response to vena caval occlusion in sheep.

The present experiments should show if vena caval occlusion (V. C. O.) results in a decrease in uterine blood flow and increase in uterine vascular resistance (UVR). We are further interested to know, if V. C. O. influences fetal heart rate (FHR) and fetal blood pressure (BP).