Na,K-Atpase in renal tissue of rats in the dynamics of experimental nephritis]

The authors undertook comparative study of the Na, K-ATPase activity in the red cells, ghost corpuscles, and in the cortex and medulla of kidneys of rats with experimental glomerulonephritis (GN) induced by injection of nephrotoxic serum (NTS), during an acute course of the process (1 and 2 weeks after NTS injection) and in chronic affection of the kidneys (10 weeks after NTS injection). The activity of the enzyme both in the red cells and in the ghost corpuscles was reduced significantly, by 28 and 22%, respectively, in the acute period of the disease (one week after NTS injection) but was restored to normal values in the period of chronic affection of the kidneys. The activity of the enzyme did not change in the cortex during the whole period of the study, but in the medulla it diminished in the acute period of the disease and remained reduced (by 27% on the average) during the chronic phase. It is concluded that reduction of the enzyme activity in the studied objects was not caused by the presence of endogenous inhibitors of the enzyme. It is suggested that reduction of Na, K-ATPase activity in the renal medulla may be one of the factors of increase of Na and water excretion in the urine in the chronic phase of GN.     

Antiarrhythmic effect ofRodiola rosea and its possible mechanism

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 8, pp. 175–176, August, 1993     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

The Effects of Ante- and Postnatal Hypoxia on the Central Nervous System and Their Correction with Peptide Hormones

Ante- and postnatal hypoxia significantly worsened the postnatal development of animals. The posthypoxic behavioral model included hyperactivity and decreased learning ability, these being typical manifestations of attention deficit disorder. A peptide constellation prevented and significantly improved posthypoxic postnatal development and eliminated the majority of negative behavioral changes.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Endocrine functions in hypertensive rats of the NISAG strain exposed to epinephrine

Endocrine functions were investigated in normotensive (Wistar) and hypertensive (NISAG) rats before and on days 3, 7, and 21 after subcutaneous epinephrine administration. Rats of the NISAG strain are characterized by elevated plasma levels of aldosterone and thyroxine and lowered plasma levels of immunoreactive insulin, and their endocrine system develops a much stronger response to a single epinephrine injection than does that of Wistar rats. This is manifested in a still higher aldosterone level, elevated corticosterone and insulin concentrations, and reduced thyroxine content in the plasma. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 495–498, May, 1996     

Analysis of psychomotor activity in children with spastic infantile cerebral palsy by using the computer-assisted test system "Rhythmotest"

The paper considers how to obtain quantitative characteristics of sensomotor responses while tracing, learning, and reproducing rhythmical stimuli of different frequency and modality which can be used to assess psychomotor activity, perception, attention, short-term memory in schoolchildren with infantile cerebral paralysis. The results of examinations of children with this condition are given and analyzed.     

Dynamics of child's cognitive development in transition to schooling

Intensive maturation of arbitrary attention occurs in the making of higher mental functions in children in transition to schooling. The study has yielded standard indices of changes in some higher mental functions at the age of 6-8 years, which makes it possible to make a timely objective diagnosis in mental and neurological practice to predict the child's development, and to provide a required complex of medical and pedagogical corrective measures.