Treatment of isografted 9L rat brain tumors with beta-5-o-carboranyl-2'-deoxyuridine neutron capture therapy.

beta-5-o-Carboranyl-2'-deoxyuridine (D-CDU) is a nontoxic pyrimidine nucleoside analogue designed for boron neutron capture therapy of brain tumors. In vitro studies indicated that D-CDU accumulates to levels 92- and 117-fold higher than the extracellular concentration in rat 9L and human U-251 glioma cells, respectively, and persists for several hours at levels 5-fold higher than the extracellular concentration. Furthermore, D-CDU was not toxic to rats injected i.p. with up to 150 mg/kg. On the basis of these studies, D-CDU was evaluated as a neutron capture therapy agent using rats bearing stereotactically implanted intracranial 9L tumors at single i.p. doses of 30 mg/kg and 150 mg/kg of D-CDU (20% 10B enriched), given 2 h before irradiation with thermal neutrons. Boron concentrations in tumors 2 h after dosing were 2.3 +/- 1.6 and 7.4 +/- 1.3 micrograms boron/g tissue (mean +/- SD), corresponding to tumor/brain ratios of 11.5 +/- 3.6 and 6.8 +/- 2.0 micrograms boron/g tissue for the low and high doses, respectively. All untreated animals died within 28 days, whereas half survived at days 32, 55, and 38 for groups receiving neutrons only, 30 mg/kg D-CDU, and 150 mg/kg D-CDU, respectively. Odds ratios of all treatment groups differed significantly from the untreated group (P < 0.002; logrank test). The median survival time for the 30 mg/kg-treated group but not for the 150 mg/kg-treated group was significantly longer than for rats treated with neutrons only (P = 0.036), which may correlate with the decreased tumor selectivity for D-CDU observed at the higher dose. Additional pharmacodynamic studies are warranted to determine optimal dosing strategies for D-CDU.

Immunological and virological effects of long term IL-2 therapy in HIV-1-infected patients.

We report the long-term outcome of 27 HIV-infected patients treated for over 3 years with IL-2 and binucleoside analogues. These patients experienced a sustained increase in CD4 cells and a decrease of proviral DNA with infrequent IL-2 cycles. In three cases, virus could not be isolated from activated peripheral cells. A high frequency of HIV-1-specific memory CD4 T cells was found in the patients studied. IL-2 maintains specific effector cells and reduces the pool of infected cells in patients, albeit treated only with binucleosides.

Reading reversals and developmental dyslexia: a further study.

The pattern of errors in reading isolated words was studied in two groups of children with respect, particularly, to reversals of letter sequence and letter orientation. One group (the Institute group) consisted of children 8 to 10 years old who had been diagnosed "dyslexic" according to medical and psychoeducational criteria. The other (the School group) included all the children in a second-year elementary school class (see Liberman, Shankweiler, Orlando, Harris and Berti, 1971) who fell into the lowest third on a standard test of reading achievement. Although the Institute children were somewhat poorer in word recognition than the backward readers selected purely on psychometric grounds, the groups did not differ significantly in the incidence of reversal errors. Also, for both groups, reversals represented a small proportion of the total number of reading errors. The performance of the two groups differed in two respects: in relation to directional bias in letter reversals and in the presence or absence of a significant correlation between letter-reversing and word-reversing tendencies. It was concluded from this that directional problems do not loom large in importance in most cases of reading backwardness, but may provide an additional source of difficulty for some dyslexic children. Other aspects of the error pattern were remarkably the same for both groups. The bulk of reading errors made by both groups reflect their common difficulties in phonemic segmentation of words in the lexicon, in phonetic recoding, and in mastery of the orthography--difficulties, in short, with linguistic characteristics of words rather than with their properties as visual patterns.

Children's memory for recurring linguistic and nonlinguistic material in relation to reading ability.

Good beginning readers typically surpass poor beginning readers in memory for linguistic material such as syllables, words, and sentences. Here we present evidence that this interaction between reading ability and memory performance does not extend to memory for nonlinguistic material like faces and nonsense designs. Using an adaptation of the continuous recognition memory paradigm of Kimura (1963) we assessed the ability of good and poor readers in the second grade to remember three different types of material: photographs of unfamiliar faces, nonsense designs, and printed nonsense syllables. For both faces and designs, the performance of the two reading groups was comparable; only when remembering the nonsense syllables did the good readers perform at a significantly superior level. These results support other evidence that distinctions between good and poor beginning readers do not turn on memory, per se, but rather on memory for linguistic material. Thus they extend our previous finding that poor readers encounter specific difficulty with the use of linguistic coding in short-term memory.

Whole Language vs. Code Emphasis: Underlying assumptions and their implications for reading instruction.

Promoters of Whole Language hew to the belief that learning to read and write can be as natural and effortless as learning to perceive and produce speech. From this it follows that there is no special key to reading and writing, no explicit principle to be taught that, once learned, makes the written language transparent to a child who can speak. Lacking such a principle, Whole Language falls back on a method that encourages children to get from print just enough information to provide a basis for guessing at the gist. A very different method, called Code Emphasis, presupposes that learning the spoken language is, indeed, perfectly natural and seemingly effortless, but only because speech is managed, as reading and writing are not, by a biological specialization that automatically spells or parses all the words the child commands. Hence, a child normally learns to use words without ever becoming explicitly aware that each one is formed by the consonants and vowels that an alphabet represents. Yet it is exactly this awareness that must be taught if the child is to grasp the alphabetic principle and so understand how the artifacts of an alphabet transcribe the natural units of language. There is evidene that preliterate children do not, in fact, have much of this awareness; that the amount they do have predicts their reading achievement; that the awareness can be taught; and that the relative difficulty of learning it that some childen have may be a reflection of a weakness in the phonological component of their natural capacity for language.

[Incidence and manifestations of the heterozygosity of the gene causing diabetes]. / Chastota i proiavlenie geterozygotnosti gena, vyzyvaiushchego diabet

A model of intermediate inheritance of diabetes mellitus is given, according to which juvenile diabetes developes in persons homozygous for the mutant gene, and a part of heterozygous carrier of the mutant gene has late diabetes mellitus. A large group of diabetes cases (about 50%), which are not due to direct diabetes heredity, is taken into account. Calculations are carried out on the basis of Hardy-Weinberg law from the patient questionaire data. The frequency of juvenile diabetes (developing within first thirty years) is 0,028% in the Leningrad population, the frequency of heterozygous diabetes gene carrier being 3,28%. Penetrancy of the diabetes gene in heterozygous state, as estimated from registrable (clinically expressed) forms of the disease, is 8,4%. The risk of juvenile diabetes in children, if one of the parents has juvenile diabetes, is 1,65% (3,3%-1/2), the frequency of heterozygous carriers in the population being 3,3%. The analysis of questionaire data of diabetes patients produced results, which were close to expected and indirectly confirmed the accurancy of the model proposed.

[Various aspects of blood platelet function of patients who have sustained an ischemic stroke or myocardial infarct and of their relatives]. / Nekotorye osobennosti funktsional'nogo sostoianiia trombotsitov krovi u bol'nykh, perenesshikh ishemicheskii insul't ili infarkt miokarda, i u ikh rodstvennikov.

The authors examined the functional properties of platelets (adhesion, serotonin content and its absorption by the cells) in patients with atherosclerosis who had suffered an ischemic stroke or myocardial infarction, as well as in their relatives and in healthy subjects (control). All the patients were comparable as to the age. In the atherosclerotic patients distinct disturbances of the platelet functional properties were revealed. These disturbances consisted in an increase of the adhesive-aggregation activity of the platelets and a lowering of the serotonin absorption by them. Similar disturbances were revealed in the relatives of the atherosclerotic patients including those who were phenotypically healthy. The data obtained made it possible to conclude that the above disturbances of platelet function were, probably, genetically predetermined, and created an inclination to thrombogenic processes in persons with aggravated heredity as regards atherosclerosis.

[Serotonin concentration and transport in the blood platelets of ischemic stroke patients and their relatives]. / O soderzhanii serotonina i ego transporte v trombotsitakh krovi bol'nykh s ishemicheskim insul'tom i ikh rodstvennikov.

Serotonin levels and transport were studied in patients with ischemic stroke (n = 31), their relatives (n = 50) and clinically healthy subjects (n = 45). A statistically significant difference was found in the absorption of exogenic serotonin in the patients and relatives. It has been shown that if judged by serotonin levels, the distribution curves in the control subjects patients with ischemic stroke and their relatives correspond to a model of the polygenic type of the heredity of the traits studied.

[Indicators of lipid metabolism and the blood lipid peroxidation system in men with regard to hereditary predisposition to atherosclerotic vascular pathology]. / Pokazateli lipidnogo obmena i sistemy perekisnogo okisleniia lipidov krovi u muzhchin s uchetom nasledstvennoi predraspolozhennosti k ateroskleroticheskoi sosudistoi patologii.

Lipid metabolism and the blood lipid peroxidation system were examined in 56 military males living in rather similar conditions. The parameters in question were compared in the following groups: (1) control subjects, including healthy individuals without a family history of atherosclerotic vascular abnormalities; (2) healthy subjects with a family history of atherosclerosis; (3) patients with coronary heart diseases. There were significant differences only in single cases between the groups. The application of a system of grids setting upright the distribution curves for the parameters under study proved to be effective in finding significant differences between the groups, showing the value of the hereditary factors in the development of atherogenic lipid changes.

[The effect of heredity and environmental conditions on the development of atherogenic metabolic shifts]. / Vliianie nasledstvennosti i uslovii sredy na razvitie aterogennykh sdvigov obmena.

Lipid metabolism and lipid peroxidation (LPO) were studied in residents of St. Petersburg (healthy subjects without atherosclerosis history, healthy relatives of atherosclerotic patients, postmyocardial infarction patients, post-apoplectic patients and coronary heart disease sufferers) versus matched subjects living in rural area. Altogether 215 patients were examined. Besides genotype factors, lipid metabolism and LPO were found responsive to environmental factors. These were especially potent in changing the activity of superoxide dismutase, glutathione peroxidase, catalase. In those living in the country myeloperoxidase, superoxide dismutase and catalase activity was higher than in city population. The latter exhibited, though, higher activity of glutathione peroxidase. It is evident that more advantageous ecological conditions have distinct antiatherogenic action on lipid metabolism and LPO, especially, suggesting possible treatment of atherosclerosis by moving to more healthy locality as regards environmental pollution.

[Comparative study of peripheral circulation, lipid metabolism and hemocoagulation in families with atherosclerosis and diabetes mellitus]. / Sravnitel'noe issledovanie sostoianiia perifericheskogo krovoobrashcheniia, lipidnogo obmena i gemokoaguliatsii v sem'iakh bol'nykh aterosklerozom i sakharnym diabetom.

AIM: The study of peripheral circulation (PC) in patients with atherosclerosis (AS), diabetes mellitus (DM) type I and II as well as their close relatives to clarify correlations between circulatory disorders, disturbances of lipid metabolism (LM) and hemocoagulation. MATERIALS AND METHODS: The patients and their relatives were divided into 3 groups: with AS, DM type I and II. Individuals without relevant hereditary predisposition served control. A total of 564 subjects were examined. Thermography (TG), TV capillaroscopy of the nail bed (TVCNB), measurements of total blood cholesterol (TBC), high density lipoproteins (HDLP) cholesterol, triglycerides, coagulation time, plasma recalcification, free heparin, fibrinogen concentration, calculation of the atherogenic and prothrombin indices were conducted. RESULTS: Microcirculation suffered most of all, especially in patients and their relatives with AS and DM type I. TVCNB detected morphological changes of the capillaries confirmed by TG. DM patients and their relatives, especially those with DM type I had most distinct morphological shifts. CONCLUSION: The above PC disorders result from lipid metabolism and hemocoagulation abnormalities affecting blood rheology. In DM patients and their relatives especially in those with DM type I specific alterations of the capillary structure in DM and hereditary predisposition to DM are a contributing factor.

[Indicators of lipid metabolism and lipid peroxidation system in patients with different types of lesions of the vessels of the lower limbs]. / Pokazateli lipidnogo obmena i sistemy perekisnogo okisleniia lipidov u lits s razlichnymi tipami porazhenii sosudov nizhnikh konechnostei.

A total of 66 patients were investigated with IR imager and television capillaroscopy for the blood circulation in the vessels of low extremities as well as for the values of lipid metabolism and the system of lipid peroxidation. According to the status of the vascular system in the low extremities the examinees were divided into the groups with the normal status of the vascular system, the groups with the signs of venous insufficiency, microcirculatory disorders and atherosclerosis of major vessels. With the disorders of microcirculation in low extremities staged increments in the atherogenic shifts in the exchange were demonstrated. It was suggested that atherosclerotic changes in the arteries could be preceded with the hemodynamic changes in the venous and capillary systems due to rheological disorders due to the development of hypercoagulation which accompanied dyslipoproteinemias and other atherogenic shifts in the metabolism.