Micronodular transformation as a novel mechanism of VEGF-A-induced metastasis.

How and why tumors metastasize is still a matter of debate. The assumption is that mutations render tumor cells with a metastatic phenotype, enabling entrance in and transport through lymph or blood vessels. Distant outgrowth is thought to occur only in a suitable microenvironment (the seed and soil hypothesis). However, the anatomical location of most metastases in cancer patients suggests entrapment of tumor cells in the first microcapillary bed that is encountered. We here investigated how vascular endothelial growth factor-A (VEGF-A) attributes to the metastatic process. We describe here that VEGF-A enhances spontaneous metastasis by inducing intravasation of heterogeneous tumor cell clusters, surrounded by vessel wall elements, via an invasion-independent mechanism. These tumor clusters generate metastatic tissue embolisms in pulmonary arteries. Treatment of tumor-bearing mice with the antiangiogenic compound ZD6474 prevented the development of this metastatic phenotype. This work shows that tumors with high constitutive VEGF-A expression metastasize via the formation of tumor emboli and provides an alternative rationale for anti-VEGF-A therapy, namely to inhibit metastasis formation.

[Nicotinic acid in the treatment of chronic circulatory failure in patients with ischemic heart disease]. / Nikotinovaia kislota v lechenii khronicheskoi nedostatochnosti krovoobrashcheniia u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Examined were 98 patients with chronic forms of ischemic heart disease, mainly atherosclerotic cardiosclerosis with different degrees of cardiac insufficiency. Two groups were distinguished. Patients of the first group received traditional treatment while patients of the second group received also nicotinic acid agents. It was found that inclusion of nicotinic acid in the complex treatment of patients with ischemic heart disease increased the therapeutic efficacy.

[The significance of the blood kinin system indices for the diagnosis of latent forms of rheumatism]. / Znachenie pokazatelei kininovoi sistemy krovi dlia raspoznavaniia skrytykh form revmatizma.

A study of the kinin and fibrinolytic systems of the blood in 280 rheumatic patients with isolated or prevailing stenosis revealed that latent forms of rheumatism were characterized by an increase of kininogenesis, reduction of kininase capacity of the blood and depression of fibrinolysis in the absence of acute-phase reactions which allows to use these data a supplementary informative test for the diagnosis of the latent course of rheumatism.

Injury and physiological responses of Larrea tridentata (DC) Coville exposed in situ to sulphur dioxide.

The response of shrubs of Larrea tridentata (DEC) Coville (creosotebush) exposed to sulphur dioxide (SO(2)) was evaluated using in situ plants of the Majove Desert. Larrea was exposed to acute levels of 0.3 to 2.0 microl litre(-1) SO(2) for periods up to 13 days using field chambers or an open-air fumigation system. Plants exposed in the spring exhibited considerable leaf injury (necrosis and defoliation) when exposed to 2.0 microl litre(-1) SO(2), and in the autumn had leaf injury when exposed to >0.4microl litre(-1) SO(2). Injured plants had higher transpiration rates, less negative water pressure potentials, and/or lower photosynthetic rates than control plants. It is likely that Larrea would not be injured by the typically low SO(2) concentrations and dry environmental conditions of the Mojave Desert. However, if injury were to occur, it would be accompanied by changes in plant-water relations and photosynthesis, followed by recovery after the SO(2) stress was removed.

[Microflora of the sputum and indicators of natural resistance in patients with acute pneumonia]. / Mikroflora mokroty i pokazateli estestvennoi rezistentnosti u bol'nykh ostroi pnevmoniei.

The paper is concerned with the results of quantitative studies on the sputum of 106 patients with acute pneumonia. Etiological structure of acute pneumonia, the dependence of a clinical course of disease on a sputum microflora composition type and some indices of natural resistance and immunity were shown.

[Sputum microflora in acute pneumonia based on the data from a quantitative study]. / Mikroflora mokroty pri ostroi pnevmonii po dannym kolichestvennogo issledovaniia.

In this work the data obtained in the quantitative investigations of sputum samples from 106 miners having acute pneumonia are presented. These investigations were carried out twice at the peak of the disease to determine the possible infective agent. The virological study of nasal impression smears by immunofluorescence and the serological study of paired sera made it possible to establish the viral and bacterial nature of the disease in 12% of cases. The expediency of the quantitative investigations of sputum, carried out twice, in combination with the study of the biological properties of opportunistic microorganisms was shown. Streptococcus pneumoniae proved to play the most important etiological role in the appearance of acute pneumonia in miners. This infective agent was detected in 82% of patients by the inoculation of sputum samples in "diagnostic" dilutions (10(-5) and higher). The associations of pneumococci with staphylococci, hemolytic bacteria and Neisseria were found to be capable of playing a significant role in the development of acute inflammation in pulmonary tissue, especially in those cases when these associations were isolated from highly diluted sputum (10(-5)).

The population factor.

PIP: Reducing population growth is essentil to Egypt's broader efforts to improve facilities, services, and the phsycial quality of life. Although a family planning program has existed since the mid-1950s, the 2.7% annual rate of population growth has not changed in 30 years. Nasser and the other "free officers" who seized power in 1952 became concerned about the adverse effects of the rapidly growing population, but perhaps out of concern with a possible religious backlash, they confined themselves to launching studies and subsidizing several dozen private family planning clinics. From 1962-72, the number of private clinics grew from 28 to 480, and family planning was introduced in government healthclinics in 1965. Such clinics are mainly located in rural areas and are staffed by doctors and other personnel who are not members of the local community and are not very effective at promoting family planning. Local girls and women called Rayadet were recruited to promote the idea to birth control in local communities. By 1970, 12.6% of Egyptians were using reliable contraception. A national survey 12 years later found 34% using contraception, buth the figure seems high. Approximately 60-65% of eligible couples would need to practice birth control for Egypt to reach a less than 1% annuel increase. The Egyptian government hopes to slow population growth to 1% by the year 2000, but major problems of motivation remain especially among the rural poor. Several factors may lead to success of the family planning effort: 1) financial and technical support from international family planning sources has grown rapidley and is likely to remain high; 2) the mortality rate has dropped from 17.8/1000 in 1952 to about half that level, while the rate of natural increase is about the same, suggesting that future reductions in the birth rate will translate to a reduced rate of natural increase, and that parents will be less reluctant to practice faimly planning if there is a greater chance that their children will survie; 3) the trend away from pills should ease the workload of clinics; 4) the government program to re-involve the dayas, traditional health workers whose primary function is that of midwife, in the government health care system, thus extending and enhancing its outreach and effectiveness; and 5) the government and the majority of Egyptians believe that population control is a pressing need. Increases in individual opportunities and income combined with a growing desire for material amentities will provide an economic incentive to keep families small. The single biggest challenge will be to reach the rural areas, especially in Upper Egypt, where illiteracy rates are high and access to radio and television is limited.^ieng

Family Planning and the religious issue.

PIP: The question of whether family planning is compatible with Islam is not a new issue. An eminent 11th century teacher declared that the earliest followers of the prophet practiced contraception with the knowledge of the prophet, who did not forbid it. The issue has always been controversial, but the usual attitude has been 1 of tolerance. The question has become more pressing in the past few decades with the increased urgency of controlling population growth. The success or failure of the birth control program will depend partly on the active support of the Islamic leadership. A 1982 survey showed that 19.5% of Egyptian men and women believed that family planning was somewhat or completely against their religious beliefs, and another 10.1% said they did not know. 38% of these people answered affirmatively to a question on whether anything in the religious books forbids birth control. In the mid-1930s, Egypt's Grand Mufti, the country's most authoritative interpretor of Islamic law, issued a religious decree permitting contraception, thus allowing establishment of birth control clinics in Egyptian citites. In 1964, Sheikh Hasan Ma'mun encouraged the use of contraception based on the changing needs of the Muslim people. Since 1980, religious leaders have played a major role in public education efforts of the State Information Service (SIS) by speaking out on the acceptability of birth control in the eyes of Islam. However, about 45,000 of Egypt's approximately 50,000 mosques are private and almost entirely immune from government control, and they have traditionally been a haven for critics of the Egyptian government. As the government has become more committed to family planning, their opposition has increased. The argument of some Sheikhs that birth control is a Western effort designed to weaken Egypt is countered by the SIS which points to the use of contraception in other countries: 87% in Belgium, 78% in England, 70% in the US, 6% in Bangladesh, and 2% in Nepal.^ieng