Lowered levels of bicarbonate in seminal plasma cause the poor sperm motility in human infertile patients

Both the adenylate cyclase activity and the motility of human sperm were stimulated by bicarbonate with the same concentration dependency. The correlation between bicarbonate levels in semen and the motility of sperm from the patients with male infertility was investigated. Bicarbonate in semen was found to originate mainly from the seminal vesicles, and a significant positive correlation was observed between bicarbonate levels and volume of semen. The motility of infertile sperm was also found to correlate positively to the seminal levels of bicarbonate. These results suggest that the lowered levels of bicarbonate in semen are at least in part responsible for the poor sperm motility in infertile patients, as a result of the failure in the activation of sperm adenylate cyclase.     

Per capita gross national product and summarized odds ratio for epidemiologic studies on the relationship between passive smoking and lung cancer.

The summarized odds ratios of epidemiologic studies on the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer by country were recalculated, using the odds ratio values in a 1992 report entitled, "Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders" by the US Environmental Protection Agency. The relationship between the summarized odds ratio and per capita gross national product (GNP) in 1964 was studied by the country. The graphic relationship between the summarized odds ratio (ordinate) and GNP (abscissa) showed an upward convex curve. The summarized odds ratios of a developing country (China) and developed countries (USA, Western Europe) in 1964 indicated a very weak association, while those of other countries (Greece, Hong Kong, and Japan) were slightly greater than unity (1.0). This means that ETS in the developing and developed countries in 1964 hardly affected lung cancer, whereas that in the other areas affected lung cancer somewhat. Socioeconomic status in developed countries is far better than that in developing countries, and factors related to socioeconomic status may affect the summarized odds ratio. It is recognized that cancer is diagnosed clinically some years after cancer risk factors appear. If the socioeconomic status involves some risk factors which affect lung cancer, the relationship between the summarized odds ratio and the GNP may be significant. Therefore, we can forecast that the summarized odds ratio of Japan will decrease to close to unity and that that of China will increase in the future because of economic growth, making it possible for the Chinese Government to adopt a policy to reduce the influence of ETS on health.     

Intracarotid low dose bradykinin infusion selectively increases tumor permeability through activation of bradykinin B2 receptors in malignant gliomas

Intracarotid low dose bradykinin infusion can selectively increase permeability in brain tumor capillaries. However, the mechanism by which bradykinin selectively increases transport into brain tumors and not normal brain has not been clearly defined. This study therefore sought to determine whether the mechanism by which bradykinin increases tumor permeability specifically involves the bradykinin B2 receptor in brain tumor tissue. In permeability studies, 27 Wistar rats with RG2 gliomas were utilized and a unidirectional transport, K_i, of radiolabeled [¹⁴C] sucrose was determined using quantitative autoradiography. Bradykinin (10 μg kg⁻¹ min⁻¹) increased the transport of sucrose to tumors 2.1-fold compared to saline infusion alone (p<0.001). The uptake of sucrose in tumors was significantly inhibited by the bradykinin B2 receptor antagonist,

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-Arg, [Hyp³, Thi^5,8,

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-Phe⁷]-bradykinin (p<0.01), but not by the B1 receptor antagonist, des-Arg⁹, [Leu⁸]-bradykinin. The distribution of B2 receptors in normal brain and tumor tissue was examined by immunohistochemistry using the B2 receptor antiserum, AS 424. High levels of B2 receptors were detected in intracerebral RG2 glioma and brain surrounding tumor (BST), but not in normal brain tissue. These results indicate that the permeabilizing effects of bradykinin are mediated through bradykinin B2 receptors, and that differences in distribution of B2 receptors between tumor tissue and normal brain may be responsible for the selective effects on tumor tissue.     

Angiogenesis and lymphangiogenesis and expression of lymphangiogenic factors in the atherosclerotic intima of human coronary arteries

Little information regarding the development of lymphangiogenesis in coronary atherosclerosis is available. We immunohistochemically investigated the correlation among intimal neovascularization (CD34 for angiogenesis and lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1] and podoplanin for lymphangiogenesis), the expression of lymphangiogenic factors (vascular endothelial growth factor [VEGF]-C and VEGF-D), and the progression of atherosclerosis using 169 sections of human coronary arteries from 23 autopsy cases. The more the atherosclerosis advanced, the more often the neointimas contained newly formed blood vessels ( P < .0001). Vascular endothelial growth factor-C was expressed mostly in foamy macrophages and in some smooth muscle cells, whereas VEGF-D was abundantly expressed in both. The number of VEGF-C-expressing cells, but not that of VEGF-D-expressing cells, was increased as the lesion advanced and the number of intimal blood vessels increased ( P < .01). Lymphatic vessels were rare in the atherosclerotic intima (LYVE-1 vs CD34 = 13 vs 3955 vessels) compared with the number seen in the adventitia (LYVE-1 vs CD34 = 360 vs 6921 vessels). The current study suggests that VEGF-C, but not VEGF-D, may contribute to plaque progression and be a regulator for angiogenesis rather than lymphangiogenesis in coronary atherosclerotic intimas. Imbalance of angiogenesis and lymphangiogenesis may be a factor contributing to sustained inflammatory reaction during human coronary atherogenesis.     

Intraspecies diversity of Cryptococcus laurentii as revealed by sequences of internal transcribed spacer regions and 28S rRNA gene and taxonomic position of C. laurentii clinical isolates

The intraspecies diversity of an opportunistic yeast pathogen, Cryptococcus laurentii, was revealed by analysis of the sequences of the internal transcribed spacer regions and the 28S rRNA gene. Ten strains of C. laurentii were grouped into two major phylogenetic groups and were further divided into at least seven species. Four of the strains isolated from patients did not represent a single species but showed heterogeneity. These results suggest that C. laurentii is a genetically heterogeneous species, and this must be taken into consideration when identifying C. laurentii clinical isolates.     

Tridimensional distribution of markers of neurotransmitters within the “accumbens area” of normal human brains

The distribution of glutamate decarboxylase and choline acetyltransferase in the accumbens area of five neurologically normal human brains was investigated. (1) For rostrocaudal distribution, frozen samples were taken by the punching method from several transverse sections (150 μm) of the accumbens area and the caudate-putamen were assayed. The glutamate decarboxylase activity was highest in the middle of the accumbens area. The choline acetyltransferase activity in the accumbens area was the same as that in the caudate-putamen at the rostral half and gradually decreased caudally, while the caudate-putaminal choline acetyltransferase remained unchanged throughout. (2) For a mapping of the distribution of both enzymes, a pair of transverse sections of the accumbens area was cut into1mm × 1mm square blocks by the grid microdissection method. The glutamate decarboxylase activity was highest at the ventromedial part; the glutamate decarboxylase-rich area could be reconstructed as a confined ellipsoid zone deep in the accumbens area. The choline acetyltransferase activity was patchily distributed in the rostral half of the accumbens area.Although the demarcation of the human nucleus accumbens inferred from choline acetyltransferase and glutamate decarboxylase distribution is not precise, it is clear that the accumbens area which corresponds to the animal nucleus accumbens is separated from the remainder of the striatum.     

Failure in learning task and loss of cortical cholinergic fibers in microsphere-embolized rats

 The present study was undertaken to elucidate the pathological changes in learning and memory functions and in the metabolism of cortical cholinergic neurons following microsphere embolism in the rat. Microspheres (48 μm) were injected into the right internal carotid artery of rats. Learning and memory functions were measured 7 or more days after the embolism by active and passive avoidance, and water maze tasks. In the biochemical study, cortical acetylcholine and choline contents, and choline acetyltransferase activity were measured. Cortical acetylcholinesterase-containing fibers were quantitatively estimated in the embolized rat. The active and passive avoidance, and water maze tasks were impaired in the microsphere-embolized rat. In the histochemical study, the density of cortical acetylcholinesterase-containing fibers of the ipsilateral hemisphere of the microsphere-embolized rat was decreased, but cell density was unchanged. Furthermore, microsphere embolism decreased the cortical acetylcholine concentration and choline acetyltransferase activity and increased the choline concentration. The results suggest that microsphere embolism causes severe damage to cortical cholinergic neurons, which may be, at least in part, related to the impairment of learning and memory functions in the sustained brain ischemia. Received: 28 December 1995 / Accepted: 20 September 1996     

Synaptic inputs to GABAA and GABAB receptors originate from discrete afferent neurons.

gamma-Aminobutyric acid (GABA) inhibits neurons by acting at GABAA and GABAB receptors but it is not known whether the two receptors are associated with discretely separate afferent inputs or whether GABA released from a single presynaptic neuron activates both receptors. Intracellular recordings were used to show that, in the lateral amygdala and ventral tegmental area of the rat, distinct sets of GABA-containing neurons provide the synaptic input to GABAA and GABAB receptors. Synaptic potentials resulting from GABAA receptor activation (blocked by bicuculline) and from GABAB receptor activation (blocked by 2-hydroxysaclofen) occurred spontaneously but as unrelated events. Furthermore, the two components of evoked synaptic potentials were differentially inhibited by agonists acting presynaptically (muscarine and 5-hydroxytryptamine). The finding that GABA acting at GABAA and GABAB receptors originates from distinct sets of presynaptic fibers suggests that two groups of GABA-containing neurons might be generally distinguishable in the mammalian nervous system.