CO2 reactivity and autoregulation in fetal brain

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in nearterm rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO₂ was observed in rabbit fetuses. The CO₂ reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO₂ reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.     

Novel antifungal antibiotics maniwamycins A and B. I. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological properties

Two antifungal antibiotics maniwamycins A and B were isolated from the culture broth of a strain of actinomycetes, which were classified as Streptomyces prasinopilosus. These antibiotics were isolated by resin absorption and extraction with EtOAc and purified by column chromatography. Both antibiotics were found to be new azoxy substances from their physico-chemical properties. They showed broad antifungal spectra.     

Purification and characterization of aplysianin E, an antitumor factor from sea hare eggs

An antitumor factor, aplysianin E, inducing tumor lysis was purified to apparent homogeneity from the supernatant of a homogenate of eggs of the sea hare Aplysia kurodai. Purified aplysianin E was a 250-kDa glycoprotein containing three different subunits. This factor was half-maximally active at 2-114 ng protein/ml and lysed all the tumor cells tested but did not lyse normal white or red blood cells. Aplysianin E was labile on treatments with heat, low pH, urea, guanidine, sodium lauryl sulfate, and periodate, but not with proteases or organic solvents, Aplysianin E completely inhibited the syntheses of DNA, RNA, and protein by tumor cells within 2 h and caused their complete cytolysis within 15 h. Tumor lysis by aplysianin E was inhibited by N-acetylneuraminic acid, suggesting that recognition of the sugar moiety is a key step in cytolysis induced by aplysianin E. Aplysianin E also prolonged the survival of mice bearing syngeneic MM46 ascites or solid tumors. These results suggest that aplysianin E, found in an invertebrate, the sea hare, is a new antitumor factor.     

Clinical significance of selective middle hepatic venography

Selective middle hepatic venography was performed in 86 patients who had been scheduled to undergo liver resection because of hepatobiliary diseases. Special catheters were used of which tips were bended counterclockwise at an angle of 45 degrees. Successful middle hepatic venograms were obtained in 65 cases (76%). Abnormal findings were observed in 27 cases (42%), and it was difficult to diagnose them by ultrasonography or computed tomography. Selective middle hepatic venogram is very useful to understand surgical anatomy of the liver in each case preoperatively. In 5 cases of giant tumor, middle hepatic venography is necessary to identify the exact site of the tumor. Selective middle hepatic venography is considered to be one of the indispensable, examinations for liver resection.     

A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions.

Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.     

Effect of clot removal on cerebral vasospasm

The effect of clot removal on cerebral vasospasm was studied in 104 patients with aneurysmal subarachnoid hemorrhage (SAH). The series included patients who fulfilled all of the following criteria: operation was performed by Day 3 after the ictus; the patient's preoperative clinical grade was between Grades I and IV; there was no rebleeding; computerized tomography (CT) showed only SAH; and carotid angiograms were performed by Day 2 and repeated between Days 7 and 9. Both the degree of SAH on CT and angiographic vasospasm were graded from 0 to III. The relationship of the SAH grade in the basal frontal interhemispheric fissure (IHF) to the presence of vasospasm at the A2 segments of the anterior cerebral artery and the relationship of the SAH grade in the sylvian stems to the presence of vasospasm at the M1 segments of the middle cerebral artery were analyzed. Correlation of preoperative and postoperative SAH grades with the angiographic vasospasm grades, with the incidence of symptomatic vasospasm, and with the low-density area on CT could be found in the A2 and M1 territories. Decrease of cisternal blood measured by CT after the operation did not relate directly to the reduction of vasospasm. When the SAH was Grade II or III in the basal frontal IHF, the angiographic vasospasm grades at the A2 were significantly lower in patients with surgery via the interhemispheric approach than in those with surgery via the pterional approach. Symptomatic vasospasm occurred in two of the eight cases operated on by the interhemispheric approach compared with 11 of the 22 cases approached via the pterional route. In patients with a pterional approach, there was no significant difference in severity of vasospasm in the M1 territory between the side of approach and the opposite side. No consistent relationship could be found between the time interval from SAH to operation and the severity of vasospasm. While clot removal may ameliorate cerebral vasospasm, its effect per se does not seem to be significant.     

Moment analysis of drug disposition in kidney. II: Urine pH-dependent tubular secretion of tetraethylammonium in the isolated perfused rat kidney

Effects of urine pH on the renal tubular secretion of an organic cation (tetraethylammonium, TEA) and an organic anion (p-aminohippurate, PAH) were investigated using the isolated erythrocyte-perfused rat kidney. The method was based on a multiple indicator dilution experiment and noncompartmental moment analysis. Treatment with sodium bicarbonate and sodium dihydrogen phosphate increased and decreased urine pH, respectively, but affected neither the condition of the perfused kidney nor the renal handling of albumin and inulin. In TEA studies, the increase of urine pH prolonged the mean residence time in renal epithelial cells (T cell) and reduced the apparent secretion intrinsic clearance, but did not influence the volume of distribution in the kidney (Vd drug). The decrease of urine pH did not affect these kinetic parameters. By contrast, PAH secretion was constant against the change of urine pH. Since any change in the basolateral membrane transport is reflected in Vd drug, the net transport from blood to cells can be regarded as similar under these treatments. On the other hand, the prolonged T cell of TEA with the increased urine pH suggested a slow transport from cells to lumen across the brush-border membranes. The present results coincide with the hypothetical mechanism that organic cations are secreted via an active transport system, coupled to the countertransport of H+ into cells. In conclusion, the present method is useful to separately evaluate the transmembrane transport across both sides of the renal epithelial cells in a morphologically intact kidney.