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In this study, we tested brain surface cooling as a new method of inducing selective brain hypothermia, and evaluated its effects on focal cerebral ischemia using a cat model of transient middle cerebral artery (MCA) occlusion. Cats underwent 1 h of MCA occlusion followed by 5 h of reperfusion. Brain surface cooling was induced for 4 h during and after MCA occlusion in the hypothermia group, but not in the normothermia group. Brain surface cooling was performed using saline perfusion into the subdural space. Rectal temperature, brain surface temperature, and deep brain temperature were monitored, and regional cerebral blood flow (rCBF) and somatosensory evoked potential (SEP) were serially measured. After 5 h of reperfusion, water content was also measured. Although the rectal temperature was maintained at about 37 degrees C, the brain surface temperature decreased rapidly to 33 degrees C and was maintained at that temperature. For 3 h following reperfusion, the rCBF was lower in the hypothermia group than in the normothermia group. At 4 and 5 h after reperfusion, the recovery of SEP amplitude was significantly more enhanced in the hypothermia group than in the normothermia group. In the gray matter, the water content was significantly more diminished in the hypothermia group than in the normothermia group. These results demonstrate that our method is useful for protecting the ischemic brain from a transient MCA occlusion. This method may be adapted for neurological surgery.

The preS2 region of the hepatitis B virus (HBV) has been reported to have human polymerized albumin receptor (PAR) activity, which correlates with viral replication. Here, we studied the genomic sequence of the preS region from rare patients lacking PAR activity, despite active viral replication. PAR and DNA polymerase activity was identified in 178 HBe antigen-positive HBV carriers, and a significant correlation between 2 markers was shown, except in 2 hepatitis patients lacking PAR activity. Nucleotide sequences of the preS region of HBV from both patients were examined by direct sequencing of PCR products. In one patient, a 45-base deletion was found to overlap half of the putative polymerized human albumin binding site in the preS2 region. In the other patient, a point mutation at the first nucleotide of the start codon of the preS2 region of HBV was found. There was no such genomic change in the 3 control HBV sequences. These results indicate that the preS2 region is necessary for binding of polymerized human albumin, and this is the first report of naturally existing mutant virus with no or low PAR activity.

We developed a monoclonal antibody (MoAb) (clone 5E8) against an antigen on the bile canalicular membrane of rat hepatocyte. By immunoblotting, MoAb 5E8 detected a band of 110 kD. In this study, we used the phage display technique to identify the target antigen recognized by MoAb 5E8. We screened a random phage display library expressing 12-mer peptide sequences and identified a peptide sequence, FHFNPYTGHPLT, as an epitope. We compared this peptide sequence with those of dipeptidyl peptidase IV (DPP IV, E.C.3.4.14.5) and Cell-CAM105, which proteins were located by a database search based on the information of tissue localization and approximate molecular weight of the MoAb 5E8 antigen, and sequence similarity with a region in DPP IV (amino acids 225-233) but not with Cell-CAM105 was found. In addition, we immunohistochemically stained various tissues (liver, small intestine, and kidney) of Japanese Fischer 344 rats, known to be deficient for DPP IV, with MoAb 5E8 and showed that the expression of MoAb 5E8 antigen was negligible or weak. In contrast, tissues sampled from the same organs of Sprague-Dawley rats, known to express DPP IV, were positively stained. These findings suggest that the antigen recognized by MoAb 5E8 is DDPIV and its major epitope is located in amino acids at positions 225-233.

From these experimental results, the author has reached the following conclusion: The choroid possesses abundant blood vessels, and inasmuch as they carry a large amount of blood on account of their large tubular space, they also have such structural formation as to enable their distension or contraction greatly to influence the volume of intraocular contents. Moreover, as the autonomic nerves distributed in the eye are connected with the wall of vessels in a compact network of nerve fibers, the width of the choroidal vessel can be regulated by the autonomic center ; and thus the intraocular pressure seems to be regulated by an increase or a decrease in the amount of intraocular circulating blood. On the other hand, the ciliary body likewise seems to take a part in the adjustment of the eyepressure as the width of vessels, the permeability of blood vessel walls, and the aqueous production are all controlled by the autonomic nerve, and because the contraction of ciliary muscles, as already mentioned, also exerts a great influence on the intraocular pressure. Therefore, the author believes that a regional adjustment of eye pressure is being performed by these mechanisms, working as they are in conjunction with each other, and maintaining a harmonious relation among themselves under the control of the autonomic center.

The aim of this study was to determine suitable image parameters and an analytical method for phase-contrast magnetic resonance imaging (PC-MRI) as a means of measuring cerebral blood flow volume. This was done by constructing an experimental model and applying the results to a clinical application. The experimental model was constructed from the aorta of a bull and circulating isotonic saline. The image parameters of PC-MRI (repetition time, flip angle, matrix, velocity rate encoding, and the use of square pixels) were studied with percent flow volume (the ratio of actual flow volume to measured flow volume). The most suitable image parameters for accurate blood flow measurement were as follows: repetition time, 50 msec; flip angle, 20 degrees; and a 512 x 256 matrix without square pixels. Furthermore, velocity rate encoding should be set ranging from the maximum flow velocity in the vessel to five times this value. The correction in measuring blood flow was done with the intensity of the region of interest established in the background. With these parameters for PC-MRI, percent flow volume was greater than 90%. Using the image parameters for PC-MRI and the analytical method described above, we evaluated cerebral blood flow volume in 12 patients with occlusive disease of the major cervical arteries. The results were compared with conventional xenon computed tomography. The values found with both methods showed good correlation. Thus, we concluded that PC-MRI was a noninvasive method for evaluating cerebral blood flow in patients with occlusive disease of the major cervical arteries.

Efficacy of the percutaneous transluminal coronary recannalization (PTCR) therapy was evaluated by weighting infarct-related coronary artery segments in 28 consecutive patients with acute myocardial infarction. The study focused on the influences of the time interval from the onset of chest pain to PTCR (PTCR-Time) and on the post-infarct left ventricular regional wall motion in conjunction with the serum levels of GOT, LDH and CPK and with PTCR-Time. PTCR success rate was 84.0%, and re-occlusion rate was 4.0%. The thrombolysis in myocardial infarction grade 2, however, was observed in 7 (33.3%) of 21 cases with successful PTCR. There was no significant difference in PTCR-Time between the PTCR success and nonsuccess groups. Significant correlations were observed between the PTCR-Time and each peak value of standardized serum levels of LDH and CPK, and between the PTCR-Time and the post-infarct regional wall motion abnormality. There were also significant correlations between the standardized serum level of each of these three enzymes and the post-infarct regional wall motion abnormality. It was clearly demonstrated that the earlier the recannalization of the infarcted artery was achieved, the less extensive the myocardial damage in quantitative and qualitative aspects.

We made a scanning electron-microscopic study of the angioarchitecture of the rabbit iris using vascular resin casts, and compared the vascular structure in miosis to that in mydriasis. There were three vascular layers in the iris: the anterior capillary layer, arteriolo-venular layer and posterior capillary layer. The anterior capillary layer was a network which covered the anterior surface of the iris. The posterior capillary layer was a peculiar network composed of many capillary folds, which were arranged radially. The arteriolo-venular layer was sandwiched between the two capillary layers. In this layer, arterioles and venules ran radially toward the pupil. The peripupillary region lacked the posterior capillary layer. In miosis, the vessels of the peripheral iris were straightened radially, while those in the peripupillary region were folded. In mydriasis, the vessels were very tortuous in the peripheral region, while those in the peripupillary region were stretched laterally. The change in the angioarchitecture of the iris was suited to pupillomotoric activity.

Human adenovirus type 12 (Ad 12) was inoculated through subtentorial route into inbred newborn mice (C3H/BifB/Ki), and sequential changes of the brain and tumor induction were examined by histological and immunofluorescent methods. Two days after virus inoculation, Ad 12 specific tumor antigen (fluorescent T-antigen) appeared in the cells of ependymal and subventricular matrix layers, choroid plexuses and leptomeninges in the subtentorial as well as the supratentorial brains. After 10 days, these fluorescent positive cells decreased gradually in number but still remained focally beneath the ependyma. Sixty days later, early tumor nodules were detected in the same regions in which remained the fluorescent cells. After 107 days, neurological signs and well-developed tumors were noted in 25 of 63 (30.1%) mice examined. In the cerebellum, both of T-antigens and tumors were limited around the IVth ventricle, but not in the granular layers. Histomorphologically, the tumors were of primitive neuroectodermal origin and consisted of the cells resembling immature matrix cells in the subventricular zone. These findings strongly suggest that the virus has a selective affinity to the remaining matrix cells, but not to cerebellar granular cells, at least, in newborn mice.

The macrophage migration inhibition activity [MI activity) was stable in sensitized lymphocyte-to-marcophage ratios of 1:5 to 1:20 in mice. Antigen protein concentrations under 100 mug/ml did not induce nonspecific macrophage migration inhibition. Inhibition of tumor proliferation and survival was observed after a combined injection of BCG and MH-134 cells. After a single injection of MH-134 tumor cells, MI activity was reinforced and prolonged, demonstrating the clear effects of BCG as adjuvant. In DDS mice MI activity was weakened in the regional lymph node after a subcutaneous injection of just above or below 10(5) Ehrlich cancer cells previously treated with mitomycin C. This finding suggests the presence of an optimal tumor antigen concentration.

First of all, we investigated the origin, the construction and distribution of the bronchial arteries and veins in adult rabbits, and then observed various changes of the blood vessels in experimental cavities and caseous foci and also studied the effects of streptomycin and isoniazide on the blood vessels of the cavity wall. The summary findings of the present experiments are described in the following. 1) In ten out of the fifteen rabbits emloyed, the bronchial artery originates from the right supreme intercostal artery; in three cases, in addition to this origin, it originates also from the left supreme intercostal artery; and in another case from the intercostal thoracic artery; while in the remaining one from the arc of the aorta. 2) The bronchial veins are divided into the extra-pulmonary and the intra-pulmonary veins. The former arises from the submucous blood vessels located in the proximal part of the third bronchus, and running along with the bronchial artery, finally empties into the superior Vena cava; while the latter, originating from the submucous capillaries in the distal part of the third bronchus, and after anastomosing with one another in the capsule of the bronchus, is communicated with the pulmonary veins. 3) In the caseous foci, although blood vessels are obliterated, capillaries are newly formed around the main trunks of the pulmonary artery and vein as well as around their residual branches. 4) These caseous foci are supplied with arterial blood from the bronchial arteries, the blood vessels in the bronchial wall, and the newlyformed vessels of pulmonary arterial origin. 5) The capillaries in the cavity wall are classified into three types according to their origins; namely, Type I, those regenerating from fine branches of the pulmonary vessels; Type Ⅱ, those regenerating from the main trunk of the pulmonary vessels; and Type Ⅲ, those regenerating from the bronchial artery situated in the orifice of the drainage bronchus. 6) The tuberculous cavities only in the orifice of the drainage bronchus receive an abundant supply of arterial blood directly from the bronchial artery, but those in other regions receive a scanty blood supply indirectly from the anastomoses between the bronchial artery, its sister vessels and the pulmonary artery. 7) The regeneration of blood vessels in tuberculous foci has been confirmed to occur not only in the bronchial artery and its sister blood vessels but also in the pulmonary artery and vein as well. 8) The constructions of blood vessels in the cavities treated with streptomycin or isoniazide present no significant difference from those of the control. 9) The regeneration of blood vessels and hyperemia in the cavity wall of the cases treated with streptomycin present no significant difference from those observed in the control, but the cases treated with isoniazide show marked hyperemia, newly-formed vessels, and occasional bleedings.

Using a direct immunofluorescent method, histological locations of immunoglobulins (IgG, IgM, IgA and IgD of heavy chain, and kappa and lambda of light chain) and complement components (C3 and C4) were studied in 78 brain tumors, which included 24 astrocytomas, 6 metastatic tumors, 5 medulloblastomas, 4 malignant lymphomas, 15 meningiomas, 8 schwannomas, 8 pituitary adenomas, and 8 other miscellaneous brain tumors. IgG-positive cells were observed in the perivascular regions of astrocytomas, but were more marked in those of high grade, metastatic tumors and meningiomas. Malignant lymphomas demonstrated IgG and IgM-positive cells accompanied by either kappa of lambda light chains. C3 and C4 were much less evident in these tumors. Pituitary adenomas showed slight positive stains for both immunoglobulins and complement components on the blood vessel walls, Immune reactions against brain tumors were discussed including the clinical application of autologous lymphocyte infusion in malignant gliomas and combination chemotherapy in intracranial malignant lymphomas.

Partial excess of chromosome 1 (q25-q32) was noted in malignant cells from all of 10 patients who had disorders such as non-African Burkitt's lymphoma, adult T-cell leukemia, myelofibrosis, malignant lymphoma, chronic lymphocytic leukemia or chronic myelocytic leukemia in blast crisis. The break points on chromosome 1 were at centromere, q12, q21, q23, q25 and q32. Variations in the specific region of the long arm of chromosome 1, q25-q32, were thought to be important in the evolution of malignant cell proliferation.

For the purpose to clarify whether or not the cells of regional lymph nodes and spleen of the tumor bearing individual develop the antitumor activity the author observed the proliferation of JTC-11 cells in vitro by mixing with the lymph-node and spleen cells from the mice bearing Ehrlich ascites tumor in solid form. After 24- to 48 -hour incubation the antitumor activity was estimated from the number of proliferated JTC-11 cells. As the result, it has been found that one week after implantation of tumor the regional lymph-node cells acquire the inhibitory activity against the proliferation of JTC-11 cells. The spleeen cells also show a marked inhibitory effect on the turner cell proliferation but two weeks after implantation these inhibitory activities of the cells both from lymph node and spleen are largely retarded three to four weeks when the host is emanciated by the growing tumors. Discussions are made on the inhibitory mechanisms from the viewpoint of immune reaction and on the transplantability of tumor cells without any rejection.

For the purpose to study in vivo changes of the mice bearing Ehrlich ascites tumor with special emphasis on the problems of cellular antibody and serum antibody, a series of experiments such as neutralization tests in vivo and in vitro study of the effect of lymph-node cells from the tumor bearing animals on target cells were carried out, and the findings thus obtained are briefly summarized as follows : 1. Regional lymph-node cells from the mouse transplanted with Ehrlich ascites tumor cells show a marked cytotoxic action on their cultured target cells, JTC-11, synergistically with serum from mouse bearing Ehrlich cancer. 2. The tumor cells inoculated with lymph-node cells from the tumor bearing animals showed a retardation in growth and finally regressed. 3. Spleen and lymph nodes of tumor bearing animals showed a marked increase in weight.

Ring DNA from rat liver mitochondria has been examined by circular dichroism (CD) in the region of the 225 to 320 m/~ and the followings have been clarified. The ring DNA gives a CD spectral curve somewhat different from linear DNA from nuclei, showing a big positive peak at 266 m/~ and a small negative band at 243 m!~. That is, the positive CD band of ring DNA shifted by about 7 m/~ to the shorter wavelength side from the band of the ordinary nuclear DNA, 273 m!~. Negative band appeared at the same region as that of linear DNA but reduced in depth. Heat denaturation of the ring DNA induced a red shift of the positive band, by about 4 mp., but no change in negative band. From these experimental results it has been concluded that the ring DNA has highly twisted conformation and high in G.C contents, both of which are responsible for the blue shift of the CD spectrum.

99mTc-DTPA-galactosyl human serum albumin (Tc-GSA) is a new liver-imaging agent which binds specifically to hepatic binding protein. The purpose of this study was to evaluate the usefulness of Tc-GSA in quantitatively evaluating hepatic ischemia-reperfusion injury in the rat. Regional hepatic ischemia was induced by clamping the left hepatic artery and the left portal vein for 5 to 45 min. A hepatic accumulation index (t90) was obtained on the basis of the dynamic data. A significant difference of this index was observed between all ischemic groups and the control. In conclusion, 99mTc-GSA appears useful for evaluating the hepatic ischemia-reperfusion injury.</P>

Iliac arteries were occluded in adult mongrel dogs to investigate pelvic hemodynamics. When the unilateral common iliac artery was occluded, the blood flow making a "stopover" within the pelvis was found to be significantly less than that of anatomical hemodynamics even under a resting condition. The blood flow decreased more significantly under exercise loading than under a resting condition, which demonstrates the presence of the "steal" phenomenon. This only occurs in the collateral circulation in the pelvis formed by two arterial systems which are related in a series. In deciding the appropriacy of reconstruction for the internal iliac artery in patients with aorto-iliac occlusive disease, this "steal" phenomenon should be kept in mind. In most cases, ischemic symptoms in pelvic organs may be due to a simple decrease of the blood flow supplied to the pelvis, or due to the "steal" phenomenon. If the pelvic region is in the state of ischemia owing to the "steal" phenomenon, reconstruction of the blood vessels flowing into the pelvis is not required.

The aim of this study was to investigate the usefulness of magnetic resonance (MR) imaging in the evaluation of renal function, with particular attention to the effects of water load. Ten healthy volunteers underwent dynamic MR imaging after an injection of gadolinium diethylene-triaminepenta-acetic acid (Gd-DTPA) as a contrast agent to evaluate renal function by the following four methods: the positive method [longitudinal relaxation time (T1) shortening is the dominant effect], the negative method [transverse relaxation time (T2) shortening is the dominant effect] and two intermediate methods by switching the Gd-DTPA concentrations used in the positive and negative methods. A prolonged cortical peak time and a reduced medullary peak level were observed by the positive method under a dehydrated condition, suggesting that these variables were slightly influenced by Gd-DTPA concentrated in the medulla. By the negative method, low signals due to T2* (T2* is the effective transverse relaxation time, typically shorter than T2) shortening appeared in the medulla under normal conditions, but these signals were unclear when the subject was under an overhydrated condition. These results indicate that water metabolism, in addition to imaging parameters and Gd-DTPA dose levels, should be considered when renal function is evaluated by dynamic MR imaging. Analysis of both the pattern of MR images and the time-signal intensity curves may be useful in the evaluation of renal function. The results also indicate that the positive method is preferred when the patient is overhydrated as it allows the evaluation of the local renal kinetic function by recording changes in the regional contrast agent levels.

Effects of propranolol on ischemic segmental function were studied in anesthetized open-chest dogs. Two segment-length gauges were used for measuring the regional myocardial function: one was sutured on to the left ventricular surface perfused by the anterior descending coronary artery (ischemic zone) and the other was on to that perfused by the circumflex coronary artery (normal zone). A bolus of propranolol (0.5 mg/kg) was injected into the right femoral vein. Five min later, the left anterior descending coronary artery (LAD) was completely occluded for one mine and thereafter released. Then a second coronary occlusion for 20 min was performed; an interval of 20 min was allowed between two occlusions. Propranolol, in the ischemic segment, apparently decreased the extent of paradoxical lengthening in the late systole following one min LAD occlusion, and facilitated improvement of segmental function after release of the occlusion. Moreover, the extent of abnormal stretching induced by 20 min occlusion during early systole, was also reduced by propranolol pretreatment. In contrast, compensatory increase in shortening by the normal segment was disturbed by propranolol. These results suggest that propranolol might exert a favourable influence on the segmental myocardial function during either transient or maintained myocardial ischemia.

The cytoskeletons of two established chick embryo cell (CEC) lines were examined by fluorescence and electron microscopy and compared with those of control cells and cells transformed by Rous sarcoma virus (RSV). In normal CEC, many stress fibers were observed. On the other hand, stress fibers were disorganized in nontransformed spontaneously established CEC, non-tumorigenic CEC partially transformed with a chemical carcinogen, and tumorigenic RSV-transformed CEC. In the normal CEC, actin filaments formed several bundles along the processes of the cell. Stereo-images of the peripheral region revealed bundles of filaments which were located along the attached side to the substrate. A fine well preserved network of filaments was also observed. On the other hand, in spontaneously established, partially transformed and RSV-transformed CEC, a fine network of filaments, but no actin cables, was found. These results support previous evidence that the cytoskeletal changes themselves are not directly related to the transformation or tumorigenicity of cells.