An immunohistochemical study of lymphocytes occurring in heart allografts in rats.
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Animals↗
Biomedical subjects
K Kogure
Publications and source records attributed to K Kogure.
[Health problems treated by primary care physician].
For the purpose of clarifying functions expected of primary care physicians (PC physicians) in Japan, a study of the types and frequencies of health problems seen in primary care clinics located in three areas, together with consultation/referral rates of the patients to other institutes. The study was conducted using ICHPPC-2 (Japan version) which had been compiled by WONCA as a classification of diseases. In order to obtain much more generalized characteristics of the primary care, clinics located in the city, suburban district and remote places in the mountains were studied. The results were as follows: 1) The health problems treated by the clinics in each of the three areas were respectively: 162 types/7,207 items/4 months: 303 types/17,519 items/2 years: and 280 types/61,916 items/2 years. 2) The consultation/referral rates were under 2%. 3) PC physicians treated over 98% of the health problems encountered. This was found by the investigation, which had been intended to disclose a range of so-called COMMON DISEASES treated by PC physicians themselves, based on a relation between the referral rates and the types of health problems. The above findings suggested that the COMMON DISEASES should include at least 95% of the health problems which had been treated by the PC physicians. This corresponded to approximately 100 types of diseases.
Humans↗
[Evaluation of cerebral intravascular blood flow by time density curve study of intravenous digital subtraction angiography].
Time density curve (TDC) can be reconstructed from the data of intravenous digital subtraction angiography (IVDSA). We evaluated peak time (PT) and modal transit time (MOTT) of the TDC as the probable indicator of cerebral intravascular blood flow. Cerebral IVDSA and single photon emission CT (SPECT) were performed on 12 patients of ischemic cerebrovascular disease, which consisted of 3 internal carotid artery (ICA) occlusions, one middle cerebral artery (MCA) occlusion, one anterior cerebral artery (ACA) branch occlusion and 7 lacunar infarctions. We classified former 4 patients as occlusion group and latter 8 as reference group. In 3 patients (2 ICA and one MCA occlusions), SPECT study revealed definite hypoaccumulation in the MCA territory of occlusive side. Two regions of interest (ROI) were placed on the territories of right and left middle cerebral arteries in the frontal view of cerebral IVDSA. Digital data processor fitted gamma curve to the TDC of each ROI, and calculated PT and MOTT. The absolute lateralities of PT and MOTT of MCA territory was significantly (p less than 0.05) larger in occlusion group than reference group. Patients with hypoaccumulation in SPECT had significantly (p less than 0.02) larger laterality of MOTT than patients with isoaccumulation. One ICA occluded patient without hypoaccumulation in corresponding MCA territory had relatively small laterality of MOTT similar to the patients of ACA branch occlusion and lacunar infarction. These results suggest that PT and MOTT are possible to detect the laterality of the intravascular blood flow in MCA territories caused by major artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiography, Digital Subtraction↗
[Detection of interferon-gamma and IL-6 producing cells in cerebrospinal fluid cells in the central nervous system infectious diseases using immunocytochemistry].
To evaluate the relationship between cytokines and cerebrospinal fluid (CSF) cells, we detected interferon (IFN)-gamma and interleukin (IL)-6 producing cells in CSF from the patients with central nervous system (CNS) infectious diseases by immunocytochemistry. Five CSF cell smears from three herpes encephalitis patients, three from a patient with EB virus radiculoneuritis, four from the three patients with purulent meningitis, five from five patients with viral meningitis were obtained during early or subacute stages of diseases. Control CSF cell smears were taken from twenty seven patients with motor neuron disease, Parkinson's disease and spinocerebellar degeneration. Immunocytochemistry using specific polyclonal anti-IFN-gamma and IL-6 sera were used to detect each producing cell. Simultaneously, individual positively immuno-reactive cells were morphologically classified macrophage or lymphocyte. The IFN-gamma positive cells immunostained with specific antibody showed brown-colored deposits within the cytoplasm whereas no deposit was in the nucleus (Fig. 1). These phenotype of IFN-gamma positive cells were considered to be lymphocytes or macrophages. However, IFN-gamma-positive macrophages were predominantly seen at the early stages of herpes simplex encephalitis and purulent meningitis. The percent of IFN-gamma positive cells in total CSF cells obtained from the patients with the CNS infectious diseases was 2.3-38.7 as shown in Table 1. The IL-6 positive cells (Fig. 2) were also found early in the course and in subacute stages in the CNS infectious diseases and ranged from 2.5-50 percent in total CSF cells (Table 1). In contrast neither IFN-gamma- nor IL-6-positive cells were detected in non-inflammatory diseases (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)
Central Nervous System Diseases↗
[Pathophysiology of cerebral ischemia].
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Animals↗
Effects of hepatic inflow occlusion on changes in plasma potassium, histamine, and norepinephrine in rats.
To evaluate the effects of hepatic inflow occlusion without the shunt, the physiological differences were compared in three groups of rats in which the hepatoduodenal ligament was occluded for 15 min, 30 min, and 60 min. The survival rate significantly decreased in the 60 min occlusion group (53.6%) when compared with that of the 15 min and 30 min occlusion groups (95% and 91.6%, respectively). The significant differences in the changes in blood pressure (BP), the values of plasma potassium, histamine (HIS), norepinephrine (NE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the values of hematocrit (HT) were also observed between the 30 min and 60 min occlusion groups. The results indicate that, in rats, there is a high probability of an irreversible state to shock after 30 min hepatic inflow occlusion when veno-venous bypass is not applied. The values of plasma HIS and NE and the values of HT in portal blood were significantly greater than those in the general circulation. The results suggest that splanchnic congestion may have a greater influence than hepatic ischemia has in contributing to the deterioration of the physiological state.
Animals↗
Failure of basic fibroblast growth factor to prevent postischemic neuronal damage in the rat.
It has been reported that basic fibroblast growth factor (bFGF) can increase neuronal survival and neurite extension, and that it further antagonizes the excitotoxicity of glutamate in in vitro hippocampal neurons. We examined the effects of bFGF on neuronal damage after transient forebrain ischemia. Rats were subjected to 20 min of cerebral ischemia in a four vessel occlusion model. Thirty minutes before induction of ischemia, bFGF (0.3-300 nM) or bFGF (300 nM) with heparin was applied to the hippocampal CA1 subfield. Morphological changes in the CA1 subfield were evaluated 7 days after ischemia and compared with those in the vehicle-injected group. A single injection of bFGF did not prevent postischemic neuronal damage in the hippocampal CA1, but these results do not rule out an effect of bFGF on neuronal damage after ischemia.
Animals↗
Alterations of [3H]inositol 1,4,5-trisphosphate binding in the postischemic rat brain.
Chronological changes of [3H]inositol 1,4,5-trisphosphate (IP3) binding sites were determined after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. One day after the ischemia, [3H]IP3 binding sites decreased significantly compared with the control values in the lateral segment of the caudate putamen and the cerebral cortex, both supplied by the occluded MCA. Moreover, 3 days after the ischemia, a significant decrease of [3H]IP3 binding sites was observed in the substantia nigra of ischemic side. In the ipsilateral thalamus, however, there was no alteration until 1 week after the ischemia, and then [3H]IP3 binding sites increased significantly 2 weeks (P less than 0.05) and 4 weeks (P less than 0.01) after the ischemia. Based on the present study, we speculate that different mechanisms associated with signal transduction systems may be responsible for exo-focal postischemic delayed neuronal changes in the thalamus and the substantia nigra. The increase of [3H]IP3 binding sites of the thalamus in the chronic stage may be new evidence of plasticity related to neurotransmission.
Animals↗
Exo-focal postischemic neuronal damage in the rat brain: alteration of [3H]forskolin binding using in vitro autoradiography.
We studied the alteration of intracellular signal transduction using quantitative autoradiography of the second messenger system in order to clarify the mechanisms of delayed neuronal damage in the remote areas of rat brain after transient focal ischemia. Chronological changes of [3H]forskolin binding sites were measured to demonstrate the striatal-nigral pathway after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks and 4 weeks of recirculation. [3H]Forskolin binding sites were found to be markedly decreased in the lateral segment of the caudate putamen supplied by the occluded MCA after 90 min of ischemia with no recirculation. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, marked reduction of [3H]forskolin binding sites was observed in the ipsilateral substantial nigra which lay outside the ischemic areas. This postischemic delayed phenomenon observed in the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. The delayed reduction of [3H]forskolin binding sites in the substantia nigra observed in the present study indicates that striatonigral terminal degeneration at presynaptic sites is caused by precedent ischemic damage of the ipsilateral caudate putamen and that exo-focal postischemic neuronal death is caused by a transsynaptic process associated with the ischemic foci.
Adenylyl Cyclases↗
The effects of maternal ethanol exposure on neurotransmission and second messenger systems: a quantitative autoradiographic study in the rat brain.
The effects of maternal ethanol exposure on neurotransmission and second messenger systems were examined in rats using histochemistry and in vitro autoradiography. Thirty % ethanol was administered to pregnant rats from gestational day 7 to the day of delivery. Quantitative autoradiography was used to map muscarinic cholinergic, dopamine D2, adenosine A1, and inositol 1,4,5-trisphosphate binding sites, as well as to localize adenylate cyclase and protein kinase C. We found no difference in the patterns of staining with acetylcholinesterase and Timm's stain between control and prenatally ethanol-exposed rats on postnatal day (PN) 30. In the ethanol-exposed rats, [3H]forskolin binding sites were increased during early development in the CA1 subfield of the hippocampus and the occipital cortex; [3H]phorbol ester binding sites were increased in the cortex, striatum, and hippocampus; hippocampal muscarinic cholinergic sites were increased on PN4 and 30; adenosine A1 binding was reduced on PN10 in most regions examined, but was increased in the CA1 subfield on PN30; dopamine D2 receptor levels were significantly reduced on PN30 in the striatum; and IP3 receptors were decreased in most regions studied, but particularly in the cerebellum. Thus, some of these changes were transient and others were long-lasting. Although histopathological abnormalities were minimal, the alterations of binding sites in the cerebellum (the coordination center) and in the hippocampus (related to memory and learning) that were detected may contribute to the behavioral and mental deterioration seen in the fetal alcohol syndrome.
Animals↗
Alteration of second messenger systems after transient cerebral ischemia in gerbils: protective effect of pentobarbital and an autoradiographic analysis.
The postischemic alteration of second messenger systems in the gerbil brain was analyzed by receptor autoradiography using [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]inositol 1,4,5-trisphosphate (IP3). The alteration of the [3H]PDBu binding in striatum and hippocampus was milder than that of the [3H]IP3 binding 5 h and 7 days after 10-min ischemia. The administration of pentobarbital prevented a decrease in the [3H]IP3 binding sites in all areas 5 h and 7 days after ischemia. These results suggest that the disruption of intracellular calcium homeostasis may play an important factor in ischemic brain damage.
Animals↗
Temporal profile of the effects of pretreatment with brief cerebral ischemia on the neuronal damage following secondary ischemic insult in the gerbil: cumulative damage and protective effects.
We examined the response of the gerbil brain to secondary ischemic insult following pretreatment with brief ischemia at intervals of 5 min, 1 and 6 h, 1, 2, 4, 7 and 14 days. Two minutes of bilateral carotid artery occlusion produced no histopathological brain damage, whereas 3 min of occlusion caused a moderate to severe reduction in the number of hippocampal CA1 pyramidal cells. Two-minute occlusion followed by 3-min occlusion at 5-min, 1- and 6-h intervals resulted in almost complete destruction of CA1 neurons. Additional neuronal damage was observed in the striatum at a 1-h interval and in the thalamus and the neocortex at 1- and 6-h intervals. The neuronal damage was most severe at a 1-h interval. Two-minute ischemia followed by 3-min ischemia at intervals of 1, 2, 4 and 7 days, however, caused a marked protective effect, and the hippocampal CA1 neurons were preserved. The protective effect was not observed at a 14-day interval and following pretreatment with 1-min ischemia. Thus, pretreatment with brief ischemia leads to complex responses of the brain to secondary ischemic insult; cumulative damage at intervals of 1-6 h and protective effects at intervals of 1-7 days.
Animals↗
Sequential changes in muscarinic acetylcholine, adenosine A1 and calcium antagonist binding sites in the gerbil hippocampus following repeated brief ischemia.
We performed quantitative autoradiography to determine sequential alterations in the binding of muscarinic cholinergic and adenosine A1 receptors and of an L-type calcium channel blocker in the gerbil hippocampus following repeated brief ischemic insults. [3H]Quinuclidinyl benzilate (QNB). [3H]cyclohexyladenosine (CHA) and [3H]PN200-110 were used to label muscarinic and adenosine A1 receptors and L-type calcium channels, respectively. Changes at 1 h, 6 h, 1 day, 4 days and 1 month after three 2-min ischemic insults were compared with changes after single 2- or 6-min ischemia. Two-minute ischemia, which causes no histopathological neuronal damage, produced no persistent alterations in binding sites. We observed a transient and mild increase in binding activities, especially in [3H]CHA binding, at 1 h of recirculation. Following 6-min ischemia and three 2-min ischemic insults. [3H]QNB and [3H]PN200-110 binding decreased by more than 50% in the CA1 subfield by 1 month, but [3H]CHA binding decreased transiently by 20-30% at 4 days when delayed neuronal death of hippocampal CA1 pyramidal cells took place. Reductions in binding, especially in [3H]QNB binding, following three 2-min ischemic insults were greater and appeared earlier than those after 6-min ischemia. Furthermore, alterations extended to the CA3 subfield and the dentate gyrus following repeated insults. Thus, alterations in receptor binding after repeated ischemic insults were greater than those after equivalent single period of ischemia.
Adenosine↗
Postischemic spontaneous hyperthermia is not a major aggravating factor for neuronal damage following repeated brief cerebral ischemia in the gerbil.
Brief and non-lethal cerebral ischemia produces most severe neuronal damage when such ischemia is induced repeatedly at 1-h intervals. We examined whether spontaneous postischemic hyperthermia is an aggravating factor for the cumulative damage following repeated ischemia in the gerbil. We maintained body and cranial temperature at normothermia throughout the initial reperfusion period, but could not observe an amelioration of histopathological brain damage following two 2-min bilateral carotid artery occlusions at a 1-h interval as compared to hyperthermic conditions. The results suggest that postischemic hyperthermia is not a major aggravating factor for the cumulative damage following repeated ischemic insults.
Animals↗
Amelioration of brain damage after focal ischemia in the rat by a novel inhibitor of lipid peroxidation.
We studied the effects of 2-(allyl-1-piperazinyl)-4-n-amyloxyquinazoline fumarate (KB-5666) on brain edema and histological neuronal damage in rats with focal ischemia and on lipid peroxidation in brain homogenates and brain mitochondria in vitro. KB-5666 (3-100 microM) inhibited lipid peroxidation in brain homogenates and mitochondria, and also inhibited mitochondrial swelling. In a rat with middle cerebral artery occlusion, administration of KB-5666 (3 and 10 mg/kg) immediately after ischemia prevented the formation of brain edema in the cortex and ameliorated the histological neuronal damage in the same area, but failed to do so in the striatum. These results indicate that KB-5666 is a potential inhibitor of lipid peroxidation that could possibly prevent ischemic complications such as formation of brain edema and neuronal damage. Further, these results suggest that lipid peroxidation may play an important role in the pathogenesis of ischemic damage after focal ischemia.
Animals↗
Neutrophil as a mediator of ischemic edema formation in the brain.
We investigated the contribution of neutrophils to brain edema formation using a transient focal ischemia model in rats. Rats were given anti-neutrophil monoclonal antibody (RP3) intraperitoneally to deplete circulating neutrophils. In RP3-treated rats, ischemic brain edema formation 1 day after reperfusion was significantly decreased compared to that of saline-treated control rats. We speculate that chemical mediators released by infiltrating neutrophils alter vascular permeability and play an important role in post-ischemic brain edema formation.
Animals↗
Postischemic alteration of [3H]forskolin binding sites in selectively vulnerable areas: an autoradiographic study of gerbil brain.
The postischemic alteration in forskolin receptor binding sites 1 h to 1 month after transient cerebral ischemia was studied in the gerbil. Forskolin binding showed marked reduction in the striatum at an early stage of recirculation, whereas a transient increase was seen in the frontal cortex, the hippocampal regions, and the thalamus. The dentate molecular layer and the parietal cortex revealed no significant changes in the forskolin receptor binding. However, a significant reduction in the forskolin receptor binding was found in these areas after 48 h or 7 days of recirculation. These results suggest that the neuronal damage in the selectively vulnerable areas following transient cerebral ischemia may process with different mechanisms.
Animals↗
Induction of HSP70 mRNA after transient ischemia in gerbil brain.
Heat shock protein (HSP) plays an important role in stress responses of cells. Inductions of HSP70 mRNA, amyloid precursor protein (APP) mRNA, and tubulin mRNA within hippocampal CA1 and parietal cortex in gerbil brains were examined at 1 h to 7 days after 10 min of bilateral common carotid artery occlusion using Northern blot analyses. In contrast to the induction of HSP70 mRNA, no induction was observed in APP mRNA or tubulin mRNA. Regional differences in the induction of HSP70 mRNA were found. CA1 cells produced less amount of HSP70 mRNA than cortical cells at 8 h after the transient ischemia. Transient global ischemia is known to result in the selective neuronal death of hippocampal CA1 cells days after reperfusion. Our results suggest that the regional difference in the induction of HSP70 mRNA may relate to the regional difference of the vulnerability of neuronal cells after transient ischemia.
Amyloid beta-Peptides↗