To define the associated cerebrovascular hemodynamic alterations in neonatal asphyxia, the anterior cerebral arteries (ACA) and the internal cerebral veins (ICV) were examined by Doppler ultrasound in 12 term asphyxiated and 22 control infants. In the control infants, the cerebral blood flow velocities in both ACA and ICV increased gradually in the first month of life. There were no significant differences in the blood flow velocities between the control and asphyxiated infants without major neurological impairment. On the other hand, in all asphyxiated infants with major neurological impairment, abnormally high blood flow velocities in ACA and ICV (>+3 SD above the means for the control infants) and an abnormally low index of cerebral circulatory resistance (RI) values (<0.55) were observed within a few days after birth, and thereafter the blood flow velocities decreased during the first month. In conclusion, the high blood flow velocities in ACA and ICV, and the low RI values within a few days after birth, and the decrease in the blood velocities during the first month may be considered as signs of a grave prognosis for future neurological development in asphyxiated infants.

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Lymphocytes, especially thymocytes, are highly radiosensitive and undergo “interphase death” shortly after low-dose irradiation. In this study, reagents that inhibit Ca²⁺-dependent signals were found to reduce radiationinduced interphase death in mouse thymocytes. Thymocytes irradiated in vitro were incubated for appropriate time periods with a calcium (Ca) chelator, Ca channel blockers, protein kinase C (PKC) inhibitors, or calmodulin (CaM) inhibitors. Cell viability was then measured by trypan blue dye exclusion. Data obtained by chelation of Ca²⁺ with EGTA indicated that interphase death was a Ca²⁺-dependent process and that Ca²⁺ was required in both the early and late stages of the process. Interphase death was strongly suppressed by the addition of Co²⁺ and La³⁺ ions which inhibit both receptor-operated and voltage-gated Ca channels, but not by the addition of specific voltage-gated Ca channel blockers. This suggests that Ca²⁺ might enter through receptor-operated Ca channels into irradiated cells. Involvement of PKC in inducing interphase death was supported by the results of experiments with PKC inhibitors such as H-7 and staurosporin. Calmodulin appeared to be uninvolved in inducing cell death. These results suggest that the induction of radiation-induced interphase death requires Ca²⁺, and that depletion of Ca²⁺ or disturbance of the Ca²⁺-dependent signal can reduce interphase death.

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The activity of monoamine oxidase (MAO) in human blood platelets provides an index of the state of activity of the monoamine system in the central nervous system. To understand the effects of cerebral radiotherapy on intracerebral monoamine metabolism, blood platelet MAO activity in ten patients with brain tumors was tested before and after administration of 10, 20, and 30 Gy irradiation. The control group consisted of 15 patients with malignancies other than brain tumor who had undergone radiotherapy: five with pelvic tumors, five with mediastinal tumors, four with cervical tumors, and one with a tumor in the axilla. The blood platelet MAO activvty of these patients was also tested before and immediately after 10, 20, and 30 Gy irradiation. Platelet-rich plasma obtained from venous blood was used to test the blood platelet MAO activity. An RI method was employed using tyramine as the substrate. The results are presented in units of disintegrations per minute (dpm) relative to the number of platelets. The patients who received cerebral irradiation and the control group, who received mediastinal and pelvic irradiation, showed the greatest decline in the number of blood platelets after 20 Gy irradiation. Irradiation of the neck or axilla, where red bone marrow is sparsely distributed, only slightly decreased the number of blood platelets. This implied that the decrease in the number of platelets depends on the amount of red bone marrow irradiated. Irradiation did not change blood platelet MAO activity in the control group. In the cerebral irradiation group, blood platelet MAO activity increased 40% after 20 Gy irradiation and 60% after 30 Gy. These increases were significant (p<0.01) compared to the MAO activity before irradiation. In both groups, blood platelets in the vascular bed were irradiated. A notable increase of blood platelet MAO activity after irradiation was observed only in the cerebral radiation group. This might be explained by its reflection of the change in the intracerebral amine metabolic system. The results suggest that cerebral irradiation which is focused on the region to be treated may eventually influence the mental state of a patient by affecting the intracerebral monoamine metabolism, especially serotonin.

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Isoforms of creatine kinase (CK) MM were analyzed in serum from normal subjects and patients with neuromuscular diseases using a specific monoclonal antibody. This specific antibody can inhibit the activity of the CK-M subunit containing lysine at the C-terminal residue, tissue-type CK-M, but does not inhibit the CK-M subunit that does not contain lysine at the C-terminal residue, serum-type CK-M. The change by muscle exercise of biochemical markers in serum was examined in healthy subjects and in those with neuromuscular disease. Muscle exercise (mountain climbing) increased serum total CK to 2-5 times that before exercise. Tissue-type CK-M increased more than serum-type CK-M in serum obtained 3 hours after reaching the top of the mountain. In myogenic diseases, progressive muscular dystrophy had high total-CK activity (6380±4263 IU/1), and both tissue-type CK-M and serum-type CK-M were highly active, 2968±1962 and 3412±2301IU/1, respectively. Myotonic dystrophy and myopathy due to hypothyroidism also had high total CK activity. The rate of increase of tissue-type CK-M was greater than that of serum-type CK-M. The results indicate that tissue CK is continuously released into the blood stream due to muscle damage by diseases such as myogenic diseases. On the other hand, a slight change of total CK was observed in neurogenic disease. Tissue-type CK-M increased more than serum-type CK-M, and was correlated with the clinical state. The combination of total CK and CK-MM isoform was considered to be a more sensitive marker than total CK, GOT (AST) or other biochemical markers for diagnosis of the stage of neuromuscular disease.

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Effects of Sasa senanensis Rehder extract (SE) on gastric lesions induced by water-immersion and restraint (WIR) or ethanol administration and gastrointestinal transport of carbon powder were investigated in rats and mice. Mucosal lesions and hemorrhagic cicatrices in the regio corpus ventriculi were produced by WIR. These gastric lesions were prevented by 5 and 10ml/kg SE, p.o. In the pathological observations, SE suppressed the deep hemorrhagic necrosis of mucosa and deciduation of the mucosal layer induced by WIR. Increases in adrenal weight and the ratio of adrenal weight to body weight (mg%), and decreases in spleen weight and its mg% induced by WIR were inhibited by administration of SE. SE also prevented gastric lesions induced by ethanol. The degeneration of gastric mucosa by ethanol was suppressed by 5 and 10ml/kg SE, p.o.; especially, the erosion of surface epithelium was markedly inhibited by SE. The gastrointestinal transport distance of carbon powder in mice was increased by 10ml/kg, p.o. SE. The results suggest that the protective effect of SE on the gastric lesions induced by WIR or ethanol is due to the enhancement of mucosal resistance and mucosal protection.

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We previously demonstrated that changes in brain monoamine levels 4 weeks after withdrawal from repeated administration of beta-phenylethylamine (PEA) are different from changes 4 weeks after methamphetamine (MAP) withdrawal. Monoamine oxidase (MAO) is physiologically important in the metabolism of monoamines. In the present study, we measured MAO activity radiometrically 4 weeks after the withdrawal from repeated PEA or MAP administration in rats. Reverse tolerance to stereotyped behavior was induced after repeated administration of PEA or MAP in rats and was maintained for at least 4 weeks after withdrawal of either drug. To measure MAO activity, either 5-hydroxytryptamine (5-HT) (a specific substrate for type A MAO), or benzylamine (a specific substrate for type B MAO) was used as a substrate. There was no significant change in MAO activity after withdrawal of either drug. We concluded that MAO is not responsible for the changes in brain monoamine levels observed after withdrawal from repeated PEA or MAP administration in rats.

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Through double staining and electron microscope investigation, the Innervation of neurons containing thyrotropin-releasing hormone (TRH) by neurons containing gamma-aminobutyric acid (GABA) in the rat hypothalamic paraventricular nucleus (PVN) was studied. To visualize the location of GABA and TRH, Vibratome sections of the hypothalamic region were stained using a preembedding double immunostaining technique using the antisera of GABA and TRH. Both the silver-gold intensified (SGI) peroxidase-antiperoxidase complex (PAP) -3, 3'-diaminobenzidine (DAB) method, and the PAP-DAB method were employed. The presence of DAB reaction products and silver-intensified gold-substituted DAB reaction products demonstrated immunoreactivities for TRH and GABA, respectively. Many TRH-like immunoreactive (TRH-LI) cell bodies and processes, containing numerous TRH-LI granular vesicles, were detected in the medial and periventricular and in the dorsal parvocellular parts of the PVN. The parvocellular and magnocellular parts of the PVN also contained numerous GABA-like immunoreactive (GABA-LI) fibers, but no GABALI cell body was detected in the PVN. Small, clear, GABA-like immunonegative vesicles and some large, densely-cored, GABA-LI vesicles were observed in GABA-LI axon terminals. On observation of double-immunostained sections of the rat hypothalamic PVN, TRH-LI neurons came into contact with both GABA-LI and GABA-like immunonegative axon terminals, and GABA-LI axon terminals were found to occasionally form symmetrical synapses on TRH-LI nerve cell bodies and processes. Our findings suggest that GABA-containing neurons may innervate TRH neurons, thereby regulating their secretory activity and/or other functions, via synapses in the rat hypothalamic PVN.

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A 35-year-old female was admitted because of rapidly progressing general fatigue, severe steroid-resistant anemia, and icterus. The serum direct bilirubin was 4.3 mg/dl, serum indirect bilirubin 2.3 mg/dl, hematocrit 7.2%, hemoglobin 3.4 g/dl and RBC 7.7×10⁴/mm³. The Coombs' direct test was strongly positive with anti-IgG, but negative with anti-IgM and anti-C3. Conventional therapy with very high doses of methyl-prednisolone i.v. (1000 mg/ day), cyclophosphamide (75 mg/day), and transfusion of washed packed red cells was unsuccessful. Tests performed in vitro showed that, among various commercial preparations of gammaglobulin, sulfonated gammaglobulin most effectively inhibited agglutination, or dissociation, of the Coombs' positive erythrocytes of the patient. Thus, for 12 consecutive days, the patient was given i.v. infusions of 5 g of sulfonated gammaglobulin every other day. Her condition improved rapidly and no further transfusions of packed red cells were required. Therapy with prednisolone was rapidly tapered off and she was discharged after 6 months with an almost normal hematologic pattern. Since then she has remained in excellent health for 3 years, receiving only small doses of prednisolone (5 mg/day) . The results indicate that commercial gammaglobulin preparations can be evaluated in vitro for effectiveness in inhibition of agglutination, or dissociation of already agglutinated Coombs' positive erythroctyes. This gammaglobulin preparation, injected intravenously, induced a rapid beneficial effect in a patient with steroid-resistant autoimmune hemolytic anemia. The rationale and the mechanisms responsible for the success of this treatment are discussed.

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The innervation of neurons containing oxytocin by gamma-aminobutyric acid (GABA) -containing neurons was examined by electron microscopy using a method of pre-embedding peroxidase-antiperoxidase (PAP) to show GABA with post-embedding immunocolloidal gold staining (IGS) to show oxytocin in the same tissue sections. GABA-like immunoreactive (GABA-LI) terminals were distributed throughout the rat hypothalamus and were abundant in all parts of the paraventricular nucleus (PVN) . Ultrastructural observation revealed that GABA-LI axon terminals, containing immunoreactive granular vesicles (70-80 nm in diameter), formed synapses with cell bodies and processes of the magnocellular and parvocellular neurosecretory neurons in the PVN. In the combined PAP-IGS preparations, PAP-labeled GABAergic axon terminals appeared at times making synaptic contacts with IGS-labeled oxytocin-immunoreactive cell bodies and processes. These findings provide morphological evidence for direct synaptic influence of GABAergic elements on the secretory activity of oxytocin-containing neurons in the rat hypothalamic PVN.

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A rare case of gastric cancer and its solid metastatic brain in tumor is reported. This patient underwent successful concomitant surgery for both the brain tumor and gastric cancer. There was no neurological deficit or carcinomatous pain. The indication for simultaneous gastric and cranial surgery is discussed.

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One case each of a spinal epidural and a subdural abscess is presented and utility of MRI as a diagnostic measure in these paraspinal suppurative diseases is discussed. MRI examination of a 21-year-old male with back pain, fever and quadriparesis revealed a linear lesion in the cervical epidural space. Lumbar tap yielded purulent fluid containing Staphylococcus aureus, thus diagnosed as spinal epidural abscess. Along with improvements with successful antibiotic therapy, the lesion was observed to disappear on MRI. Upon examination of an 82-year-old female with a fever and paraplegia, lumbar tap yielded pus with Escherichia coli and myelo-CT and MRI detected subdural masses in the low thoracic to the lumbar region, thus diagnosed as spinal subdural abscess. The rostral-caudal extension of the lesion was more precisely depicted by MRI. Concomitant spinal cord infarction at T-12 and L-1 escaped detection by MRI but was most relevant to the neurological signs. In this study MRI seemed to be a more suitable diagnostic tool than myelography or myelo-CT because MRI is non-invasive and repeatable, does not require potentially hazardous contrast medium and sagittal scanning of spinal cord is available which gives more precise information on the longitudinal extent of lesions.

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The laboratory methods used to prepare scientific illustration photographs are demonstrated. In particular, close-up photographic techniques, that reveal overlooked or invisible details of scientific evidence, are included.

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