Diffuse axonal injury in severe head trauma.
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Biomedical subjects
Publications and source records attributed to T Otsuka.
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Hyposensitization therapy with each of three sea squirt antigens, Gi-rep (molecular weight [MW] 106,000), Ei-M (MW 22,800), and DIIIa (MW 9980), have succeeded in 72%, 90%, and 36% of patients with sea squirt allergy, respectively, within the first year, and the effect has been maintained during subsequent 4-year maintenance therapy. All available sera from some of the hyposensitized patients were also examined for IgE and IgG titers against the most effective therapeutic antigen, Ei-M, and it was revealed that the Ei-M-specific IgG titer increased rapidly in the successfully hyposensitized patients, regardless of the therapeutic antigen used, except for a few patients. Furthermore, the high specific IgG titer, as well as the therapeutic effect, was maintained during the subsequent maintenance therapy. No such increase in the specific IgG titer was detected in all unsuccessfully hyposensitized patients. In contrast, the Ei-M-specific IgE titer was practically unchanged in all allergic patients, independent of the therapy. Therefore, the effect of the hyposensitization therapy was closely dependent on the induction of the specific IgG capable of competing with the specific IgE for a certain asthma-inducing antigen, like DIIIa. The apparently low therapeutic efficiency of DIIIa was attributed to its relatively low immunogenicity to induce the specific IgG.
We studied the conduction system of 65 cases of proven active or healed myocarditis and related diseases among 7120 autopsy samples. For this purpose, we prepared serial sections by Lev's method. The pathological diagnoses were idiopathic acute myocarditis (5), giant cell myocarditis (3), chronic myocarditis (13), healed myocarditis (22), sarcoidosis (4), collagen or autoimmune disease (13) and complication of cachexia (5). Among all the autopsy cases, Fiedler's myocarditis was found in only one case, but myocarditis was revealed in 19 out of 30 cases of dilated cardiomyopathy, and 15 out of 25 cases of sick sinus syndrome. Conduction system lesions were divided into two groups. In older cases manifesting mainly arrhythmia, the SA node, atrial muscle and AV node were involved concomitantly with perimyocarditis. In younger cases mainly showing heart failure, the RBB, LBB and Purkinje fibers were damaged by endomyocarditis. Histologically, interstitial myocarditis was observed in the former group and parenchymatous myocarditis in the latter.
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Because of technical difficulties, the pharmacokinetics of neocarzinostatin (NCS) have not been thoroughly evaluated in patients with malignant glioma. The authors produced anti-NCS antibody by immunizing rabbits with NCS and established a means of quantifying tissue levels of NCS with enzyme-linked immunosorbent assay. In one patient given a bolus injection of 1 mg of NCS intra-arterially, the concentration of drug in neoplastic tissue at 25 minutes (0.1136 micrograms/g) was higher than that in blood at 20 minutes and was retained for a longer period. Rapid entry of NCS into the tumor cavity was observed at 5 minutes. In two postoperative cases, NCS applied topically to the tumor site (50 and 100 micrograms) was retained at high levels (0.2941 and 3.33 micrograms/ml) even after 48 hours, although no NCS was detected in blood after 60 minutes. NCS concentrations as low as 1 microgram/ml demonstrated cytocidal effects, and a delay in tumor growth was observed even at an NCS level of 0.1 microgram/ml, despite the fact that the half-life of NCS is extremely short (3 seconds in serum). Because its cytotoxic effect seems to be very rapid, it appears more important to obtain a high initial NCS concentration than to maintain a constant blood level.
The authors studied the localization of neocarzinostatin (NCS) in cultured cells and in tumor-bearing rats by means of immunofluorescent staining. Anti-NCS antibody was obtained through immunization of rabbits with NCS. Cellular uptake of NCS was dose-dependent (1.0 to 1000 micrograms/ml) in 9L rat gliosarcoma cells in monolayer. In monolayer cells of 9L, KMG-4 (derived from human glioblastoma), and KMS II (human ependymoma) treated with 1 mg/ml of NCS, drug uptake occurred within a few seconds. Accumulation was much higher in the cytoplasm than in the nucleus and, although nuclear uptake increased slightly over time, there appeared to be no increase in total cellular uptake. Mitotic cells, which were spherical in culture, showed greater intracellular accumulation than other cells. There was no significant difference in uptake among non-mitotic cells. Cells surviving 20 hours of treatment retained accumulation as high as that in killed cells. In KMG-4 monolayers, cytoplasmic and nuclear NCS distribution still differed, whereas 9L monolayers exhibited more even intracellular distribution. In 9L spheroid models treated with 1 mg/ml of NCS, the drug permeated almost all layers within 10 minutes, and at 120 minutes had heavily accumulated in the central necrotic areas. In rats with transplanted brain tumors, NCS selectively accumulated in neoplastic tissues following intra-arterial administration. However, NCS uptake by arterial endothelium was also seen, which suggests the potential for vascular toxicity. The therapeutic value of NCS is discussed in terms of its pharmacokinetic characteristics.
It is difficult to diagnose blunt intestinal injury, despite of the progress of radiological diagnostic procedures, if patient has an altered mental status or an associated injury which hampers abdominal physical findings. So we conducted a prostective study about usefulness of peritoneal tap and lavage on the diagnosis of blunt abdominal injury. From September 1987 to August 1988 we performed peritoneal lavage in 36 patients and investigated the diagnostic accuracy of this method for detecting each organ injuries. We adopted conventional criteria "RBC greater than or equal to 100000/mm3, WBC greater than or equal to 500/mm3" and also employed new supplementary criteria "WBC greater than or equal to RBC/150 (if RBC/is positive), Amylase or Alkaline phosphatase greater than or equal to RBC/10000, GOT or GPT greater than or equal to RBC/40000". The diagnostic accuracy rates were 1) intestinal injury: WBC-sensitivdty (se) 75%, Specificity (sp) 100% 2) small intestinal injury; AMY-se 100%, sp 90%, Alp-se 100%, sp 100% 3) hepatic injury; GOT or GPT-se 100%, sp 91%. These satisfactory results can be obtained by employment of the new supplementary criteria. Peritoneal tap and lavage is easy to perform but is sometimes found to have poor fluid return. So we recommend to adopt the authentic method of peritoneal lavage. We concluded from this study that if these new supplementary criteria are employed peritoneal lavage can be useful to diagnose blunt intestinal injury.
Fluid management, electrolyte balance and nutritional support had been examined for 14 days in 39 patients of severe head injury under intracranial pressure (ICP) monitoring. When ICP value exceeded 25 mmHg, barbiturate was administered in addition to the conventional therapy. Restriction of fluid administration should depend upon ICP values. When the ICP value was 20 mmHg or less and basal cisterns or ventricular systems were not obliterated in serial CT scan, fluid administration was not restricted in most patients. Mean urine volume was measured 2500 ml/day and mean water balance was measured about 0 to 700 ml/day with large deviation. Urine output and specific gravity was checked every hour and water balance was evaluated every day. When excess urine output or dehydration was recognized, additional fluid was given to keep within 500 ml/day in water balance. Through the examination, no patients of dehydration nor azotemia were experienced. Out of 39, 22 were survived and 17 were expired. In expired patients, 13 patients was recognized dead or brain death within 72 hours of injury. In two patients (one is suffered from severe brainstem injured patient with corpus callosal hemorrhage and another patient with post operative cerebral swelling) cerebral herniation was recognized about 72 hour after injury. Remaining 2 patients died after 7 days. Patients with hypernatremia were recognized 3 (13.7%) out of 22 survivals, and 14 (82.4%) out of 17 expired patients. It was recognized more common within 3 days of injury. Hypernatremia more than 160 mEq/l was accounted 5 (29.4%) in expired patients, but non in survivals.(ABSTRACT TRUNCATED AT 250 WORDS)
A substantial number of leukemic blast colonies were formed when conditioned medium of human bladder carcinoma cell line 5637 was added as a stimulator. Recombinant colony-stimulating factor (CSF) also stimulated leukemic blast cell proliferation, leading to colony formation. Furthermore, serum CSF levels in some patients with acute myelogenous leukemia (AML), as detected by sensitive enzyme-linked immunosorbent assay (ELISA), were high. These observations prompted us to study further the expressions of hematopoietic growth factor genes. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in the leukemic blast cells from about 30% of patients with AML by Northern blot analysis using strict hybridization conditions with or without in vitro blast cell enrichment. These findings suggest that the expression of cytokine genes including the GM-CSF gene reflects in vivo phenomena, although no clear relationship between expression of the genes and serum CSF level has been established. Gene encoding tumor necrosis factor alpha (TNF-alpha), lymphotoxin (LT) and transforming growth factor beta (TGF-beta) were sometimes expressed in some malignant hematological cell lines and also some fresh leukemic cells.
To investigate whether coronary artery disease is detected noninvasively, we correlated calcification on computed tomography (CT) with coronary angiographic (CAG) findings in 90 consecutive patients including 48 with angina pectoris or myocardial infarction. The mean age was 52.2 years and 83% were men. CT scans without contrast enhancement (3 sec scan time) were obtained at 1 cm thickness from the ascending aorta to cardiac apex to identify calcification in coronary arteries. Results; CAG revealed of 50 patients, and stenosis was present more often at calcified vessels on CT. (table; see text) Calcification occurred more often in 2 or 3 vessel disease. However, stenotic segments were not always calcified. We conclude that CT is sensitive for the detection of calcification and an important method for the diagnosis of coronary artery disease.
We studied hyperthermia for malignant tumors of the extremities, and obtained the following findings. In osteosarcoma cultured cells from OST (Human) and Dunn (Mouse), proliferation was clearly inhibited on being heated to 42 approximately 43 degrees C. On heat-treating the femurs of pigs, a rise in temperature to 42.5 degrees C or above was observed so that an antitumor effect could be anticipated. Moreover, no abnormal rise in temperature in the tissues surrounding the bone and light microscopy revealed no particular abnormalities. Clinically, a rise in temperature above 42.5 degrees C was observed in the majority of the malignant bone tumors (4 cases of osteosarcoma and 1 case of chordoma) and soft tissue tumors (1 case of epithelioid sarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, malignant melanoma and osteosarcoma) of which 2 cases were metastatic tumors. Before administration, 7 patients complained of pain, 4 of whom (57%) experienced an alleviation following treatment. Also in 5 (50%) out of 10 cases a shrinking of the tumor was observed and especially, in the case of soft tissue tumors a tendency towards a softening of tumor texture was seen.
Sulbactam/cefoperazone (SBT/CPZ), a new antibacterial drug, was administered to 14 cases with respiratory infections for a duration of 5 approximately 13 days at a daily dose of 4 g. Diagnoses of these patients were 7 respiratory tract infections, and 7 bronchopneumonias. The underlying diseases were chronic pulmonary emphysema in 6 cases, bronchial asthma in 2 cases, and one each of bronchiectasis, diffuse panbronchiolitis and lung cancer with bronchoesophageal fistula. All patients had underlying respiratory diseases and/or were more than 70 years old. The rate of clinical efficacy was 78.6%. The incidence of penicillinase production by isolated bacteria was 18.2% and that of cephalosporinase was 63.6%. SBT/CPZ was expected to be more effective than CPZ alone in 3 cases judging from the susceptibility of the bacterial strains concerned, to antibiotics. No side effects were observed. We conclude that SBT/CPZ is useful in the treatment of respiratory infections of patients of advanced age and/or with underlying respiratory diseases.
A 39-year-old Japanese female who had been followed as chronic myelogenous leukemia (CML) since 1984 was admitted to our hospital because of dizziness. On admission, platelet count markedly increased (245 X 10(4)/microliters) in spite of daily administration of busulfan 2 mg. She was diagnosed as accelerated phase CML with thrombocytosis. So we tried to use interferon alpha (IFN-alpha) finally given in a dose of 9 X 10(6) U daily by subcutaneous injection. After that, platelet count decreased to 70 X 10(4)/microliters and megakaryocyte count in bone marrow decreased from 887.5/microliters to 395.7/microliters. But we had to stop IFN-alpha because of severe side effects.
Stab wounds of the chest occupy an important position in penetrating thoracic injuries in Japan. A retrospective review of 117 patients with stab wounds of the chest admitted to our hospital over the past 12 years (from 1975 to 1987) revealed some factors that might influence their mortality. Seven patients died from trans-diaphragmatic injuries of intra-abdominal organs. The management of intra-abdominal injuries was very important in thoracic stab wounds. Many of the patients with stab wounds of the precordial chest (danger zone) had cardiac or major vascular injuries, and the mortality rate of them was high. The mortality rate of the patients with stab wounds of the right lateral thorax was high, because many of them had trans-diaphragmatic liver injuries. We thought that right lateral thorax as well as precordial chest is the danger zone in thoracic stab wounds. Survival rate in the patients whose circulatory condition had been unstable when they admitted was very low. Five DOA (dead on arrival) patients with stab wounds of the chest required emergency room thoracotomy (ERT). One of them survived. Survival rate in the DOA patients with stab wounds of the chest was higher than that in the DOA patients with blunt thoracic injuries. ERT for cardiac insufficiency following stab wounds of the chest was thought an effective procedure for surviving. Survival rate of the patients with cardiac stab wounds was 63.6 per cent.
Though the therapeutic efficacy of glucocorticoids on bronchial asthma has been attributed mainly to their anti-allergic and anti-inflammatory effects, the possibility of intervention of glucocorticoids in bronchial asthma might be an important parallel process. However, little is known about the mechanism of glucocorticoid action on tracheal muscle and there is insufficient basic information about the glucocorticoid receptor of tracheal muscle. Accordingly we set out to analyze the glucocorticoid receptor of bovine tracheal muscle. Bovine tracheal muscle was used because it is plentiful enough for biochemical analysis. Our results showed that a small amount (0.08 pmol/mg.protein) of glucocorticoid binder of high affinity (kd = 4.6 nM) was present in the cytosol of bovine bronchial muscle. The binder did not show any affinity for estradiol, dihydrotestosterone or andronsterone, but showed a low affinity for progesterone. Furthermore, the binder underwent salt-dependent variation of its molecular form (9.2S under low salt condition and 4.6S under high salt condition) typical of steroid receptors. These results indicated the presence of a glucocorticoid receptor in the tracheal muscle, suggesting that glucocorticoid acts on bronchial muscle in therapeutic practice on bronchial asthma.
We have isolated cDNA clones encoding human IL-3 from libraries constructed in a modified pcD mammalian expression vector by using mRNA prepared from activated human T cell clones. Amino acid sequence of human IL-3 deduced from DNA sequence of these cDNA clones agrees with that predicted from genomic sequence except at amino acid position 27. Northern blotting analysis and S1 nuclease analysis show that almost all activated T cell clones express IL-3 mRNA with kinetics similar to that observed in mouse T cell clones. However, striking difference was found in the level of granulocyte-macrophage-CSF and IL-3 mRNA expressed in activated human T cells. In contrast to mouse T cell clones, granulocyte-macrophage-CSF mRNA is expressed at least two orders of magnitude more abundant than IL-3 mRNA. Yeast Saccharomyces cerevisiae carrying human IL-3 cDNA fused downstream to alpha-factor leader sequence expressed and secreted biologically active IL-3. Several different rat anti-peptide antisera have been used to confirm the presence of human rIL-3 immunochemically. The immunoreactive human IL-3 expressed in transiently transfected COS7 cells or in yeast was observed to be heterogeneous. Human rIL-3 expressed in COS7 cells has multipotential CSF activity in semisolid cultures of bone marrow cells, and selectively induced the proliferation of My-10+ marrow or cord blood cells in liquid cultures.
A technique employing silica particles was used to remove cells producing endogenous colony-stimulating factor (CSF) to allow measurement of the level of colony-forming units in culture (CFU-C) in human bone marrow cells. In comparison with the glass-adherence technique, this new approach resulted in a more complete degree of removal of CSF-producing cells and formation of more colonies. This method seems to be useful for performing an accurate assay of exogenous CSF.
Bestatin, (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine, is a small molecular immunomodifier. Effects of this compound on human immune function were studied, in vitro, using the human B-cell colony formation technique. B-cell colonies were obtained from enriched B-cell populations placed in conditioned methylcellulose medium containing stimulators and irradiated T-cells as feeders. Addition to the culture of Bestatin at concentrations of 0.1 microgram/ml and 1 microgram/ml led to a significant increase (P less than 0.05) in the number of B-cell colonies and this effect was abolished when irradiated T-cells were not added to the culture. Bestatin increased soluble factor production induced by phytohemagglutinin (PHA)-stimulated T-cells. Such findings suggest that T-cells probably mediate this stimulatory effect of Bestatin on B-cell colony formation.