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A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.

Interaction between the receptor for advanced glycation end products (RAGE) and its ligands has been implicated in the pathogenesis of various inflammatory disorders. In this study, we establish an in vitro binding assay in which recombinant human high-mobility group box 1 (rhHMGB1) or recombinant human S100A12 (rhS100A12) immobilized on the microplate binds to recombinant soluble RAGE (rsRAGE). The rsRAGE binding to both rhHMGB1 and rhS100A12 was saturable and dependent on the immobilized ligands. The binding of rsRAGE to rhS100A12 depended on Ca2 and Zn2, whereas that to rhHMGB1 was not. Scatchard plot analysis showed that rsRAGE had higher affinity for rhHMGB1 than for rhS100A12. rsRAGE was demonstrated to bind to heparin, and rhS100A12, in the presence of Ca2, was also found to bind to heparin. We examined the effects of heparin preparations with different molecular sizesunfractionated native heparin (UFH), low molecular weight heparin (LMWH) 5000Da, and LMWH 3000Da on the binding of rsRAGE to rhHMGB1 and rhS100A12. All 3 preparations concentration-dependently inhibited the binding of rsRAGE to rhHMGB1 to a greater extent than did rhS100A12. These results suggested that heparin's anti-inflammatory effects can be partly explained by its blocking of the interaction between HMGB1 or S100A12 and RAGE. On the other hand, heparin would be a promising effective remedy against RAGE-related inflammatory disorders.

(1) Das intravenos injizierte Kongorot wurde in normalem Zu-stand durch die Nieren im Harn sparlich oder gar nicht ausgeschieden. (a) Durch die Phlorhidzingabe kam der Farbstoff im Harn vor. Diese Erscheinung hangt mit der Tatsache zusammen, daB das Phlorhidzin auf die Permeabilitat der Niere steigernd wirkt. (b) Bei Muskelanstrengung wird der Farbstoff in geringen Mengen im Harn ausgeschieden. Dies beruht auf dem erhohten Filtrationsdruck in der Niere infolge der Blutdrucksteigerung. (c) Diuretika haben keinen EinfluB darauf. (2) Die normale Froschhaut laBt das Kongorot von innen nach auBen oder in umgekehrter Richtung nicht durchpassieren. (a) Durch Phlorhidzinapplikation wird der Farbstoffdurchtritt in beiden Richtungen moglich. (b) Durch die Wirkung von Phlorhidzin nahm der elektrische Ruhestrom der Froschhaut allmahlich ab. (3) Hinsichtlich der Erregbarkeit des Nervmuskelpraparates des Frosches ubt das Phlorhidzin auf den Schwellenwert eine erniedrigende Wirkung aus.

1) The effect of acetylcholine and vagostigmine on isolated muscle of frog and nerve-muscle preparations, with single induction shocks was studied. 2) Direct application of acetylcholine or vagostigmine to the muscle preparation produces a depressant action on the excitability as well as on the shortening height of the maximum contraction. The effects are more marked when the two drugs are applied simultaneously or successively than when applied separately. 3) Direct application of acetylcholine or vagostigmine to the nervous portion of the nerve-muscle preparation also produces a slight depressant action on the excitability of muscle to indirect stimulation applied to the nerve. 4) The applicability of the chemical transmission theory to amphibian muscles was discussed.

(1) We studied the permeability of erythrocytes (human, an, chicken and frog), collodion membrane_ and frog's urinary bladder, to urea and its associated substances, alcohols and glucose. (2) Hemolysis of human erythrocytes to urea, its derivates and alcohol, is due to the penetration of these substances through the erythrocytes membrane. (3) Among urea and its associated substances, it was observed that the hemolysis time of human erythrocytes was inversely proportinal to the molecular weight of these substances. (4) Chicken erythrocytes were far less permeable to urea than human erythrocytes. (5) Hemolysis time to guanidine showed no difference between human and chicken erythrocytes. (6) Frog's urinary bladder in a living condition has a high degree of semipermeability to urea. When it is injured or dead, it behaves like collodion membrane.

1) The total amount of ACh yielded from the electric organ was enormously high, and estimated to 8.5 - 15.0γ (average 12.0γ) per gramm of the tissue weight. There was no difference in the content of ACh between the stimulated and non-stimulated organs. 2) The total amount of ACh of the central nervous system and skeletal muscle of the electric ray was 4.4-5.2γ and 0.0- 1.1γ per gramm of the tissue weight respectively. ACh has not been proved from the intermediate muscle. 3) The activity of Ch E was enormously high in the electric organ ; it diminished gradually from the central nervous system, then from the skeletal muscle, and lastly from the intermediate muscle. If the enzyme activity of the electric organ is taken as unity, then that of the central nervous system, skeletal muscle and intermediate muscle corresponds to 0.026, 0.018 and some thousandth times of that of the electric organ respectively. 4) The enzyme activity of the central nervous system and skeletal muscle of the gold fish corresponds to 0.07 and 0.017 of that of the electric organ respectively. 5) There was a close parallelism between the content of ACh and the activity of Ch E in some tissues of the electric ray.

Die ortliche Reizung durch die subkutan injizierten sulfonamid-praparate ist uberhaupt viel schwacher als diejenigen der Vaccine. Ihre Wirkung ist vor allem durch eine Vermehrung der Histiozyten im Subkutangewebe nicht nur am Injektionsort, sondern auch an der anderen Korperseite charakterisiert. Die Histiozyten entstehen hauptsachlich aus den ortsansassigen Fibrozyten. Es steht aber noch dahin, inwieweit die so vermehrten Histiozyten zur Heilung der Streptokokkensepsis u. a. beitragen konnen.

Trimebutine at low concentrations (6 X 10(-9)-1.4 X 10(-8) M) slightly enhanced the twitch response of isolated guinea pig ileum induced by transmural stimulation. At high concentrations (2 X 10(-8)-2 X 10(-7) M), however, it inhibited the twitch response in a dose dependent manner. This inhibitory effect of trimebutine was reversed by naloxone (8.1 X 10(-9) M). These results suggest that trimebutine has an opiate-like action on the myenteric plexus.

A 67-year-old male patient initially showed memory disturbance followed by tremors a year later. The symptoms rapidly aggravated to dementia and Parkinsonian symptoms, and the patient died 2 years and 6 months after the onset at the age of 69 years and 5 months. Autopsy revealed numerous senile plaques in the cerebral cortex and Alzheimer's neurofibrillary tangles in the inferior temporal lobe and hippocampus. A number of Lewy bodies were found in the cerebral cortex and brain stem. Lewy bodies were found abundantly in the third layer of the pyramidal cells in the gyrus parahippocamalis. The distribution of Lewy bodies in the cerebral cortex was similar to that of inflated cells in Pick's disease.

An ultrafiltration method employing a Centrifree filter for determining the unbound fraction of estradiol was studied. Centrifugation was performed under conditions similar to those in vivo. Good correlation was recognized between this method and the equilibrium dialysis. This method was employed to determine the unbound fraction of estradiol in the serum and the peritoneal fluid of 26 infertility patients classified according to their menstrual dates. The total estradiol and progesterone contents in the peritoneal fluid were high after ovulation. There was no significant difference in the percentage of unbound estradiol in the serum among various groups. In the peritoneal fluid, however, the percentage of unbound estradiol for the day 12-14 patients was 4.5 +/- 0.2% in contrast with 3.8 +/- 0.4% for the day 15-18 group (p less than 0.05) and 3.5 +/- 0.1% (p less than 0.05) for the day 19-28 group. Moreover, the fraction (4.5%) of unbound estradiol in the peritoneal fluid of a patient with luteinized unruptured follicle (LUF) syndrome was comparable with that of patients in the follicular phase. The difference between the percentage of unbound estradiol in the peritoneal fluid before and after ovulation is considered to be due to the transudation of follicular estradiol in the follicular phase and the exudation of estradiol from the corpus luteum into the peritoneal cavity in the luteal phase.

Protective effects of clinically used drugs against adriamycin (ADM)-induced toxicity were studied in ICR mice. The control mice, which were administered 15 mg/kg of ADM twice, survived 7.48 +/- 1.99 days (mean +/- S.D.). The survival times of mice treated with the following drugs, expressed as a percent of that of the control group, were 293.6% for coenzyme Q10 (Co Q10, 2 mg/kg), 402.2% for dextran sulfate (MDS, 300 mg/kg), 121.6% for flavin adenine dinucleotide (20 mg/kg), 236.3% for adenosine triphosphate disodium (50 mg/kg), 213.7% for reduced glutathione (100 mg/kg), 121.6% for phytonadione (50 mg/kg), 155.2% for inositol nicotinate (Ino-N, 500 mg/kg), 335.5% for nicomol (1000 mg/kg), 157.5% for nicardipine (10 mg/kg) and 123.3% for dipyridamol (50 mg/kg). Anti-hyperlipemic agents such as MDS, nicomol, Ino-N and Co Q10 strongly protected against the ADM-induced toxicity, and the mice administered these drugs lived significantly longer than the control mice. The mechanism of the protective effect was discussed.

Metaplastic bony tissue along with hyperplastic mucosal epithelium showing no atypism was detected in biopsy materials from a Yamada type I gastric polyp. The tissue was metaplastic woven bone associated with calcification. Histogenesis of the bone formation is as yet unknown. This is the first reported case of the presence of metaplastic bone accompanied by hyperplastic gastric mucosa so far.

Human peripheral blood mononuclear cells (PBM) were separated into sheep erythrocyte rosette-forming (Es+) and non Es+ cells by the Ficoll-Hypaque gradient sedimentation method. Thirty-eight percent of the Es+ cells formed rosettes with dog erythrocytes and were designated as Es+Ed+ cells. The remaining Es+ cells were designated as Es+Ed- cells. Only a few non Es+ cells formed rosettes with dog erythrocytes. Among Es+Ed+ cells, T4 antigen-positive cells were observed approximately 1.7 times as often as T8 antigen-positive cells, when measured by staining with OKT4 or OKT8 monoclonal antibody. Among Es+Ed- cells, however, T4 and T8 antigen-positive cells were observed in almost equal proportion. Preincubation of PBM with OKT11 monoclonal antibody, but not with OKT4 monoclonal antibody, inhibited the rosette formation with dog as well as sheep erythrocytes. These results indicated that Es+Ed+ cells were a subpopulation of T-cells in which a majority of the cells were T4 antigen-positive, and that the binding sites of dog erythrocytes on human T-cells was closely linked with that of sheep erythrocytes.

Temporal bone histopathological findings of two patients with trisomy 18 syndrome are described. Many of the abnormalities previously described were seen in the present cases; namely, atresia of the external auditory canal, aberrant course of the tensor tympani muscle, malformed stapes, aberrant course of the facial nerve with an obtuse angulation at the first genu and displacement of geniculate ganglion cells into the internal auditory canal, shortened cochlea with decreased spiral ganglion cell population, and vestibular anomalies, such as bony and membranous blockage of the superior semicircular canal. Moreover, an extremely underdeveloped malleus and incus continuous with a persistent Meckel's cartilage were observed.

Effects of afferent stimulation of the lingual nerve (LNAS) on gastrointestinal motility and the reflex pathways which mediate the response to LNAS were investigated in rats. LNAS induced excitatory, inhibitory or biphasic responses in the stomach, duodenum and proximal colon. These responses continued after bilateral vagotomy, but were abolished after additional bilateral splanchnicotomy or transection of the spinal cord between Th4 and Th5. The inhibitory, excitatory and biphasic responses induced by LNAS were not affected by decerebration. Both after administration of atropine (0.2 mg/kg, i.v.) and guanethidine (3-5 mg/kg, i.v.), LNAS-induced excitatory and inhibitory responses were abolished in most cases, but the slight inhibitory response in the stomach and duodenum to LNAS remained in a few cases. These results suggest that the reflex centers which cause LNAS-induced excitatory and inhibitory responses are located in the dorsal nucleus of vagus and that the reflex pathways include the vagus and splanchnic nerves.

Six pregnant women with convulsions between 25 to 40 weeks of gestation were experienced. Among them, 4 patients were diagnosed as having intracranial hemorrhage and two as simple eclampsia. With the aid of brain CT scan, one case of arteriovenous malformation was detected and treated surgically with good prognosis for both the mother and the fetus. Two patients were diagnosed to have cerebral hemorrhage with subsequent penetration into the lateral ventricles and were treated conservatively. Their fetuses were delivered alive by cesarean section, but the mothers expired. The other patient with cerebral hemorrhage was treated surgically, and both the mother and the fetus survived. One of the simple eclampsia patients was noted to have a growth retarded fetus at 32 weeks of pregnancy with subsequent intra-uterine death, but the mother recovered after conservative treatment. Another patient at 40 weeks of pregnancy was also treated conservatively and both the fetus and the mother survived. Brain CT scan findings differed between these two eclampsia patients; local brain edema for the second patient and generalized brain edema for the first patient. Thus more active application of brain CT scan is recommended in managing pregnant patients with convulsions.

A line of chick embryo cells (CEC) was obtained from CEC treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The cells, designated CHCC-OU2, were contact-inhibited, formed no colony in soft agar and did not produce tumors when inoculated into syngeneic chickens. The electron microscopic examination and reverse transcriptase assay showed no virus production from the cells. Subgroup A avian sarcoma virus (ASV) and Newcastle disease virus replicated well in the cells of this cell line.

Thirty-eight patients were operated on for mitral stenosis between March 1979 and September 1981. Thirty-six of them were examined as to their age, symptom duration, chest roentgenograms, electrocardiograms and echocardiograms to obtain various indices of left ventricular function. The usefulness of these indices as preoperative risk factors for predicting postoperative low cardiac output syndrome (LOS) was investigated. Cases which had values of ejection fraction, cardiac index, percent fiber shortening or mean velocity of circumferential fiber shortening less than 0.45, 2.0 l/min/m2, 25% and 0.80 circ/sec, respectively, in the preoperative echocardiographic examination were associated with a greater chance of postoperative LOS. Each of these factors was independently useful as a risk factor in cardiac surgery for mitral stenosis. Moreover, it was revealed that the combination of a preoperative percent fractional shortening (%FS) of less than 30% and a cardiac index smaller than 2.0 l/min/m2 indicated a strong predisposition toward postoperative LOS.

A rapid method was devised for the detection of virus particles in wart specimens. The upper layer of warts was cut perpendicularly to the surface, and the freshly cut surface was lightly touched to an electron microscope grid. The grid was then stained with a small drop of phosphotungstate and observed electron microscopically. On the specimen grid thus prepared, papillomavirus particles were easily discriminated from tissue debris. Papillomavirus particles were detected in 71% of verrucae plantares, 78% of verrucae palmares, 50% of verrucae vulgares and 75% of condylomata acuminata by the present method.

Protection of Escherichia coli NIHJ and C57BL mice from the effects of 60Co gamma-rays provided by S-alk(en)yl-L-cysteines and their hydantoin derivatives was examined. E. coli (10(6) cells/ml) suspended in a 20 mM aqueous solution of one of the drugs was irradiated with 60 Gy of gamma-rays. Five week-old male mice were exposed to 5.0-9.5 Gy of gamma-rays after a single intraperitoneal injection of 0.75 mmol/kg body weight of each compound. In both E. coli and mice, S-allyl compounds afforded more effective radioprotection than S-propyl compounds. The replacement of the alpha-hydrogen of S-substituted cysteines by methyl groups decreased the radioprotective effect. Hydantoin derivatives were much more radioprotective than the original sulfur-containing amino acids. Especially, DL-5-allylthiomethyl-5-methylhydantoin had a remarkable radioprotective effect in mice. The gamma-radiolysis mechanism of thiomethylhydantoin derivatives was discussed in connection with the radioprotective effect of the drugs.