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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.

Recording the motility of the stomach as well as the small intestine by the balloon method in the dogs decerebrated and unanesthetized, we found a factor conditioning the inhibitory effect of the intestinal motility to the stimulation of the perpheral cut-end of cervical vagus nerves. The results may be summarized as follows: (1) The stimulation of the peripheral cut-end of the cervical vagus nerve frequently produces the yarious patterns and degrees of inhibition of the intestinal motility of the stomach as well as of the small intestine. (2) The inhibitory effect still appears after the severing of the vagus nerves at the caudal end of the esophagus, but is obliterated and reversed to the augmentory when the splanchnic nerves are bilaterally severed. (3) The cause of the inhibition is attributable to the strong excitation of the intestinal inhibitory centers brought about by the central stimulating action of the anoxemia resulting from the stimulation of the cervical vagus nerves, and the reversal of the response is due to the peripheral stimulating action of the anoxemia upon the intestinal muscles, its central action being excluded from the action on the intestine by the severing of the splanchnic nerves.

In order to produce vomiting in the dogs decerebrated and unanesthetized, apomorphine or copper sulfate was administered. The behaviors of both the inspiratory and the expiratory muscles were studied through the course of the act of vomiting by the electromyographic technique. The results are summarized as follows: (1) The most significant signs of vomiting seems to be the recurrent vomiting volleys from the vomiting center each of which is produced abruptly and transiently. (2) The peculiarities of the vomitng volley consist in the simultaneous discharges of both the inspiratory and the expiratory muscles, resulting in the so-called retching movement. (3) The vomiting volleys, in their rhythm, seem to arise independent of the respiratory center, but the former are capable of affecting the respiratory centers at any respiratory phase. (4) The acceleration of the breathings observed prior to the retching seems to be due to the invigorated activity of the respiratory centers affected directly by the administration of the vomiting agents without an intermediate step by the vomiting centers. (5) The simultaneous contraction of the diaphragm and the abdominal muscles are merely a component of a peculiar type of the respiratory movements, namely, that of the retching. (6) The glottis muscles are, however, ruled out from the principle described in (2): the closer of the glottis muscles contracts during the retching, while the opener is completely inhibited.

By prepariug over 100 thin slices from 77 cases of urinary calculi mainly consisted of vesical calculi and immersing them in various solvents, the solubility of these calculi has been examined by polarization microscopy from the standpoints of the composition and structure of urinary calculi. (1) MgNH4P04·6H20 (struvite) has been found to be most soluble and it is the best example in the dissolution of urinary calculi; and as for the solvents, Versene proved to be the best solvent. (2) The alkaline pH seems to have an intimate relationship with the dissolution of uric acid calculi. (3) Calcium oxalate proved to be insoluble in any solvent. In addition, no difference in its stability against solvents could be recognized in its monohydrate or dihydrate: (4) Cystine dissolved in the 10% Versene solution. (5) Amorphous-like substance apparently was dissolved slightly in 0.5% urease solution at 37°C, however, it is not possible to dissolve this substance completely, From these results calcium oxalate and amorphous-like substance seem to be the most difficult substances to dissolve, and therefore, the bearing they have on the dissolution of urinary calculi seems to most significant. In the present stage where little is known of real etiologic factors concerning the formation of urinary calculi, in the clinical application of the dissolution of stones further studies need to be carried on, but from the very nature of construction of urinary calculi, the local dissolution methods seem to be rather difficult at present, and rather somatic dissolution in connection with prophylaxis against recurrent stones seems to be the direction in which future studies need to be carried out.

1. Quantitative examinations were made on the effect of benadryl and neoantergan on the histamine release in vitro from chopped skin of dogs and in vivo from rat skin. For estimation of the in vitro histamine release by biological method, a chemical procedure for separating the diffused-out histamine from mixed antihistamines was carried out. 2. Both antihistamines caused a fairly marked release of histamine from chopped skin tissues in comparatively higher concentrations. This action was synergistic with histamine-releasing effect of sinomenine and anaphylatoxin. 3. In lower concentrations, however, both antihistamines inhibited the in vitro histamine-releasing effect of sinomenine and anaphylatoxin. 4. Administration of a comparatively large amount of benadryl markedly depleted the skin histamine of a rat in vivo but smaller amount clearly suppressed the histamine depletion by subsequently administered sinomenine. 5. Based on the evidence of such dual action of antihistamines, some considerations were made on the site of action of these agents.

In our country it has been believed that there is no histoplasmosis here in Japan. However, from the above clinical signs, radiological characteristics, laboratory tests, pathological and mycological examinations, and experimental findings, we believe this is the first case of histoplasmosis in Japan.

This study was performed on 17 hyperthyroid patients and 15 healthy controls. The patients were under propylthiouracil (PTU) therapy at a dosage of 3 x 100 mg/day for one month. Blood samples, taken at the beginning and on the 30th day of therapy, were analyzed for hormonal parameters (T3, T4, TSH), lipid peroxidation endproduct [thiobarbituric acid reactive substances (TBARS)] and antioxidant status parameters: glutathione (GSH), glutathione peroxidase (GSH-Px) and CuZn superoxide dismutase (CuZn SOD). Hyperthyroid patients were observed to have significantly higher TBARS, GSH and CuZn SOD levels than controls (P < 0.05, P < 0.001, P < 0.001, respectively). PTU therapy caused a relief in oxidative stress as reflected by significantly decreased TBARS levels (P < 0.001) and a selective modification in the antioxidant status parameters: significant decreases in GSH and CuZn SOD levels (P < 0.001) and a significant increase in GSH Px (P < 0.01) activity. Our findings suggest a selective modification of the antioxidative profile in hyperthyroidism. PTU should also be considered as an in vivo antioxidant, in addition to its antithyroid action.

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.

We applied an in situ polymerase chain reaction (PCR) hybridization method in order to detect human T-lymphotropic virus type I-infected cells in routinely-processed paraffin sections of the lung from 13 autopsied patients with adult T-cell leukemia (ATL). Previously reported protocol resulted in somewhat non-specific staining in our sections. Therefore, we used a hot start PCR method using specialized commercially-available polymerase in order to increase the specificity. Of 6 patients with ATL cell invasion into the lungs, 4 exhibited strong positive staining of almost all invading ATL cells. In contrast, 7 patients without ATL cell invasion into the lungs did not demonstrate any significant reactivity. Since the method described here is a relatively simple hot start method and does not yield false-positives, it may allow us to determine whether human T-lymphotropic virus type I (HTLV-I) associated disorders are related to lymphocytes integrating the HTLV-I genome.

Gamma-Glutamylpropargylglycylglycine (gamma-Glu-PPG-Gly) was isolated as a metabolite of propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine gamma-lyase) from human blood incubated with D,L-propargylglycine in the presence of L-glutamate and glycine, and identified by fast-atom-bombardment mass spectrometry, indicating that human blood can metabolize propargylglycine to gamma-Glu-PPG-Gly. When whole blood was incubated with 2 mM D,L-propargylglycine in the presence of 10 mM L-glutamate and 10 mM glycine at 37 degrees C for 16h, 0.094+/-0.013 micromol of gamma-Glu-PPG-Gly was formed per ml of whole blood. When erythrocytes were incubated under the same conditions for 16h, 0.323+/-0.060 micromol of gamma-Glu-PPG-Gly was formed per ml of erythrocytes, suggesting a large contribution of erythrocytes to gamma-Glu-PPG-Gly formation in whole blood. The apparent Km value of gamma-Glu-PPG-Gly formation in human erythrocytes for D,L-propargylglycine was 0.32 mM. The observed rate of gamma-Glu-PPG-Gly formation and the Km value for D,L-propargylglycine suggest that metabolism of propargylglycine to gamma-Glu-PPG-Gly can play a definite biological role in human subjects who are loaded with propargylglycine.

Experimental beta-alaninuria was induced in rats by injection of (aminooxy)acetate (AOA), a potent inhibitor of aminotransferases, in order to elucidate the pathogenesis of hyper-beta-alaninemia. A 27-fold increase of beta-alanine (BALA) excretion was induced by subcutaneous injection of 1 5 mg of AOA per kg of body weight. A 13-fold and a 9-fold increase of beta-aminoisobutyric acid (BAIBA) and gamma-aminobutyric acid (GABA), respectively, were also induced simultaneously by the AOA injection. Identification of BALA and BAIBA isolated from the rat urine was performed by chromatographic and mass spectrometric analyses. The effects of AOA injection on the tissue levels of these amino acids were also studied. Contents of BALA in the liver and kidney and GABA in the brain increased significantly in response to AOA injection. The present study indicates that BALA transaminase is involved in hyper-beta-alaninemia.

Corticoids are well known for their immunosuppressive properties. Interleukin-10 (IL-10) is an intrinsic antiinflammatory peptide in immune diseases, originally identified as cytokine synthesis inhibitory factor. We examined the effect of hydrocortisone sodium succinate (HSS) on the production of IL-10 by human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy volunteers and cancer-burden patients were preincubated separately with or without HSS for 1 h, then stimulated with 5 microg/ml lipopolysaccharide (LPS). Production of IL-10 by human PBMCs was detected with LPS stimulation and its production was higher in cancer-burden patients than in normal volunteers, although this was not statistically significant. HSS suppressed production of IL-10 by LPS-stimulated PBMCs in a dose-dependent manner both in normal volunteers and in cancer-burden patients. These results indicate that, in addition to their antiinflammatory properties, corticoids act to restore the immunosuppressive states even in cancer-burden states

The effect of intracarotid infusion of etoposide on the permeability of the blood-brain barrier (BBB) and brain-tumor barrier (BTB) was investigated using a model of rats injected with C6 glioma cells. Fifty four glioma-bearing rats were divided into 3 groups and treated with 0, 3, or 15 mg/kg of etoposide infused into the internal carotid artery. BBB or BTB permeability was evaluated qualitatively by the leakage of Evans blue (6 animals in each group) or quantitatively by the diffusion of carboplatin [cis-diammine (1,1-cyclobutane-dicarboxylato) platinum(II); CBDCA] (12 animals in each group) into the normal brain or the tumor tissue. BBB and BTB disruption augmented significantly in proportion to the dose of etoposide. The degree of disruption of BTB was greater than that of BBB, but the rate of disruption of BBB in proportion to increasing the dose of etoposide was higher than that in the BTB. Histopathologically, no obvious changes were observed in the animals of either the control group or the 3 mg/kg group but degenerative changes in the neurons of the hippocampus of the infused hemisphere were seen in the 15 mg/kg group. This change is thought to be caused by apoptosis because of the positive reaction with TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Our results suggest that intracarotid infusion of etoposide can increase drug delivery of concurrent antitumor agents into tumor tissue, but cerebral parenchymal cell damage is expected with a higher dosage of etoposide. Therefore, the dosage of etoposide for intracarotid infusion should be lower than 15 mg/kg in order to reduce neurotoxicity of both etoposide and concurrent anticancer drugs.

Forty-one hands of 37 patients with idiopathic carpal tunnel syndrome treated by endoscopic carpal tunnel release (ECTR) were followed up for more than one year after surgery. Surgical results were evaluated using Kelly's criteria, the Semmes-Weinstein test, the static and moving 2-point discrimination tests, tip-pinch strength, and motor and sensory nerve conduction studies. Clinical results, according to Kelly's criteria three months after surgery, were excellent or good in 36 hands, and fair or poor in five hands. No recovery was evident at six months and 12 months after surgery in fair and poor hands. Based on these findings, we conclude that a neurolysis of the median nerve and release of constriction of the thenar muscle branch should be performed using the conventional open technique for patients with poor results three months after ECTR if the patients are dissatisfied with ECTR results

To better understand the spread of hepatitis C virus (HCV) infection, we studied the association of HCV infection with similarly transmissible hepatitis B virus (HBV) infection and with hepatitis A virus (HAV) infection, which is supposed to be related to a nosocomial transmission of HCV. This was done by studying the presence or absence of antibodies to these viruses, as well as hepatitis B surface antigen, in a population of 1,398 inhabitants with abnormal liver function tests or history of liver disease and/or blood transfusion. This group was drawn from a group of 7,905 examinees screened for liver disease in 26 districts of Okayama prefecture, Japan. The prevalence of antibody-positive cases increased with age for those viruses. Small but significantly increased odds ratios were obtained among anti-HCV antibodies (HCVAb), anti-hepatitis B core antibodies (HBcAb) and anti-hepatitis A antibodies (HAVAb). After adjusting odds ratios by logistic regression analysis, a significant association was present only between HCVAb and HBcAb. The distribution of age-adjusted prevalences (AAP) of HCVAb in 26 districts was significantly wider than those of HBcAb or HAVAb. The district-based AAP of HCVAb, but not of HBcAb and HAVAb, correlated significantly with the district-based prevalence of infectious hepatitis having a tendency of chronicity reported in 1953-1955. Adjusted odds ratios calculated by logistic regression analysis of the virus markers showed that HCVAb was significantly associated with a past history of blood transfusion. Thus, the spread of HCV infection is speculated to have been triggered by blood transfusion, particularly from paid donors initially, followed by transmission by nosocomial or close person-to-person contact.

The subject of this study is the electromyographic investigation of the velopharyngeal sphincter structures. Seventy-five patients underwent examination, both patients with symptoms of velopharyngeal insufficiency and patients who were thought to have latent pathological sphincter changes based on local findings. A control group of 10 healthy examinees was also investigated. On the basis of electromyographic findings we divided patients into 2 groups: 57 patients without neuromuscular disorders and 18 patients with neuromuscular disorders of the velopharyngeal sphincter. Twelve patients from the latter group had acute, and 6 had chronic lesions of the velopharyngeal sphincter. Particular cases of illness within these 2 groups were investigated further. This study shows the usefulness of electromyography for diagnosing the exact causes of velopharyngeal insufficiency and for choosing the best approach to treatment.

Our purpose was to investigate developmental alterations of human alpha-fetoprotein (AFP) oligosaccharides in maternal serum by lectin affinity electrophoresis and to compare the AFP glycoforms in maternal serum with those in umbilical cord serum and amniotic fluid. AFP glycoforms were separated by affinity electrophoresis with concanavalin A (Con A), lentil lectin (LCA), erythroagglutinating phytohemagglutinin (E-PHA) and Allomyrina dichotoma lectin (allo A) and detected by sensitive antibody affinity blotting. In maternal serum, increased proportions of Con A-nonreactive AFP (AFP-C1), LCA strongly-reactive AFP (AFP-L3) and E-PHA-reactive AFP (AFP-P4 and AFP-P5) decreased gradually during the early gestational weeks. Allo A-nonreactive AFP (AFP-A1 and asialo-AFP) were found only in amniotic fluids during early gestational weeks. The percentages of these glycoforms at full term were almost the same among those body fluids. Since the glycoforms of maternal serum AFP were close to those of umbilical cord serum AFP, lectin-affinity electrophoretic analysis of maternal serum AFP may be useful for evaluating the developmental state of fetus by examining the nature of AFP sugar chain.

A double-masked, randomized, placebo-controlled study was conducted to evaluate the effectiveness of lodoxamide tromethamine 0.1% eyedrops in preventing inflammatory cell accumulation in the tear fluid of patients with vernal conjunctivitis. A 1-week baseline period was followed by 4 weeks of treatment with either lodoxamide tromethamine 0.1% ophthalmic solution or placebo in 30 symptomatic subjects with vernal conjunctivitis. Cytological evaluation of tear fluid was performed before and after the treatment. In the lodoxamide-treated group, but not in the placebo-treated group, the number of neutrophils (P = 0.051) and eosinophils (P = 0.020) in the tears significantly decreased at the end of 4 weeks when compared with baseline (Wilcoxon-signed rank test). It was concluded that lodoxamide treatment was significantly more effective than the placebo in terms of reducing inflammatory cells in the tear fluid in vernal conjunctivitis. This objective inhibition of inflammatory cells may be associated with clinical relief.

Serum levels of total amylase, pancreatic type (P-type) isoamylase, and salivary type (S-type) isoamylase were measured in obese children (153 subjects; mean age, 10.1 years old; 86 boys and 67 girls) before and after weight reduction therapy. Serum amylase activities were determined using p-nitrophenylmaltoheptaoside as a substrate, with or without an antibody added to inhibit the S-type isoamylase. Serum levels of total amylase, P-type isoamylase and S-type isoamylase activities were significantly decreased in obese children with an obesity index more than 50%. S-type and P-type isoamylases showed negative correlation with the obesity index, the correlation coefficient being slightly larger in S-type than in P-type isoamylase. Analysis of the serum amylase activities in obese children who underwent weight reduction treatments showed a negative correlation only between the differences in S-type isoamylase activity and the differences in the obesity index. It may be concluded that the S-type isoamylase activity in serum of obese children is decreased and that it can be increased by reducing their body weight.

We developed a reliable system for the irradiation of xenografted tumors in mice which allows for accurate local irradiation under specific pathogen-free conditions. The system presented here consists of acrylic supports for mice and an acrylic box connected to a pump through 0.22 microns pore-sized filters. Mice with xenotransplanted tumors growing on their right hind legs were set on the supports and put into the box in a laminar flow hood. The tumors of 7 mice were irradiated simultaneously with X-rays of 6 and 10 MV generated by a linear accelerator at a dose rate of 3.1-4.7 Gy/min. The air was ventilated through filters during irradiation in the closed box. Microorganism tests confirmed that no bacteria entered or left the box. One of the significant characteristics of this setup is that it allows for irradiation under conditions of acute hypoxia, which is obtained using an integrated tourniquet. The dose variation among 7 tumors was less than 1%. The rest of the mouse's body was shielded effectively by a half-field technique and a lead block. As a result, the whole body dose for the mice was 0-4% of the total dose absorbed by the tumor. Due to the high dose rate and the ability to irradiate 7 mice simultaneously under specific pathogen-free conditions, this new system can be considered a time-saving and valuable tool for radiation oncology research.