[Variety of pharmacological action of beta agonists].
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Publications and source records attributed to M Adachi.
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The effects of ovomacroglobulin (OMG), an alpha 2-macroglobulin-like protease inhibitor, were tested on periodontal surgical would healing in 60 Wistar rats. The animals were divided into two groups, one receiving topical application of 0.1% wt/wt OMG ointment and the other receiving ointment base (base). Rats were killed at one, three and seven days after surgery for histological and immunohistochemical observation. Compared with base group samples, OMG samples displayed enhanced capillary formation on anti-laminin-stained sections from day-3 specimens and a greater quantity of collagen fibers on Azan-Mallory-stained sections from day-7 specimens. Results were quantified using an automatic computerized pixel image analyzer. Hematoxylin-eosin-stained sections revealed that the length of regenerated junctional epithelium was shorter in the OMG group than in the base group. The data indicate that the application of OMG to surgical wounds accelerated fibroblast growth, collagen deposition, and capillary formation in granulation tissue. Thus, OMG could be a useful healing promoter for flap surgery.
Ultrastructural observations were performed to further characterize the human megakaryocytic leukemia cell line, CMK, and its subclone, CMK11-5. We found that particles derived from CMK11-5 cells had cytoplasmic projections and no nucleus, and that some particles contained alpha granules. Incubation with ADP induced fibrinogen receptors on the surface of these particles. Furthermore, the particles had glycoprotein Ib antigen on their surfaces, and attached nonreversibly to rabbit aortic subendothelium, showing associated morphological changes similar to those observed in normal platelets. CMK and CMK11-5 are the first megakaryocytic cell lines that have been found to release particles that have some of the same functions as normal platelets. In particular, CMK11-5 seems to be a useful model for studying megakaryocyte function.
We present a case of myelodysplastic syndrome (MDS), which developed into an overt leukemic phase in a 15-year-old female with a rare constitutional abnormality [46,XX,t(2;11) (q31;p13)]. The patient entered complete remission after 3 months of chemotherapy. On chromosome analysis during remission, the t(2;11) (q31;p13) abnormality was detected in all metaphases of both the bone marrow cells and PHA-stimulated peripheral blood lymphocytes. Her father also had the same karyotype. This case seems to be of value as a reference for the study of the significance of constitutional chromosome abnormalities in MDS.
To determine whether Oriton IgE kit, a new kit for the measurement of allergen-specific IgE antibodies, is useful in screening allergen-specific antibody, we measured the titers of IgE antibodies against 11 different allergens (house dust 2, Dermatophagoides farinae, Japanese cedar, ragweed pollen, egg white, milk, cat epithelium, dog epithelium, Candida, Alternaria and Aspergillus) with the Oriton IgE kit, and the results were compared to those of intradermal tests and RAST in 103 allergic patients and 10 normal subjects. There was a clear correlation between IgE antibody titers measured by the Oriton IgE kit and the RAST. The correlation coefficient was 0.76 (p less than 0.01) and the total correspondence rate was 85.9%. We also found strong correlation between the Oriton IgE kit and RAST in IgE antibody titer against 5 different allergens, Dermatophagoides farinae, Japanese cedar, ragweed pollen, egg white and Candida. The correlation coefficient was over 0.70. The correspondence rate, sensitivity and specificity of the Oriton IgE kit to intradermal tests was 71.8%, 45.3% and 87.8% respectively. The sensitivity of the Oriton IgE kit was slightly higher, while the specificity was slightly higher in RAST, although the differences were not statistically significant between these methods. Correspondence rate of the Oriton IgE kit was similar to that of RAST. These results suggested that the Oriton IgE kit is useful in screening allergen specific IgE antibodies.
We report our recent findings on the diagnosis, incidence, appearance of the trachea at autopsy, and surgical treatment of acquired trachobronchomalacia. In the diagnosis of this disease, continuous dynamic CT scanning (1 slice/0.6 second) from inspiration to deep expiration was better than X-ray cine recording. It is difficult to observe the most collapsed airway on coughing using bronchofiberscopic recording, because its duration time was estimated to be 1/10 second by X-ray cine recording, whereas the findings at one instant were easily recorded by video-bronchoscopy on coughing. The degree of severity of this disease was classified into three groups. 1st degree 0-50% narrowing of airway caliber, 2nd degree 50-75%; and 3rd degree 75-100%. Severity of 2nd or 3rd degree was present in 542 (12.7%) of 4283 patients suffering from chest disease who underwent bronchoscopy. Seventy-two percent of patients were aged 50 to 80 years. Third degree tracheomalacia was found in 131 patients with an incidence of 3.1%, which increased from 2.2% at 50 years to 6.2% at 80 years. The autopsy findings of the trachea consisted of fragmentation of the tracheal cartilage and extension of the membranous portion. The pathogenesis may be varied with different types of collapse of the airway, including the saber sheath type and the crescent type. Surgical treatment consists of prevention of the airway collapse by wrapping the airway with Marlex mesh and bonding Lyodura (lyophilized dura mata) with fibrin glue, which is more reliable than the span plasty proposed by Nissen.
To investigate the role of thromboxane (Tx) A2 and prostaglandin (PG) I2 in the development of airway responsiveness after ozone exposure, we measured the airway responsiveness to inhaled methacholine (Mch), TxB2 and 6-keto-PGF1 alpha levels in bronchoalveolar lavage fluid (BALF) in 18 dogs after ozone exposure. Airway responsiveness to Mch was determined by Astograph (7 Hz oscillation method), and ozone exposure was carried out for 2 hr at an ozone level of 3.01 +/- 0.05 ppm (mean +/- SEM). Airway responsiveness to Mch increased significantly after ozone exposure (p less than 0.001). TxB2 levels in BALF were not affected by ozone exposure, but the levels of 6-keto-PGF1 alpha decreased significantly after ozone exposure (p less than 0.001). The ratio of TxB2/6-keto-PGF1 alpha increased significantly after ozone exposure, and the change in this ratio correlated significantly with the change of airway responsiveness to Mch (p less than 0.01, r = 0.654). These results suggest that airway hyperresponsiveness after ozone exposure is induced by the relative increase of TxA2 due to the decrease of PGI2.
We evaluated the inhibitory effect of S-1452, a specific thromboxane (Tx) A2 receptor antagonist on the increase of airway responsiveness in 7 dogs after ozone exposure. Airway responsiveness to inhaled methacholine (Mch) was determined by Astograph (7 Hz oscillation technique), and at the same time TxB2, 6-keto-prostaglandin (PG) F1 alpha, PGE2 levels and total cell counts in the bronchoalveolar lavage fluid (BALF) were measured. Ozone exposure was carried out for 2 hr at an ozone level of 3.04 +/- 0.02 ppm (mean +/- SEM). Airway responsiveness to Mch increased significantly after ozone exposure (p less than 0.01), and this hyperresponsiveness was inhibited significantly by pretreatment with S-1452 (p less than 0.02). TxB2 and PGE2 levels in BALF did not change after ozone exposure, but the levels of 6-keto-PGF1 alpha decreased significantly after ozone exposure (p less than 0.05). Total cell counts in BALF increased significantly after ozone exposure (p less than 0.02). The decrease of 6-keto-PGF1 alpha levels and the increase of total cell counts were not affected by pretreatment with S-1452. These results suggest that S-1452 is protective against the increase of airway responsiveness induced by ozone exposure, and that TxA2 plays an important role in the hyperresponsiveness. But hyperresponsiveness may not be induced by hyperproduction of TxA2, but by the relative increase of TxA2 to PGI2.
smg p21A and -B (smg p21s) are ras p21-like small GTP-binding proteins (G proteins) with the same putative effector domain as ras p21s. Both smg p21A mRNA and smg p21B mRNA were detected in CMK, a human megakaryocytic leukemia cell line, and their levels were markedly elevated by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which caused the differentiation of this cell line into more mature megakaryocytes. The smg p21 protein molecules also increased during the TPA-induced differentiation of CMK cells. The mRNA level of glycoprotein IIb (GPIIb), a typical marker of the megakaryocytes, was increased by this treatment, but the time course of the increase in the smg p21 mRNA levels as more rapid than that of the increase in the GPIIb mRNA level. Ha-ras p21 mRNA was undetectable, but both Ki- and N-ras p21 mRNAs were detected in CMK cells and their levels were also increased during TPA-induced differentiation of CMK cells, although to a lesser extent than those of smg p21 mRNAs. Protein kinase C inhibitors inhibited the basal and TPA-induced smg p21A mRNA level, but cyclic AMP-elevating prostaglandin E1 or Ca(2+)-mobilizing ionomycin did not inhibit them. Cycloheximide enhanced the basal and TPA-induced smg p21A mRNA levels. Actinomycin D blocked the TPA-induced smg p21A mRNA levels, but showed no detectable effect on the elevated smg p21A mRNA level which was induced by pretreatment with TPA. A dramatic increase in the smg p21 mRNA levels was also observed in other leukemia cell lines during TPA-induced differentiation. These results suggest that TPA stimulated expression of the smg p21A gene, presumably through the action of protein kinase C at the transcriptional level rather than at the post-transcriptional level, in hematopoietic leukemia cells.
Using polyester, we prepared a new material for chest wall reconstruction. The polyester mesh has the same rigidity and elasticity as Marlex tracheal mesh. From January 1987 through July 1991, we performed chest wall reconstruction using the polyester mesh in 8 patients with lung cancer, 9 with empyema after open drainage, 2 with metastatic chest wall tumors, 1 with a primary osteogenic giant cell tumor originating from the rib and 1 with radiation dermatitis and costal chondritis. Three or more ribs were resected in 17 patients. The defects of the chest wall were reconstructed with the polyester mesh covered with a GORE-TEX soft tissue patch to achieve air tightness. Fifteen cases have passed at least one year with no sign of infection. In conclusion, the polyester mesh prevents flail chest and seems to be a satisfactory material for chest wall reconstruction.
In order to assess mortality patterns of Japanese physicians, the mortality during a 12 year period (July 1978-June 1990) among male members of the Chiba Medical Association was studied. The overall mortality among physicians was significantly lower than the general male population in Chiba prefecture (standardized mortality ratio [SMR] = 0.69). Physicians were found to have lower cause-specific mortality from cancer (SMR = 0.71), cerebrovascular disease (SMR = 0.42), pneumonia and bronchitis (SMR = 0.63), accidents (SMR = 0.37), and suicide (SMR = 0.29) than the general population, but to have higher mortality from senility (SMR = 1.75). When compared to the total working population and the professional and technical workers, all-cause mortality for physicians did not differ. Mortality from ischemic heart disease was significantly higher during 1979-1983, but was similar during 1984-1988. Analysis by specialty showed that during 1979-1983 internal medicine physicians had a lower mortality than surgeons, but this reversed during 1984-1988 with the former having a higher mortality than the latter. Over the whole period, no difference in mortality existed between internists and surgeons. A cohort of 2,502 male members that is being followed, showed that the mortality of physicians was lower than the general population. However, no significant difference between the internists and surgeons was observed in both overall and major cause-specific mortality.
The usefulness of the Noise-Field Test was studied in 196 normal eyes and 146 eyes of low-tension glaucoma patients (including 74 eyes of early glaucoma) who had never perceived their filed defects. The noise-field spontaneously generated on a 21-inch home television screen through a non-transmitting channel was utilized for the test. A white mark 5 mm in diameter was stuck on the center of the screen as a fixation point. At a distance of 30 cm, the subjects were asked to watch the screen, gazing at the fixation point with one eye for 3-5 seconds, checking to see whether the flickering area on the noise-field diminished or disappeared. The test was performed 3 times on each eye. In 136 glaucoma eyes, the field defects detected by static perimetry (Humphrey) were clearly identified in the Noise-Field Test. In normal eyes, a scotoma was noted on the blind spot in 6 eyes, The sensitivity and specificity was 93.2% and 96.9%, respectively. The Noise-Field Test can be an excellent method in screening for low-tension glaucoma which is easily missed by tonometric screening only.
There are no definite criteria for the indication of surgery in lung cancer with mediastinal lymph node involvement. During the past 20 years, 100 patients (76 patients with adenocarcinoma and 24 patients with squamous cell carcinoma) have undergone thoracotomy for lung cancer with mediastinoscopic positive lymph nodes at our hospital. Of these, relatively curative resection was performed on 13 patients. The 5-year survival rate in these 13 patients was 28%, which was significantly higher than the 0% in 42 patients with relatively non-curative resection and the 0% in 26 patients with absolutely non-curative resection. The 5-year survival rate was 9% in both T1 (n = 14) patients and T2 (n = 37) patients. No T3 (n = 21) and T4 (n = 9) patients survived 3 years. The 5 year survival rate in patients with squamous cell carcinoma was 12% and that in patients with adenocarcinoma was 0%, but there was no significant difference. The survival rates of T1 and T2 patients were significantly higher than that of T3 patients (p less than 0.02 and p less than 0.005) respectively. Contralateral mediastinal lymph node metastasis (N3) was observed significantly more frequently in patients with adenocarcinoma (38%) than in those with squamous cell carcinoma (13%), but there was no significant difference in the survival rate. In N2 patients, the survival rate was compared between those with mediastinal nodal involvement of an early stage (N2-1) and those with lymph node metastasis of more advanced stage (N2-2) according to the lobe bearing the primary cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder due to a deficiency or abnormality of glycoproteins (GPs) IIb and IIIa, but its genetic basis remains to be determined. We analyzed the genes for GPIIb and 3'GPIIIa in 3 patients with GT and in 7 control subjects by Southern blot. No large deletions or insertions were detected in these genes in any patient with GT. Furthermore, the GPIIb and GPIIIa mRNAs derived from the platelets of patients with GT could be amplified using the reverse transcriptase-polymerase chain reaction (RT-PCR). This finding indicates that the mRNAs of the patients with GT are considered to be normally transcribed. The molecular defects of the GPIIb.
We continuously monitored blood oxygen saturation in the internal jugular vein during selective cerebral perfusion for aortic arch operations and evaluated its efficacy as an indicator of cerebral oxygen metabolism. The selective cerebral perfusion method was applied in 11 patients who underwent operations for aortic arch replacement. Blood oxygen saturation in the internal jugular vein was continuously monitored at the bulbus jugularis with a fiberoptic catheter during the operation. Perfusion flow of 500 ml/min was continued for 134.7 +/- 14.9 minutes under moderate hypothermia at 25 degrees C, and bilateral temporal arterial pressure was 40 to 60 mm Hg. Blood gas data were used to estimate oxygen consumption, oxygen extraction ratio, and lactate uptake in the cerebrum. No patients had postoperative cerebral complications. Cerebral oxygen consumption was 2.93 +/- 0.4 ml/min/100 gm under general anesthesia at 36 degrees C. While selective cerebral perfusion at 25 degrees C decreased consumption to 0.92 +/- 0.39 ml/min/100 gm, it fell to about 30% of its former value. Blood oxygen tension in the internal jugular vein showed no significant correlation with rectal temperature. Selective cerebral perfusion did not significantly affect cerebral lactate uptake. In contrast, blood oxygen saturation in the internal jugular vein was significantly affected by temperature and cerebral flow during selective cerebral perfusion, and blood oxygen saturation in the internal jugular vein correlated closely with cerebral oxygen extraction ratio (r = 0.91). Cerebral oxygen metabolism was thus well maintained, and continuous monitoring of blood oxygen saturation in the internal jugular vein was found to serve as a useful indicator under selective cerebral perfusion during operations for aortic arch replacement.
The usefulness of QRST time-integral (IQRST) values of 12-lead electrocardiograms for diagnosing a prior myocardial infarction complicated by left bundle branch block (LBBB) was determined. The study consisted of 25 patients with LBBB (11 with and 14 without myocardial infarction). The IQRST values in each lead point of 12-lead electrocardiograms were calculated. Data from 607 normal subjects were used as controls and mean +/- 2 standard deviations was regarded as the normal range. The following parameters were derived: number of leads less than the normal range of IQRST values (nQRST) and sum of the differences between the normal mean IQRST value and IQRST value of a given patient in leads where this value was less than the normal range (sigma QRST). The criteria of nQRST (12-lead) greater than or equal to 5 and sigma QRST (12-lead) greater than or equal to 500 microV in 12-lead electrocardiograms were selected on a relative cumulative frequency distribution and demonstrated the presence of a myocardial infarction in LBBB with a sensitivity of 82% and a specificity of 100% for each. With regard to the localization of the myocardial infarction, the criterion of sigma QRST (V1-6) greater than or equal to 300 microV in leads V1-6 of 12-lead electrocardiograms demonstrated the presence of an anterior myocardial infarction in the LBBB with a sensitivity of 88% and a specificity of 77%. It was difficult to localize an inferior myocardial infarction in patients with LBBB by using IQRST values of inferior leads.(ABSTRACT TRUNCATED AT 250 WORDS)
A cDNA coding for the human A-type endothelin receptor (ETA) was cloned from a human placenta cDNA library. The cDNA contained the entire coding sequence for the 427 amino acid protein with a relative Mr of 48,722. The deduced amino acid sequence of the human ETA was, respectively, 94% and 93% homologous with the sequence of bovine ETA and rat ETA, but was only 64% homologous with that of the human ETB receptor. Upon expression in COS-1 cells, the human ETA receptor showed binding activity to ETA, with the highest selectivity to ET-1. Northern blot analysis showed that the mRNA of human placenta ETA consists of one species 5 kilo-nucleotides in length, and the same analysis for the uterus, testis, heart and adrenal gland of Cynomolgus monkey showed that the cognate mRNAs are widely distributed.
Four kinds of gangliosides, namely GM1a, GD1a, GD1b and GT1b and their sulfated derivatives were examined for antiviral activities against human immunodeficiency virus type 1 and abilities to modulate CD4 antigen on the cell surface. The infection of human T cells with the virus was markedly inhibited by treatment with the sulfated gangliosides at a concentration of 10 micrograms/ml, while the non-sulfated gangliosides had only weak antiviral activities. The sulfated gangliosides completely inhibited syncytium formation induced by HIV-1 at 30 micrograms/ml. The CD4 antigen on the surface of T cells became hardly detectable after treatment with them. They did not damage cells, nor prolong the activated partial thromboplastin time at concentrations of up to 100 micrograms/ml, suggesting that they may have little side effect in vivo.