Purification and properties of enzymes related to steroid hormone synthesis.
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17-Hydroxysteroid Dehydrogenases↗
Biomedical subjects
T Morikawa
Publications and source records attributed to T Morikawa.
Effect of unilateral pulmonary vagotomy on respiratory control in man.
We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.
Carbon Dioxide↗
Vertebrate collagenase inhibitor. I. Tripeptidyl hydroxamic acids.
A series of tripeptidyl analogues carrying hydroxamic acid residue at the C-terminus of the molecule were synthesized, and their inhibitory activities against vertebrate collagenase and other metalloenzymes including bacterial collagenase were examined. Both Z-Pro-Leu-Ala-NHOH and Z-Pro-D-Leu-D-Ala-NHOH showed highly specific and potent inhibitory activity against tadpole and human skin collagenases with an IC50 of 10(-6) M order.
Amino Acid Sequence↗
Pharmacological activities of synthetic human cholecystokinin-33 of which tyrosine was sulfated by arylsulfotransferase.
The pharmacological activities of synthetic human CCK-33, in which a tyrosine molecule was sulfated by arylsulfotransferase, were investigated in the rat and the guinea-pig. The activities were compared with those of non-sulfated CCK-33 (CCK-33NS), CCK-8 and CCK-4. CCK-33 was about 100 fold more potent than non-sulfated CCK-33(CCK-33NS) but was about 20 fold less potent than CCK-8 in the contraction of the isolated gallbladder of the guinea-pig. In rat pancreatic secretion, intravenous CCK-33 and CCK-8 showed almost the same activity. The potency of each was about 1000 fold more than the individual potency of CCK-33NS, non-sulfated CCK-8 (CCK-8NS) and CCK4. There were no significant differences in gastric acid stimulatory activities among CCK-33, CCK-8, CCK-4, but the activities of CCK-33NS and CCK-8NS were less than those of CCK-33 and CCK-8, respectively. CCK-33 and CCK-8 produced a reduction in the intake of powder chow in doses of 10(-8) and 3 x 10(-8) mol/kg i.p., but CCK-33NS, CCK-8NS and CCK-4 did not. In conclusion, the activities of synthetic human CCK-33 are almost the same as those of CCK-8 on exocrine pancreatic secretion, gastric acid secretion and food intake, but less than CCK-8 on isolated gallbladder contraction.
Animals↗
Pharmacological activity of angiotensin-II modified by tyrosine sulfation.
An angiotensin-II analogue with a sulfated tyrosine residue was prepared by arylsulfotransferase treatment of synthetic human angiotensin-II. Its biological activities were studied in isolated smooth muscles, and its effect on blood pressure was determined. The sulfated angiotensin-II (AII-S) was about 15-30 fold less potent than angiotensin-II (AII) for ileum contraction and gallbladder contraction. The hypertensive potency of AII-S was about 30-fold less than that of AII.
Angiotensin II↗
Vasoactive intestinal polypeptide (VIP) stimulates fibrinolytic system in the rat.
We have studied the fibrinolytic effect of VIP in rats. Intravenous injection of VIP enhanced blood fibrinolytic activity in a dose-related manner. The euglobulin fraction obtained from intact rat plasma incubated with VIP did not produce an increase in fibrinolytic activity, while dextran sulfate (DS) and urokinase (UK) showed the activity. VIP solution placed on a plasminogen-rich fibrin plate did not show fibrinolysis. VIP had neither a plasminogen activator nor plasmin activity. VIP may release plasminogen activators into the blood.
Animals↗
Cardiac output and heart rate in man during simulated swimming while breath-holding.
We measured stroke volume (SV), heart rate (HR), cardiac output (Q), arterial pressure and intrapulmonic (mouth) pressure in four healthy, male subjects during simulated swimming (i.e., performing crawl movements with the legs continuously at a constant rhythm) with and without apnea (water temperature: 31 degrees C). We wanted to see whether the exercise tachycardia response persisted, or whether the HR decreased during apnea, just as in the "diving response" of diving animals. The SV and the Q fell to half its value in the control phase (i.e., swimming with normal breathing), when the 15-s apnea was performed at a high mouth-pressure; at low mouth-pressure, SV and Q hardly changed. These results are replicates of our previous findings in man during rest in air. Due to the light work, HR increased slightly from rest, but the exercise HR did not change much during apnea with or without high mouth-pressure. The results show that man tends to preserve his exercise HR response, and does not react as an oxygen-conserving animal, whether he is in air or in water under these conditions. However, man, as well as diving animals, may well have a "diving response" as an emergency reaction, which may not be restricted to only the water environment.
Adult↗
[An epithelial myoepithelial carcinoma of the parotid gland].
A case of epithelial myoepithelial carcinoma is reported. Histologically, this tumor shows tubular and solid growth pattern. The inner layer of the tubules is composed of cells with an eosinophilic cytoplasm that is surrounded by cells with clear cytoplasms. Clear cells also manifest a solid growth pattern. Immunohistochemical and electron microscopic examinations has revealed that the cells with an eosinophilic cytoplasm have the characteristics of the ductal epithelium and that the clear cells have the characteristics of the myoepithelium. Immunohistochemically, keratin positive clear cells and S-100 protein positive ductal cells were found in our case. This suggests the existence of cells having both ductal and myoepithelial characteristics and this inspected tumor had derived from multipotential cells of intercalated ducts.
Actin Cytoskeleton↗
Ventilatory responses to chemosensory stimuli in quadriplegic subjects.
We tested the hypothesis that interruption of motor traffic running down the spinal cord to respiratory muscle motoneurons suppresses the ventilatory response to increased chemical drive. We compared the hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses, based on the rebreathing technique, before and during inspiratory flow-resistive loading in 17 quadriplegic patients with low cervical spinal cord transection and in 17 normal subjects. The ventilatory response was evaluated from minute ventilation (VE) and mouth occlusion pressure (P0.2) slopes on arterial oxygen saturation (SaO2) or on end-tidal PCO2 (PACO2), and from absolute VE values at SaO2 80% or at PACO2 55 mmHg. We found no difference in the unloaded HVR or HCVR between the quadriplegic and normal subjects. In the loaded HVR, the delta VE/delta SaO2 slope tended to decrease similarly in both groups of subjects. The delta P0.2/delta SaO2 slope was shifted upwards in normal subjects, yielding a significantly higher P0.2 at a given SaO2. In contrast, this rise in the P0.2 level during loaded HVR was absent in quadriplegics. Loaded HCVR yielded qualitatively similar results in both groups of subjects; delta VE/delta PACO2 decreased and delta P0.2/delta PACO2 increased significantly. The results show that the ventilatory chemosensory responses were unsuppressed in quadriplegics, although they displayed a disturbance in load-compensation, as reflected by occlusion pressure, in hypoxia. We conclude that the descending drive to respiratory muscle motoneurons is not germane to the operation of the chemosensory reflexes.
Adolescent↗
Mechanism of membrane damage induced by the amphipathic peptides gramicidin S and melittin.
The action of gramicidin S and melittin on human erythrocytes, Staphylococcus aureus and Escherichia coli was studied as an extension of the previous study (Katsu, T., Ninomiya, C., Kuroko, M., Kobayashi, H., Hirota, T. and Fujita, Y. (1988) Biochim. Biophys. Acta 939, 57-63). These amphipathic peptides stimulated the release of membrane phospholipids outside cells in a concentration range causing permeability change. The shape change of erythrocytes from normal discoid to spiculate form was observed just prior to the release of membrane components. We have proposed the following action mechanism of gramicidin S and melittin. The peptide molecules were predominantly accumulated in the outer half of the bilayer, deforming the erythrocyte cell into crenature. A large accumulation made the membrane structure unstable, resulting in the release of membrane fragments and the simultaneous enhancement of permeability. The action mechanism of these peptides was compared with that of simple surfactants.
Bee Venoms↗
Afferent and cardiodynamic drives in the early phase of exercise hyperpnea in humans.
The ventilatory and cardiac responses to voluntary and passive exercise were studied in 20 healthy subjects. These responses to passive leg exercise were also studied in 23 patients with spinal cord transection at the level of T5-T12. In the normal subjects, minute ventilation (VE) increased abruptly from the first breath after the onset of the two types of exercise. In contrast, cardiac output (Q) increased gradually in voluntary exercise, exhibiting significant augmentation from the fifth breath. Q changed insignificantly in passive exercise. In the patients with spinal cord transection, neither VE nor Q changed with passive exercise. These results suggest that ventilatory responses at the onset of mild exercise are related to drives from the moving limbs. We could not detect any evidence to support cardiodynamic hyperpnea at the onset of exercise.
Adolescent↗
[Adult T-cell leukemia (chronic type) with unusual surface phenotype CD 4+5+8-, Leu 7+ at acute crisis].
Chronic adult T-cell leukemia with surface phenotype CD 4+5+8-, Leu 7+ at acute crisis was presented. A 43-year-old female visited our hospital complaining of generalized lymphadenopathy and skin rash in December, 1973. Peripheral blood picture and histological findings of skin led to the diagnosis of malignant lymphoma (leukemic type). Intermittent chemotherapy kept white blood cell count less than 25,000/microliters for more than 9 years. In January, 1983, abnormal lymphocytes began to increase and reached 100,000/microliters or over in a few months. Surface marker study showed their phenotype as CD 4+5+8-, Leu 7+ and anti-ATLA antibody was positive in the patient, her son and her daughter. Intensive chemotherapy was ineffective and she died in August, 1983. Histological diagnosis of lymph-nodes on autopsy was malignant lymphoma (diffuse, small cell type). This case is considered unusual in both clinical course and surface phenotype of its leukemic cells.
Adult↗
[An autopsy case of IgE myeloma].
An autopsy case of IgE myeloma, 85-year-old male is reported. He was admitted to our hospital on November 17, 1987 due to pain of left humerus. Osteolytic and osteoporotic foci were found in left humerus, ribs, spinal column and femurs. Complete blood countings were as follows: RBC 3.23 x 10(12)/L, Hb 11.3 g/dl, WBC 6.3 x 10(9)/L, platelet 173 x 10(9)/L. Blood smear showed red cell rouleaux formation without myeloma cells. Examination of bone marrow revealed hypoplasia with 52% myeloma cells which were stained with anti-IgE and antilambda antisera by peroxidase anti-peroxidase method. Total serum protein level was 7.7 g/dl. Monoclonal protein was observed at fast gamma-region by cellulose-acetate electrophoresis. On immunoelectrophoresis, this monoclonal protein made specific M-bow against anti-IgE and anti-lambda antisera. The IgE level in serum and urine were 7.8 x 10(6) IU/ml and 2.4 x 10(3) IU/ml by radio-immunoassay respectively. He was died owing to renal failure on September 7, 1988. Postmortem examination showed infiltration of myeloma cells in bone marrow, spleen, kidneys, lungs and generalized lymph nodes.
Aged↗
[Prevention of renal toxicity of cisplatin by administration of bismuth subnitrate].
The effect of pretreatment with bismuth subnitrate (BSN) for prevention of the renal toxicity of cisplatin (CDDP) was examined in 44 patients with lung cancer (43 non-small cell and one small cell lung cancer). In non-small cell lung cancer cases, the effect of the antitumor activity of chemotherapeutic drugs was observed in 62% of patients pretreated with BSN, and 42% in the group without pretreatment with BSN. No antitumoral activity of chemotherapeutic drugs was suppressed by treatment with BSN. In the group without pretreatment of BSN, serum creatinine and BUN were in proportion to the number of administrations of chemotherapeutic drugs. On the other hand, no renal toxicity was shown in the group with pretreatment by BSN. No protective effect against myelosuppression with pretreatment by BSN was demonstrated, perhaps because of the influence of anti-cancer drugs apart from CDDP.
Adult↗
[A clinical trial of microcomputer software for calculation of aminophylline dosages].
I made microcomputer software for the pharmacokinetic calculation of appropriate administration doses of aminophylline for the treatment of status asthmaticus. It consists of three programs for determination of initial doses, four for determination of maintenance doses, and four for calculation of the pharmacokinetics parameters (Vd, Ke, CL, T1/2). The parameters were estimated 376 times during 151 attacks in 84 patients with bronchial asthma. Vd, Ke, and CL were calculated as below, and the wide variation in the values suggests that individual programs for theophylline therapy should be made for each patient. I concluded that these microcomputer programs were useful in creating an individual administration program. Distribution volume (Vd): 385 +/- 106 ml/kg (n = 115) Elimination rate constant (Ke): 0.155 +/- 0.0878/h (n = 176) Clearance (CL): 61.8 +/- 14.3 ml/kg.h (n = 85)
Aminophylline↗
[A method of cisplatin administration with the aid of high-dose bismuth subnitrate, and their pharmacokinetics].
Twelve Patients with malignant neoplasms were treated in twenty-five courses with high-dose Cisplatin and high-dose Bismuth Subnitrate. The pharmacokinetics of Bismuth Subnitrate and Cisplatin were studied in several courses. Bismuth Subnitrate was administered orally at a dose of 150 mg/kg/day for 10 days, and an average dose of 108 mg/m2 of cisplatin was administered intravenously on the 6th day after Bismuth Subnitrate administration. The concentration of Bismuth in blood and urine showed a similar increase, reaching a plateau 5 days after, and peaking 12 days after starting administration. It is estimated that 10-day administration of high-dose Bismuth Subnitrate was appropriate to maintain an adequate concentration of Bismuth for preinduction of Metallothionein in organs. The pharmacokinetics of cisplatin in plasma indicated as follows. a) In terms of the nephrotoxic factors, the Cmax of platinum did not increase dose-dependently, and total clearance of platinum was constant under the same time of injection; b) As for the antitumor effect, AUC of ultrafilterable (free) platinum increased dose-dependently. From the standpoint of pharmacology, high-dose Bismuth Subnitrate was believed to reduce the nephrotoxicity of cisplatin without reducing its antitumor effect.
Administration, Oral↗
Paralysis of respiratory muscles and hypoxic ventilatory chemoreflex.
We investigated the hypothesis that if the chest and abdominal respiratory muscles are paralyzed, the stimulatory hypoxic ventilatory response (HVR) would be less. We compared the HVR in low cervical cord-transected tetraplegics and in normal subjects during unloaded and mechanically loaded breathing. The results demonstrated that the tetraplegics' HVR was unsuppressed, although they displayed a disturbance in load compensation. We conclude that the descending drive to respiratory muscle motoneurons is not germane for the proper operation of the hypoxic chemoreflex.
Humans↗
[An autopsied case of idiopathic interstitial pneumonia, showing a remarkably elevated serum level of CA 19-9].
Discussed herein is an autopsied case of a 30-year-old male with Idiopathic Interstitial Pneumonia (IIP) manifesting a markedly elevated CA 19-9 in the serum (maximum, over 120,000 U/ml). Despite a careful examination, no malignant lesion was found. The postmortem examination revealed a marked elevation of CA 19-9 in the serum and in the lung tissue. Further immunohistochemically regenerative bronchiolar and alveolar epithelial cells were more intensely positive for CA 19-9 than in our controls. These CA 19-9 positive cells for the most part, were found to stain with alcian blue. It is considered that IIP induces activation of sialyl-transferase in these cells.
Adult↗