Preparation of peptidyl hydroxamic acid derivatives which inhibit interstitial collagenases.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
T Morikawa
Publications and source records attributed to T Morikawa.
Polarized Cu LIII absorption study of a Bi2Sr2CaCu2O8 single crystal.
Explore the source record for details and available documents.
Journal Article↗
New plastic plates which enhance neurite extension in culture: roles of bisphenol-A and tricyclodecanyl units for growth and orientation of neurites on plastic plates with microstructures.
In order to study molecular mechanisms of contact guidance of neurites, dissociated culture of adult mouse dorsal root ganglion (DRG) cells was performed for 6 species of plastic plates different in monomer compositions. Microstructures (grooves of 5-10 microns wide and 1 micron deep) were grafted on the plates so as to guide neurite growth in their axial direction. Neurites were longer and more oriented on plates with larger water contact angle. The distribution of neurites was uneven between grooves and steps of the microstructures, exhibiting a bell-shaped curve in relation to the water contact angle of the plastic. These indicate that hydrophilic properties of the plastic plate surface, due to the presence of bisphenol-A and tricyclodecanyl units, are crucially involved in the elongation and orientation of neurites.
Animals↗
Molecular identification and comparison of the starch synthase bound to starch granules between endosperm and leaf blades in rice plants.
Normal (nonglutinous) rice plants (Oryza sativa and O. glaberrima) contain more than 18% amylose in endosperm starch, while waxy (glutinous) plants lack it in this starch. In contrast, leaf starch contained more than 3.6% amylose even in waxy plants. SDS-PAGE analysis of proteins bound to endosperm starch granules in the normal plants revealed a single band with a Mr of 60 kd, whereas waxy plants did not exhibit a similar band. The activity of starch synthase (NDP-glucose-starch glucosyltransferase) was completely inhibited by antibody against the 60-kd protein. Thus, we conclude that the 60-kd protein is the waxy protein encoded by the Wx allele, which also plays a role in the synthesis of nonglutinous starch in endosperm tissue. In leaf blades, the proteins bound to starch granules separated into five bands with Mr's of 53.6 to 64.9 kd on SDS-PAGE. Analysis of these proteins by immunoblotting using antiserum against Wx protein and inhibition of starch synthase activity by the synthase antibody revealed that none of these proteins was homologous to Wx protein. We suggest that the synthesis of amylose in leaf blades is brought about by a protein encoded by a gene(s) different from the Wx gene expressed in the endosperm.
Amylose↗
Effect of platelet-activating factor on cortisol and corticosterone secretion by perfused dog adrenal.
Administration of platelet-activating factor (PAF) to perfused adrenal increased cortisol and corticosterone secretion. With hexadecyl PAF (C16PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), the increase was significant at 1 nM and maximal at 10 nM. The responses to 10 nM octadecyl PAF (C18PAF; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) were one fourth of those to 10 nM C16PAF. The addition of C16PAF to dispersed adrenal cells significantly increased cortisol and corticosterone production at 0.1 nM and 10 nM, respectively. C16PAF was about 1000 times more potent than histamine on a molar basis in respect to cortisol response in both perfused adrenal and dispersed adrenal cells. The results suggest that PAF induces cortisol release from dog adrenal.
Adrenal Cortex↗
The effect of hydrogen peroxide on smooth muscle tone, mucus secretion and epithelial albumin transport of the ferret trachea in vitro.
The effect of hydrogen peroxide (H2O2) was examined on baseline and on methacholine- and phenylephrine-stimulated smooth muscle tone, mucus volume and lysozyme outputs, and epithelial albumin transport of the ferret whole trachea in vitro. H2O2 (10 microM-10 mM) had no significant effect on tracheal smooth muscle tone but produced concentration-dependent increases in mucus volume, lysozyme and albumin outputs. The potential difference (P.D.) across the trachea was not changed by H2O2. Exposure of the trachea to H2O2 (1 mM) for 2 h reduced the smooth muscle contractions and lysozyme outputs due to methacholine (1 microM) and phenylephrine (10 microM). Methacholine-induced albumin output was significantly increased by H2O2 but that due to phenylephrine was not significantly affected. Exposure to H2O2 had no significant effect on the mucus volume output produced by methacholine or phenylephrine. Thus H2O2 directly stimulates submucosal gland secretion, including secretion from serous cells, and epithelial albumin transport across the ferret trachea but has no effect on tracheal smooth muscle tone. H2O2 reduces methacholine- and phenylephrine-induced smooth muscle contractions and serous cell secretion. H2O2 causes hyperresponsiveness of albumin output to methacholine but not to phenylephrine.
Animals↗
Epilepsy associated with hemiplegia: 1. Seizure manifestations.
1. The seizure manifestations of patients with hemiplegia were reminiscent of partial seizures. The motor manifestations were notably asymmetrical and impairment of consciousness was mild. Nevertheless, tonic seizures, identified by electroclinical correlation were found in 49 patients (88%) although they were predominantly unilateral or asymmetrical. 2. Unclassified seizures characterized by ictal automatisms, which mimic complex partial seizures was observed in 5 patients (9%). 3. Late epileptic seizures of the HHE syndrome were regarded as psychomotor seizures by Gastaut et al. In the present study, however, complex partial seizures were found in only 3 at 28 patients with HHE syndrome (11%) whereas tonic seizures in 23 of these patients (82%). One possible reason for this discrepancy is bias in the selected patient population, because those with transient hemiplegia were not included, and infrequently occurring partial seizures might have been missed. Further study is therefore needed to determine whether the HHE syndrome is associated with complex partial seizures or predominantly unilateral tonic seizures.
Cerebral Cortex↗
Vertebrate collagenase inhibitor. II. Tetrapeptidyl hydroxamic acids.
To develop a potent and specific collagenase inhibitor, a series of tetrapeptidyl hydroxamic acids were synthesized, based on the previous findings with tripeptidyl derivatives (Chem. Pharm. Bull., 38, 1007-1011, 1990). Among the series of tetrapeptidyl derivatives synthesized, R-Gly-Pro-Leu-Ala-NHOH and R-Gly-Pro-D-Leu-D-Ala-NHOH were found to be highly specific and potent inhibitors against vertebrate collagenase with an IC50 of 10(-6) M order, where R stands for Boc or acyl group. Analysis of their structure-activity relationships showed a characteristic feature of the substrate-binding site of collagenase as follows: 1) the S1 subsite forms a shallow hydrophobic pocket, although glycine residue corresponds to the subsite of the natural collagen substrate: 2) the S2 subsite constitutes a bulky pocket with less requirement for hydrophobicity: 3) the S3 subsite preferentially accommodates Pro residue: and 4) the accommodation of the P4-P1 subsites of peptidyl collagenase inhibitor to the S4-S1 subsites is required to form a tight binding of its hydroxamic acid moiety to the zinc ion at the catalytic site of the enzyme. The introduction of an enantiometric dipeptide unit, D-Leu-D-Ala, to the P2-P1 subsites demonstrated an increased binding capacity to the extended S4-S1 subsites of collagenase, thus providing proteinase-resistant inhibitor.
Amino Acid Sequence↗
[Temporary spontaneous remission in Ki-1 (CD30) lymphoma with gastric lesion].
A case of 56 year-old man with Ki-1 (CD30) lymphoma is reported. He noticed cervical lymph node swelling and was admitted with temporary diagnosis of gastric adenocarcinoma in February 1986. His physical examination showed several from 1 to 4 cm size enlarged cervical and axillary lymph nodes. His first lymph node biopsy demonstrated the histological picture of malignant lymphoma. After 20 days his second lymph node biopsy demonstrated the picture of necrosis. Second gastric biopsy showed the picture of neither gastric cancer nor malignant lymphoma, in spite of his first gastric biopsy finding with adenocarcinoma that turned out to be malignant lymphoma by later reinvestigation. After word those lymph nodes disappeared and have not been palpable for about ten months. In October 1987, elevated LDH value, lymph node swelling and gastric lesion were again observed and sixth gastric biopsy demonstrated the picture of malignant lymphoma. He was treated with anti-lymphoma drugs. After his partial remission, he died of gastrointestinal bleeding in April 1988. Specimens of both first lymph node biopsy and sixth gastric biopsy were examined with cell markers for infiltrated cells and were positive for Ki-1/Ber-2H. His final diagnosis was Ki-1 lymphoma.
Antigens, CD↗
[Pilot study of multi-cyclic combination chemotherapy in small cell lung cancer].
Explore the source record for details and available documents.
Aged↗
[Three cases of subacute panencephalitis showing asterexis-like movements].
We reported 3 cases with subacute sclerosing panencephalitis (SSPE) showing recurrent and involuntary motor phenomena. Their electroclinical correlates were analyzed using CCTV-EEG. Clinically, they slanted their trunks and/or heads, and dropped their upper limbs momentarily only when their antigravity muscles were suitably contracting (sitting, standing, or stretching out their arms). Electrographically, the motor phenomena corresponded with the occurrence of periodic synchronous discharges (PSD) (in one-to-one manner). EMG potentials associated with the muscle contraction subsided at the very moment. These motor phenomena observed in patients with SSPE were discussed in relation to asterexis.
Adolescent↗
Purification and characterization of 3 alpha-hydroxysteroid dehydrogenase from chicken hepatic cytosol.
From the cytosol fraction (supernatant fluid at 105,000 g) of chicken liver, 3 alpha-hydroxysteroid dehydrogenase was purified to an apparently homogeneous state by differential precipitation with ammonium sulfate, followed by column chromatographies with DE 51, DEAE-Toyopearl, and Sephadex G-100. Finally the dehydrogenase was purified 103-fold on the basis of the cytosol fraction. Polyacrylamide gel electrophoretic analysis in the presence of sodium dodecyl sulfate (SDS) revealed that molecular weight of the purified enzyme was 66 kDa, while that of the native dehydrogenase in the absence of SDS was estimated as 660 kDa or more from the peak of the enzyme in elution profile from Sephacryl S-200 column chromatography. The dehydrogenase required NADPH specifically for reduction of 3-oxo group of 5 beta-androstanedione (Km = 1.6 microM). Optimal temperature for 3-oxo reduction was 50 C in incubation for 10 min.
3-Hydroxysteroid Dehydrogenases↗
[A case of adult T cell leukemia with calcium deposits in the liver].
Explore the source record for details and available documents.
Aged↗
Interaction of wasp venom mastoparan with biomembranes.
Mastoparan-induced changes in the K+ permeability of rat peritoneal mast cells, human erythrocytes, Staphylococcus aureus and Escherichia coli were examined. Mastoparan did not efficiently increase the K+ permeability of cells except for S. aureus. The release of membrane phospholipids was also observed from S. aureus cells in the concentration range of the permeability enhancement. Mastoparan stimulated histamine release from mast cells, independently of a small efflux of K+. Mastoparan became markedly effective to E. coli cells whose outer membrane structure was chemically disrupted beforehand, showing that the peptide can enhance the permeability of the cytoplasmic membranes of both Gram-positive and -negative bacteria. In experiments using liposomes, mastoparan increased the permeability of the liposomes composed of egg phosphatidylethanolamine and egg phosphatidylglycerol, which are the lipid constituents of the cytoplasmic membrane of E. coli cells, while it showed a weak activity to the liposomes composed of egg phosphatidylcholine and cholesterol. The latter result related closely to the fact that this peptide acted weakly on erythrocytes and mast cells in which acidic lipids constitute a minor portion. Mastoparan decreased the phase transition temperature of dipalmitoylphosphatidylglycerol liposomes, but it did not affect that of dipalmitoylphosphatidylcholine liposomes. These results indicate that mastoparan penetrated into membranes mainly containing acidic phospholipids and disrupted the membrane structure to increase the permeability. The action of the wasp venom mastoparan was compared with that of a bee venom melittin.
1,2-Dipalmitoylphosphatidylcholine↗
[Alleviation of cisplatin toxicity by high-dose bismuth subnitrate and pharmacokinetics of bismuth subnitrate and cisplatin].
Twelve patients with several malignant neoplasms, including lung and gastrointestinal carcinoma were treated with high-dose Cisplatin and high-dose Bismuth Subnitrate. Therapeutic efficacy and protective effect of high-dose Bismuth Subnitrate on toxicity of Cisplatin were evaluated in twenty-five courses of treatment. The Pharmacokinetics of Bismuth Subnitrate and Cisplatin were also studied in several courses. Bismuth Subnitrate was administered orally at a dose of 150 mg/kg/day for 10 days and a dose of 80-150 (Mean 108) mg/m2 of Cisplatin was administered intravenously on the day six of Bismuth Subnitrate administration. Toxicities of high-dose Cisplatin were minimal under administration of high-dose Bismuth Subnitrate and therapeutic efficacy was observed in several patients. The pharmacokinetics of Bismuth Subnitrate in plasma and urine demonstrated that 10 days administration of high-dose Bismuth Subnitrate was appropriate to maintain adequate concentration of Bismuth for preinduction of Metallothionein in organs. The pharmacokinetics of Cisplatin in plasma and urine demonstrated that deposition of total and ultrafilterable (free) platinum in blood were well described by a biphasic manner with a very rapid first phase and a very prolonged second phase, and that urine excretion of platinum was similar to the conventional manner. This study demonstrated that concurrent administration of high-dose Bismuth Subnitrate can permit the administration of high-dose Cisplatin with minimal toxicity and appropriate antitumor effect.
Adult↗
In vitro metabolism of testosterone on hepatic tissue of chicken (Gallus domesticus).
Among the subcellular fractions of chicken liver homogenates, the microsomal and cytosol fractions were most active in metabolism of testosterone with mutually different enzymological features. On the other hand, the nuclear and mitochondrial fractions had far lower activity of metabolizing the steroid. Metabolism by the cytosol fraction: the following steroids were identified as the metabolites of testosterone. 5 beta-Dihydrotestosterone (17 beta-hydroxy-5 beta-androstan-3-one), 5 beta-androstane-3 alpha,17 beta-diol and its 3 beta-epimer, 3 alpha-hydroxy-5 beta-androstan-17-one and its 3 beta-epimer and 5 beta-androstanedione. Metabolism by the microsomal fraction: from testosterone under aerobic condition, androstenedione was obtained as the major metabolite, besides the minor polar metabolites, production of which diminished when incubated in the atmosphere of carbon monoxide. From the results, testosterone was accepted to be firstly converted by the cytosol fraction into 5 beta-dihydrotestosterone which was then reduced to 5 beta-androstane-3 alpha,17 beta-diol and its 3 beta-epimer. These diols were further converted partially to 3 alpha -and 3 beta-hydroxy-5 beta-androstan-17-ones. These pathways were supported by the results of our incubation study with 5 beta-dihydrotestosterone and 5 beta-androstanedione as substrates. By the microsomes, testosterone was aerobically and anaerobically transformed to androstenedione as the major metabolite. Throughout our incubation experiments, no 5 alpha-reduction of a delta 4-3-oxo-steroid was detected in the chicken liver.
Animals↗
Cardiac responses to hypoxia and hypercapnia in spinal man.
The purpose of this study was to evaluate the effect of interruption of the descending supraspinal sympathetic outflow on heart rate control during exposures to chemical stimuli. We investigated the heart rate responses to progressive isocapnic hypoxia and hyperoxic hypercapnia using the rebreathing technique and quantified the relationship between heart rate (HR), oxygen saturation (SaO2), alveolar PCO2 (PACO2), and minute ventilation (VE) in 16 chronic tetraplegic subjects with low cervical spinal cord transection. The HR responses were determined from the linear slopes of HR on SaO2 and HR on PACO2. We found that mean resting heart rate was within normal range; 66 +/- 3 (SEM) beats min-1. HR increased as oxygenation fell or CO2 tension rose. The mean tetraplegic delta HR/delta SaO2 was 0.83 +/- 0.14 beats min-1 per 1% fall in SaO2 and that of delta HR/delta PACO2 was 0.30 +/- 0.13 beats min-1 per mmHG rise in PACO2. The HR and VE responses to either hypoxia or hypercapnia were related in the tetraplegic subjects. We conclude that the stimulatory HR responses to chemical stimuli are not suppressed by cervical spinal cord transection. Thus, the descending sympathetic activity does not underlie the HR acceleration by chemical stimuli.
Adolescent↗
Gaucher's disease type I. Report of a case with prominent deposition of ceroid in splenic endothelial cells and intestinal smooth muscle fibers.
A case of type I Gaucher's disease in a 39-year-old male is reported. Autopsy showed marked enlargement of the spleen (3,070 g) and infiltration of typical Gaucher's cells in the spleen, liver, bone, marrow, gastrointestinal tract, lymph nodes and adrenal glands. The diagnosis of Gaucher's disease was ascertained by the very low beta-glucosidase activity of cultured subcutaneous fibroblasts and the high content of glucocerebroside in the spleen tissue. A peculiar finding in this case was prominent deposition of brown pigment in endothelial cells of the spleen and smooth muscles fibers of the gastrointestinal tract, urinary bladder and prostate. Histochemical examination revealed that the granules in endothelial cells and smooth muscle fibers were ceroid. Such deposition of ceroid has never been reported previously in Gaucher's disease. Ceroid deposition in generalized smooth muscle fibers is known as brown bowel syndrome, and is highly suggestive of severe vitamin E deficiency. Although other symptoms of vitamin E deficiency were not noticed in this case, some malnutritional condition might play a role in prominent deposition of ceroid in lysosomes, possibly together with deficient activity of a lysosomal enzyme.
Adult↗