D-Penicillamine toxicity in mice. II. Concentrations of Cu, Zn, and Fe related to development of toxicity.
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Biomedical subjects
Publications and source records attributed to T Takeda.
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In the rat kidney the presence of the kallikrein-like pro-phe-argnaphthylester esterase activity was demonstrated by a simultaneous coupling azo dye method. The enzyme was identified as a serine-protease because it was inhibited by preincubation with diisopropyl-fluorophosphate and unaffected by sodium iodoacetate. Since kallikrein is a serine-protease and prophe-arg-naphthylester is a synthetic and sensitive substrate for kallikrein, the enzyme activity revealed by this method was considered to represent kallikrein, although non-kallikrein esterase activity is not totally excluded. The enzyme activity was localized mainly in the outer stripe of the outer medulla, with focal extensions primarily only in the lower half of the cortex corresponding to the medullary rays.
Intracellular recording of dark adapted photoreceptors of Hermissenda crassicornis (Opisthobranchia, Gastropoda, Mollusca) revealed the occurrence of depolarizing waves even after blockade of synaptic transmission and postsynaptic potentials by application of low Ca2+ and high Mg2+ solution. Dim illumination increased the frequency of depolarizing waves. These observations show that Hermissenda photoreceptors have discrete waves which have been demonstrated mainly in arthropod photoreceptors. An histogram of intervals between successive discrete waves under continuous dim illumination was exponential, which is characteristic of a Poisson process. Frequency of discrete waves increased linearly depending on numbers of incident photons to the eye. Comparison of probabilities of eliciting a response to brief dim flashes of various intensities to theoretical Poisson sum curves, together with statistical analysis, indicate that the absorption of single photon is sufficient to evoke a discrete wave.
Morphological studies on spontaneous systemic amyloidosis were conducted on 222 senescence-accelerated mice (SAM) (P) and on 150 mice in the senescence-resistant series (R). Among the pathologic findings, amyloidosis showed the highest incidence in both SAM (79.7%) and R (32.7%). Although an extensive deposition of amyloid was evident in some aged mice in the R series, a more severe amyloidosis occurred with a higher incidence in the P series. There was a statistical significance between the incidence of amyloidosis and age, in both the P and R series. There were no differences in organ distribution and mode of amyloid deposition between the P and R series or between the sexes. In about 60% of the amyloid-positive cases in the 28 killed SAM and 7 mice in the R series, there were no signs of inflammation or neoplasm. The morphological features in SAM more closely resembled those seen in cases of murine spontaneous senile amyloidosis than the features seen in cases of experimentally induced amyloidosis. This model is expected to be a valuable tool with which to assess the relationship between amyloid deposition and the aging process or senescence, perhaps even cases of human senile amyloidosis.
1. Responses to light of an identified motorneuron (LP1) were recorded simultaneously with those of an identified Hermissenda photoreceptor (the lateral Type B) following three days of training with paired light and rotation. 2. These responses were significantly different when compared to responses of cells from animals trained with unpaired stimuli and from naive animals. 3. The differences of the LP1 responses can be explained as a consequence of the photoreceptor response changes. 4. The same training with paired stimuli has been shown to produce behavioural changes which satisfy criteria for vertebrate associative learning. 5. The observed neural correlates are consistent with previous findings which indicate that membrane changes within the Type B cell bodies play a causal role in associative learning of the nudibranch mollusc, Hermissenda crassicornis.
The palmar aponeurosis removed from ten patients with Dupuytren's contracture was studied using morphological and biochemical approaches. The histological characteristic of Dupuytren's contracture is the presence of numerous nodules among the lamellar structures of the collagen fibres. In the nodules, there are many active fibroblasts which are surrounded by immature fibres and metachromatic substances demonstrated by toluidine blue staining. Ultrastructurally, the active fibroblasts have the characteristics of myofibroblasts, as previously reported by Dr. Gabbiani. We found that some fibroblasts have intracellular collagen fibrils in the cytoplasm. When assayed by Siegel and Martin's method, lysyl oxidase activity of the palmar aponeurosis was significantly higher in Dupuytren's contracture than in normal hands. Biochemical studies such as electrophoretic analysis of mucopolysaccharides, determination of uronic acid and collagen contents were undertaken to compare the aponeurosis of Dupuytren's contracture with normal cases. The uronic acid contents were higher in Dupuytren's contracture than in the controls. However, no difference between the two groups was found in the collagen contents and in the composition of the mucopolysaccharides. These characteristic features; existence of myofibroblasts and intracellular collagen fibrils and increase in the activity of lysyl oxidase probably play a significant role in the establishment of flexion contracture of the fingers in Dupuytren's contracture.
1 The anti-hypertensive effects and safety of labetalol have been evaluated in multicentre clinical trials in Japan based on unified study protocols. The results of three studies are reported. 2 A total of 178 patients with essential hypertension were treated with labetalol for 12 weeks, 127 of them with labetalol alone (monotherapy) and the other 51 with labetalol plus diuretics (combined therapy). 3 Satisfactory antihypertensive effects were achieved in 76 of the 119 assessable patients in the monotherapy group and 25 of the 49 in the combined therapy group. The mean daily doses of labetalol were 329 mg in the monotherapy group and 374 mg in the combined therapy group. Seven patients (six in the monotherapy group; one in the combined therapy group) were withdrawn from the trials due to side-effects. 4 Sixty-one patients with hypertension were treated with labetalol alone or combined with diuretics for 6 months or longer. In most of these patients, good blood pressure control was achieved. No patients had to discontinue the treatment due to side-effects. The mean daily doses of labetalol were stabilised in and after week 8 of the treatment at an average of 260 mg in the monotherapy and 450 mg in the combined therapy. Tolerance to the anti-hypertensive effect did not develop. 5 Thirty patients with phaeochromocytoma were treated with labetalol and good blood pressure control was achieved in 21 of them. The effects of labetalol were better in patients with predominantly adrenaline-secreting tumours, and better in patients with sustained hypertensive type than in those with paroxysmal hypertensive type.
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The activity of serum angiotensin-converting enzyme (S-ACE) was determined spectrophotometrically in 45 patients with hyperthyroidism (30 untreated and 15 treated and euthyroid patients), 14 patients with hypothyroidism, and 135 normotensive healthy subjects. S-ACE was significantly higher in the patients with untreated hyperthyroidism (51.6 +/- 1.9 less than SE greater than nmol.min/ml) than in the healthy controls (28.6 +/- 0.6 nmol.min/ml; P less than 0.001). On the other hand, S-ACE was found to be within the normal range in patients with hypothyroidism (23.2 +/- 1.3 nmol.min/ml). In patients with hyperthyroidism, S-ACE gradually fell into the normal range as the thyroid function became normalized, and there were significant positive correlations between S-ACE and the plasma T3 or T4 concentration (r = 0.60 and P less than 0.001; r = 0.61 and P less than 0.001, respectively ). S-ACE had no definite relation to blood pressure, serum glutamic oxaloacetic acid transaminase, or glutamic pyruvic acid transaminase. When the physicochemical characteristics of the enzyme in the sera of hyperthyroidism patients were compared with those in sarcoidosis patients, similar peak activities of S-ACE on gel chromatography and identical Michaelis constants were obtained; the effects of ethyldiaminetetraacetic acid, SQ14225, and pH on the enzymatic reaction were also similar in both diseases. Thus, hyperthyroidism is considered to be one of the diseases in which S-ACE is elevated. The elevation of S-ACE might be directly or indirectly related to the hyperthyroid state. In addition, it is suggested that the enzyme characteristics are identical in hyperthyroidism and sarcoidosis.
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Altered prostacyclin metabolism may underlie essential hypertension. In this study, responses of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha: a stable metabolite of prostacyclin) to infused norepinephrine (NE) were compared in 14 normotensive subjects (NT) and 20 untreated patients with essential hypertension (EH). In addition, changes in systemic hemodynamics following NE-infusion were compared with changes in plasma 6-keto-PGF1 alpha. The subjects were all hospitalized and placed on a diet containing 6-8 g of salt per day. Blood pressure was recorded directly through the brachial artery, cardiac output (CO) was determined with the dye-dilution technique using cuvette and total peripheral vascular resistance (TPR) was calculated before and 60 min after NE-infusion. Arterial plasma 6-keto-PGF1 alpha was also determined before and after NE-infusion. The rate of NE-infusion was adjusted to elevate mean arterial pressure (MAP) by 10-15%. Plasma 6-keto-PGF1 alpha was radioimmunoassayed. Elevation of MAP was 13.0 +/- 1.2 (SE) in NTs and 11.7 +/- 1.4% in EHs. After NE-infusion, CO and TPR both significantly increased in NTs, while only CO increased significantly in EHs. Changes in CO and TPR were both significantly different between the two groups (p less than 0.01). Initial plasma 6-keto-PGF1 alpha was reduced in EHs as compared with NTs (174 +/- 15 vs 295 +/- 41 pg/ml, p less than 0.02). However, during NE-infusion, the increase in plasma 6-keto-PGF1 alpha was greater in EHs than in NTs (p less than 0.01). There was a significant negative correlation between changes in TPR and plasma PG (r = -0.36, p less than 0.05). The results indicate that responses of systemic hemodynamics and plasma 6-keto-PGF1 alpha to infused NE are different in the NT and EH groups, and that the absence of changes in TPR in EHs may be related to a marked increase in circulating prostacyclin. These findings, together with the reduced initial levels of plasma 6-keto-PGF1 alpha in EHs, probably represent altered prostacyclin metabolism in essential hypertension.
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We conducted a therapeutic trial with cefmenoxime in the field of otorhinolaryngology on a total of 14 subjects including 7 cases of otitis media, 5 cases of peritonsillar abscess, 1 case of chronic sinusitis and 1 case of congenital aural fistula. 1. The effective rate for peritonsillar abscess was extremely high being judged 'markedly effective' in 3 cases and 'effective' in 2 cases. 2. The effective rate for otitis media was also remarkably high; it was judged effective in 85.7% of the cases. It is thought that this is probably due to the fact that therapy and supervision were carried out on inhospital patients. 3. The 1 case of chronic sinusitis and the 1 case of congenital aural fistula were each judged 'effective' and 'markedly effective'. The only side effect observed was a slight case of skin eruption in 1 of the patients.
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A protein was isolated from amyloid fibrils extracted from the liver of an inbred strain of mice (senescence-accelerated mouse) characterized by a high frequency of age-associated systemic amyloidosis. This 5200-dalton protein has a different electrophoretic mobility from the murine protein AA. Its amino acid composition also differs from that of murine protein AA and from the amyloid protein in SJL/J, the only strain for which the spontaneous occurring amyloid has been characterized biochemically and immunochemically. Sequence analysis of the protein also revealed a blocked N-terminus. Immunochemically, the protein did not react with antisera against mouse immunoglobulin components. The antiserum against the protein did not react with murine protein AA, mouse immunoglobulin components, or with mouse normal liver protein. Thus, we have characterized an amyloid protein that is distinguishable from previously reported murine amyloid proteins and is not related to immunoglobulins. The possible relationship between this protein, designated ASSAM, and ASc in human senile cardiac amyloidosis is considered.