The immunological properties of thyroglobulins (Tg) of individual patients, obtained from a thyroid tumor and its adjacent tissue were compared, using conventional or monoclonal antibodies against human Tg. The thyroid tumors studied were non-functioning thyroid carcinomas and functioning thyroid adenomas. In contrast to non-functioning tumors, Tg from the functioning tumors was generally iodinated at a level close to that of normal tissue, and Tg from the tissue adjacent to the tumors had a very low iodine content. The conventional antiserum and monoclonal antibodies, B2F, seemed to recognize the conformation of Tg, while C6G showed a high affinity to Tg even when unfolded or denatured. In most cases, Tg isolated from the tissue adjacent to a tumor showed a higher affinity to antibodies than Tgs of the tumor tissue, as determined by the inhibitional effect of these Tgs against the binding of standard Tg and antibody. Furthermore, the Tg of the adjacent tissue was immunologically different in nature from the standard Tg obtained from a normal thyroid gland. From these results, Tgs of tumor and the adjacent tissue in individual patients were heterogeneous in immunological property, regardless of iodine content.

Adenocarcinoma↗

PubMed1985

Purification and characterization of guinea pig liver morphine 6-dehydrogenase.

Morphine 6-dehydrogenase, which catalyzes the dehydrogenation of morphine to morphinone, has been purified about 440-fold from the soluble fraction of guinea pig liver with a yield of 38%. The purified enzyme was a homogeneous protein on polyacrylamide gel disc electrophoresis and isoelectric focusing. The molecular weight and isoelectric point of the enzyme were 29,000 and 7.6, respectively. The enzyme utilizes both NAD and NADP as a cofactor, and the Km values were 0.12 mM for NAD and 0.42 mM for NADP. The Vmax values for morphine were 588 milliunits/mg of protein (with NAD) and 1600 milliunits/mg of protein (with NADP). The Km values for morphine were 0.12 mM (with NAD) and 0.49 mM (with NADP). The enzyme also exhibited activity for morphine-related compounds: nalorphine, normorphine, codeine, and ethylmorphine; however, 7,8-saturated congeners such as dihydromorphine and dihydrocodeine were poor substrates. The enzyme was inactivated by removal of 2-mercaptoethanol from the enzyme solution. The inactivated enzyme was rapidly recovered by the addition of 2-mercaptoethanol. Phenylarsine oxide and CdCl2 (dithiol modifiers) inhibited competitively toward cofactor binding and noncompetitively toward morphine binding. These results suggest that the enzyme possesses the essential thiol groups, probably vicinal dithiol, at or near the cofactor-binding site. Using the partially purified enzyme, 8-(2-hydroxyethylthio)dihydromorphinone was isolated as the product and identified by UV, mass, and NMR spectra. It was confirmed that morphinone proposed as the dehydrogenation product was nonenzymatically and covalently bound to 2-mercaptoethanol. Accordingly, the isolated morphinone-2-mercaptoethanol conjugate must be formed by two steps: enzymatic production of morphinone from morphine and then nonenzymatic binding of 2-mercaptoethanol to morphinone.

Alcohol Oxidoreductases↗

PubMed1985

[The immunochemical properties of thyroglobulin in human thyroid tumors in reaction to rabbit anti-human normal thyroglobulin-serum].

Interactions between antiserum (rabbit anti-human normal thyroglobulin-serum) and human thyroglobulin preparations (obtained from the tissues of the normal thyroid gland, thyroid adenoma, and carcinoma) were compared by inhibition effect with the binding between 131I-labeled standard thyroglobulin and antiserum, set up by a double antibody RIA. Thyroglobulins isolated from normal glands (designated as Nor-Tg) have a high affinity to the antiserum. In contrast, thyroglobulins in follicular adenoma or adenomatous goiter (designated as Ad-Tg) decrease the potency of the affinity to the antiserum. Furthermore, thyroglobulins in papillary or follicular carcinoma (designated as Ca-Tg) markedly decrease such a potency. With the t-test, the inhibition curves of Nor-Tgs are almost parallel to each other. Most of the inhibition curves of Ad-Tgs and Ca-Tgs are not parallel to the curve of Nor-Tg 1 (P-value for non-parallelism less than or equal to 0.05). Therefore, it seems that Tg preparations obtained from tumor tissue are heterogeneous in terms of specificity and/or affinity to antiserum, judging from the results of the non-parallel inhibition curves. The present results also show that the contribution of iodine content in Tg has little or no effect on the nature of Tg-immunogenicity.

Adenoma↗

PubMed1985

Sclerosing hemangioma of the lung. Immunohistochemical characterization of its origin as related to surfactant apoprotein.

Lung tissues from 13 patients with pulmonary sclerosing hemangioma were studied with antibody against surfactant apoprotein, Factor VIII-related antigen, or lysozyme. Surfactant apoprotein was detected in the cytoplasm of the cells lining cystic spaces and papillary projections. Surfactant apoprotein was found in a small number of stromal cells with abundant eosinophilic or clear cytoplasm and round to oval nuclei, which were characteristic in pulmonary sclerosing hemangioma as the main component. Surfactant apoprotein was also found in the stromal cells with small, dark nuclei similar to the lining cells. The lining and stromal cells contained neither Factor VIII-related antigen nor lysozyme. Our demonstration of surfactant apoprotein in these cells provides further support for the idea that pulmonary sclerosing hemangioma primarily consists of epithelial cells with differentiation to type II pneumocytes, as was deduced from ultrastructural investigations.

Adolescent↗

PubMed1985

The breakdown of an emergency system following a gas explosion in Osaka and the subsequent resolution of problems.

Osaka, a modern urban metropolis in Japan, experienced a tragic gas explosion in 1970 when the dispatch room of the City Fire Department was in the process of being moved to a new building. Many unforseen problems arose during this disaster: eg, there was an overall lack of leadership, confusion of communication, a need for triage, and lack of control of mass media. The Osaka Medical Association organized a committee to resolve these problems. Their conclusions and recommendations were that a control headquarters be established at the scene of disaster, the number of ambulances and EMTs be increased, disaster tags be utilized, a special radio frequency be created, and a computer-aided command and control system for fire fighting and ambulance services be introduced. These recommendations have all been followed.

Adolescent↗

PubMed1985

Prevalence of a human retrovirus in native Japanese: evidence for a possible ancient origin.

The origin of a human retrovirus (ATLV or HTLV-I) is, at present, unknown although carriers of the virus have been found in Japan, the Caribbean basin and Africa. By means of a sero-epidemiological study, the Ainu people of Hokkaido, located in the northernmost island of Japan, were shown to have antibody to the virus in high frequency. Since the Ainu are regarded as descendants of the pre-agriculture native population of northern Japan, this finding appears to indicate that the retrovirus was already present in the aboriginal Japanese of prehistoric times.

Adolescent↗

PubMed1985

A field study of infection with human T-cell leukemia virus among asian primates.

Asian nonhuman primates were surveyed seroepidemiologically for natural infection with human T-cell leukemia virus (ATLV/HTLV) or a closely related agent. Materials from various primates (three genera [Macaca, Presbytis, and Hylobates], 17 species, totalling 1,079 animals) under natural conditions were obtained in the field study. Virus infection was determined by the indirect immunofluorescence test using HTLV-specific antigens. Animals seropositive for HTLV were found only among macaques originating from various localities, toque monkeys in Sri Lanka (17.5%), crab-eating macaques in Thailand (1.3%), stumptailed macaques in Thailand (1.5%), rhesus monkeys in Thailand (3.3%), and Celebes macaques in Indonesia (16.9%). Langurs and gibbons were seronegative. Thus the wide distribution of HTLV in nature among various macaques suggests that the introduction of this virus into primates occurred in ancient times.

Animals↗

PubMed1985

Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs.

Metabolic acidosis due to organic acids infusion fails to elicit hyperkalemia. Although plasma potassium levels may rise, the increase is smaller than in mineral acid acidosis. The mechanisms responsible for the different effects of organic acid acidosis and mineral acid acidosis remain undefined, although dissimilar hormonal responses by the pancreas may explain dissimilar hormonal responses by the pancreas may explain the phenomena. To test this hypothesis, beta-hydroxybutyric acid (7 meq/kg) or hydrochloric acid (3 meq/kg) was infused over 30 min into conscious dogs (n = 12) with chronically implanted catheters in the portal, hepatic, and systemic circulation, and flow probes were placed around the portal vein and hepatic artery. Acid infusion studies in two groups of anesthetized dogs were also done to assess the urinary excretion of potassium (n = 14), and to evaluate the effects of acute suppression of renal electrolyte excretion on plasma potassium and on the release/uptake of potassium in peripheral tissues of the hindleg (n = 17). Ketoacid infusion caused hypokalemia and a significant increase in portal vein plasma insulin, from the basal level of 27 +/- 4 microU/ml to a maximum of 84 +/- 22 microU/ml at 10 min, without changes in glucagon levels. By contrast, mineral acid acidosis of similar severity resulted in hyperkalemia and did not increase portal insulin levels but enhanced portal glucagon concentration from control values of 132 +/- 25 pg/ml to 251 +/- 39 pg/ml at 40 min. A significant decrease in plasma glucose levels due to suppression of hepatic release was observed during ketoacid infusion, while no changes were observed with mineral acid infusion. Plasma flows in the portal vein and hepatic artery remained unchanged from control values in both acid infusion studies. Differences in renal potassium excretion were ruled out as determinants of the disparate kalemic responses to organic acid infusion compared with HCl acidosis. Evaluation of the arteriovenous potassium difference across the hindleg during ketoacid infusion demonstrates that peripheral uptake of potassium is unlikely to be responsible for the observed hypokalemia. Although the tissue responsible for the different kalemic responses could not be defined with certainty, the data are compatible with an hepatic role in response to alterations in the portal vein insulin and/or glucagon levels in both acid infusion studies. We propose that cellular uptake of potassium is enhanced by hyperinsulinemia in ketoacid infusion, and release of potassium results from increased glucagon levels in HCl acidosis. Whether the changes in plasma potassium that other types od organic acid acidosis produce are accounted for by a similar hormonal mechanism remains to be determined.

3-Hydroxybutyric Acid↗

PubMed1985

Effects of atropine and gastric inhibitory polypeptide on hepatic glucose uptake and insulin extraction in conscious dogs.

Previous studies comparing the effects of oral, intraportal, and peripheral venous administration of glucose in conscious dogs demonstrated a significant increase in hepatic extraction of insulin only after oral glucose, but similar hepatic uptake of glucose after oral and intraportal glucose, which was greater than that after peripheral intravenous glucose infusion. This study evaluated the effect of atropine blockade of the parasympathetic nervous system on the increased fractional hepatic extraction of insulin and the role of gastric inhibitory polypeptide (GIP) on augmented hepatic uptake of oral glucose in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery, and catheters in the portal and hepatic veins and carotid artery. Since atropine infusion decreased absorption of glucose, and in order to achieve comparable portal vein levels of glucose and insulin, the dogs receiving atropine were given 1.9 +/- 0.1 g/kg glucose, compared with the control dogs who received 1.1 +/- 0.1 g/kg. The percentage of the glucose load that was absorbed was greater in the dogs not given atropine (80 +/- 4 vs. 44 +/- 7%), but because of the different loads, the absolute amount of glucose absorbed was similar in both groups (20.2 +/- 1.6 vs. 21.7 +/- 4.1 g). Although delayed by atropine, the peak portal vein glucose and insulin concentrations and the amounts presented to the liver were similar in both groups. However, the increased portal vein plasma flow and fractional hepatic extraction of insulin observed after oral glucose was not observed in the dogs infused with atropine. The net hepatic glucose uptake after oral glucose was significantly less at 10, 20, and 45 min in the atropine-treated dogs, and the area under the curve over the 180-min period was 44% less. However, the latter was not statistically significant. Infusion of GIP with peripheral intravenous glucose did not increase hepatic uptake of glucose or the fractional hepatic extraction of insulin compared with peripheral intravenous glucose alone. These results indicate an important role for parasympathetic innervation in the augmented fractional hepatic extraction of insulin, and increased portal vein plasma flow after oral glucose. Although a relationship between the augmented fractional extraction of insulin and the net hepatic glucose uptake may exist, it does not necessarily indicate that the former is required for the latter. Such parasympathetic innervation may be involved in the greater removal of glucose by the liver after oral compared with peripheral glucose administration. The augmented hepatic uptake of glucose and fractional hepatic extraction of insulin after oral glucose doesn not appear to be mediated by gastric inhibitory polypeptide.

Administration, Oral↗

PubMed1985

Effect of metabolic clearance rate and hepatic extraction of insulin on hepatic and peripheral contributions to hypoglycemia.

Effects of alterations in metabolic clearance rates, hepatic extraction, and plasma concentrations of insulin on hepatic and peripheral contribution to hypoglycemia and glucose counterregulation were studied in conscious dogs. Since insulin and sulfated insulin had markedly different metabolic clearance rates (34 +/- 1 vs. 16 +/- 1 ml/kg per min, respectively) and fractional hepatic extraction (42 +/- 1% vs. 15 +/- 2%, respectively), biologically equivalent amounts infused intraportally produced twofold higher hepatic vein and artery sulphated insulin concentrations and concentrations that were 30% higher in the portal vein. This significantly larger arterial/portal concentration ratio (0.67 vs. 0.45, respectively) permitted assessment of differential distribution of insulin on glucose turnover using [3-3H]glucose. Insulin and sulfated insulin (1 and 2 mU/kg per min) caused similar hypoglycemia. While insulin transiently suppressed glucose production and increased glucose disappearance, sulfated insulin had significantly greater effects on glucose disappearance and clearance, without suppression of glucose production. Despite similar hypoglycemia, sulfated insulin caused greater increment in glucagon. 3 mU/kg per min insulin caused more rapid and greater hypoglycemia, greater glucose clearance, and greater glucagon increments without suppression of glucose production, which indicates that with larger doses of insulin counterregulation can absolutely mask the suppressive effect of insulin. The effects of insulin and sulfated insulin were evaluated using euglycemic clamp to eliminate interference from stimulated counterregulation. Sequential infusion of 1 and 2 mU/kg per min of both insulins suppressed endogenous glucose production to 0 at 150 min, which indicates that the apparent lack of a hepatic effect of sulfated insulin during hypoglycemia was masked by greater counterregulation. This greater counterregulation may reflect greater peripheral glucose clearance, and prevented greater hypoglycemia than after the same insulin doses. The results indicate that the different rates of removal and the total metabolic clearance rate caused different concentrations and relative distribution between the portal and arterial blood compartments, leading to the significantly different contributions by the liver and peripheral tissues to the same hypoglycemia.

Animals↗

PubMed1985

The biological actions of deoxypodophyllotoxin (anthricin). I. Physiological activities and conformational analysis of deoxypodophyllotoxin.

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Animals↗

PubMed1985

Morphology of ectopic ventricular beats and their relationship to ventricular tachycardia in acute myocardial ischemia.

The features of ventricular arrhythmia in coronary spasm induced by ergonovine were examined to elucidate the characteristics of ventricular arrhythmia in acute myocardial ischemia. The coupling intervals and configurations of the QRS wave of the premature ventricular beats (PVBs) were extremely variable, even in the same individual and at the closer time phases. The prematurity index (R-R'/QT) of PVBs with the right bundle branch block (RBBB) pattern was significantly smaller than with the left bundle branch block (LBBB) pattern. The vulnerability index (R-RX QT/R-R') of PVBs with the RBBB pattern was significantly larger than with the LBBB pattern. The incidence of PVBs with the RBBB pattern (50.4%) was slightly larger than with the LBBB pattern (40.5%). PVBs deteriorated into ventricular tachycardias (VTs) in 29 (24.8%) of 117 cases with the RBBB pattern and in 11 (11.7%) out of 94 cases with the LBBB pattern. Thus, PVBs with the RBBB pattern were more likely to progress to VT than with the LBBB pattern. But it is difficult to assess the clinical significance of PVBs from their QRS morphology alone, because 11 (27.5%) of 40 cases of VT were initiated by PVBs with the LBBB pattern.

Acute Disease↗

PubMed1985

[Cerebellopontine angle surgery and intraoperative monitoring of the auditory function. The significance and interpretation of changes of evoked potentials based on animal experimental models].

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Animals↗

PubMed1985

Deterioration of auditory evoked potentials during cerebellopontine angle manipulations. An interpretation based on an experimental model in dogs.

Evoked action potentials from the internal auditory meatus portion of the cochlear nerve (IAM-EAP's) and brain-stem auditory evoked potentials (BAEP's) from the vertex were simultaneously recorded during cerebellopontine angle (CPA) manipulations (retractions of the cerebellar hemisphere and the cochlear nerve) in dogs. The BAEP changes noted in these dogs were the same as those seen in patients. The IAM-EAP's showed graded deterioration related to BAEP changes. The results are as follows: Prolongation of the I-V interpeak latency of BAEP's, the most common finding during CPA manipulations, is the reflection of prolongation of the I-II interpeak latency, which is caused by conduction impairment or block of the nerve impulses between the extracranial portion of the cochlear nerve and the brain stem. The operative manipulations representing stretch or compression injury to the cochlear nerve in the CPA leads to an acute traumatic cranial nerve root lesion--a retrocochlear lesion. The obliteration of all BAEP components including wave I cannot be caused by conduction block. This is caused by occlusion of the internal auditory artery. Wave I of the BAEP's and the P1-N1 complex of the IAM-EAP's are important indicators of cochlear blood flow during surgical intervention. As possible causes of internal auditory artery obstruction, mechanical distortion of the relationship between the anterior inferior cerebellar artery (AICA) and the internal auditory artery at the junctional portion, mechanical vasospasm of the AICA-internal auditory artery complex, and ensuing no-reflow phenomena are discussed. Evoked action potentials are expected to be a useful intraoperative real-time monitor during CPA surgery that can detect rapid changes derived from cochlear artery insufficency. The real-time aspects can overcome some of the disadvantages of BAEP monitoring.

Animals↗