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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.

The effects of prostaglandin (PG) I2 and the agents which affect PG and thromboxane (TX) generating systems on cyclical reductions of blood flow in the partially constricted coronary artery of anesthetized dogs were examined. Cyclical reductions were eliminated by PG I2, but not by PG D2, and were augmented by 15-hydroperoxy arachidonic acid and tranylcypromine that inhibited synthesis of PG I2. The cyclical reductions were also eliminated by Cu-chlorophylline that inhibited synthesis of PG E2 and accelerated synthesis of TX A2, but were not by imidazole and 1-methyl imidazole that inhibited synthesis of TX A2. The results in this and in the previous studies indicate that not TX A2 but PG E2 participates as an inducer while PG I2 participates as an inhibitor in cyclical reductions of coronary blood flow.

Hemodynamic responses to isometric exercise were compared between 9 normotensive subjects (NT) and 16 patients with essential hypertension (EH) before and during high salt intake. The subjects were hospitalized and placed on a diet containing 6g of salt per day. Baseline hemodynamic studies were carried out on supine subjects before and 3 min after isometric exercise (30% of the maximal voluntary handgrip). Plasma concentration of norepinephrine (PNE) was also measured. Brachial arterial pressure was directly recorded and cardiac output (CO) was measured by the dye-dilution technique using a cuvette. The hemodynamic studies were repeated on the 5th day of a high salt diet (16g of salt per day). Retention of sodium was calculated on a daily basis by measuring the actual intake of sodium and 24-hour urinary excretion of sodium. Pressor responses to isometric exercise were significantly greater in the EH than in the NT group. Patterns of hemodynamic responses were different in the 2 groups, i.e., the elevation of arterial pressure was maintained by an increase in CO in the NTs, while it was maintained by increases in CO and total peripheral vascular resistance (TPR) in the EHs. The increase in CO was significantly greater in the NT than in the EH group [15 +/- 3 (mean +/- SE) vs 7 +/- 1%, p less than 0.05]. Although the salt loading reduced heart rate similarly in both groups (-9.0 +/- 2.1, p less than 0.01, in the NTs and -11.9 +/- 2.9%, p less than 0.01, in the EHs), the high salt diet did not significantly alter mean arterial pressure (MAP), CO or TPR in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Crackles were recorded from six patients, four with tuberculosis and two with chronic bronchitis. It was observed by waveform and spectral analysis that most of the frequency components of a crackle were limited within a range of 0.1 to 1 kHz. Characteristically, waveforms of crackles were separable into two segments, initial "starting segments" and subsequent "decay segments." It is suggested that the former represents a shock wave caused by an abrupt opening of the airway and that the latter is a damped sinusoid caused by this shock wave exciting a resonator in the lung. It is speculated that the starting segment is determined by the pressure ratio at the site of the airway opening, and the decay segment by the resonant frequency and the quality factor of the resonator. Because transmission of a crackle is highly directional the waveforms recorded on the chest wall are modified by the positional relationship between the sound source and the microphone.

A sensitive chromogenic assay for p-hydroxybenzoic acid, laccase activity, and angiotensin I converting enzyme activity is described. The method relies on the oxidative coupling of 2,2'-azino-di(3-ethylbenzothiazoline-6-sulfonic acid) and p-hydroxybenzoic acid. Lacase catalyzes the formation of a deep-purple compound, which shows a broad absorption between 530 and 630 nm with a maximum at 593 nm (the molar absorption coefficient was calculated to be 26,900). By means of this chromogenic coupling reaction, a spectrophotometric method for the assay of laccase activity and estimation of the amount of p-hydroxybenzoic acid was developed; laccase activity in the range 1-10 pmol protein could be estimated with a 10-min incubation time. Angiotensin I converting enzyme was also assayed by the laccase-catalyzed indicator reaction, using p-hydroxybenzoyl-glycyl-histidyl-leucine as the substrate, and N alpha-carbobenzoxy amino acid urethane hydrolase as the coupling enzyme.

Induction of 6-thioguanine (TG) resistance by chemical mutagens was examined in a line of cells derived from a human epithelial teratocarcinoma cell clone. The cells, designated as P3 cells, have a stable diploid karyotype with 46(XX) chromosomes, including a translocation between chromosomes 15 and 20. Efficient recovery of TG-resistant mutants induced by the direct-acting mutagens: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10 -tetrahydrobenzo[a]pyrene (BPDE); and benzo[a]pyrene (B[a]P); activated in a cell-mediated assay, required an expression time of 7 days and a saturation density of 2 X 10(4) cells/60-mm petri dish. The TG-resistant mutant cells induced by MNNG and BPDE maintained their resistant phenotype 4-6 weeks after isolation. This mutant phenotype was associated with a more than 10-fold reduction in hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity relative to that of the parental P3 cell line, which was shown to catalyze the formation of 4.6 pmoles inosine-5'-monophosphate (IMP)/min/microgram protein. Induction of TG resistance was also observed in P3 cells cocultivated in a cell-mediated assay with human breast carcinoma cells, which are capable of polycyclic aromatic hydrocarbon (PAH) metabolism, after treatment with the carcinogenic PAHs: B[a]P, chrysene, 7,12-dimethylbenz[a]anthracene (DMBA), and 3-methylcholanthrene (MCA). The degree of mutant induction in this assay was related to the carcinogenic potency of these PAHs in experimental animals. The most potent mutagen was DMBA, followed in decreasing order by MCA, B[a]P, and chrysene. DMBA, at 0.4 microM, increased the frequency of mutants for TG resistance from 2 for the control to about 200 TG-resistant mutants/10(6) colony-forming cells (CFC). Benzo[e]pyrene (B[e]P) and pyrene, which are not carcinogenic, were not effective in the assay. None of the PAHs was mutagenic in the P3 cells cultivated in the absence of the PAH-metabolizing cells. These results indicate that the P3 cells can be useful for the study of mutagenesis at the HGPRT locus by direct-acting chemical mutagens, as well as by chemicals activated in a cell-mediated assay.

Slow cyclic fluctuations were frequently observed in blood pressure of the distal portion of the partially constricted coronary artery of anesthetized dogs. Lowering the mean peripheral coronary blood pressure below 50% of the control value was required for initiation of fluctuations. Each fluctuation in pressure was composed of 2 phases; the phase of rise and phase of fall. Almost invariably, the phase of rise and phase of fall were accompanied by increase and decrease in coronary blood flow, respectively. When the mean peripheral coronary blood pressure fell below 20% of the control value during the phase of fall, systolic bulge and elevation of the ST segment of surface ventriculra electrocardiogram occurred. Period duration of each fluctuation ranged from 30 sec to 14 min. The cyclic fluctuations in pressure, flow, electrocardiogram and left ventricular wall motion were eliminated by nitroglycerin, but were not affected by phentolamine, propranolol, atropine, cervical vagotomy, and stellectomy.

By in situ hybridization on chromosome, phytohemagglutinin (PHA)-stimulated lymphocytes obtained from normal individuals showed slight polymorphism in terms of distribution of rDNA among Nucleolar Organizer Region (NOR) chromosomes probably due to racial differences, although their interindividual distinct polymorphism had been reported in the U.S.A. Three chronic and one acute myelogenous leukemias (CML and AML) and one chronic monocytic leukemia (CMoL) were also analysed for the distribution of rDNA among NORs. The distribution patterns in leukemia cells were found to be significantly different from those in the cells of normal individuals. Although genetic alteration of normal leukocytes was not disregarded, the changes of rDNA distribution in leukemia cells are demonstrated in this study. The Ph1 chromosome in CML carried a greater amount of rDNA. The rDNA distribution in Ph1-negative cells obtained from patients showed almost the same pattern as that of Ph1-positive cells. In AML, the t(8;21) carried a smaller amount of rDNA. Trisomic chromosome 21 in CMoL carried extra rDNA copies on its NOR. Based on these data, leukemia cells seem to show variability of rDNA distribution especially on marker chromosomes, contrary to the non-polymorphic patterns of normal lymphocytes. Thus a strong relationship between marker formation and abnormal distribution of rDNA could be suggested.

There have been only two reports of severe hepatotoxic reaction caused by meglumine iodipamide. Lately we experienced such a reaction in an 66-year old female with chronic intrahepatic cholestasis. After drip infusion cholangiography was performed by infusing 40 ml. of 50% meglumine iodipamide (Biligrafin) intravenously, the patient developed nausea and abdominal pain. Her serum transaminase rose to more than 2,000 K-A units on the third day and gradually returned to normal by the 18th day. The macrophage migration inhibition test of her blood was positive for meglumine iodipamide. Accordingly some delayed type of hypersensitivity in the above reaction could be considered. When a larger amount than a recommended dose of meglumine iodipamide is infused in cholangiography, a severe hepatotoxic reaction might be induced, especially in icteric cases.

Clinical findings and structural alterations of the kidney in 3 patients with Takayasu's arteritis (TA) and associated glomerulonephritis are described. Clinical evidence of renal disease included persistent proteinuria and microscopic hematuria in all patients. Renal histology showed proliferative glomerulonephritis in 2 of the 3 patients. In 1 patient in whom sequential examination of the kidney was possible, glomerular changes had progressed in severity, in parallel with the expansion of arterial damage of TA. Prednisolone therapy induced a complete disappearance of systemic symptoms of TA and an improvement of proteinuria and hematuria. These findings suggest that TA, which quite possibly results from an immune response to disseminated antigen(s), may occasionally induced glomerulonephritis as a part of its histological expression.

To investigate myeloid cell maturation, we established a panel of monoclonal antibodies that recognize myeloid cell nuclear antigens. One of these monoclonal antibodies was used to purify a specific protein complex (PC) from a human spleen. This PC, which is present at high levels in peripheral blood monocytes and granulocytes, contains a protein that is the cystic fibrosis (CF) antigen. The purified PC was shown to inhibit the activity of casein kinase I and II but not cAMP-dependent protein kinase, protein kinase C, v-abl tyrosine kinase, or insulin receptor tyrosine kinase. The observed Ki values for casein kinases I and II purified from several sources were 1 microM or less. Furthermore, the addition of the purified PC to a nuclear extract from human cells was able to prevent protein kinase-mediated stimulation of RNA polymerase activity. The unique inhibitory character of the PC and its elevated levels in monocytes and granulocytes and of the CF antigen in CF patients implies that this complex may be associated with myeloid cell functions and perhaps with the cause or consequence of the clinical manifestations of CF.

The effects of a stable prostaglandin I2 analogue, ZA 36374, on recurring reduction of blood flow in the partially constricted canine coronary artery were compared with those of prostaglandin I2. Intravenous bolus injections of 0.3 micrograms/Kg ZK 36374 and 0.15 micrograms/Kg prostaglandin I2 eliminated the recurring reductions. Intravenous infusion of 0.1 micrograms/Kg/min ZK 36374 and 0.01 micrograms/Kg/min prostaglandin I2 also eliminated the recurring reductions. The results indicate that although weaker than prostaglandin I2, ZK 36374 is effective in eliminating recurring reduction in coronary flow related to coronary vasospasm and/or thrombosis.

Electrographic changes associated with cyclical reduction of blood flow in partially constricted one or two coronary arteries of anesthetized dogs were examined. In the preparations with single vessel constriction, cyclical ST elevation occurred along with cyclical reduction of coronary blood flow below 25% of the control value. The ST elevation was associated with reciprocal ST depression in the contralateral ventricular surface. In the preparations with double vessel constriction, cyclical reduction of flow frequently occurred in both vessels. The reduction of flow in one vessel occurred not synchronously with that in another vessel in the majority of preparations. The reduction of flow in both vessels was associated with ST elevation in the corresponding areas of the left ventricle. Premature ventricular contractions frequently occurred at the beginning of or immediately after disappearance of ST elevation, or when ST elevation persisted for more than 10 min. Ventricular fibrillation frequently occurred in the preparations with double vessel constriction.

This study examined the immunohistochemical findings in renal arterioles from biopsy specimens, and related the findings to those of light and electron microscopy. The renal biopsy specimens were obtained from 57 normotensive patients with primary glomerular diseases or idiopathic hematuria, 14 hypertensive patients with associated primary glomerular diseases, 4 patients with essential hypertension and 1 with primary aldosteronism. The tissue slices for the immunohistochemical study were processed with FITC-labelled rabbit antihuman immunoglobulin antisera. Deposits of IgM were detected on the renal arterioles in 16 of the hypertensive patients (84%), but in only 7 of the normotensive patients (12%). The difference in incidence was significant (p less than 0.005). C3 was almost always deposited in the renal arterioles regardless of whether the patient was hypertensive or normotensive. IgG, IgA or fibrinogen were demonstrated only in a few cases, and albumin in no cases. When sections stained with horseradish peroxidase-conjugated anti-IgM antibody were compared under a light microscope with the adjacent PAS-stained sections, it was demonstrated that IgM was deposited only in the portions of the arteriolar walls which showed hyalinotic changes. Electron microscopic examination demonstrated that electron-dense deposits in the subendothelial or intercellular spaces of arteriolar walls were more frequent in the hypertensive patients (11 of 14 cases, 79%) than in the normotensive patients (5 of 18 cases, 28%, p less than 0.05). The deposits appeared to be similar to those which are often found in the glomeruli of patients with glomerulonephritis and which are considered to be immune complexes. These findings suggest that some immunologic mechanism mediated by IgM antibody might be a factor in the development of hypertensive vascular lesions.

The dilatation of the aortic valve portion was evaluated by angiography in 70 patients with aortitis syndrome (Takayasu's arteritis). The diameter at aortic valve commissure was 20 +/- 2.8 min/M2 (NS, vs control) in 46 patients without aortic insufficiency (AI), 23 +/- 2.0 (p less than 0.02, vs without AI) in 11 patients with AI (I or II in grade), 27 +/- 2.0 (p less than 0.01, vs I or II in grade) in 13 patients with AI (III or IV in grade). The diameter was 20 +/- 2.0 in 13 normal control cases and 20 +/- 4.0 in 6 patients with rheumatic AI. The diameters at the levels of aortic valve annulus, sinus of Valsalva and ascending aorta increased also significantly in the patients with AI secondary to aortitis syndrome. The diameter at aortic valve commissure in 24 patients with AI was correlated (r = -0.48, p less than 0.05) to the diastolic blood pressure. Any diameter at the aortic valve portion was not different significantly by the complication of systolic hypertension (greater than or equal to 180 mmHg) in both groups of cases with and without AI. These results indicated that the dilatation of the aortic valve portion was observed in the patient with AI secondary to aortitis syndrome and might be the primary and common cause of AI in all grades, and that the dilatation might not be accelerated by the associated hypertension.

Localization of cellular oncogenes (c-onc) near the break points of translocations in tumor cells has indicated involvement of these genes in neoplastic growth. Enhanced transcription of the cellular homolog (c-abl) of the transforming sequence of Abelson murine leukemia virus was observed in K3D, which was one of the cloned cell lines of 7,12-dimethylbenz[a]anthracene-induced rat erythroblastic leukemia. Since the c-abl activation was not observed in the parent cell line (K2D) from which K3D was derived and the latter was different from the former in the presence of a new marker chromosome, t(3;12), this marker may play a role in the expression of c-abl in K3D cells. In contrast to the human c-onc assignments, few rat c-onc assignments have been reported. In situ molecular hybridization studies assigned c-abl to the 3q12 site of the normal chromosome 3 and to the break point of the translocation t(3;12) in K3D cells. Another break point in this translocation chromosome 12p11 involves the nucleolar region, and the 3;12 translocation may involve c-abl and nucleolar cistrons. These results provide evidence of secondary c-onc activation during karyotypic evolution of cloned malignant cells.

In this 72-year-old male patient, large amounts of amyloid substances were deposited in the mesenchymal organs, but not in the parenchymal organs. Histochemical and electron microscopic studies revealed large amounts of amyloid substances and amyloid fibrils in the skeletal and smooth muscle tissues. In the skeletal muscle tissues, where large amounts of amyloid substances were deposited, glycosaminoglycan was also markedly deposited, especially chondroitin-4-sulfuric acid. The concentrations of silicon were also markedly increased in the amyloid fibrils. The concentrations of nickel and cobalt were increased but those of zinc were decreased in all organs measured, although both nickel and cobalt in another case of amyloidosis experienced were within normal values.

Benz[a]anthracene (BA) and its derivatives containing methyl and/or ethyl groups in the 7 and/or 12 positions were tested for their ability to induce chromosome aberrations (CA) in rat bone marrow cells and for their mutagenicity to Salmonella typhimurium TA100 or TA98. The incidence of aberrant cells induced by the BA derivatives, given in lipid emulsion as a single-pulse dose of 50 mg/kg body weight into the caudal vein, was in the order: DMBA greater than EMBA greater than MEBA greater than other BA derivatives = control. The alkyl groups, at least 1 methyl group, at the 7 and 12 positions of BA seemed to be necessary to induce CA, although DEBA having ethyl groups at both the 7 and 12 positions of BA did not induce CA. DMBA or EMBA induced not only gaps and breaks but also exchanges and multiple CA, while the CA induced by other BA derivatives consisted of only gaps and breaks. 7MBA and 12MBA which exhibit carcinogenic activity intermediate between that of DMBA and BA induced few CA in the present system. However, the correlation coefficient between the logarithm incidence of aberrant cells and the carcinogenicity index calculated from the data of 9 BA derivatives including both 7MBA and 12MBA was 0.792. The relative mutagenicities of the BA derivatives with TA100 in the presence of hepatic S9 from polychlorinated biphenyl (PCB)-treated rats were in the order: BA greater than 7MBA greater than DMBA greater than 12MBA greater than 7EBA greater than EMBA greater than MEBA greater than 12EBA = DEBA = control. The results with TA98 were essentially the same as those with TA100. The results with TA100 in the presence of hepatic S9 from phenobarbital (PB)-treated rats were in the order: DMBA greater than 12MBA greater than 7MBA greater than 7EBA greater than BA greater than EMBA = MEBA greater than 12EBA = DEBA = control. These findings reveal no obvious relation between the mutagenic activities of the BA derivatives with the PCB-S9 or PB-S9 activating systems and their capacities to induce CA or their reported carcinogenicities. The incidence of CA induced by the dihydrodiols implicated as the metabolic precursors of the active diol epoxide metabolites of several of these BA derivatives was also tested. BA 3,4-dihydrodiol, like BA itself, induced few CA. However, the corresponding dihydrodiols of DMBA, 12MBA and 7MBA, induced relatively high levels of CA.(ABSTRACT TRUNCATED AT 400 WORDS)

The molecular weight of Streptomyces subtilisin inhibitor (SSI), a protein proteinase inhibitor, and that of the complex of SSI and subtilisin BPN' [EC 3.4.21.14] were determined by a sedimentation equilibrium method in 25 mM phosphate buffer, at pH 7.0, ionic strength 0.1 M (NaCl), 25.0 degrees C. The molecular weight of SSI was found to be 23,000 over a wide concentration range, 0.01-10 mg/ml, the range used for inhibitory, spectrophotometric, and kinetic measurements. Based on the amino acid sequence, the molecular weight of SSI has been calculated to be 11,500 (Ikenaka, T., et al. (1974) J. Biochem. 76, 1191-1209); therefore, the molecular weight of 23,000 obtained above suggests that SSI is in a dimeric form under usual conditions in the concentration range of 5 X 10(-7)-5 X 10(-4) M. The molecular weight of the subtilisin BPN'-SSI complex was determined to be 78,000 in the concentration range of 0.03-5.0 mg/ml by sedimentation equilibrium of the crystallized preparation and by that of a mixture of subtilisin BPN' and SSI treated as a multicomponent-polydisperse system. The molecular weight obtained here, combined with the results of binding stoichiometry (Inouye, K., et al. (1977) J. Biochem. 82, 961-967) that showed that one mol of SSI (molecular weight, 11,500) and one mol of the enzyme (molecular weight, 27,500) are tightly bound (Kd less than 1 nM), demonstrate that one mol of dimeric SSI binds two mol of the enzyme to form a stable complex, E2I2.

The amino acid sequence of a lysozyme, (B-enzyme), from Bacillus subtilis YT-25 was determined by conventional methods. B-Enzyme comprised 117 amino acid residues and had a heterogeneous sequence in the amino-terminal region. The amino acid sequence of B-enzyme was different from those of all other lysozymes the sequences of which are known. However, the partial amino acid sequence of Ser(74) to Ser(97) of B-enzyme was homologous with that of the active-site region of hen egg-white lysozyme (Ser(36) to Ser(60], which includes one of the catalytic amino acids, Asp(52). It is interesting that B-enzyme has an amino acid sequence homologous with that of the gag protein p25 of the AIDS virus ARV-2.

Sprague-Dawley rats were immunized with liver-specific protein. Kupffer cells and hepatocytes were prepared by the enzyme digestive procedure, and macrophage-depleted lymphocytes were prepared by the glass adherence method. Lymphocytes were incubated with macrophages or with Kupffer cells during the antigenic stimulation of mitomycin-C-treated hepatocytes for 90 h, and 3H-thymidine incorporation of lymphocytes was analyzed. The proliferation of lymphocytes cultured with macrophages was increased, but the proliferation of lymphocytes cultured with Kupffer cells was decreased in the rats immunized with liver-specific protein. And cytotoxicity to hepatocytes was increased after lymphocyte-Kupffer cell culture in the immunized rats. On the other hand, the proliferation of lymphocytes and cytotoxicity to hepatocytes were not significantly increased in normal rats. In the immunized rats lymphocytes cultured with macrophages showed a proliferative response to the membrane of hepatocytes, but inhibition of the lymphoproliferative response by Kupffer cells is considered to be due to destruction of hepatocytes (and thereby removal of antigen).

The induction of cell differentiation by a combination of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], recombinant gamma-interferon (rec gamma-IFN), and a lipopolysaccharide from E. coli (LPS) was studied in a clonal population (clone-9) of human promyelocytic HL-60 leukemia cells in vitro. Treatment of clone-9 cells with 10(-9) to 10(-7)M 1,25-(OH)2D3 yielded a macrophage cell differentiation. The addition of 10 or 100 U/ml of gamma-IFN and 2 or 10 micrograms/ml LPS caused a further increase in expression of the different differentiation markers. The most pronounced effects involved increases in cell attachment to the surface of tissue-culture Petri dishes and in lysozyme, nonspecific esterase, and cytolytic activities. The combined treatment with 1,25-(OH)2D3 and rec gamma-IFN and LPS also caused an increase in the percent of multinucleated giant cells. These results indicate the effectiveness of combining different agents in inducing cell differentiation in HL-60 cells. A similar approach may be useful in controlling myeloid leukemias in vivo.

Blood glucose, free fatty acid and insulin responses to oral glucose and the fasting serum lipids were measured in 3 groups: 32 non-obese (mean age: 47.5 years) and 9 obese (mean age: 84.5 years), male patients with coronary heart disease and 12 non-obese male controls (mean age: 46.5 years). The oral glucose tolerance tests were repeated after 3 years in 16 of the non-obese patients with coronary heart disease. The results were as follows: 1) Glucose tolerance was impaired in 19 of 32 non-obese patients (59.4%). There was a significant correlation between impaired glucose tolerance and hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia). 2) In obese patients FFA levels at 30, 60, and 120 min after oral glucose administration were significantly elevated and FFA decrease was delayed with a drop to minimum levels at 180 min. 3) The insulin response after oral glucose administration in the group of non-obese patients with normal glucose tolerance was similar to that of non-obese controls. In the group of non-obese patients with impaired glucose tolerance, serum insulin levels went up to normal levels, but the peak was delayed. The serum insulin levels in obese patients were significantly higher than those of controls of 0, 60, 120, and 180 min. After 3 years the change in insulin response to oral glucose was not related to anginal symptoms or ECG findings, but was related to body weight change in patients with minor changes in glucose tolerance. 4) The metabolic pattern in the non-obese group with impaired glucose tolerance resembled that of "mild diabetes" in delayed response of insulin and FFA, and mild hyperlipidemia. These findings suggest that obesity may contribute to hyperinsulinemia in patients with coronary heart disease and that impaired glucose tolerance observed in patients with coronary heart disease is in part due to "latent diabetes".

Recently galactosyltransferase has been noted as a new tumor marker. In this report galactosyltransferase activity was measured in sera of various diseases including malignant tumors and the levels of the enzyme activities were compared. The levels of the enzyme were higher in sera of malignant tumors and liver diseases than those in sera of other diseases. In malignant tumors little organ specificity was found with respect to the levels of galactosyltransferase activities. The levels of the enzyme were considered to have no relation to carcinoembryonic antigen or alpha-feto protein. On the other hand, in liver diseases the levels of the enzyme were correlated to the severity of liver damage. Therefore, it is reasonable to presume that the elevation of serum galactosyltransferase activity is caused chiefly by malignant tumors and liver damage.

An autopsy case of a 74-year-old male who had shown clinically hypothyroidism due to chronic atrophic thyroiditis (Hashimoto's thyroiditis), and pathologically necrotizing myopathy as a remote effect of gastric cancer was reported. Morphological features of this necrotizing myopathy was those of carcinomatous myopathy rather than those of hypothyroid or diabetic myopathy. As for the pathogenesis of the necrotizing myopathy (as a Group IV of polymyositis of Walton and Adams), the malignancy might have played an important role as a trigger of the secondary immunological abnormality upon a pre-existing longstranding immune disorder of Hashimoto's thyroiditis. Pseudomembranous colitis, which was thought to be related to antibiotics. (Lincomycin), was also briefly discussed.

Mechanisms for cyclical reduction in peripheral blood pressure and flow of partially constricted coronary artery of anesthetized dogs has been examined. In 64 of 97 preparations, cyclical reduction in coronary blood pressure and flow developed 3 to 32 min after the beginning of constriction. Period duration of the cyclical reduction ranged from 1 to 32 min. The cyclical reduction was frequently associated with elevation of the ST segment of surface electrocardiogram, systolic bulge of the left ventricle and excitation of afferent cardiac sympathetic nerve fibers. In the preparations in which cyclical reduction was not produced by constriction, a brief stretching of the constricted portion provoked the cyclical reduction. Segmental or diffuse narrowing of the constricted coronary artery which occurred during the reduction in pressure and flow was demonstrated by selective arteriography. Also, segmental spasm in the constricted coronary artery was demonstrated by photography. No obvious difference in the constricted of the artery was observed histologically between the preparations in which cyclical reduction developed and those in which cyclical reduction was not produced. The results indicate participation of vasospasm in the cyclical reduction of blood pressure and flow in partially constricted coronary artery.

The inhibition of renin release by angiotensin II (AII) is well documented. However, the interaction of this short loop feedback mechanism of AII with the sympathetic nervous system is still unclear. This study was designed to investigate the possible functional relationship between AII and the beta-adrenergic receptors with respect to renin release in vivo. First, the effect of propranolol on captopril-induced renin release was examined in conscious rats. Secondly, the effect of AII on isoproterenol-induced renin release was determined. Captopril (1 mg/Kg) increased plasma renin activity (PRA) from 1.6 +/- 0.3 ng/ml/hr to 4.5 +/- 0.6 ng/ml/hr (p less than 0.01). In contrast, there was no significant change in PRA in rats which received both captopril and propranolol (before 0.9 +/- 0.2 ng/ml/hr, after 1.3 +/- 0.3 ng/ml/hr). Thus, propranolol attenuated the increase in PRA caused by captopril. Isoproterenol infusion (0.1 micrograms/Kg/min) provoked a significant increase in PRA (before 1.3 +/- 0.4 ng/ml/hr, after 6.6 +/- 1.7 ng/ml/hr, p less than 0.01). AII infusion in combination with isoproterenol also increased PRA from 1.6 +/- 0.4 ng/ml/hr to 5.2 +/- 0.3 ng/ml/hr (p less than 0.01). AII in this dose did not suppress isoproterenol-induced renin release. These results suggest that the beta-adrenergic receptor mediating renin release is functionally located distal to the AII receptor in the short loop mechanism controlling renin release.

Hamster ovaries explanted at 21:00 h on the day of pro-oestrus were incubated with talopeptin, a potent microbial inhibitor of collagenases, until 10:30 h on the next morning. A talopeptin concentration of 0.16 mM completely blocked ovulation in vitro. The blocking effect decreased markedly in ovaries excised at 23:00 h or later. The results suggest that proteolysis by collagenases is indispensable for the ovulatory process in the hamster.

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.

The effect of acids on activity of afferent sympathetic nerve fibers from the left ventricle has been examined. Action potentials were derived from the upper thoracic communicating rami of the left side of anesthetized dogs. Application of a solution of lactic acid to the left ventricular surface caused excitation in both myelinated and unmyelinated fibers. The minimum concentration required for excitation was 7.5-75 mug/ml for the unmyelinated fibers and 375-750 mug/ml for the myelinated fibers. Excitation of the unmyelinated fibers induced by coronary occlusion was suppressed by pretreatment with sodium bicarbonate, 500 mg/kg. However, excitation of the myelinated fibers was influenced little by the agent. Pretreatment with a large dose of Trasylol failed to suppress excitation induced by coronary occlusion. The result suggests that acidosis plays a role in excitation of the unmyelinated fibers induced by myocardial ischemia, but not in excitation of the myelinated fibers.

Scytalidium lignicolum acid protease B, a pepstatin-insensitive acid protease, was modified by 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) with the concomitant loss of its enzyme activity, and an EPNP-labeled peptide was isolated from the thermolysin-digest of the modified enzyme by HPLC. The amino acid sequence of the peptide was determined to be Ile-Leu-Glu-Thr-Gly, which corresponds to the sequence of residue Nos. 51-55 of the enzyme. The results of treatment of the labeled peptide with hydroxylamine suggested that the EPNP moiety is ester-linked to Glu53 of the enzyme. The amino acid sequence around Glu53 of the acid protease B showed high homology with those around the active site Asp residues of calf chymosin and porcine pepsin. These results show that it is highly possible that Glu53 of the acid protease B is one of the amino acid residues involved in its catalytic activity.