Peripheral blood monocytes from patients with systemic lupus erythematosus (SLE) were isolated and examind for the presence of surface bound immunoglobulins by immunofluorescence technic using FITC labelled F(ab)₂ fragment against IgG, A, and M.
In 8 out of 20 patients examined, when tested with anti-IgG, increase amount of fluorescent staining was demonstrated. On the other hand, the staining of IgA and IgM were minimal, and were not significantly different from those of monocytes from normal volunteers. Although the staining of IgG on monocytes surface seemed to be mostly from in vivo formed immune complexes, there were no correlations between the amount of IgG and the levels of serum complement nor the levels of circulating immune complexes.
These results indicate the possibility that the monocytes from patients with SLE can interact with circulating immune complexes in vivo.

View full abstract

Monocyte Fc receptor(Fc R)functions were studies in patients with systemic lupus erythematosus (SLE) by examining rosette formation and phagocytosis of monocytes using anti-Rh antibody coated red blood cells (EA).
The rosette index (R.I.), which is an expression of the average number of EA attached to a monocyte surface, was significantly higher with SLE monocytes than with normal controls. In contrast, the phagocytosis index (P.I.), which is an expression of the average number of EA phagocytosed by a monocyte, was significantly lower. Kinetic studies revealed that between active SLE and control monocytes, there were no differences in EA kinetics after EA had attached to the monocyte surface membrane. A close correlation was obtained between the R.I. values and the concentration of gamma-globulins (R=0.69). A negative correlation was found between the R.I. values and the levels of serum complement (CH₅₀: R=-0.65, C₃: R=-0.62, C₄: R=-0.49). There were no significant correlations among the R.I. values and the levels of circulating immune complexes, the grade of hematuria, the degree of proteinuria and histological findings of the kidney. P.I. values did not correlate with any of these parameters.
These results suggest that Fc R functions of peripheral blood monocytes are increased in patients with SLE and are closely related to disease activity.

View full abstract

Tha cause of ST-T changes with QRS high voltage in essential hypertension was investigated using Frank lead vectorcardiograms. Submaximal treadmill exercise was performed according to the modified Bruce protocol. The patients were divided into three groups. Group N consisted of 29 normal subjects; Group I (ischemic heart disease) consisted of 10 patients with angina pectoris and 16 patients with angiographically documented narrowing of one or more coronary arteries and Group H (essential hypertension) was subdivided into four groups according to ECG findings: Group H-1 of 30 subjects with normal ECG, Group H-2 of 20 subjects with QRS high voltage (S_v1+R_v6 35 mm) with normal ST-T pattern, Group H-3 of 20 subjects with QRS high voltage with ST-T changes but no “strain pattern” and Group 4 of 20 subjects with QRS high voltage and “strain pattern”. After exercise, the maximum spatial QRS vectors shifted posteriorly and to the left in all groups. In Group N, the maximum spatial T vector was reduced in magnitude, and directed anteriorly, superiorly and to the left after exercise. The T loop configuration showed no significant changes, though slightly rounded and inscribed uniformly. In Group I, the maximum spatial T vector decreased in magnitude as in Group N, but was directed in significantly more ways than in Group N. In a few cases, the vectors were extremely dislocated upward. The T loop configurations had wide variation. This variation of the T loop after exercise was characteristic of Group I. In group H, the maximum spatial T vector was also reduced in size, while the azimuth, elevation and spatial QRS-T angle moved in the opposite direction of Group N, as cardiac hypertrophy beveloped. Analysis of T loop configuration changes induced by exercise strongly suggested that the ST-T changes in Group H-3 were related to primary changes due to myocardial ishemia. Effects of exercise on spatial T vectors and T loop configurations in Group H-4 were quite different from those in Group I, so that the ST-T changes in this group seemed to be secondary changes in association with QRS high voltage.

View full abstract

Two monoclonal antibodies (NH-1 and NH-2 abs) were produced by immunizing BALB/c mice with a null-acute lymphoblastic leukemia (null-ALL) cell line, NALL-1, and fusing the mouse spleen cells to mouse myeloma cell line, P3-NS-1/1-Ag4-1. The resulting hybrid cells were screened, and two stable monoclonal ab-producing cell lines were isolated by repeated clonings. Reactivities of the abs were analyzed using an indirect membrane immunofluorescence test against cultured cell lines, normal peripheral blood cells, bone marrow cells, lymph node cells, spleen cells, hematopoietic tumor cells and non-hematopoietic tumor cells. NH-1 ab reacted exclusively with monocytes and leukemia cells of null-All, acute myelocytic leukemia, acute promyelocytic leukemia, acute monocytic leukemia and chronic myelocytic leukemia in blast crisis (CML-BC). NH-2 ab did with leukemia cells from some cases of null-ALL and CML-BC. Mature granulocytes and lung adenocarcinoma cells also reacted with NH-2 ab.
When HL-60 cells were cultured with dimethylsulfoxide, expression of NH-1 reactive antigen (NH-1 ag) on the differentiated HL-60 cells was decreased, but NH-2 ag was not expressed. When NALL-1 cells were cultured with NH-1 or NH-2 ab, NH-2 ag modulated, but NH-1 ag did not. Immunoglobulin of both abs was IgG and did not exhibit complement-dependent cytotoxic activity.
These results indicate that NH-1 ag was a differentiation ag expressed commonly by immature hematopoietic tumor cells and monocytes, and NH-2 ag may be a unique common ALL ag which is also expressed on mature granulocytes and lung adenocarcinoma cells.

View full abstract

In vitro oxidation of metallic mercury by catalase and hydrogen peroxide generated by the glucose-glucose oxidase system, D-alanine-D-amino acid oxidase system and xanthine-xanthine oxidase-superoxide dismutase system was investigated.
In vitro oxidation of metallic mercury by catalase and hydrogen peroxide generated by the reaction with glucose and glucose oxidase was observed in erythrocytes and crystalline beef liver catalase solution. The uptake depended on the concentration of glucose oxidase and nearly logarithmically increased with the increasing concentration of glucose oxidase. Similar oxidation of metallic mercury was observed in the solution of catalase, D-amino acid oxidase and D-alanine. The uptake also nearly logarithmically increased with increasing concentration of D-amino acid oxidase. In vitro oxidation of metallic mercury by catalase and hydrogen peroxide generated by the reaction system xanthine, xanthine oxidase and superoxide dismutase was observed. Oxidation of metallic mercury similar to that in the xanthine-xanthine oxidase system was observed in the solution of human plasma, hemolysate and erythrocytes containing superoxide dismutase and catalase.
These results suggest that hydrogen peroxidase generated by oxidase has an important role in the uptake of metallic mercury vapor.

View full abstract

In vitro reduction of mercuric ion to metallic mercury by superoxide anion, NADPH, NADH and acatalasemic mouse liver homogenate was investigated.
Superoxide anion generated by the xanthine-xanthine oxidase system reduced mercuric ion to metallic mercury in vitro. The reduction rate was inceresed linearly by the increasing concentration of xanthine oxidase. The reduction of mercuric ion by superoxide anion was increased by the addition of cytochrome c and nitro blue tetrazolium. The reduction of mercuric ion was inhibited in the presence of superoxide dismutase and catalase. The rate of reduction of mercuric ion by acatalasemic mouse liver homogenates was higher than that by normal mice liver homogenate. The reduction of mercuric ion by mouse liver homogenate was inhibited by the generation of superoxide anion, but the reduction rate by acatalasemic mouse liver homogenate was higher than that of normal mouse homogenate. NADPH and NADH reduced mercuric ion to metallic mercury. The reduction decreased in the presence of mouse liver homogenate.
These results indicate that metabolism of mercury is influenced by the balance of oxidation and reduction systems

View full abstract

Exhalation of metallic mercury from acatalasemic and normal mice intraperitoneally injected with mercuric ion (²⁰³HgCl₂) and the mercury uptake by acatalasemic and normal mice exposed to metallic mercury vapor (²⁰³Hg⁰) were investigated.
Exhalation of metallic mercury from acatalasemic mice injected with mercuric ion was higher than that from normal mice. The mercury uptake by normal mice exposed to metallic mercury was higher than that by acatalasemic mice. The liver and brain of acatalasemic mice were higher in the content than those of normal mice. On the other hand, mercury content in heart, lungs, blood and kidneys of acatalasemic mice was lower than in normal mice. The brain/blood concentration ratio of acatalasemic mice was higher than in normal mice. The distribution of mercury in the organs of acatalasemic mice injected with mercuric ion were similar to those of normal mice.
Those results indicate that actalase has an important role in the uptake of metallic mercury, and the balance of reduction and oxidation systems influence the metabolism of mercury.

View full abstract

The metabolites phenylglucuronide (PhG) and phenysulfate (PhS) in urine samples collected from male, chemical fiber factory workers were analysed by high performance liquid chromatography (HPLC). Even when the phenol concentration was below the threshold limit value of 5 ppm, phenol metabolites could be analyzed by HPLC. The PhS/PhG ratio was not constant, probably because work conditions varied among individuals. The concentration of atmospheric phenol could be estimated from the regression equations using the PhG, PhS and total phenol (PhG+PhS) levels in urine.

View full abstract

After two volunteers were exposed to 65.0 ppm ethylbenzene for 3 hours, the metabolites of ethylbenzene in their urine, mandelic acid (MA), hippuric acid (HA) and phenylglyoxylic acid (PhGA) were analyzed. The metabolites were excreted in the urine in the order of MA>HA>PhGA. The highest value of excretion of metabolites was observed six to ten hours after the beginning of exposure. MA/PhGA and HA/ PhGA mole ratios of total excretion in urine were 3.5 and 2.6, respectively.

View full abstract

An embryologic study of rat hippocampal formation was performed. By the silver sulfide method for light microscopy, the same positive reaction as in adult rats was observed in 20-day rats in the same regions: the border between stratum radiatum and stratum pyramidale of h₃ and h₄, hilus fascia dentata (h₅) and stratum multiforme of Gyrus dentatus.
These regions corresponded to the site of mossy fiber endings. In the silver sulfide method modified for electron microscopy, deposits of silver grains were observed in mossy fiber endings of 8-day rats, and the morphology of mossy fiber endings of 14-day rats was similar to that of adult rats. These results suggest that these areas begin to mature in 8 days and complete maturation in 20 days after birth.

View full abstract

Metabolites of brominated benzenes in rabbits, rats and mice after a single oral administration were examined with ECD-GC and MS-GC. The major metabolites found in the urine of the three kinds of animals were bromophenol, mercapturic acid, thiophenylacetic acid and sulphuric methylates. A significant increase in mercapturic acid and thiophenylacetic acid was found in urine after administration of low brominated benzenes, whereas remarkable sulphuric methylate excreation was observed after administration of tribromobenzene. Unchanged bromobenzenes were remarkable in the urine of high-brominated benzene-administered animals. Debromination from which debrominated bromobenzenes and bromophenols in excretions result are best ascertained by an enzymatic reaction of the mixed function oxygenase system. The biological half life of each metabolite and unchanged bromobenzene correlated with the number of the substituted aromatic bromine atoms.

View full abstract

Movement of brominated benzenes in rats and mice was investigated. The concentration of o-dibromobenzene in several tissues and organs reached the highest value within 10 hours of a single oral administration and then decreased rapidly. The accumulation of o-dibromobenzene in tissues and organs was in the descending order of adipose tissue, liver (=pectoral muscle), kidney, brain and blood. A similar tendency was observed in mono-and tribromobenzene administered animals. The concentration of hexabromo-benzene following continuous intraperitoneal administration reached the highest value 16.3 (liver) to 28.8 days (brain) after the administration. The biological half life of hexabromobenzene ranged from 2.0 (kidney) to 4.1 days (brain) in the first phase of excretion, and from 5.2 (kidney) to 7.3 days (adipose tissue) in the second phase of excretion. Accumulation of hepatic triglyceride due to administration of brominated benzenes occurred. A decrease in the percentage of arachidonic acid among total fatty acids was observed after the administration of brominated benzenes. It is suggested that accumulativeness of brominated benzenes becomes higher with the number of bromine atoms. Clonic toxicity induced by these compounds needs to be investigated in this connection.

View full abstract

The formative mechanism of debrominated compounds was investigeted. The excretion rate of tribromobenzene metabolites into the rat urine was enhanced by pretreatment with phenobarbital, and the amount of debrominated bromophenol in urine was greater than that of sulfur containing compounds after phenobarbital pretreatment. on the other hand, sulfur containing compounds were predominant in the urine of rats pretreated with glutathione. Incubation of tribromobenzene with the 10, 000 g supernatant of rat liver homogenate from rats pretreated with phenobarbital resulted in an increase in 3.5-dibromophenol. The above effect was accelerated remarkably by NADH and NADPH. These results demonstrate two metabolic pathways in the debromination of tribromobenzene: one to sulfur containing compounds and another to bromophenol bodies.

View full abstract

Pregnant ddN mice were injected with 15, 000 I.U. of water miscible vitamin A intraperitoneally on day 8 of pregnancy. Fetuses were removed surgically on day 18. Twenty of them were selected randomly to be sectioned horizontally and stained with hematoxylin and eosin solution for histological observation of the malformed ossicles.
The malleus, incus and stapes were suggested by the observations to have developed directly from branchial arch cartilage: the former two from Meckel's cartilage and the latter from Reichert's cartilage.
That the stapes was isolated might lend support to the theory of dual origin of the footplate.
The above results were discussed with embryological and bibliographical considerations.

View full abstract

In order to assess the change in the pituitary prolactin (PRL) reserve during development, serum prolactin response to TRH and serum LH response to LH-RH were studied in 247 normal children aged from 1 to 18 years. The basal PRL level, of which the geometric mean (-1SD and +1SD) was 7.1 (4.6-11.0)ng/ml, was not affected by bone age or sex. The maximum increment in serum PRL above the baseline level (max.ΔPRL) correlated well both with the integrated secretion of PRL (p<0.001) and with the serum PRL releasing value per minute computed from the mathematical model of Okuno et al. (1977): C=α/β-α·Q0/V(e-αt-e-βt)+C0e-βt [α: rate constant for PRL release, β: rate constant for PRL elimination, Q₀/V: serum PRL releasing value per minute]. Hence, max.ΔPRL can serve as a reliable index of the pituitary PRL reserve. The max.ΔPRL increased with advancing age until early puberty in both sexes. Thereafter, however, the max.ΔPRL decreased in doys, while it continued to increase in girls. In parallel with the increase in max.ΔPRL, the pituitary LH reserve increased with advancing age until early puberty in boys and until late puberty in girls. In each of the individuals, studied, the rise in the LH reserve always preceded that in the PRL reserve. It seemed likely that in prepubertal children the pituitary PRL reserve was modulated by LH-RH, but aftre puberty by testosterone and estrogen as well.

View full abstract

A murine IgM monoclonal antibody specific for human Ia antigen was purified by Sephacryl S-300 chromatography from ascites obtained from BALB/c mice inoculated with the antibody-secreting hybridoma. The anti-Ia antibody (H-2) was reacted with Neocarzinostatin (NCS) in the presence of carbodiimide. The resulting mixture was chromatographed on a Sephacryl S-300 column. The first fraction was shown to contain H-2-NCS conjugate, but not free NCS, by the elution profile, as well as by the Sarcina lutea growth inhibition assay. A membrane immunofluorescence test with anti-NCS and anti-mouse immunogloblin demonstrated specific localization of H-2-NCS on the cell surface of Ia-bearing NALL-1 cells. No localization of NCS was shown when the cells were incubated with free NCS. H-2-NCS inhibited the growth and ³H-TdR incorporation of NALL-1 cells 100 times more potently than free NCS alone, when the cells were reacted with the drugs at 4°C for 30 min. and culutured further for 14 hrs. These results indicate that the H-2-NCS cnojugate retained both NCS and antibody activities, and exerted antibody-targeting NCS cytotoxicity in vitro. Thus the conjugate should be useful for cancer immunochemotherapy.

View full abstract

In vivo antitumor activity of anti-Ia monoclonal IgM antibody (H-2)-Neocarzinostatin (NCS) conjugate (H-2-NCS) was evaluated in immunosuppressed newborn hamsters implanted with a transplantable human leukemia cell line (BALL-1). After intraperito-neal injection of H-2-NCS, hamsters preinoculated i.p. with BALL-1 cells survived longer than hamsters treated with control solutions (p<0.001). The control solutions included nonimmune monoclonal IgM-NCS conjugate, H-2 antibody, free NCS and phosphate-buffered saline. Growth inhibition of subcutaneously implanted BALL-1 tumors was not observed in hamsters injected i.p. with H-2-NCS or H-2 monomer subunit antibody-NCS conjugate. These results indicate that H-2-NCS was effective against i.p. implanted BALL-1 tumors, but was not effective against s.c. implanted tumors.

View full abstract

L-form cells are generally pleomorphic and show variety in size ranging from 0.2 μm to more than 10 μm in diameter. We investigated the ultrastructure of the cell membrane of such variable L-form cells derived from Staphylococcas aureus 209P in terms of membrane particle distribution by freeze-fracture replica electron microscopy. The specimens were prepared by immediate freezing in liquid nitrogen without any chemical fixatives followed by freeze-fracture with Eiko FD-2. We focused on the structure of the P face only. The particles were densely dispersed on the cell membrane of mediumsized cells (0.4-4 μm). Large (>4 μm) and small (0.2-0.4 μm) cells showed very few particles. In conclusion, the medium-sized cells were growing actively, while large and small cells were not growing.

View full abstract

It is well known that serum albumin, γ-G-globulin and glycoprotein increase in urine after physical load. There are two ways, the Donaggio reaction and ASPRO method (a new acid soluble glycoprotein assay using coomassie brilliant blue G-250), to measure glycoprotein and other acid soluble protein for estimating the physical load. This investigation was performed to identify the composition of protein detected by the Donaggio reaction (DRPSu) and of perchloric acid soluble protein detected by the ASPRO method in urine (ASPROu). In DRPSu, albumin, α₁-acidglycoprotein, α₂-HS-glycoprotein, Zn-α₂-glycoprotein, α₁-antitrypsin, α₁-antichymotrypsin and transferrin were recognized by double diffusion, single radial immunodiffusion and immunoelectrophoresis. In ASPROu, the same proteins as above were recognized according to the same immunological methods. However, a different ratio of protein components was recognized between DRPSu and ASPROu by SDS-PAGE. The perchloric acid soluble protein in urine before and after exercise from high school boys was measured by the ASPRO method, and a significant difference was recognized between before and after exercise.

View full abstract

Japan's medical expenditure has been growing rapidly year by year, and the rate of the national subsidy has inevitably been rising too. This has consequently become an urgent financial problem for the Government along with the Pension problem.
Linked to this, there is also the bad financial state of the Society-managed Health Insurance Scheme, which is one of the main health insurance schemes in Japan, along with the Government-managed Health Insurance Scheme and the National Health Insurance Scheme, and which had been financially better-managed than the others.
In this study, the author examined the factors influencing the financial balance of 1570 societies in this scheme from 1974 to 1981, by analyzing 20 of 213 items obtained from the report on striking a financial balance.
The results are summarized as follows:
(1) ‘The ordinary financial balance of each society’ is influenced by both ‘the type of enterprise’ and ‘the type of society’, with the former more influential than the latter.
(2) Among societies, there are greater differences of factors, such as ‘the sex ratio of insured persons’, ‘the total costs for health and welfare facilities’, ‘the ratio of costs for health education’, ‘the ratio of costs for preventive measures’, ‘the ratio of costs for promotion of sports’, ‘the costs for additional benefits per one insured person’, ‘the costs for additional benefits per one dependant’, ‘the total costs for benefits per capita’, than other factors, when the author compares them.
(3) From the result of the correlation analysis among the factors, ‘the mean age of insured persons’ shows a high correlation not only with ‘the ordinary financial balance of each society’ but also with many other factors. ‘The total costs for health and welfare facilities’ does not directly reflect the health care activity of each society.
(4) ‘The number of insured persons’ has not directly influenced ‘the ordinary financial balance of each society’ but shows the financial stability of the society among the special type of society.
(5) To show the synthetical character of each society, such factors as ‘the average monthly standard remuneration’, ‘the type of enterprise’, ‘the type of society’ and ‘the number of insured persons’ are adequate in respect of the total financial balance.
In the same way, ‘the total costs for benefits per capita’, ‘the number of insured persons’ and ‘the costs for additional benefits per one dependant’ are adequate in respect of expenditure.
(6) In excluding the confounding factors in the analysis, it can be seen that ‘the average monthly standard remuneration’, ‘the mean age of insured persons’ and ‘the number of dependants per one insured person’ have a significant influence on ‘the ordinary financial balance of each society’.

View full abstract