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Rats were injected intraperitoneally with copper-lactate daily for over 160 days (total dose of 30 mg copper in each animal). At 120 to 160 days of copper administration, animals developed symptoms similar to those of Wilson's disease, i.e., kidney functional disturbances, proteinuria, aminoaciduria, decreased blood ceruloplasmin oxidase activity and increased urinary copper excretion. Cirrhosis was found in some animals. Tubular necrosis of the kidneys, liver fibrosis and tigrolysis of thalamic nerve cells were also found. Copper depositions were observed in liver parenchymal cells, renal tubular epithels, thalamus glia cells and on the Descemet's membrane of the cornea. The similarities between induced copper- intoxication in rats and Wilson's disease are discussed.

Analysis of the chromosomes of a cloned human hepato-blastoma cell line, HUH-6-clone 5 by Q-, G- and C-banding revealed numerical and structural chromosome aberrations. The modal number of chromosomes was 49. Trisomies #12 and 20 were present in most of the cells, and 8q isochromosome was detected in all of the cells analyzed. High levels of alpha-fetoprotein production by this cell strain were also demonstrated.

Cytoplasmic immunoglobulin G (IgG) in normal human epidermis was defined by a peroxidase-labeled antibody method. A correlation between cytoplasmic staining and the serum level of IgG was found. Epidermal cells containing IgG were not present when the serum level of IgG was less than 1000 microgram/ml.

A transplantable plasma cell leukemia cell line, designated as S27, was established from a 12-month-old female New Zealand Black mouse (NZB); serum showed polyclonal elevation of gamma globulin with agarose-agar gel electrophoresis. Immunoelectrophoretic analysis of the serum showed precipitation lines in the IgG1, IgG2a, IgG2b and IgM regions. The amount of serum immunoglobulin increased rapidly with tumor growth. S27 cells proliferating in the spleen contained simultaneously IgG1, IgG2a, IgG2b in the cytoplasm as revealed by indirect immunofluorescence. Membrane immunofluorescence revealed IgG1 on the tumor cell surface. S27 cells were transplantable to syngeneic NZB mice with inoculation of spleen cell suspension, and showed the same histological and immunological findings as those of the original mouse. These findings imply that a single clone of plasma cells has the capacity to produce more than one class of immunoglobulin.

The effect of glucosamine on phenotypic mixing between vesicular stomatitis virus (VSV) and avian sarcoma virus (ASV) was studied. Phenotypic mixing decreased with increase in glucosamine concentration, and, in the presence of 20 mM glucosamine, was no longer detectable. In the presence of 20 mM glucosamine, cells still produced 10(2)--10(3) focus forming units (FFU) of ASV and 10(6) plaque forming units (PFU) of VSV per milliliter. These results suggest that cells producing a relatively large amount of ASV (more than 10(3) FFU/ml) are essential for phenotypic mixing of VSV with ASV.

Sixty-four patients with confirmed bronchial asthma were treated with HC 20-511 (Ketotifen). HC20-511 was evaluated to be very effective in 6.3%, effective in 50.0% and slightly effective in 10.9% of these patients. The appearance of reactive basophils was inhibited by HC 20-511 in 5 out of 6 cases of reaction to house dust, in all three cases with buckwheat allergy to their allergen and in 7 out of 11 cases to anti-IgE. These results confirm that HC 20-511 inhibits type I allergic reactions induced by specific allergen and IgE.

Fifty patients with chronic myelocytic leukemia (CML) grouped into four stages on the basis of clinical and hematological results were analyzed with chromosomal banding techniques. Of the 50 patients, 48 hand the "standard" type of Ph1 translocation, t(9 ; 22) (q34 ; q11) and the remaining 2 had Ph1-negative diploid karyotype. The frequency of numerical chromosomal changes and/or structural chromosomal changes other than the Ph1 translocation varied with the stages; the frequency was 1 of 28 cases (3.6%) for patients in stage I (chronic phase), 5 of 11 (45.5%) in stage II (early stage of blastic phase), 11 of 13 (84.6%) in stage III (blastic phase) and 2 of 7 (28.6%) in stage IV (remission phase). Numerical changes in hyperdiploid leukemic cells correlated well with the appearance of extra #8 and extra Ph1 In 5 cases with hypodiploid leukemic cells, one of the #7 pair was absent in 4 cases and Y in 1 case. As structural changes, partial excess of chromosome 1, isochromosome 17q, isochromosome 1q, tdic (20p+ ; 21q-), del (7) (q11), t(2p+ ; 11p-), #12q+ and Xp+ were observed. Chromosomal analysis alone is not the best marker to diagnose the onset of blastic phase; however, it is a useful parameter when considered in combination with clinical and hematological results.

The levels of hippuric acid in the urine of people exposed to toluene vapour were measured by paper chromatography, direct colorimetry, high performance liquid chromatography and gas chromatography. The control was a similar group not exposed to toluene vapour. The values were analyzed statistically, conversion equations calculated, and the propriety of these equation discussed. Since the three chromatographic methods gave similar values, the measurement of urinary hippuric acid by these methods can be used as an index of toluene exposure. The colorimetric method gave higher levels the chromatographic methods, especially for the urine of people not exposed to toluene. This may have been due to glycine conjugates (other than hippuric acid) developing a similar color, resulting in elevated values for hippuric acid. This colorimetric method should be used with caution for biological evaluation of workers with low toluene exposure.

A permeable cell system has been developed by treatment with digitonin for studying in vitro DNA replication of chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in digitonin-treated permeable cells was analyzed by electrophoresis in agarose-gel. Autoradiography of the agarose-gel revealed that [32P]dCTP was incorporated in SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated the complete replication of SV40 DNA and chromatin with a full number of nucleosomes. The digitonin-treated permeable cell system will serve as a useful system for studying in vitro DNA replication of chromatin.

The effect of Picibanil, a streptococcal agent, on the development of liver injury after operations for urogenital cancer was studied retrospectively in the light of serum alanine aminotransferase (ALT) activity. The series comprised 32 cases receiving Picibanil and 33 controls with otherwise comparable clinical backgrounds. Picibanil reduced the incidence of postoperative ALT rise over 50 U/l within 6 weeks but increased it thereafter. The increase in ALT activity after 6 weeks was relatively small and was seen more often in patients given blood transfusions. It was interpreted as retardation and suppression of ALT rise and as being related to the induction of interferon or to immunopotentiation. Other antihepatotoxic effects of Picibanil, due to its antioxidant activity, for example, may also account for the prevention of the early postoperative rise in ALT activity.

The effects of oral and intravenous thyrotropin-releasing hormone (TRH) were studied in 11 male, chronic schizophrenic inpatients in an open trial and a double-blind, crossover design. The general beneficial effects of TRH as assessed on the Brief Psychiatric Rating Scale were not obtained, although improvement of contact, apathy and emotional rapport was observed in a few patients. Serum prolactin, L-triiodothyronine and thyroxine were assayed throughout the study. Since the effects of TRH on behavior were not related to changes in these endocrine factors, the mechanism of action might be independent of its original functions on the pituitary-thyroid axis.

In a 41-year-old male with diabetes mellitus well controlled with insulin (50 units/day), hypoglycemia developed after starting disopyramide treatment (200 mg/day) for correction of tachycardia. Lower levels of blood glucose and smaller amounts of urinary sugar persisted until disopyramide was withdrawn even after reducing insulin to a minimum dose of 20 units/day. The insulin requirement increased again thereafter to the original dose. These results indicate that disopyramide had a hypoglycemic effect in this patient.

After the Second World War, the field of medicine has changed remarkably in Japan. A comprehensive health and medical care system has been organized to meet the increasing needs and demands for health and medical care services. Health centers have played an important role in promoting health care activities in the community. The authors describe the development of health centers and other health care facilities in Japan. The authors propose that it is necessary to build a new health facility specifically designed for public health nurse activities, termed a "public health nurse station". The authors also describe the status of the health care facilities in service and the activities of the stations and evaluated them. It is concluded that the stations have brought many changes in the field of health and medical care; moreover that the station should not become a substitute for a health center but should be a facility for public health nurse activities in a community. Health centers should also play important roles for comprehensive medical services in the future.

The effects of coenzyme Q10 (Co Q10) on potassium ion release, membrane potential and fluidity of rabbit red blood cells were studied. Co Q10 inhibited the increased potassium ion release induced by cetylamine or lysolecithin from the cells. Co Q10 slightly decreased the membrane potential monitored by changes in fluorescence intensity of cyanine dye, 3,3'-dipropyl-2,2'-thiodicarbocyanine iodide [diS-C3-(5)], and also slightly decreased the membrane fluidity measured by using 1,6-diphenyl-1,3,5-hexatriene (DPH). These effects of Co Q10 on the membrane are considered to be due to its membrane stabilizing activity by interaction with lipid bilayers of the membrane.

Treatment of respiratory syncytial (RS) virus with Triton X-100 in solutions of low ionic strength solubilized not only glycoproteins but also some non-glycosylated proteins. Rate zonal sedimentation of the solubilized materials resulted in separation of the glycoproteins from the other components, i.e. one fraction predominantly composed of two glycoproteins each with molecular weight (mol. wt.) of approximately 100,000 and 53,000 was obtained. Electron microscopic observation of this fraction revealed numerous club- or rod-shaped fine structures, suggesting that these were spikes of RS virus. After removal of Triton X-100 the structures aggregated and formed oligomers and polymers.

The experiment was designed to observe the possible relation between myelopoietic and erythropoietic activities of circulating nucleated cells. Wistar rats were lethally irradiated with 60Co, 100 r once. Two days after irradiation the bone marrow cells had faded completely. At this stage animals were conjugated with normocythemic or polycythemic rats by aortic anastomoses. After conjugation the aplastic bone marrow of the irradiated animal rapidly regained its hemopoietic activity in cases having normocythemic and polycythemic partners. Active erythropoiesis and myelopoiesis were found 96 h after parabiosis in those having normocythemic partners. In animals having polycythemic partners, however, erythropoiesis was successfully suppressed. An increase in lymphoid cell numbers was found in place of decreased erythroid cells, but there was no change in the myeloid cell proliferation rate. No hemopoietic precursor cells or immature cells were found in circulating blood all through the experimental period before and after parabiosis. The data suggest that circulating nucleated cells have marked erythropoietic activity. Erythropoietic cells may be somehow related to lymphoid cells independent of myelopoietic activity.

A 30 year old female patient diagnosed as acute lymphoblastic leukemia (ALL) with hand mirror like configuration of lymphoblastic-lymphocytic cells is reported. Although the leukemia was resistant to conventional chemotherapeutic regimens, the patient always looked well and survived for more than 20 months. Surface marker analysis showed that the cell was non-T, non-B, and not reactive to antiserum against common ALL antigen. A cytogenetic study of all the analyzable metaphases of the direct bone marrow preparation had a normal female karyotype. The clinical and hematological course is described. The immunological significance and the influence of hand mirror cell on chemosensitivity and prognosis are discussed.

In 156 cases of gastric cancer, levamisole (LMS) was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started 3 days before operation. This medication was repeated for more than one month. The survival rate up to two years after surgery was studied. The survival rate was not affected in patients with Stage I and II gastric cancer, but in patients with Stage III, the difference in the survival rate between the LMS group and the control group was significantly higher than that in the control group (p less than 0.05). In patients with Stage IV, the survival rate in the LMS group was higher than that in the control group although the difference was not significant. In patients of Stage III and IV, the effect of LMS on the survival rate was highest in cases with curative resection (p less than 0.01). In cases with noncurative resection, the difference between the LMS group and the control group was greatest (24.4%) 12 months after surgery but not significant (p less than 0.5), and also in cases without resection the difference between the two groups was greatest (20.3%) 12 months after surgery but not significant (p less than 0.2).

We report herein the results of anterior or posterior neural decompression with spinal stabilization in 16 patients with spinal metastases. Intractable back pain was relieved in 14 patients (87.5%) and 4 had complete pain relief. Neurologic recovery was observed in 8 out of 13 patients (61.5%) who had some neurologic deficits before surgery. The activities of daily living improved in 7 of 9 (77.7%), and 5 out of 8 patients (62.5%) who had been unable to walk before surgery became ambulatory after surgery. The average operation time was 3h 15 min with an average blood loss of 2150 ml. No patient died within 1 month after surgery and the median survival was 19.1 months. The results indicated that, if properly indicated, anterior or posterior neural decompression and spinal stabilization is a safe and effective treatment for patients with spinal metastases to improve the quality of life for the patients' remaining years.

APEX nuclease is a mammalian DNA repair enzyme having apurinic/apyrimidinic (AP) endonuclease, 3'-5'-exonuclease, DNA 3' repair diesterase and DNA 3'-phosphatase activities. It is also a redox factor (Ref-1), stimulating DNA binding activity of AP-1 binding proteins such as Fos and Jun. In the present paper, a cDNA for the enzyme was isolated from a rat brain cDNA library using mouse Apex cDNA as a probe and sequenced. The rat Apex cDNA was 1221 nucleotides (nt) long, with a 951-nt coding region. The amino acid sequence of rat APEX nuclease has 98.4% identity with mouse APEX nuclease. Using the rat Apex cDNA as a probe for Northern blot analysis, the size of rat Apex mRNA was shown to be approximately 1.5 kb. Its expression was compared in 9 rat organs on postnatal days 7 and 28. Although Apex mRNA was expressed ubiquitously, the levels varied significantly, suggesting organ- or tissue-specific expression of the Apex gene. The highest level was observed in the testis, relatively high levels in the thymus, spleen, kidney and brain, and the lowest level in the liver. The level of expression at postnatal day 28, with the exception of the testis, was almost the same as or lower in respective organs than that at postnatal day 7. Postnatal developmental changes of Apex mRNA expression in the testis and thymus were further studied. The expression in testis was markedly increased on postnatal days 21 and 28. The expression in thymus increased once at postnatal day 14, and then decreased. The developmental changes of Apex mRNA expression in testis and thymus suggest that APEX nuclease is involved in processes such as recombinational events.