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Biomedical subjects

Y Hamashima

Publications and source records attributed to Y Hamashima.

At least 91 records · Page 5Linked to original sources
PubMed1985

Histamine metabolism in skin of MRL/l mice.

Of several murine autoimmune models, MRL/Mp-lpr/lpr (MRL/l) mice are the most attractive from a dermatopathological point of view, because their skin lesions resemble the erythematous lesions of systemic lupus erythematosus (SLE). In order to clarify the pathogenesis of lupus dermatoses, histamine and its metabolizing activities in the skin of MRL/l mice were investigated. The specific activities of histamine-N-methyltransferase (HMT) in the skin of MRL/l mice were significantly lower than those in the skin of control mice i.e., MRL/Mp-+/+ (MRL/n), C57BL/6J, and BALB/c mice. In the dorsal lesional skin of MRL/l mice, HMT activities were markedly lower than those in normal abdominal skin. In addition, age-related analysis of HMT levels in the dorsal skin of MRL/l mice revealed that HMT activities reached their maximum at the age of 2 or 3 months and then decreased at 4 or 5 months when skin manifestation appeared: however, HMT activities in the abdominal skin increased almost linearly with age. There were no significant differences in histamine content in these mice, and diamine-oxidase activities were not detected in any skin specimens. From these results, it is suggested that impaired histamine metabolism is a particular biochemical feature of the skin of MRL/l mice.

Age Factors↗
PubMed1985

Pathogenesis of lupus dermatoses in autoimmune mice. IV. Association between cutaneous immunoglobulin deposition and anti-single-stranded DNA antibodies in sera.

The skin of New Zealand, MRL and BXSB mice was immunohistopathologically examined in order to study the appearance of skin immunoglobulin (Ig) deposition and its correlation with the occurrence of anti-single-stranded (ss) DNA antibodies in sera. Our studies revealed Ig deposition at the dermoepidermal junction (DEJ) in non-lesional skin and a significant age-related correlation between skin Ig deposition and serum anti-ssDNA antibodies. However, immunofluorescent study of autoimmune mice using anti-ultraviolet-irradiated DNA antiserum failed to demonstrate DNA antigens at the DEJ.

Aging↗
PubMed1985

Two natural killer-cell subpopulations distinguished by heat sensitivity.

We examined the effect of heat on natural killer-cell activity and found that two different natural killer-cell subpopulations can be distinguished by their heat sensitivity; one subpopulation loses natural killer-cell activity at 41 degrees C, and the other is not affected. In a single-cell assay, the ability of natural killer cells to conjugate to K 562 cells was not affected by incubation at 41 degrees C, but the killer activity of natural killer cells after conjugating to K 562 cells was reduced at 41 degrees C. Therefore it is likely that the difference in heat sensitivity between the two subpopulations is due to postbinding cytolytic events. Tetracaine, which influences cytolytic events, was used to examine whether or not the two natural killer-cell subpopulations can be distinguished by tetracaine sensitivity. However, it was found that tetracaine inhibits natural killer-cell activity equally for both of these natural killer-cell subpopulations.

Hot Temperature↗
PubMed1985

The reliability of the tracing-method of fine cardiac fibrosis at a magnification of x10--preliminary study for quantitative analysis of fibrosis in large tissue sections of hearts with cardiomyopathy.

to define the reliability of the tracing method of fine fibrosis at low magnification (x10), the percentage area of fine fibrosis was compared between the traced pictures at magnifications of x10 and x250, using an image analyzer (Olympus VIP-21). A total of 25 tissue areas, each approximately 4 x 7 mm, from the inner and middle thirds of the left ventricular free wall and ventricular septum were selected from ten hearts with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and were stained with Masson trichrome. The percentage areas of fine fibrosis traced at a magnification of x10 correlated well with those traced at a magnification of x250 (Y = 1.08X - 1.1, r = 0.95, P less than 0.01). It is concluded that the overall percentage area of fibrosis is the same at magnifications of x10 and x250, despite the fact that at x10 one is unable to detect individual fibers which can be detected at x250. The tracing method of fine cardiac fibrosis at a magnification of x10 is reliable. Therefore, fine fibrosis in large tissue sections of hearts with cardiomyopathy, such as entire transverse sections of the left ventricular wall, can be quantitatively analyzed by this method.

Cardiomyopathies↗
PubMed1985

Kawasaki disease.

Kawasaki disease, a pathologic syndrome known to occur in children, was first described in 1967 as mucocutaneous lymph node syndrome by Kawasaki. The disease occurs chiefly in infants under 4 years of age, presenting with symptoms similar to scarlet fever or Stevens-Johnson syndrome. The changes are found at postmortem and consist of multiple aneurysms and thrombosis, which occur predominantly in the coronary arteries and are responsible for sudden death in most cases. Kawasaki disease is a systemic, acute inflammatory disease entity and in the early stages shows diffuse, necrotizing necrosis. Vasculitis affects primarily the arterioles, venules, and capillaries. Once aneurysmal dilatation has taken place, the wall of the coronary aneurysm becomes thin and the basic structures are destroyed by infiltration of inflammatory cells, which is followed by scar formation within 1 month from the onset of the disease. Coronary arterial lesions are nowadays responsible for the increase of myocardial infarction among the patients. Causes of sudden death include acute ischemia from obstruction or narrowing of the main coronary artery due to thrombosis, thickening of the vascular walls, myocarditis, rupture, and involvement of the conduction system by inflammatory infiltrates, resulting in complete atrioventricular block.

Blood Vessels↗
PubMed1985

Single stranded DNA binding antibodies in patients with obstructive jaundice.

An elevation of single stranded (ss) DNA binding antibodies was present in patients with biliary tract stones and/or tumor of the biliary tract or of the pancreas. The incidence of the appearance of ssDNA binding antibodies was 22 percent in cases of non-obstructive jaundice and 50 percent in those with obstructive jaundice. The incidence was particularly high (70 percent) in patients with obstructive jaundice of over 50 days duration. No significant correlation was seen between the levels of ssDNA binding antibodies and the serum total bilirubin. However, a significant correlation was observed between the levels of ssDNA binding antibodies and the serum IgM.

Adult↗
PubMed1985

Rationale for bone marrow transplantation in the treatment of autoimmune diseases.

Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (greater than 2 mo) or male BXSB (H-2b) mice (9 mo) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (less than 2 mo), the recipients survived for more than 3 mo after the bone marrow transplantation and showed no graft-versus-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnormal T-cell functions were restored to normal. The newly developed T cells were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considerable involution, as in the case of BXSB or MRL/1 mice in the present studies. These findings suggest that marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice.

Animals↗
PubMed1985

Number and size of myocytes, amount of interstitial space and extent of disarray of the hearts in patients with systemic hypertension and asymmetric septal hypertrophy.

Wall thickness, the extent of disarray, the number and the size of myocytes and the amount of interstitial space were measured in the ventricular septum (VS) and left ventricular (LV) free wall in hearts of 6 patients with chronic systemic hypertension and asymmetric septal hypertrophy (ASH). Twenty-five subjects (15 with no cardiac disease, and 10 with systemic hypertension) without ASH served as the controls. In the six patients with ASH, the degree of ASH ranged from 1.3 to 1.6. The extent of disarray in VS was 20% in one heart and within normal limits (mean +/- SD = 3 +/- 3%) in the other 5. The size of myocytes increased both in the VS and LV free wall and the VS/LV ratio ranged from 0.9 to 1.0. There was no significant difference in the % area of interstitial space between hearts with ASH and controls, and the VS/LV ratio ranged from 0.9 to 1.1. The number of transmural muscle layers (number of myocytes) was 680 +/- 90 in the VS and 440 +/- 40 in the LV free wall of these with ASH, and 500 +/- 60 in the VS and 490 +/- 60 in the LV free wall of control subjects. The VS/LV ratio of the number of myocytes ranged from 1.3 to 1.7 and was correlated with the VS/LV ratio of wall thickness. Although the sample is small, our findings suggest that most hearts from patients with chronic systemic hypertension and ASH have no diffuse disarray in the VS and that ASH probably occurs secondary to pressure overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Macroscopic hemorrhagic infarction following selective coronary thrombolysis in acute myocardial infarction.

Macroscopic hemorrhagic infarction was studied in 14 autopsied hearts with selective coronary thrombolysis (SCT) after acute myocardial infarction (AMI). In all patients urokinase, 240,000 - 720,000 units, had been selectively injected into ischemia-related coronary artery at 2 - 7 hours after the onset of AMI. The degree of stenosis after SCT was 90 - 99% in 13 patients and 100% in one patient. According to the duration of illness at death, the 14 patients were classified into 3 stages; stage I: 4 - 9 hours; stage II: 15 hours to 11 days; stage III: 19 days to 12 months. Three hearts in stage I had no macroscopic hemorrhage. In stage II, marked and diffuse hemorrhage in the infarct area was macroscopically evident in 6 of 7 hearts. In a stage II patient, extravasation of contrast medium into the myocardium was found at 3 hours after the onset of AMI. In stage III, 4 hearts had massive fibrosis or granulation in the left ventricular wall without macroscopic hemorrhage. Cardiac rupture was seen in 4 of 10 patients from stages I and II. It is concluded that macroscopic bleeding appears in most patients with AMI treated with coronary thrombolysis. In the majority of cases, the hemorrhage increases gradually after SCT and becomes macroscopically definite approximately 15 hours after the onset of AMI. Rarely, massive bleeding appears earlier. Hemorrhagic infarction is replaced by massive fibrosis after approximately 2 weeks.

Aged↗
PubMed1985

Hepatomegaly and splenomegaly in Kawasaki disease.

Pathologic studies of the liver were performed on 30 autopsied cases of Kawasaki disease. The cases were classified into four groups (stages I-IV), and stage IV was further divided into two subgroups according to the duration of the illness at the time of death. Liver weights were markedly increased in stage II (12-25 days) and in stage III (28-36 days) but returned to normal in stage IVb (7 months to 6 years). Likewise, spleen weights were also markedly increased in stages II and III. Stage I (0-9 days) and stage II were characterized by acute inflammation in portal area, and degree of inflammatory changes decreased gradually. There was significant correlation between hepatomegaly and the degree of inflammation in portal areas, but not with definite heart failure or the use of drugs. These data suggest that the pathogenesis of hepatomegaly in acute-stage Kawasaki disease involves the inflammation in portal areas and/or latent heart failure.

Child↗
PubMed1985

Synthesis and antibacterial activity of 6315-S, a new member of the oxacephem antibiotic.

The synthesis and in vitro activity of 7 beta-difluoromethylthioacetamido-7 alpha-methoxy-3-[[1-(hydroxyethyl)-1H- tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylic acid sodium salt, 6315-S, are described. 6315-S shows good antibacterial activity against Gram-positive and Gram-negative bacteria, being especially highly active against clinical isolates of Staphylococcus aureus resistant to either ampicillin or methicillin. The structure-activity relationship of related 1-oxa and 1-thia cephems is also presented.

Bacteria↗
PubMed1985

Genetic studies on the skin lupus band test in New Zealand mice.

We found that the lupus band test (LBT) is frequently positive in the tail skin in NZB and NZB X NZW (B/W) F1 hybrid mice. Genetic mode of development of this positivity was investigated in female NZB, NZW, B/W F1 hybrid and B/W F1 X NZW back-cross mice and the incidences were 60%, 0%, 100% and 42% by 12 months of age, respectively. It was found that B/W F1 hybrid mice showed not only a higher incidence but also an earlier onset of LBT positivity than did the parental NZB mice. These findings suggested that a single dominant locus in NZB strain determines the appearance of a positive LBT and that this trait is to a great degree intensified by the involvement of NZW gene(s) in B/W F1 hybrid mice. Linkage studies indicated that the NZB gene is to some extent linked to H-2 complex. In addition, there were significant associations between the LBT positivity and the appearances of anti-dsDNA antibodies and renal disease in B/W F1 X NZW back-cross mice. Thus, it is suggested that the NZB-LBT gene is the gene itself or closely linked, on chromosome 17, to that related in part to the occurrence of anti-DNA antibodies and renal disease. There was a lack of retroviral gp70 deposition at the dermo-epidermal junction in NZB and B/W F1 hybrid mice, in that the gp70 is the predominant antigen in the immune complexes deposited in the diseased renal glomeruli.

Animals↗
PubMed1985

The influence of thymic abnormalities on the development of autoimmune diseases.

The relationship between thymic abnormalities and development of autoimmune diseases was studied in MRL/l and NZB/NZW F1 (NZB/W F1) mice. Thymic abnormalities, including plasma cell infiltration into the thymus, were observed in 25% of MRL/l mice as early as 1 mo and in all mice after 2.5 mo. The thymic abnormalities preceded both infiltration of lymphoid cells into the kidney and salivary glands, and also preceded an increase in the titer of circulating immune complexes (CIC). When MRL/l and NZB/W F1 mice were divided into two groups for each strain at the critical age when the mice had begun to show thymic abnormalities, the group with abnormal thymuses showed more marked pathological findings in other organs and a higher level of CIC than the group with more normal appearing thymus. In addition, the group with abnormal thymus demonstrated lower responsiveness of their lymphocytes in mixed-lymphocyte culture than the group with normal thymus. Thymus grafts from donors of autoimmune or non-autoimmune strains into nude mice revealed that thymic functions, reconstitutive of immunologic parameters of nude mice, are rapidly lost with age. These results suggest that morphological and functional abnormalities of the thymus are involved in the pathogenesis of autoimmune diseases.

Age Factors↗
PubMed1985

IgA containing circulating immune complexes and IgA anti-single stranded DNA antibodies in patients with obstructive jaundice.

Elevated levels of IgA containing circulating immune complexes (IgA-CIC) and IgG containing (IgG-) CIC were detected in patients with obstructive jaundice due to biliary tract stones and/or tumour of biliary tract or pancreas. Levels of serum IgA were also elevated, and correlated with the levels of IgA-CIC. The levels of IgA and IgG anti-single stranded (ss) DNA were elevated, and there was a significant correlation between the levels of IgA-CIC and IgA anti-ssDNA antibodies. The cause of IgA-CIC increase in patients with obstructive jaundice might be due not only to simple obstruction of biliary tract but also to other factors such as a tissue destruction.

Adult↗
PubMed1985

Effect of FUT-175, a new synthetic protease inhibitor, on the development of lupus nephritis in (NZB x NZW) F1 mice.

FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulphonate), a new synthetic protease inhibitor, was administrated to (NZB x NZB) F1 mice in order to examine its influence on the development of autoimmune diseases. A dose (400 mg/kg of body weight) of FUT-175 has both prophylactic and curative effects on the development of lupus nephritis: mice showed a significantly low percentage of proteinuria, a marked decrease in BUN levels, and the lowest degree of glomerular damages. Dexamethasone had almost the same effect as FUT-175 (400 mg/kg), but it was slightly less effective than FUT-175. These results suggest that the administration of FUT-175 may become a viable strategy for the treatment of human autoimmune diseases.

Animals↗
PubMed1985

Abnormal stem cells in autoimmune-prone mice are responsible for premature thymic involution.

Autoimmune-prone mice show premature thymic involution, including morphological and functional abnormalities. To determine why the thymic abnormalities develop in autoimmune-prone mice, transplantation of the thymus and/or bone marrow was performed. When thymuses of newborn MRL/1 (H-2k) mice were grafted into C3H/HeN nu/nu(H-2k) mice, the engrafted thymuses did not show the abnormalities which characterize the thymus in the autoimmune-prone MRL/1 mice. By contrast, when thymuses of newborn C3H/HeN or MRL/n mice were grafted into MRL/1 mice, the engrafted thymuses developed after an interval of 3 months the same morphological abnormalities as were seen in MRL/1 mice. Thus, we can conclude that premature involution of the thymus in autoimmune-prone mice may not be a genetically determined abnormality intrinsic to the thymus, but rather an abnormality secondary to other events occurring in these mice. When bone marrow of young C3H/HeN nu/nu mice was transplanted into irradiated (850 rad) MRL/1 mice, neither thymic abnormalities nor autoimmune diseases developed. Therefore, it seem likely that abnormal stem cells in autoimmune-prone mice induce thymic abnormalities, and these, in turn, are associated with the development of autoimmune diseases.

Animals↗