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Biomedical subjects

M Amari

Publications and source records attributed to M Amari.

At least 19 recordsLinked to original sources
PubMed2001

Pathological study of the diffuse myelin pallor in the anterolateral columns of the spinal cord in amyotrophic lateral sclerosis.

An immunohistochemical study using a monoclonal antibody against macrophage (Ki-M1p) was performed to examine which fiber tracts are affected in the spinal cords and brainstems of ALS patients. In 21 out of 30 ALS patients, various degrees of macrophage infiltration were observed diffusely in the anterolateral columns beyond the corticospinal tracts. On the other hand, a few macrophages were scattered in 20 non-ALS patients in the anterolateral columns outside the corticospinal tracts. In ALS brainstems, the macrophages were mainly localized in the corticospinal tracts. The result suggests that the diffuse myelin pallor in the anterolateral columns beyond the corticospinal tracts may be derived from intrinsic spinal cord lesions. Quantitative investigation using a monoclonal antibody against phosphorylated neurofilaments (SMI-31) revealed that the decrease in the numbers of small fibers would induce the diffuse myelin pallor in anterolateral columns of ALS patients. From these findings, we propose that the propriospinal bundles are candidates for the degenerating fibers in the anterolateral columns of ALS.

Adult↗
PubMed2001

Induction of lymphocyte apoptosis in rat liver allograft with ongoing rejection by FTY720.

The action mechanism of FTY720, a novel immunosuppressant, is completely different from conventional immunosuppressants. The drug, which triggers apoptosis in murine and human lymphocytes, has a potent immunosuppressive activity to prevent allograft rejection without any severe side-effect. The present study was designed to determine whether FTY720 induces apoptotic cell death in activated lymphocytes infiltrated into liver grafts with ongoing rejection. FTY720 was orally administered at 5 mg/kg to the recipients on day 3 and day 4 after grafting, when the graft rejection was histologically confirmed. The intragraft patterns of IL-2, interferon-gamma (IFN-gamma), perforin, and granzyme B gene expression were detected by reverse transcriptase-polymerase chain reaction. The treatment reversed ongoing rejection and significantly prolonged recipient survival time compared with the control group. Light microscopic observation of the graft sections stained with the DNA nick-end labelling method showed that the apoptosis in the control allografts was mainly induced in hepatocytes, while that in the FTY720-treated allografts was in infiltrated lymphocytes. The rejection therapy with FTY720 did not alter the expression of IL-2, IFN-gamma, and perforin mRNAs, but slightly decreased granzyme B expression. Our results suggest that FTY720 does not alter the intrinsic lymphocyte function to produce the rejection-related cytokines, but strongly induces apoptotic cell death in the activated lymphocytes. Thus, FTY720 affords new insight into the mechanisms underlying improvements in immunosuppressive treatments.

Animals↗
PubMed2000

Correlation of three-dimensional magnetic resonance imaging with precise histopathological map concerning carcinoma extension in the breast.

This study was initiated to clarify the ability of magnetic resonance imaging (MRI) in defining breast carcinoma extension by comparing MRI to detailed histopathological analysis. Mastectomy (n = 14) or quadrantectomy (n = 44) specimens were sub-serially sectioned and mapped in detail in 58 breast cancer patients. Morphologically, we classified the lesions utilizing MRI into three patterns in relation to their histology. Numerically, we assessed the maximum distance of carcinoma extension using MRI, mammography, and ultrasonography (US). Linear regression was calculated for each of the three imaging measurements versus histopathological measurements. Three imaging patterns were observed by MRI, (1) localized (n = 30), (2) segmentally extended (n = 19), and (3) irregularly extended (n = 5). The localized pattern showed a distinct focal mass, but in 10 cases, microscopic ductal carcinoma in situ (DCIS), or invasive lobular carcinoma, which were not depicted by MRI, existed. The segmentally extended pattern showed diffuse enhancement along duct-lobular segments, forming a 'cone' shape. Histologically, pure (n = 4) or predominant (n = 10) DCIS was distributed segmentally. The irregularly extended pattern showed thick branches extending out from the index tumor which were histologically revealed to be stromal invasion of ductal carcinoma. From the results of linear regressions, MRI was the most accurate modality in histologically measuring the extent of the cancer. When cases were limited to patients who were classified into segmentally or irregularly extended pattern by MRI (n = 24), MRI was more accurate than mammography and US, even if they were combined (P < 0.05). MRI may provide additional information concerning carcinoma extension prior to surgery, especially in patients classified into 'extended patterns' by MRI.

Adult↗
PubMed2000

Accumulation of NACP/alpha-synuclein in lewy body disease and multiple system atrophy.

OBJECTIVES: NACP/alpha-synuclein is an aetiological gene product in familial Parkinson's disease. To clarify the pathological role of NACP/alpha-synuclein in sporadic Parkinson's disease and other related disorders including diffuse Lewy body disease (DLBD) and multiple system atrophy (MSA), paraffin sections were examined immunocytochemically using anti-NACP/alpha-synuclein antibodies. METHODS: A total of 58 necropsied brains, from seven patients with Parkinson's disease, five with DLBD, six with MSA, 12 with Alzheimer's disease, one with Down's syndrome, one with amyotrophic lateral sclerosis (ALS), three with ALS and dementia, one with Huntington's disease, two with progressive supranuclear palsy (PSP), one with Pick's disease, one with myotonic dystrophy, and three with late cerebellar cortical atrophy (LCCA), and 15 elderly normal controls were examined. RESULTS: In addition to immunoreactive Lewy bodies, widespread accumulation of NACP/alpha-synuclein was found in neurons and astrocytes from the brainstem and basal ganglia to the cerebral cortices in Parkinson's disease/DLBD. NACP/alpha-synuclein accumulates in oligodendrocytes from the spinal cord, the brain stem to the cerebellar white matter, and inferior olivary neurons in MSA. These widespread accumulations were not seen in other types of dementia or spinocerebellar ataxia. CONCLUSION: Completely different types of NACP/alpha-synuclein accumulation in Parkinson's disease/DLBD and MSA suggest that accumulation is a major step in the pathological cascade of both diseases and provides novel strategies for the development of therapies.

Aged↗
PubMed1999

Fragmentation of the Golgi apparatus of Betz cells in patients with amyotrophic lateral sclerosis.

The Golgi apparatus (GA) of the large pyramidal motor neurons in the cerebral cortex (Betz cells), was examined in sixteen patients with sporadic amyotrophic lateral sclerosis (ALS), in one patient with familial ALS (FALS), and in ten non-ALS age matched controls including one patient with Huntington's disease and one patient with a brain infarct. The GA was immunostained with an antibody against the MG-160 protein, a conserved sialoglycoprotein of the medial cisternae of the organelle. In ALS, 13.2% of counted Betz cells had fragmented GA in contrast to 0.6% in the ten non-ALS controls. The fragmentation of the GA of Betz cells was identical to that previously reported in spinal cord motor neurons from patients with sporadic ALS and in transgenic mice expressing the G93A mutation of the gene encoding the Cu/Zn superoxide dismutase. The striking morphological similarity between the fragmentation of the GA observed in Betz cells and in spinal cord motor neurons suggests that a similar pathogenic mechanism is responsible for both, and that the fragmentation of the GA of the spinal cord motor neurons is not a consequence of deafferentation due to the degeneration of the Betz cells.

Adult↗
PubMed1999

Lipoprotein-free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer's disease and Down's syndrome.

About 90% of the soluble amyloid beta (sA beta) that circulates in normal human plasma is associated with lipoprotein particles. In sporadic Alzheimer's disease patients, free sA beta42 but not sA beta40 is increased approximately 2.3-fold compared with age-matched controls, although a more marked elevation (approximately 8-fold for free sA beta40 and about 20-fold for sA beta42) is found in Down's syndrome patients. The data suggest that lipoprotein-sA beta dissociation may contribute to the influx of sA beta into the brain as a result of decreased plasma clearance.

Adult↗
PubMed1998

Combination assay of CSF tau, A beta 1-40 and A beta 1-42(43) as a biochemical marker of Alzheimer's disease.

Cerebrospinal fluid samples from a total of 157 subjects consisting of 55 patients with sporadic Alzheimer's disease (AD), 34 normal controls, 23 patients with non-AD dementia, and 45 with other neurological diseases were examined by ELISA of tau, A beta 1-40, and A beta 1-42(43). The AD group had a significantly higher level of tau than the normal control group (P < 0.001), and the diagnostic sensitivity was 31% and specificity was 94%. CSF A beta 1-40 levels did not show any significant differences. Although the level of A beta 1-42(43) was decreased significantly in the AD group compared to the control group (P < 0.005), the overlap of A beta 1-42(43) levels among all groups meant that none of the AD samples exceeded the cut-off value, the mean 2SD of normal control subjects. Reduction of A beta 1-42(43) levels in AD resulted in a significant increase in the ratio of A beta 1-40 to A beta 1-42(43) (A beta ratio) as an improved marker. The diagnostic sensitivity and specificity of A beta ratio were 51% and 82% respectively. The three indexes, using the tau level and A beta ratio (tau or A beta ratio, deviation score and tau x A beta ratio), showed better sensitivity (58%, 67%, 69%) and specificity (82%, 86%, 88%) than previously reported methods. Combination assay for CSF tau, A beta 1-40 and A beta 1-42(43) in CSF is a biological marker of AD and may be useful to biochemically monitor subjects under treatment.

Adult↗
PubMed1998

Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer's disease: a study in Japan.

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.

Aged↗
PubMed1997

The in vivo induction of lymphocyte apoptosis in MRL-lpr/lpr mice treated with FTY720.

The in vitro treatment of lpr thymocytes with FTY720 resulted in a dose-dependent reduction in cell viability due to apoptosis. In order to study the effect of FTY720 in vivo, lpr mice received an oral daily dose of 1 mg/kg FTY720 for 14 days, beginning at 16 weeks of age which was when the animals were developing massive lymphoadenopathy. Compared with untreated lpr mice, FTY720-treated lpr mice had significantly prolonged lives. At 24 weeks of age, treated mice demonstrated markedly reduced weights of the spleen and lymph nodes, and the proportion of CD3+ B220+ and CD4- CD8- cells in the thymus, spleen and lymph nodes decreased markedly. In addition, in these mice the percentage of CD4+ CD8+ and CD3- B220- cells in the thymus and the percentage of CD4+ CD8-, CD4- CD8+, CD3+ B220- and CD3- B220+ cells in the spleen returned to almost the normal values observed in wild-type mice. Histological observation 1 day after the final administration of FTY720 revealed a remarkable infiltration of neutrophils in the lymphoid organs. Apoptotic cells were detected in all the lymphoid organs using in situ DNA nick-end labelling. Electron microscopy showed that the apoptotic cells were ingested by phagocytes. FTY720 therapy is thus highly effective in Fas-mutant animals with abnormally expanding lymphocytes.

Administration, Oral↗
PubMed1997

Glucose transport by mixed ruminal bacteria from a cow.

The glucose transport of mixed ruminal bacteria harvested from a holstein cow fed 5.0 kg of Italian ryegrass and 1.5 kg of flaked corn a day was investigated. The Eadie-Hofstee plot characterized two transport systems: a high-affinity, low-velocity system and a low-affinity, high-velocity system. The former system (K(m) = 16 microM; Vmax = 2.2 nmol/min/mg of protein) is considered dominant under this feeding condition based on the glucose concentration in the rumen (< 1 mM). In light of the facts that the protonophore SF6847 and the lipophilic triphenylmethyl phosphonium ion had no effect on the high-affinity system and an artificially generated proton gradient and electrical potential across the cell membrane did not increase glucose transport, a proton motive force is not be involved in the system. On the other hand, from the facts that chlorhexidine inhibited about 90% of the high-affinity system while iodoacetate showed no significant effect, and a high phosphoenolpyruvate-dependent phosphorylation of glucose was actually shown, the phosphoenolpyruvate-dependent phosphotransferase system is considered the main system in the high-affinity system. Moreover, as shown by the facts that harmaline inhibited about 30% of the high-affinity system and the artificially generated sodium gradient across the cell membrane significantly stimulated glucose transport, this system also includes sodium symport to some degree. The high-affinity system was sensitive to a decrease in pH (< 6.5) and was inhibited by the presence of sucrose, mannose, and fructose.

Animal Feed↗
PubMed1996

A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation.

A new compound with an immunosuppressive property was purified from culture filtrates of Isaria sinclairii and was chemically modified to FTY720. Rat spleen cells incubated with FTY720 demonstrated features characteristic of apoptosis--such as the absence of surface microvilli, chromatin condensation, and the formation of apoptotic bodies--by electron microscopy, and genemic DNA fragmentation by agarose gel electrophoresis. When FTY720 was administered in liver-allografted rats at a dose of 0.5 mg/kg from day 1 to day 14 after transplantation, the recipients survived significantly longer than the control group. Pretransplant treatment with 5 mg/kg of FTY720 one day before and on the day of grafting induced a remarkable prolongation of recipient survival, and three of 10 recipients survived for longer than 50 days. Furthermore, administration of FTY720 at 5 mg/kg on days 3 and day 4 after grafting also prolonged survival. In canine kidney allografting, a pretransplant 2-day course of FTY720 at 5 mg/kg prolonged graft survival. Daily administration of FTY720 in combination with CsA resulted in a significant prolongation of graft survival in a synergistic manner. In addition, FTY720 appeared to be nontoxic in canine recipients. These results demonstrated that FTY720, having a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation.

Animals↗
PubMed1993

Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum.

Bunina bodies (BBs), small eosinophilic intraneuronal inclusions in the remaining lower motor neurons, are the only pathologically specific hallmark of amyotrophic lateral sclerosis (ALS). During immunohistochemical examinations of spinal cords of patients with ALS, we noted that BBs were positive for anti-cystatin C (CC) serum. Immunoelectron microscopically, many small deposits of immunoperoxidase products were seen in the cytoplasms and dendrites of the anterior horn cells. Some immunoperoxidase products exhibited a tubular or vesicular pattern, but no rough endoplasmic reticula, mitochondria, lipofuscin granules or nuclei were detected. The presence of BBs, especially in the periphery, was marked. In an adult cat, CC was mainly localized in the medial aspects of Golgi apparatus and in lysosomes in the anterior horn cells of the spinal cord. BBs may represent an abnormal accumulation of unknown proteinous material associated with the Golgi apparatus.

Adrenal Medulla↗
PubMed1993

Diagnostic significance of skin immunolabelling with antibody against native cerebral amyloid in Alzheimer's disease.

Skin taken from patients with Alzheimer's disease (AD) and control patient groups were immunolabelled using antisera against either purified native cerebral beta protein or synthetic beta peptide. Native amyloid antiserum frequently labelled vascular walls in AD skin but rarely in control skin. Semi-quantitative analysis of the positive vessels showed a significant difference between the two groups. Sweat glands and dermal nerves were labelled in both groups. However, synthetic beta peptide antiserum showed no significant difference. Vascular wall labelling in skin with native amyloid antiserum is useful in the differential diagnosis of AD.

Aged↗
PubMed1993

Oculomotor nuclear pathology in amyotrophic lateral sclerosis.

We examined the oculomotor and/or trochlear nuclei of 27 amyotrophic lateral sclerosis (ALS) patients and 10 controls by histological and immunohistological methods. Their neurons were relatively well preserved. In 7 of 22 sporadic ALS patients (including 3/3 ALS with ophthalmoplegia) and in 4 of 5 ALS patients with dementia, some morphological changes similar to those in anterior horns (Bunina bodies, ubiquitin-positive skein-like inclusions, Lewy body-like inclusions, conglomerate inclusions and spheroids) were rarely, but clearly seen. These changes were not observed in controls. Our results suggest that the oculomotor and trochlear nuclei in ALS patients are slightly affected in a manner similar to that in the anterior horns, but the degree is less than that necessary for development of ophthalmoplegia in the majority of ALS patients.

Adult↗
PubMed1993

[A case of pontine infarction with persistent primitive proatlantal artery].

A 61-year-old woman was admitted to the hospital on September 18, 1991 because of left hemiparesis, dysphagia, and dysarthria since five days before. She was formerly pointed out diabetes mellitus and hypertension, but she did not receive any treatment. The MRI showed a high signal area in the right paramedian portion of the upper pons on T2 weighted image and proton image. The angiography showed that persistent primitive proatlantal artery originated from the left internal carotid artery and joined to the horizontal portion of the left vertebral artery. The image of carotid-vertebrobasilar system and proatlantal artery showed so severely arteriosclerotic. This is the first report of brainstem infarction with persistent primitive proatlantal artery. In this case, the pontine infarction was thought to occur on the basis of the arteriosclerosis of blood vessels and change of blood flow of carotid-vertebrobasilar system due to persistent primitive proatlantal artery.

Basilar Artery↗
PubMed1990

Alpha 1-antichymotrypsin as a possible biochemical marker for Alzheimer-type dementia.

We measured serum alpha 1-antichymotrypsin levels in 38 patients with Alzheimer-type dementia, 89 control subjects, 2 subjects with Down's syndrome, 20 with vascular dementia, 18 with Parkinson's disease, 14 with spinocerebellar degeneration, 15 with cerebrovascular disease without dementia, and 14 with Duchenne muscular dystrophy. Cerebrospinal fluid (CSF) levels of alpha 1-antichymotrypsin were also measured in 15 patients with Alzheimer-type dementia, 26 control subjects, 6 with vascular dementia, 7 with cerebrovascular disorder, and 11 with degenerative disorders. In control subjects, there were no age-related changes or sex differences. Serum and CSF levels were significantly and specifically higher in patients with Alzheimer-type dementia than in other subjects (serum, p less than 0.001; CSF, p less than 0.05). Serum levels of alpha 1-antichymotrypsin were significantly elevated in the early stage of Alzheimer-type dementia, whereas there was no definite correlation between serum levels and the degree of dementia. CSF levels of alpha 1-antichymotrypsin tended to parallel the severity of dementia. Serum levels were not correlated with CSF levels. These data indicate that serum and CSF levels of alpha 1-antichymotrypsin might be independently upregulated in Alzheimer-type dementia. We concluded that the measurement of serum levels of alpha 1-antichymotrypsin could be useful as a screening marker for Alzheimer-type dementia. In addition, CSF levels also could be a useful marker for Alzheimer-type dementia, because they might reflect the state of dementia.

Age Factors↗