Search PubMed⌕ Search

Biomedical subjects

I Nakamura

Publications and source records attributed to I Nakamura.

At least 235 records · Page 13Linked to original sources

Acute rejection of allogeneic hemopoietic progenitors by genetically resistant mice.

Natural resistance to hemopoietic allograft results in functional elimination of the graft from the host within 24 to 48 h. The resistance is specific and is directed to the cell surface target structures of an unidentified nature. These determinants are controlled by the major histocompatibility complex-linked hemopoietic histocompatibility (Hh) loci and expressed by cells of the hemopoietic system. In this study, the susceptibility of various hemopoietic progenitors, as well as the nature and the kinetics of the early rejection process, were examined by directly following the functional survival of the grafted progenitors by periodic sampling. In both F1 hybrid and inbred allogeneic hosts, multipotential progenitors for granulocyte-erythrocyte-monocyte-megakaryocyte lineages, bipotential progenitors for granulocyte-monocyte lineages and unipotential progenitors of erythrocyte, granulocyte and monocyte were susceptible to elimination. Therefore, within the limited range of comparisons, neither the lineage, nor the degree of commitment or differentiation determines the susceptibility of hemopoietic progenitors to resistance. Functional elimination of the grafted progenitors from the recipient spleen was irreversible upon cultivation in semisolid medium. The frequency of seeding in the spleen at 3 h was comparable in resistant and susceptible hosts; elimination commenced shortly afterwards and by 24 h after transplantation less than 10% of clonogenic progenitors remained functional. Activation of natural killer cells strengthened pre-existing resistance, but did not convert genetically susceptible mice to resistant. Therefore, the resistance is dependent on an effector mechanism with predetermined specificity.

Animals↗

An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters.

An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters is reported. A 33-year-old woman showed a progressive dementia and died of cardiac failure at the age of 45. Neurological examination disclosed choreatic movements, myoclonus, rigidity, and generalized convulsion. Gross inspection of the brain showed a diffuse cerebral atrophy and marked degenerations of both the subcortical gray and white matters. Microscopically, numerous and extensive argyrophilic changes such as senile plaques, neurofibrillary tangles, and granulovacuolar degenerations were observed in the brain. The present case was characterized by a severe neuronal loss in the basal ganglia, substantia nigra, dentate nucleus, and thalamus as well as a marked myelin loss and axonal damage in the cerebral white matter. This case suggested a combination of multisystemic degeneration and primary degeneration of the cerebral white matter. The pathological similarity of this case to Creutzfeldt-Jakob disease and Pick's disease is discussed.

Adult↗

Establishment of a human T-cell clone cytotoxic for both autologous and allogeneic hepatocytes from chronic hepatitis patients with type non-A, non-B virus.

A human T-cell clone (TA-NB-2) that could lyse both autologous and allogeneic hepatocytes from chronic hepatitis patients with type non-A, non-B virus (NANB) was established. This clone produced CD3+ CD8+ cytotoxic T lymphocytes and expressed an antigen specific for alpha and beta subunits of T-cell receptor. The cytotoxic activity of the clone was abrogated by incubation with anti-CD3 monoclonal antibody. Anti-HLA monoclonal antibodies did not block the lysis of the target hepatocytes by TA-NB-2 cells. The cytotoxicity of TA-NB-2 clone against hepatocytes from patients with chronic NANB hepatitis was 39.8 +/- 13.2% (mean +/- SD; n = 17) (range, 14.2-60.5%), whereas that against hepatocytes from control patients with chronic type-B hepatitis, acute hepatitis B, acute hepatitis A, or alcoholic liver cirrhosis was 4.0 +/- 7.7% (n = 12) (range, -10.8 to 14.0%). The results suggest that TA-NB-2 cells specifically recognize a hepatitis NANB-related antigen expressed on hepatitis NANB-infected hepatocytes by T-cell receptor and that the recognition is not restricted by the major histocompatibility complex antigens. The results also suggest that most, if not all, cases of chronic hepatitis due to NANB are caused by one agent; TA-NB-2 clone may be useful as a tool to identify this particular hepatitis-related antigen.

Antibodies, Monoclonal↗

Further postmortem examination of a case of familial ataxia with cerebrospinal fluid abnormality: an electron microscopic study of the intracytoplasmic eosinophilic inclusion bodies in the central nervous system.

As reported previously, the peculiar intracytoplasmic eosinophilic inclusion bodies (IEIBs) extensively appeared in the autopsied brain tissue from a 49-year-old man having familial ataxia with cerebrospinal fluid abnormality, and histochemically showed abundant proteins, but few lipids and carbohydrates. Ultrastructurally, many membrane-bound vacuoles derived from the distended cisterns of rough-surfaced endoplasmic reticulum (RER) appeared in the neurons. They were filled with fine granular, less dense materials. The IEIBs, shown as a homogeneous dense core, were found in some of the vacuoles. Similar vacuoles also appeared in astrocytes, oligodendrocytes, vascular pericytes, ependymal and choroidal epithelial cells. It is suggested that the vacuoles result from the accumulation of metabolic products in the distended RER cisterns of the cells in the central nervous system, presumably representing a genetically determined functional abnormality of the RER in protein synthesis and/or transport.

Astrocytes↗

[Intracytoplasmic eosinophilic inclusions in dorsal root ganglia and spinal nerve roots from an autopsy case of unusual familial ataxia with cerebrospinal fluid abnormality].

Studies were performed on the light and electron microscopic structures of the dorsal root ganglia (DRG) and spinal nerve roots of the 4th lumbar nerve obtained by autopsy from a 49-year-old man with unusual familial ataxia, who showed varied neurological manifestations such as progressive ataxia, action tremors, pyramidal tract signs, mild deep sensory disturbances and autonomic dysfunctions during a 30-year period of illness, and had 2 siblings, one male and female, similarly affected and close consanguineous marriages in his family. On laboratory examinations, blood chemistry disclosed no significant findings. Repeated spinal taps showed constant xanthochromia and elevated protein in the cerebrospinal fluids. A PEG and cranial CTs revealed a progressive brain atrophy. NCVs and EMGs in the extremities were within normal limits. There was no chromosomal abnormality. Light microscopically, intracytoplasmic eosinophilic inclusions (IEIs) with pale rim, which showed varied sizes and rounded shapes, occurred within neurons in the DRG, particularly in small neurons. Many of the small neurons had numerous IEIs, and several rounded granules with a high degree of eosinophilia, measuring below 5 microns in diameter. Generally the small neurons showed atrophic, while most large neurons showed no remarkable change although they had a small number of IEIs and granules located in the perikaryal periphery. Most satellite cells, and some Schwann cells in the DRG, ventral and dorsal roots had IEIs similar to those seen in the neurons. No IEIs occurred intraaxonally, and there was seen no degenerative process in the DRG and roots except a connective tissue fiber proliferation in the DRG.(ABSTRACT TRUNCATED AT 250 WORDS)

Ataxia↗

Oncogenic potential of hepatitis B virus.

The function of the X gene was clarified by examination of the transient production of hepatitis B virus (HBV) particles by transfected recombinant HBV DNA (pHBV-3 DNA) and its frameshift mutant (delta X) of the X open reading frame into hepatocellular carcinoma HuH-7 and HepG2 cells. No reduction of viral mRNAs was observed in the HuH-7 cells by the delta X mutant, whereas mRNAs underwent marked reduction in HepG2 cells. No reduction in core particle production was observed in HuH-7 cells, but in HepG2 cells reduction was considerable. To clarify the significance of the delta X mutation in the trans-acting function of the X gene in hepatoma cells, the chloramphenicol acetyl/transferase (CAT) assay was conducted. Transfection of plasmid pHBV-3 into HepG2 cells increased CAT activity of pSV2-CAT, while the delta X mutation clearly showed no stimulation of activity. On the other hand, in the HuH-7 cells, pHBV-3 exhibited no such stimulation. The trans-acting function of the X gene product in two different hepatoma cells was clearly shown to differ. Furthermore, transfection of X gene expression plasmid pKSV-HBx into mouse NIH3T3 cells increased the CAT activity of pSV2-CAT. Trans-activation was still detectable even following deletion of enhancer sequences in the pSV2CAT. The oncogenic potential of HBV is discussed with special attention to the X gene product, which may be able to activate a cellular transcription factor at the viral and cellular promotor sequences in the cells.

Animals↗

Dispermic chimera associated with dysgerminoma.

A 12-year-old female patient (Miss E.Y.) suffering from abdominal tumor was proved to be a dispermic or generalized chimera. Ninety-two percent of her red cells were group A1, the first locus of phosphoglucomutase (PGM1) 1A, 6-phosphogluconate dehydrogenase (PGD) AC and 8% of them were group B, PGM1 1A-2A, PGD A. Ninety cells out of one hundred and ten cultured lymphocytes were normal 46 XY and 20 cells were normal 46 XX. She secreted B and H substances at normal secretor range and a small amount of A substance in her saliva. The A-transferase level found in her serum was about 40% of those of group A1 individuals. The B-transferase level was in the normal range. Her hairs had B antigen and PGM1 phenotype of their root cells was 1A-2A. The cells of hair root were X chromatin-positive and Y body-negative. Her nails had lesser A antigen and potent B antigen. Major epithelial cells (approximately 75%) of her buccal mucosa expressed B antigen and minor cells expressed A antigen. The proportion of the X chromatin-positive buccal cells (15%) was lower than those in normal females (20-25%) and that of Y body-positive buccal cells (10%) was higher than those in normal females (0-3%). The surgically resected abdominal tumor was her right uterine adnexa with malignant transformation, the histological diagnosis of which was dysgerminoma. The tumor cell nest and the epithelial cells of ductal structure expressed A antigen, whereas the endothelial cells of blood vessels expressed B antigen. These findings showed that the proband's body cells arose from the two cell lines, one carrying A1 gene had normal 46 XY male karyotype and another carrying B gene had normal 46 XX female karyotype, and suggested that her right gonad which was contributed by the former cell line had a malignancy in the presence of Y chromosome.

ABO Blood-Group System↗

A3 phenotype with A1 gene-specified enzyme character in serum.

We found an active A enzyme in the serum of A3 phenotype. The level of enzyme activity, pH optimum, Km and Vmax values, and heat stability were not different from those of A1 gene-specified enzyme. Red cell membrane from anti-A agglutinable cells showed weak A enzyme activity, whereas those from unagglutinable cells did not. From these results, it was assumed that the weak A expression in the present case is due to the suppression of A enzyme production only in hemopoietic tissues. This special A3 phenotype is highly accumulated in the Toyama district (frequency of approximately 0.00086).

ABO Blood-Group System↗

[A case of familial juvenile Alzheimer's disease with apallic state at the relatively early stage and various neurological features--a clinicopathological study].

A case of familial juvenile Alzheimer's disease with apallic state at the relatively early stage and various neurological features was reported. A 33-year-old woman showed a progressive dementia followed by apallic state at the relatively early stage, and died of cardiac failure at the age of 45. Neurological examination disclosed chorea, myoclonus, rigidity, pyramidal sign, and generalized convulsion. Neuropathologically, extensive senile changes such as senile plaques, neurofibrillary tangles, and granurovascular degenerations were observed in the brain, chiefly in the cerebral cortex and limbic system. The present case was characterized by a severe neuronal loss in the subcortical gray matter such as the caudate nucleus, dentate nucleus, substantia nigra, and thalamus as well as a marked myelin loss and axonal damages in the cerebral white matter. This case suggested a combination of multisystemic degeneration and a primary degeneration of the cerebral white matter. The additional peculiar aspects in this case were the senile plaques and amyloid angiopathy in the cerebellar cortex, and the senile plaques and grumose degeneration in the cerebellar dentate nucleus. In the clinicopathological standpoint, the apallic state in this case could be attributed to a severe degeneration of the cerebral white matter in addition to the cerebral cortical deterioration. Furthermore, the occurrence of chorea and myclonus might be contributed to the severe degeneration of the caudate nucleus and to the degeneration of the dentate nucleus, particularly to the grumose degeneration, respectively.

Age Factors↗

Effects of halothane and calcium entry blockers on atrioventricular conduction-a comparative study of verapamil, diltiazem, and nifedipine.

The effects of halothane on AV nodal function were evaluated in dogs with verapamil, diltiazem, or nifedipine during atrial pacing using the technique of His-bundle electrocardiography. Fifty-one mongrel dogs were divided into six groups. Anesthesia was induced with ketamine 100 mg im. and thiamylal 25 mg/kg iv. The animals were intubated and mechanically ventilated at normocapneic levels. Anesthesia was maintained with 50% nitrous-oxide in oxygen with pancuronium 2 mg im. Dogs in groups I, III, and V were anesthetized with 0.8% halothane and 50% nitrous-oxide in oxygen. We observed interactions between halothane and intravenous administration of either verapamil 0.1 mg/kg, diltiazem 0.15 mg/kg, or nifedipine 0.01 mg/kg respectively. Dogs in groups II, IV, and VI were administered either verapamil, diltiazem, or nifedipine iv without halothane. There were prolongations of sinus cycle length (SCL) (414 +/- 10 to 542 +/- 19 msec.), atrium-His (AH) interval (73 +/- 3 to 97 +/- 5 msec.), and functional refractory period (FRP) of the AV-node (227 +/- 5 to 260 +/- 5 msec.) in halothane anesthesia in groups I, III, and V. There were more prolongations of these variables after iv administration of verapamil (SCL; 617 +/- 35, AH; 118 +/- 7, FRP of the AV node; 311 +/- 4) and diltiazem (SCL; 554 +/- 19, AH; 118 +/- 12, FRP of the AV node; 283 +/- 12) but no prolongations after nifedipine (SCL; 533 +/- 19, AH; 99 +/- 8, FRP of the AV node; 272 +/- 9). Comparing effects of calcium entry blockers with and without halothane in groups I and II, III and IV, or V and VI, there were additive depressing effects of halothane with either verapamil or diltiazem on AV nodal function. And there is a difference between the effects of nifedipine on SCL with and without halothane.

Journal Article↗

The nature of hemopoietic histocompatibility determinants. Differential sensitivity of Hh-1b and H-2b determinants to tunicamycin.

NK cell-dependent resistance of F1 hybrid mice to parental H-2b hemopoietic allografts is directed to cell surface structures controlled by the Hh-1 locus in or near the H-2D region. Crucial to an understanding of this enigmatic phenomenon is the information on the biochemical nature of the Hh-1 locus-controlled structures. Therefore, we examined the effect of tunicamycin (TM), an inhibitor of asparagine-linked glycosylation and ganglioside biosynthesis, on the expression of Hh-1 determinants in H-2b/Hh-1b lymphomas. The Hh-1b determinants on EL-4 and RBL-5 cells were no longer detectable after TM treatment, as demonstrated by the failure of the treated cells to inhibit hybrid resistance to parental H-2b bone marrow cells in vivo. This interpretation was supported by the unaltered ability of the TM-treated cells to localize in the spleens of irradiated F1 hybrid recipients. In contrast, TM caused only moderate reduction in H-2Kb and H-2Db expression as measured by binding of specific antibodies. This was accompanied by reduced susceptibility to alloimmune anti-H-2Db CTL, but not to anti-H-2Kb CTL. No decrease was found in the susceptibility to NK cell cytotoxicity in vitro. These data indicate that N-linked glycosylation or ganglioside synthesis is crucial for the expression of the Hh-1 locus-controlled target structures, but not for the H-2 class I molecules. The data also show that the Hh-1b determinants are substantially different from those which confer the susceptibility to NK cell-mediated in vitro cytotoxicity.

Animals↗

Characterization of a human monoclonal antibody with broad reactivity to malignant tumor cells.

Lymphocytes from mediastinal lymph nodes of 9 patients with primary lung cancer were fused with murine myeloma cells (P3U1). One of the clones (4G12) was stable for secretion (10 micrograms/ml) of human IgM lambda for 24 months. The antigen detected by 4G12 was sensitive to both trypsin and periodic acid-Schiff treatment. It immunoprecipitated a glycoprotein with an Mr of 65,000 upon analysis in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reduced conditions. Immunohistochemical staining demonstrated that 4G12 possessed a high reactivity to squamous cell carcinomas of the lung (29 of 29) and also reacted with other lung carcinomas [adenocarcinomas (14 of 20) and large cell carcinomas (3 of 8)] and with some nonpulmonary malignant tumors (15 of 56). However, it did not react with small cell carcinomas of the lung. No benign tumors (0 of 26) so far tested have been positive. 4G12 did not react with most of the normal tissues; an exception was that it was weakly reactive on the glandular cells of the trachea and bronchi and on the proximal tubular cells of the kidneys. Thus 4G12 showed a broad reactivity to malignant tumors (68% of lung carcinomas, 27% of nonpulmonary carcinomas, and 0% of benign tumors). The reactivity of 4G12 on tissues from squamous cell carcinomas of the lung indicated that the expression of the antigenic determinant was much more in the well-differentiated grade than in the poorly differentiated grade. Thus the antigen detected by 4G12 appears to be related to tumor differentiation. Moreover, fluorescence-activated cell sorter analysis demonstrated that the expression of the antigen epitope depended on the cell cycle (G2-M). These data suggest that the 4G12 monoclonal antibody detects a new tumor-associated antigen that is recognized by the human immune system.

Adenocarcinoma↗

Role of actin filaments in shape formation of mesenteric mesothelial cells of the bullfrog.

The role of actin filaments in the development of cellular shape in the mesenteric mesothelium of the bullfrog was studied by using a simple, new technique for making en face preparations of mesothelial sheets. By using these mesothelial cell preparations, the distribution of actin was determined by means of fluorescence microscopy with 7-nitrobenz-2-oxa-1,3-diazole (NBD)-phallacidin and that of myosin by means of immunofluorescence microscopy. Although fluorescence produced by both NBD-phallacidin and antimyosin staining was found exclusively along the margins of the cells, its intensity was altered in correspondence with changes in cell shape. For instance, tadpole-type mesothelial cells with either an irregular or very slender cell shape showed very weak fluorescence. On the other hand, frog-type mesothelial cells with a polygonal shape showed intense fluorescence at their margins and had circumferential bundles of actin filaments at their apices. Furthermore, intercellular junctions between the mesothelial cells developed as the cell shape became polygonal during metamorphosis. The present study showed that development of circumferential bundles of actin filaments and intercellular junctions may serve to establish and maintain the definitive polygonal cellular pattern in the mesenteric mesothelium of the bullfrog.

Actins↗

Isolation of genomic DNA controlling mouse melanoma antigen defined by monoclonal antibody.

We have isolated the genomic DNA controlling the expression of murine specific melanoma antigen by employing cosmid shuttle vector and monoclonal antibody. Transfection of the cosmid library derived from mouse melanoma cells into human melanomas and repeated cell sortings of the fluorescence-bright population enabled us to enrich the antigen-positive transfectants. We rescued a 34.8 kb DNA fragment from the transfectants by in vitro packaging and showed it to be responsible for the antigen expression. However, we noticed instability of the antigen expression when the selection pressure imposed by the cell sorting was removed. This seemed to be due to the fact that the insert DNA was preferentially deleted from this cosmid vector without loss of the vector sequence itself.

Animals↗