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Biomedical subjects

Y Tanuma

Publications and source records attributed to Y Tanuma.

At least 19 recordsLinked to original sources

[Microsatellite polymorphism of muscle glycogen synthase gene and non-insulin dependent diabetes mellitus].

It has been reported recently that A2 allele of muscle glycogen synthase gene determined by Xba I RFLP (restriction fragment length polymorphism) is related to the frequency of NIDDM in Finland. Using PCR-RFLP analysis, we detected no A2 allele in Japanese patients with NIDDM and control. We found a new microsatellite of CA repeat in the human muscle glycogen synthase gene, and the polymorphism of the repeat number was detected by the polymerase chain reaction. Six different alleles were observed, indicating the highly polymorphic nature of this marker. We analyzed the repeat numbers and the genotypes in diabetics and control. The allele frequencies were not significantly different between NIDDM and control. However, the allele frequencies in the patients without high total cholesterolemia was significantly different from those of control. These findings suggest that the muscle glycogen synthase gene or neighboring genes are related to one of the disease genes of diabetes mellitus without high total cholesterolemia.

Adolescent

A silencer element for the lipoprotein lipase gene promoter and cognate double- and single-stranded DNA-binding proteins.

Transfection experiments with constructs containing various 5'-deleted fragments of the human lipoprotein lipase (LPL) promoter and the chloramphenicol acetyltransferase reporter gene revealed an LPL silencer element (LSE) in the region of nucleotides -225 to -81 of the LPL gene that functioned in Chinese hamster ovary (CHO) and HeLa cells. Gel retardation competition analysis showed the presence of a nuclear factor(s) capable of binding to the sequence of nucleotides -169 to -152 of LSE (LSE-6) in a single-stranded (opposite-strand) and double-stranded specific fashion, the binding affinity being almost the same in the two binding forms. Site-directed mutagenesis indicated that almost the entire sequence of LSE-6 was necessary to form the complexes and also critical for silencing activity in CHO cells. The amounts of this binding factor(s) in CHO and HeLa cells were closely associated with transcriptional silencing activity. Photochemical cross-linking experiments indicated that the single- and double-stranded elements recognized the same binding factor(s) with molecular masses of 54 to 63 kDa and 109 to 124 kDa. The 109- to 124-kDa DNA binding factor(s) was found to be a doublet of that of the 54- to 63-kDa factor by isoelectric focusing or by increasing the time of exposure to UV irradiation. When inserted upstream of another gene such as that of the simian virus 40 enhancer/promoter of pSV2CAT, the sequence of nucleotides -190 to -143 (LSE-1) also suppressed transcription of the reporter gene in CHO cells. These results strongly suggest that the LSE plays a role in regulation of LPL gene expression by suppressing its transcription.

Animals

Accelerated decay of the cell bound C4b2a complex by serum of patients with membranoproliferative glomerulonephritis and acute poststreptococcal glomerulonephritis.

Serum from patients with membranoproliferative glomerulonephritis (MPGN) and acute poststreptococcal glomerulonephritis (APSGN) accelerated the decay of the cell bound C4b2a (C42) and C4b hemolytic activity relative to pooled normal human serum (pNHS) after 5 min incubation at 30 degrees C in EDTA-GVB. The accelerated decay of the C42 hemolytic activity was heat stable (56 degrees C 30 min) and was inhibited by monoclonal antibody against human C4 binding protein (MoAb:C4BP) or C4 binding protein (C4BP) depleted serum. C4 nephritic factor (C4NeF) was employed to stabilize the labile classical pathway C3 convertase C42 complex. Serum from patients with MPGN and APSGN reduced the C4NeF stabilizing activity. Sera from 32 of 46 patients with MPGN and all of 7 patients with APSGN reduced the C42 hemolytic activity relative to 50 normal human serum (NHS) after 5 min incubation at 30 degrees C in EDTA-GVB, and there was no relationship with the serum concentration of C4BP. In vivo, accelerated decay of C42 convertase might interfere with the clearing and processing mechanism of circulating immune complexes (IC) by reducing deposition of C3b on the IC lattice.

Acute Disease

Morphological studies on brown adipose tissue in the bat and in humans of various ages.

This review deals with the comparative observations of brown fat tissue in the bat, a hibernator, and in man, a nonhibernator. In both mammals, the brown fat is distributed in restricted portions of the body and brought into a thermogenetic activity by an acute drop in ambient temperature. Light microscopic examination was performed on the interscapular brown fat of bats captured monthly throughout one year; electron microscopic observations were made using a bat captured in April and another in September. Human perirenal brown fat was investigated light-microscopically on tissues derived from 215 fresh necropsy cases (Japanese) of both sexes aged from one month to 93 years. Brown adipose tissue was recognized only in 162 (75%) of the 215 samples, because brown fat cells were reduced by transformation into white fat cells. Human brown fat cells were classified into six types according to the morphological features of their lipid droplets. These reflect different functional states of intracellular heat production. The Type 1 (D) cell is a fat-depleted brown fat cell with a darkly stained cytoplasm; it is specific to humans. Human perirenal brown fat cells begin to show a transformation into white fat cells already at the infantile stage. This change occurs from the peripheral toward the central portion of the lobule, so that various functioning cell types remain only in the central area of the lobules. In contrast to humans, bat interscapular brown fat cells exhibit regular seasonal changes in size and lipid droplet content, so that the cells could not be classified as in humans into definite types according to the features of their lipid droplets. The most conspicuous difference between brown fat tissue in the nonhibernator and hibernator is that in the latter, white fat cells never occur within the brown fat tissue. In the hibernator, thermogenesis in the brown fat is necessary for both the arousal from hibernation and the maintenance of hibernation as well as rutting. In human perirenal brown fat tissue, darkly stained fat-depleted cells (D) occupy, with other cell types (CR, CR'), an important part in the reversible heat production cycle of the brown fat tissue. The "hypothermic" or "cold syndrome (cold injury)" is a disorder affecting inadequately protected infants in severely cold seasons, accompanied by lethargy, hypothermia and lactation refusal and revealing hemorrhagic pneumonia in necropsy. The brown fat tissue in such infants is composed exclusively of fat-depleted brown fat cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue, Brown

Two types of C3 nephritic factor: properdin-dependent C3NeF and properdin-independent C3NeF.

The IgG fraction of serum from patients with membranoproliferative glomerulonephritis (MPGN) types I and II or partial lipodystrophy (PLD) was found to contain C3 nephritic factor (C3NeF) which reacts with the alternative pathway C3 convertase C3bBb and stabilizes it. Two types of C3NeF were detected, of which one was heat sensitive (56 degrees C for 30 min) and properdin dependent (C3NeF:P) but the other was heat stable and properdin independent (C3NeF:nP). C3NeF:P was found in sera from patients with MPGN types I and II and it displayed the properties of properdin and IgG. C3NeF:P was observed in patients with reduced serum concentrations of C3 and terminal complement components (TCC), and the generation of SC5b-9 complex was increased in mixtures with normal human serum. C3NeF:nP was found in sera from patients with MPGN type II and PLD, whose sera revealed a selective decrease in C3 concentrations.

Autoantibodies

Monoclonal anti-human C3d antibodies: stabilization of the alternative pathway C3 convertase.

IgG mouse monoclonal antibody (mAb) was prepared by fusion of spleen cells from mice immunized with human C3d (mAb:C3d) using syngeneic thymocytes as feeder cells. mAb:C3d was assessed for its effect on the stabilization of the cell-bound alternative pathway C3 convertase EAC3bBb. It bound to cell-bound C3b and stabilized C3bBb at 30 degrees in the presence of EDTA-GVB. The plasma protein H reduced the stabilization effect of the stabilized C3 convertase. These results suggest that binding of antibody to C3d may stabilize C3bBb. It seems likely that such antibody induces in C3b conformational change, which increases the C3bBb complex stability.

Antibodies, Monoclonal

C3 nephritic factor and C4 nephritic factor in the serum of two patients with hypocomplementaemic membranoproliferative glomerulonephritis.

Both C3 nephritic factor (C3NeF) and C4 nephritic factor (C4NeF) were found in the serum of two patients with hypocomplementaemic membranoproliferative glomerulonephritis type 1 (H-MPGN type 1). Both stabilizing activities were associated with the IgG fraction. The serum levels of C3 and C5 were quite low, whereas the levels of early components and control proteins were in the normal range.

Adolescent

[A case of sarcoidosis associated with membranous nephropathy].

A 59-year-old woman was admitted to the hospital with a complaint of right visual disturbance. At admission, she had proteinuria and microscopic hematuria. The pulmonary X-ray showed bilateral hilar lymphadenopathy (BHL) but tuberculin test were negative. Also, bronchoalveolar lavage (BAL) and renal biopsy were performed. Bronchoalveolar lavage fluid (BALF) contained a high percentage of OKT 4 positive cells. In renal biopsy, light microscopic study showed thickening glomerular basement membrane (GBM) with tubulo-interstitial legion. Immuno-fluorescent study revealed granular deposits of IgG along glomerular capillary wall. Electron microscopic study showed subepithelial electron dense deposits of GBM, which are characteristic for membranous nephropathy (MN). It is well known that both sarcoidosis and MN are associated with immunological abnormality. This case might be significant for the study of pathogenesis of sarcoidosis.

Female

A transmission electron microscopic study of rabbit liver sinusoids with special remarks on an experimentally induced canalicular system and the "pored domes" in the endothelial cells.

Rabbits were starved for a week and then allowed to take the standard diet; the animals were sacrificed after 20 or 24 hr. One group of the animals were treated in winter, and the other, in summer. Control animals were fed solid rabbit food ad libitum. In the control rabbits, short rudimentary canaliculi and occasional small-sized pored domes were found in the thicker portions of the endothelial extension. In the animals experimentally treated in winter, well-developed meandering canaliculi with vacuolar expansions and constrictions appeared in the thicker portions and perikaryonal cytoplasm. In addition prominent pored domes were produced. The canaliculi often formed sponge-like networks with openings both to the sinusoid and the Disse's space. The development of the canalicular system and pored domes correlated to an increased blood flow through the sinusoids; this seemed to be induced upon sudden feedings after lengthy starvation. The rabbits subjected to the experimental treatment in summer exhibited no distinct development of the canaliculi and pored domes. This result was ascribed to the inhibited functions of the rabbit liver during this season.

Animals

Electron microscopic study on the hepatic sinusoidal wall of the soft-shelled turtle (Amyda japonica) with special remarks on the smooth muscle cells.

The hepatic sinusoids of the soft-shelled turtle (Amyda japonica) were examined by transmission electron microscopy. The sinusoidal wall was composed of endothelial cells, Kupffer cells and Ito cells. The basal surface of the hepatocyte facing the Disse's space was covered by a continuous basal lamina. In addition to the Ito cells, the Disse's space contains a considerable number of smooth muscle cells. Many of these were distributed sporadically, while others appeared as a sphincter circling the sinusoid. The smooth muscle cells in the Disse's space showed the following features: 1) The nucleus was located eccentrically near one end of the cell. 2) The surface vesicles and pits, mitochondria and dense patches along the myofilament bundles were all sparse as compared with those known from mammalian smooth muscle cells. 3) Cytoplasmic processes or ruffles were protruded into the Disse's space. 4) A weak basal lamina could be recognized. Sinusoidal endothelial cells were characterized by many large electron lucent lysosomes in their perikaryon and by small fenestrae in their attenuated cytoplasm. Ito cells sending out several cytoplasmic processes, possessed a single large lipid droplet on one side of the nucleus. A single cilium budding from the distal centriole into the Disse's space was found in an Ito cell. Extrasinusoidal macrophages were considerably numerous in the soft-shelled turtle liver. Some of the macrophages were apparently migrating into the sinusoid, there to presumably transform into the Kupffer cells.

Adipose Tissue

A transmission electron microscopic study on sinusoidal cells of guinea pig liver, with special reference to the occurrence of a canalicular system and "pored domes" in the endothelium.

Hepatic sinusoidal cells in the guinea pig were examined by transmission electron microscopy (TEM). A meandering canalicular system was detected in the sinusoidal endothelial cell both in thicker portions of cytoplasmic extensions and in small areas of the perikaryon. It consisted of meandering canaliculi with vacuolar expansions and constrictions, which penetrated the endothelial cytoplasm, forming as a whole a network. The canaliculi possessed more than two openings which usually communicated with the sinusoid, but occasionally poured themselves into the Disse's space. This network of canaliculi seems to permit infiltration of blood plasma. The "pored domes" recorded by Fujita and his collaborators on the glomerular endothelium of the rat and rabbit kidney were also revealed on the perikaryonal cytoplasm of the sinusoidal endothelium of guinea pig liver. Osmium-blackened lipid droplets were found in the sinusoidal endothelium, which suggested the release of lipid into the sinusoid. Short-term administrations of excessive vitamin A exerted no influence on the endothelial lipid droplets. The guinea pig is a rodent species which stores a very small amount of lipid droplets in its fat-storing cells and the so-called empty fat-storing cells were frequently detected. A single cilium was often found in the fat-storing cells in the guinea pig as in other species.

Animals

Electron microscopic studies on the sinusoidal cells in the monkey liver.

The sinusoidal wall was observed by transmission electron microscopy in crab-eating monkey livers. The perikarya of sinusoidal endothelial cells were characterized by numerous macropinocytotic vacuoles and curved smooth-surfaced tubules of high electron density. Size and spacing of fenestrae in endothelial sieve plates corresponded to essentially those in other mammalian species including the human. It was verified that the high concentration of microfilaments was responsible for the electron dense appearance of the sieve plate in tangential sections. Besides occasional overlapping of endothelial sheets, complicated interdigitations of several short lamellae originating from endothelial processes occasionally caused a layered structure of the endothelial lining. Kupffer cells were strikingly rich in lysosomes and contained large mitochondria and phagosomes. They were fixed to the endothelial lining by patches of junctional complexes identical with those between endothelial cells. Ito cells of the monkey liver demonstrated, like those of the human liver, many smooth-surfaced caveolae and vesicles along their perisinusoidal surface, suggesting their micropinocytotic activity. They also contained glycogen beta-particles which were partly gathered around lipid vacuoles. The electron dense droplets enclosed by glycogen particles as revealed in human Ito cells and regarded as immature lipid droplets retaining the chemical properties of glycogen, could rarely be confirmed in the present study. Between the Ito cell and hepatocyte there occurred many junctional complexes. The space of Disse contained, besides abundant collagen fibrils, numerous fine filaments forming irregular meshworks or bundles which resembled fibrillar material (precursor of collagen) in appearance in the dilated cisternae of the rough endoplasmic reticulum (RER) of the Ito cell. These filaments often entwined the collagen fibrils in the Disse's space as if to participate by apposition in their development. The question, whether pinocytosis-like structures of the Ito cell might be involved in the precursor transport from the cisternae of the RER to the Disse's space, remained unanswered.

Adipose Tissue

Occurrence of crystalloids in the sinusoidal endothelial cell of a crab-eating monkey liver.

An electron microscope examination of the liver of the crab-eating monkey revealed small crystalloids occurring occasionally in the thicker portion of the cytoplasmic extension of the sinusoidal endothelium. They were uniformly encased in a membrane sac which was mostly smooth-surfaced but was at several points continuous to ribosome-studded cisternae of the RER. The crystalloids were mostly polygonal in configuration and were classified into three types. Type I crystalloids, according to the grade of the complexity of their composition, represented the simplest, or original, form and were composed purely of a compact bundle of tubules measuring about 300 A in diameter. Types II and III crystalloids were composed of tubules and an electron lucent matrix. In type II crystalloids, the tubules were embedded parallel to one another in two sets of matrix layers which crossed each other at a right angle, while in type III, the matrix layers embedding the tubules cut each other at about 70 degrees. The crystalloids are presumed to have developed from a substance synthesized in the cisternae of the RER in the sinusoidal endothelial cell and their investigation may aid in elucidating the proteinic products of this RER-rich cell which have thus far remained-under dispute.

Animals

Further electron-microscope studies on the human hepatic sinusoidal wall with special reference to the fat-storing cell.

In biopsy specimens from two normal human livers, fat-storing cells and Kupffer cells were observed by electron microscopy with the following results: 1) In the human Ito cells numerous micropinocytotic caveolae and vesicles occurred either scattered beneath the plasma membrane or fused into short tubules. In the cytoplasm abutting on these structures, minute clusters of glycogen beta-particles were revealed which presumably had been synthesized in the local cytoplasm from carbohydrate (glucose) ingested by pinocytosis. 2) Lipid droplets (vacuoles) were formed within the accumulations of the glycogen beta-particles. These findings support the view that the glycogen synthesized in the Ito cells may represent a transitional compound in the process of lipid synthesis from carbohydrate. 3) Among lipid vacuoles, electron-dense droplets equally large were found, often containing electron-lucent areas in their center. On the surface of these dense droplets, compact clusters of glycogen particles adhered as if they might have permeated into the droplets. These droplets may possibly be immature lipid droplets retaining chemical properties of the glycogen in their superficial part; they remained insoluble during the preparation procedures for ultrathin sections. 4) The occurrence of the worm-like structure has for the first time been revealed in the human Kupffer cells. Besides its short tubular profiles, a more complex structure was demonstrated.

Female