Biomedical subjects
H Tamura
Publications and source records attributed to H Tamura.
Water channel AQP1, 3, and 4 in the human peritoneum and peritoneal dialysate.
To clarify the mechanism of water transport driven by osmotic gradient through "ultrasmall pores" in the peritoneum, we tried to identify water channels in the peritoneum and cells in the peritoneal dialysate. Peritoneum was surgically excised from uremic patients at the insertion or removal of a catheter. Sediment was collected from 2 L of peritoneal dialysate by centrifugation at 1500 rpm. RNA was extracted and amplified by reverse transcription-polymerase chain reaction (RT-PCR). Contamination of reticulocytes was tested by the presence of ankyrin mRNA. Peritoneal tissue expressed aquaporin (AQP) 1, 3, and 4 (AQP1 > 3 > 4). Sediment of dialysate expressed mRNA of AQP1 and AQP3 (AQP1 > AQP3). The sample did not express ankyrin mRNA, indicating that the AQP1 in the sediment did not originate from reticulocytes. These data indicate that aquaporins are present in the peritoneum and might participate in water transport. Further quantitative analysis of aquaporin messages in the dialysate might clarify the pathogenesis of water removal failure.
Allergic granulomatous angitis (Churg-Strauss syndrome) with multiple intestinal fistulas.
A 40-yr-old man who had a known diagnosis of allergic granulomatous angitis (Churg-Strauss syndrome) and had been on steroids was found to have a stone in the common bile duct. At surgery, multiple internal fistulas were found in the small bowel. Cholecystectomy, removal of the stone in the common bile duct, and resection of the small bowel because of fistulas were performed. To our knowledge, the formation of an intestinal fistula has not been reported as a clinical manifestation of allergic granulomatous angitis. This rare condition occurs in the terminal stage of this disease.
Induction of peroxisomal enzymes by dehydroepiandrosterone: metabolic activation by sulfate conjugation.
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Purification and characterization of a (1-->3)-beta-D-glucan-binding protein from horseshoe crab (Tachypleus tridentatus) amoebocytes.
A novel (1-->3)-beta-D-glucan-binding protein (T-GBP) has been purified from the amoebocyte lysate of the Japanese horseshoe crab, Tachypleus tridentatus. It is a basic protein (pI 9.2) which appears to be a homotetramer composed of subunits with an apparent mol wt of 168000 and with an amino-terminal sequence (20 residues) KSGFILTAPKSLTLGRNNRL. T-GBP exerted an inhibitory effect on the (1-->3)-beta-D-glucan-initiated coagulation cascade reconstituted with purified preparations of factor G and the proclotting enzyme from the lysate. The binding of (1-->3)-beta-D-glucans to T-GBP was evaluated by measuring the residual amidolytic activity of the clotting enzyme, the product of the coagulation cascade, using Boc-Leu-Gly-Arg-4-nitroanilide as the chromogenic substrate. The binding specificity of a wide range of (1-->3)-beta-D-glucans and other polysaccharides towards T-GBP was expressed by the relative inhibition (%) of the activation of factor G, the first protease zymogen in the pathway, which is activated by binding to (1-->3)-beta-D-glucans. T-GBP was found to have a high affinity for linear (1-->3)-beta-D-glucans, e.g. pachyman, curdlan, and paramylon. It was able to bind to (1-->3)-beta-D-glucans with side-chain branches and mixed linkage such as schizophyllan, lentinan, laminarins, yeast beta-D-glucan, and (1-->3),(1-->4)-beta-D-glucans such as lichenin and barley beta-D-glucan. Binding of pachyman to T-GBP was demonstrated by an enzyme-linked immunosorbent assay using a specific antibody (rabbit IgG) raised against T-GBP.
Mechanisms underlying orientation selectivity of neurons in the primary visual cortex of the macaque.
1. Effects of blocking intracortical inhibition by microiontophoretic administration of bicuculline methiodide (BMI), a selective antagonist for GABAA receptors, on orientation selectivity of 109 neurones were studied in the primary visual cortex (V1) of anaesthetized and paralysed monkeys. 2. The averaged orientation tuning of visual responses of cells was poor in cytochrome oxidaserich blobs of layer II/III and in layer IVc beta, moderate in layers IVb, IVc alpha and V, and sharp in the interblob region of layer II/III and in layers IVa and VI. 3. Iontophoretic administration of BMI reduced the sharpness of orientation tuning of cells to a varying extent in each layer. In most cells, furthermore, the originally ineffective stimuli induced visual responses during the BMI administration, suggesting that excitatory inputs evoked by the non-optimally oriented stimuli were masked by GABAergic inhibition. Nevertheless, the maximal facilitation was observed in the response to the optimally or near-optimally oriented stimuli. 4. There was a difference in such an effect of BMI among layers. Orientation selectivity of cells in interblobs in layer II/III and in layer IVb was sensitive to BMI whereas that of cells in layer VI was relatively insensitive to BMI, suggesting a larger contribution of excitatory mechanisms to the orientation selectivity in this layer. 5. In the orientation-selective cells, an analysis of the magnitude of excitation and inhibition evoked by stimuli at various orientations suggests that both inputs tune around the optimal orientation and their magnitudes are almost proportional to each other except at the optimal orientation. This analysis also indicates that the orientation tuning of inhibition had a less prominent peak around the optimal orientation than that of excitation. This dominance of excitation over inhibition around the optimal orientation may function to accentuate the response to the optimally oriented stimulus. 6. These results suggest that, in the monkey V1, the orientation selectivity of cells is largely dependent on the orientation-biased excitatory and inhibitory inputs which have a broader tuning profile, covering from the optimal to null-orientation, than that observed in extracellularly recorded responses at the control level.
CD4 lymphopenia and risk of infection in immunogerontologically healthy elderly people.
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Zonal distribution of sulfotransferase for phenol in olfactory sustentacular cells.
We have immunolocalized phenol sulfotransferase (PST)G, an isoform of PST in sustentacular cells which reside in the dorso-medial portion of the nasal cavity of the mouse. The same topographical pattern of gene expression has been reported for some olfactory neuron-specific genes. When several established (phenol-containing) odorants were used as substrates, mouse nasal tissue cytosol showed a significant level of PST activity, as does mouse liver cytosol. This study is the first to demonstrate that gene expression in the olfactory sustentacular cells is also organized zonally, and indicates the involvement of sulfo-conjugation in olfactory perireceptor processes, such as odorant clearance and xenobiotic detoxification.
Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene.
Mutations in beta or gamma subunit of the epithelial sodium channel (ENaC) have been found to cause a hereditary form of human hypertension, Liddle syndrome. Most of the mutations reported are either nonsense mutations or frame shift mutations which would truncate the cytoplasmic carboxyl terminus of the beta or gamma subunits of the channel, suggesting that these domains are important for the normal regulation of this channel. We sequenced ENaC in a family with Liddle syndrome and found a missense mutation in beta subunit which predicts substitution of Tyr by His at codon 618, 2 bp downstream from a missense mutation (P616L) that has been reported recently. Presence of this mutation correlates with the clinical manifestations (hypertension, hypokalemia, suppressed aldosterone secretion) in this kindred. Functional expression studies in the Xenopus oocytes revealed constitutive activation of the Y618H mutant indistinguishable from that observed for the deletion mutant (R564stop) identified in the original pedigree of Liddle. Our data suggest that the region between Pro616 and Tyr618 is critically important for regulation of ENaC activity.
Long-chain acyl-CoA hydrolase from rat brain cytosol: purification, characterization, and immunohistochemical localization.
Long-chain acyl-CoA hydrolase (EC 3.1.2.2), which is found primarily in the brain in rats, catalyzes the hydrolysis of fatty acyl-CoA thioesters. We purified this enzyme, referred to as ACH, from the rat brain cytosol. The molecular masses of the native enzyme and the subunit were estimated to be 104 and 36 kDa, respectively. The enzyme showed high activity with long-chain acyl-CoAs, e.g., with maximal velocity of 262 mumol/min/mg and Km of 5.7 microM for palmitoyl-CoA, but acyl-CoAs with carbon chain lengths of C8-18 were also good substrates. The enzyme was refractory to the inhibitory effect of diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride, but sensitive to p-chloromercuribenzoate. In the rat brain cytosol, about 90% of palmitoyl-CoA hydrolase activity was titrated by anti-ACH antibody, which accounted for over 70% of the enzyme activity found in the brain tissue. Immunoblots of the cytosol prepared from rat brain regional blocks indicated the broad distribution of ACH over the brain, with a relatively high level in the pons and medulla. Immunohistochemically, ACH was localized to neurons. In addition to various nuclei, some neuronal cells, such as mitral cells in the olfactory bulb, pyramidal cells in the cerebral cortex, and Purkinje cells in the cerebellum, were also immunostained with anti-ACH antibody. Brain cytosols prepared from ten mammalian species including human contained a single polypeptide reactive to anti-ACH antibody with molecular masses of 34-36 kDa, together with high activities of palmitoyl-CoA hydrolase. These findings suggest the physiological significance of ACH in the brain, although its precise role remains to be determined.
A distant evolutionary relationship between bacterial sphingomyelinase and mammalian DNase I.
The three-dimensional structure of bacterial sphingomyelinase (SMase) was predicted using a protein fold recognition method; the search of a library of known structures showed that the SMase sequence is highly compatible with the mammalian DNase I structure, which suggested that SMase adopts a structure similar to that of DNase I. The amino acid sequence alignment based on the prediction revealed that, despite the lack of overall sequence similarity (less than 10% identity), those residues of DNase I that are involved in the hydrolysis of the phosphodiester bond, including two histidine residues (His 134 and His 252) of the active center, are conserved in SMase. In addition, a conserved pentapeptide sequence motif was found, which includes two catalytically critical residues, Asp 251 and His 252. A sequence database search showed that the motif is highly specific to mammalian DNase I and bacterial SMase. The functional roles of SMase residues identified by the sequence comparison were consistent with the results from mutant studies. Two Bacillus cereus SMase mutants (H134A and H252A) were constructed by site-directed mutagenesis. They completely abolished their catalytic activity. A model for the SMase-sphingomyelin complex structure was built to investigate how the SMase specifically recognizes its substrate. The model suggested that a set of residues conserved among bacterial SMases, including Trp 28 and Phe 55, might be important in the substrate recognition. The predicted structural similarity and the conservation of the functionally important residues strongly suggest a distant evolutionary relationship between bacterial SMase and mammalian DNase I. These two phosphodiesterases must have acquired the specificity for different substrates in the course of evolution.
Autoimmune hemolytic anemia in patients with de novo acute myelocytic leukemia.
Autoantibody against erythrocytes has occasionally been observed in patients with de novo acute myelocytic leukemia (AML). However, it is not clear whether this autoantibody in AML patients induces frank hemolysis (autoimmune hemolytic anemia, AIHA), as seen in lymphoid neoplasms. We present two de novo AML patients who showed hemolysis due to antiglobulin test-positive and test-negative AIHA, respectively. AIHA should be considered as one cause of anemia in de novo AML patients, and blood transfusions should be given carefully in such cases to avoid harmful hemolysis.
Hemorrhagic ovarian cyst in childhood: a case report.
A 12-year-old girl with massive hemoperitoneum caused by a ruptured hemorrhagic ovarian cyst (HOC) is described. Although HOC is not common in early adolescence, it should be included in the differential diagnosis of any adnexal mass or lower abdominal pain in a girl.
A family with two sisters with collagenofibrotic glomerulonephropathy.
Collagenofibrotic glomerulonephropathy is a recently recognized disease entity. Although an autosomal recessive inheritance pattern has been suggested for this condition, there are few reports of familial cases. Only four pairs of child siblings, with histological confirmation of the glomerular lesions, have been reported. The current report describes a family including two sisters with histological evidence of collagenofibrotic glomerulonephropathy. Serum concentrations of the procollagen III peptide were elevated in the affected sisters, whereas their parents and other siblings demonstrated neither proteinuria nor increased blood levels of the procollagen III peptide. Our findings support an autosomal recessive pattern of inheritance for this type of glomerulonephropathy. They also suggest that the serum concentration of the procollagen III peptide is a useful marker for collagenofibrotic glomerulonephropathy.
Therapeutic efficacy of pamidronate in combination with chemotherapy to bone metastasis of breast cancer in a rat model.
Bone metastasis is clinically often recognized in breast cancer patients, and in the progression of bone destruction due to bone metastasis, osteoclastic bone resorption is an important step. Therefore, drugs such as bisphosphonates-which have anti-osteoclastic activity-are expected to inhibit the progression of bone metastasis. However, bisphosphonates demonstrate no cytotoxic effects for cancer cells. In the present study we have evaluated the therapeutic efficacy of pamidronate (3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid) combined with mitomycin C (MMC) on bone metastasis of breast cancer using an animal model. The model for bone metastasis was developed by injecting c-SST-2 (spontaneously developed rat mammary adenocarcinoma in a SHR rat) cells into the thoracic aorta of 45-46 day-old female SHR rats. Three weeks after the tumour cell injection, these 48 animals were divided into four groups: control, n = 16; pamidronate, n = 12; MMC, n = 10; pamidronate with MMC, n = 10). In order to evaluate therapeutic effects on bone metastasis in each animal, the whole spine was harvested for histological examination. The bone metabolic markers used were: pyridinoline/creatinine (Pyd/Cr), deoxypyridinoline/creatinine (Dpd/Cr), bone alkaline phosphatase (BAP), and osteocalcin-measured 1 week after therapy. Histological scores of bone destruction in the treatment groups were lower than those of the control, and there were no differences among treatment groups. Although the values of Pyd/Cr and Dpd/Cr in the treatment groups, including pamidronate, were significantly lower than those in the control (P < 0.05), the other markers did not differ. It was suggested that pamidronate inhibited the progression of bone resorption, mainly by osteoclast activation due to bone metastasis, and Pyd/Cr and Dpd/Cr could be useful in part as a marker which reflects therapeutic effect. However, no additional effects were observed when it was combined with MMC.
Plasma soluble interleukin-2 receptor level in patients with primary myelodysplastic syndromes: a relationship with disease subtype and clinical outcome.
To assess the hypothesis that the plasma soluble interleukin-2 receptor (sIL-2R) level may have predictive value for morbidity/mortality in patients with myelodysplastic syndromes (MDS), we determined in plasma sIL-2R level of 80 MDS patients and examined their subsequent clinical course. Compared with low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts) patients and normal subjects, the plasma sIL-2R level was significantly elevated in high-risk MDS (three other MDS subtypes and acute leukaemia following MDS) patients (high-risk MDS versus low-risk MDS, P < 0.01; high-risk MDS versus normal subjects, P < 0.01). 14/40 low-risk MDS patients developed at least one of the following during the follow-up period: erythrocyte transfusion dependence, infections requiring hospitalization, disease progression or MDS-related death. The plasma sIL-2R level was higher in these eventful subjects than in event-free low-risk subjects (P < 0.0001), and all of 10 low-risk subjects with a plasma sIL-2R level > 540 U/ml experience at least one event. By logistic regression analysis of various parameters in these 40 low-risk subjects, the plasma sIL-2R level was identified as the strongest independent parameter for predicting eventful subjects (P < 0.0047). The plasma sIL-2R level did not show a predictive value in high-risk MDS. This study revealed that the plasma sIL-2R level is significantly elevated in high-risk MDS and suggested that the plasma sIL-2R level is a valuable predictive factors for the clinical outcome in low-risk MDS.
Nitric oxide concentrations in the follicular fluid and apoptosis of granulosa cells in human follicles.
To study the relationship between follicular atresia, apoptosis, and nitric oxide (NO) generation in follicular development, steroidogenesis, NO levels in follicular fluid and apoptosis were analysed in the various sized follicles of women receiving ovarian stimulation with human menopausal gonadotrophin (HMG)-human chorionic gonadotrophin (HCG) treatments for in-vitro fertilization (IVF)-embryo transfer. The follicles were divided into three groups by diameter: large follicle, > or = 18 mm; medium follicle, > or = 12 and < or = 15 mm; small follicle, < or = 10 mm. Follicular fluid was obtained from 20 women 34 h after HCG administration, and the concentrations of oestradiol, progesterone and testosterone, and nitrite, nitrate, arginine and citrulline were measured. Granulosa cells obtained from each group of follicular fluid were stained with Hoechst dye, and nuclear morphology was examined by a fluorescence microscopy. Oestradiol and progesterone concentrations in large follicles were significantly (P < 0.01) higher than those in medium or small follicles, and testosterone concentrations in small follicles were significantly (P < 0.01) higher than those in large follicles. There were no significant differences in the concentrations of nitrite, nitrate, arginine and citrulline among three groups. The percentage of apoptotic cells with nuclear fragmentation was significantly (P < 0.01) higher in small follicles than in large follicles. The present results suggested that small follicles with poor response to HMG may undergo atresia through apoptosis. No significant difference in the follicular NO level between large and small follicles led us to speculate on a different responsiveness to NO in these two types of follicles.
Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy.
To investigate the possible role of the superoxide radical and its scavenging system in the human endometrium, the immunohistochemical distribution of superoxide dismutase (SOD), activities of SOD and lipid peroxide concentrations were studied in the human endometrium throughout the menstrual cycle and in early pregnancy. The endometrial epithelium showed a positive immunostaining for Cu, Zn-SOD and Mn-SOD throughout the entire menstrual cycle and in early pregnancy. In the stroma, weak immunostaining for Cu,Zn-SOD and moderate immunostaining for Mn-SOD were observed in the predecidual cells in the late secretory phase. Decidual cells in early pregnancy showed strong immunostaining for Cu,Zn-SOD and Mn-SOD. Total SOD activity in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the mid-secretory phase, and decreased in the late secretory phase. The total SOD activity in the endometrium of of early pregnancy was the same level as that in the mid-secretory phase. Cu,Zn-SOD and Mn-SOD activities changed in a similar manner to total SOD activity throughout the menstrual cycle and in early pregnancy. Lipid peroxide concentration in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the late secretory phase. However, lipid peroxide concentration in the endometrium of early pregnancy was the same as that in the mid-secretory phase. These results suggested that the superoxide radical and its scavenging system may play an important role in the regulation of human endometrial function.