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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 685 records · Page 38Linked to original sources

The UDP-galactose translocator gene is mapped to band Xp11.23-p11.22 containing the Wiskott-Aldrich syndrome locus.

We have cloned a segment of the human gene encoding UDP-galactose translocator by genetic complementation of its defective mutant in mouse FM3A cells. Chromosome mapping using fluorescent in situ hybridization revealed that the cloned gene hybridized to the Xp11.23-11.23 region of the X chromosome. This region is shared by the locus of Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency disorder, characterized by defective sugar chains on cell surface components. Genetic and phenotypic similarities suggest a possible link between UDP-galactose translocator and the Wiskott-Aldrich syndrome (WAS).

Animals↗

Application of carbon-11 labelled nicotine in the measurement of human cerebral blood flow and other physiological parameters.

Using positron emission tomography (PET), we measured the regional cerebral blood flow (rCBF) in five normal human subjects after intravenous injection of carbon-11 labeled (R)nicotine. The rCBF of the same subjects was measured by PET using the C15O2 inhalation steady-state method. The distribution of 11C activity in the brain after injection of 11C-(R)nicotine was almost equivalent to the CBF image obtained with the C15O2 inhalation stead-state method. The kinetics of 11C-(R)nicotine in the brain was analysed using a two-compartment model consisting of vascular and brain tissue compartments. The rCBF values obtained with 11C-(R)nicotine were higher than with C15O2 gas. The relatively long fixed distribution of 11C-(R)nicotine with a short uptake period allows stimulation studies by measurement of CBF to be performed with better photon flux and a longer imaging time than are possible with H215O.

Brain↗

A case of spontaneous intramural hematoma of the esophagus.

The authors experienced a case of spontaneous intramural hematoma of the esophagus (SIHE). This 44-year-old Japanese woman was admitted to our hospital because of chest pain accompanied by minimal hematemesis. Endoscopy revealed an elevated intraluminal bleeding bulge. Barium esophagograms showed a smooth and giant elevated intraluminal lesion. CT and MRI also revealed thickening of the esophageal wall. Fasting and intravenous hyperalimentation were prescribed on admission. The conditions improved and she became asymptomatic on the fifth day of hospitalization. Subsequent examinations by esophagography and endoscopy showed that the elevated lesion had disappeared and that the inflamed mucosal lesion had improved. The prognosis of cases of SIHE is excellent under conservative therapy, but close follow-up care is necessary.

Adult↗

A case of perianal Paget's disease associated with a sigmoid colon carcinoma.

A case of perianal invasive Paget's disease associated with a sigmoid colon carcinoma is presented. The chief complaint was perianal irritation for a year. Histologic examination yielded a correct diagnosis and abdominosacral resection with wide excision of the cutaneous component was performed. Histology of the resected specimen revealed the Paget's disease to be invasive of the dermis, the sigmoid colon carcinoma to be in Dukes' A stage and the two lesions to be different. The patient has been disease-free for more than 5 years after the operation.

Adenocarcinoma↗

The induction of recessive mutations in mouse primordial germ cells with N-ethyl-N-nitrosourea.

A specific-locus test was carried out to examine the mutagenic activity of N-ethyl-N-nitrosourea (ENU) on mouse primordial germ cells (PGC). Embryos of C3H/He mice were treated transplacentally with 30 or 50 mg ENU per kg of maternal body weight on day 8.5, 10.5, or 13.5 of gestation (G8.5 day, G10.5 day, or G13.5 day). Male and female mice that had been treated with ENU in embryonic stages were mated with female or male tester PW mice to detect recessive mutations induced in PGC. ENU induced recessive mutations at a relatively high rate in PGC at these developmental stages. The most sensitive stage was G10.5 day. On G8.5 day, the induced mutation rate in males and females was not significantly different. Cluster mutations, which originate from the limited number of PGC and cell killing, were more frequently induced at an earlier developmental stage. The induced mutation rate per unit dose of ENU (1 mg/kg) was higher in G8.5 and G10.5 day PGC than in stem-cell spermatogonia. It can be concluded that mouse PGC are more sensitive than stem-cell spermatogonia to the induction of recessive mutations by ENU.

Age Factors↗

Noonan phenotype associated with intracerebral hemorrhage and cerebral vascular anomalies: case report.

A case of a 19-year-old man with multiple characteristics of the Noonan phenotype and a massive intracerebral hemorrhage in the left putaminal region is presented. The hemorrhage was removed surgically, and the patient made a good recovery and was finally able to walk unassisted. Postoperative cerebral angiograms revealed various vascular anomalies, including a small aneurysm. To the best of our knowledge, this is the second detailed case report of an association of the Noonan phenotype with cerebral vascular anomalies presenting intracerebral hemorrhage. The etiology of this syndrome remains unknown but the possible causes of this rare association are discussed.

Adult↗

Acute promyelocytic leukemia with CD59 deficiency.

CD59 is a phosphatidyl inositol-anchored protein (which is lost in paroxysmal nocturnal hemoglobinuria (PNH) cells) with the capacity to block the formation of membrane attack complex, and protects host cells from autologous complement-mediated cytolysis. We found a patient with acute promyelocytic leukemia (APL) accompanied by disseminated intravascular coagulation (DIC), the cells of which were CD59-negative. Although the CD59 deficiency in the malignant cells was not related to PNH, we offered the possibility that DIC was induced by APL lysis secondary to the deficiency of CD59.

Aged↗

A monoclonal antibody against human decay-accelerating factor (DAF, CD55), D17, which lacks reactivity with semen-DAF.

Human decay-accelerating factor (DAF, CD55) is a phosphatidyl inositol-anchored glycoprotein consisting, from the N-terminus, of 4 short consensus repeats (SCR), a Ser/Thr (ST)-rich region providing O-glycosylation sites, and the membrane-anchoring unit. A mAb, named D17, was raised against purified erythrocyte-DAF. This mAb recognized DAF on blood cells and most cell lines as determined by flow cytometry and immunoblotting. Its reactivity was similar to but weaker than that of two other well-characterized mAbs to DAF, IA10 (seeing an epitope within SCR1) and 1C6 (seeing an epitope within SCR3). The reactivity of D17 with erythrocyte DAF became increased by treatment with sialidase/O-glycanase, suggesting that its epitope is located close to the O-glycosylation sites, probably within the ST-rich region or SCR4. D17 barely blocked the decay-accelerating activity of DAF. Using the three mAbs, tissue-associated and soluble forms of DAF were identified by SDS-PAGE/immunoblotting and immunohistochemical staining. IA10 and 1C6 recognized a 50 kDa protein in spermatozoa lysate and two proteins of Mr 70 and 55 kDa, respectively, in seminal fluid. These represented membrane-associated and soluble forms of DAF, which were neither recognized by mAb against membrane cofactor protein (MCP, CD46) and C3b/C4b receptor (CR1, CD35) nor by non-immune IgG. In contrast to IA10 and 1C6, D17 did not recognize either spermatozoa-DAF or seminal plasma-DAF, or the deglycosylated or untreated forms of them. Immunohistochemical analysis showed that testis was stained with IA10 but not with D17.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Enhancement of systemic and mucosal immune responses following oral administration of liposomes.

The effects of liposomes on the systemic and mucosal immune response were investigated using bovine serum albumin (BSA) in BALB/c mice. Following three oral administrations of varied formulations at 1-week intervals, serum BSA-specific IgG levels were increased significantly by BSA encapsulated in liposomes and moderately by a mixture of liposomes and BSA. Serum and salivary BSA-specific IgA levels were elevated by BSA-encapsulating liposomes only. Liposomes thus activate not only the systemic immune response but also the mucosal immune response following their oral administration. However, no increase in salivary IgA levels was observed by intraperitoneal or subcutaneous injection of BSA-encapsulating liposomes. The production of IgA is closely related to the oral administration of liposomes encapsulating antigens. Liposomes thus function as carriers of oral vaccines against various infections of the mucosal surface.

Administration, Oral↗

Comparative studies of larval and pupal phenoloxidase of the housefly, Musca domestica L.

1. Larval and pupal phenoloxidase of the housefly, Musca domestica L. resembled each other in some enzymatic properties, such as optimal pH, pH stability, optimal temperature and thermal stability. 2. The pI values of both enzymes were 4.85, as determined by isoelectric focusing. The molecular weights of two enzymes had a similar value (320,000 and 330,000 for larval and pupal phenoloxidase, respectively) and the molecular weights of these subunits had the same value of 60,000. 3. The aminio acid compositions of two enzymes were very similar. N-terminal amino acid sequences of larval and pupal enzymes were Glu-Glu-Ala-Thr-Val-Val-Pro-Asp-Gly- and Ala-Thr-Val-Val-Pro-Asp-Gly-Tyr-Phe-Met-, respectively, and the residues 3-9 (larval phenoloxidase) were in agreement with the residues 1-7 (pupal phenoloxidase).

Amino Acid Sequence↗

Human macrophage colony-stimulating factor levels in cerebrospinal fluid.

Macrophage colony-stimulating factor (M-CSF) levels in the cerebrospinal fluid of 14 patients with meningitis and of 14 patients suffering from a disease other than meningitis were measured using an enzyme-linked immunosorbent assay. All four bacterial meningitis patients had M-CSF levels in the cerebrospinal fluid which exceeded 1540 U/ml, and the mean value was 3333 +/- 1481 U/ml. The mean M-CSF level in the cerebrospinal fluid of the ten aseptic meningitis patients was 393 +/- 175 U/ml, which was higher than that of patients who suffered from a disease other than meningitis (179 +/- 90 U/ml) (P < 0.01). There was no clear correlation between the M-CSF levels and the numbers of white blood cells, granulocytes, or monocytes in the cerebrospinal fluid. These elevated M-CSF levels were thought to be of a local origin, since most patients with high M-CSF levels in the cerebrospinal fluid had relatively low M-CSF levels in the serum.

Adult↗

Maintenance of bone mass by physical exercise after discontinuation of intermittent hPTH(1-34) administration.

Human PTH(1-34) has been recognized for its marked anabolic effect on bone, but that effect has been reported to be lost after cessation of PTH treatment. The objective of this study was to determine the fate of hPTH-stimulated bone and whether this anabolic effect of PTH could be maintained by daily exercise. Eleven-week-old Sprague-Dawley rats were ovariectomized (OVX) and human PTH(1-34) (30 micrograms/kg) was injected subcutaneously three times per week for 12 weeks beginning one week after surgery. After the cessation of PTH treatment, treadmill exercises were performed for 8 weeks (15.7 m/min, 1 h/day, 5 days/week). The results of histomorphometric assessment in the proximal tibial metaphysis demonstrated that hPTH treatment partially prevented OVX-induced cancellous bone loss. Eight weeks following the cessation of PTH treatment, PTH-stimulated bone mass went back to the OVX control level. Daily exercise did maintain PTH-stimulated bone mass; however, this exercise did not increase the bone mass in PTH-untreated OVX rats.

Animals↗

Brown-Mclean syndrome associated with corneal endotheliitis in a pseudophakic eye.

A healthy 65-year-old woman had uncomplicated unilateral extracapsular cataract extraction followed by iridocapsular intraocular lens (IOL) implantation. Three and one half years after surgery, the inferior cornea developed marked edema with moderate retrocorneal precipitates, a phenomenon that recurred three more times during her eight-year postoperative course. Values obtained by laser flare cell meter coincided with each recurrence of corneal edema. Each occurrence was managed well by steroid therapy. Corneal endothelial cell density of the affected eye changed from a presurgical value of 3,260 cells/mm2 (central) to 553 (upper), 519 (central), and 363 (inferior). The intraocular lens was not touching the cornea, and there were no signs of general and local herpetic infections. The recurrent corneal edema responded well to steroid therapy, suggesting concurrent corneal endotheliitis and Brown-Mclean syndrome.

Aged↗

Stability of liposomes in vitro and their uptake by rat Peyer's patches following oral administration.

To evaluate the usefulness of liposomes as a carrier for the targeted delivery of antigens to gut-associated lymphoid tissue, liposomal stability and uptake by rat Peyer's patches were investigated. Liposomes composed of distearoylphosphatidylcholine, phosphatidylserine, and cholesterol (DSPC-liposome), or dipalmitoylphosphatidylcholine, phosphatidylserine, and cholesterol were stable in acidic solution (pH 2.0), diluted bile, and pancreatin solution. Following the oral administration of liposomes to rats, rhodamine B-PE incorporated in the lipid phase of DSPC-liposomes was preferentially taken up by Peyer's patches in the lower ileum. The uptake of rhodamine B-PE from DSPC-liposomes larger than 374 nm in mean diameter was high. Orally administered DSPC-liposomes of a large diameter thus appear to serve effectively as a vehicle for delivering antigens to Peyer's patches.

Administration, Oral↗

Uptake of phosphatidylserine liposomes by rat Peyer's patches following intraluminal administration.

Uptake of the nonabsorbable marker 6-carboxyfluorescein was investigated both free and encapsulated in liposomes as a function of their surface charge and hydrodynamic diameter in rat Peyer's patch and nonpatch tissue. Significant uptake of the marker occurred only when encapsulated in liposomes consisting of at least 25 mol% phosphatidylserine and was highest in Peyer's patches. 6-Carboxyfluorescein encapsulated in liposomes equal to or greater than 374 nm was preferentially taken up by Peyer's patches. There was a trend to higher uptake in lower intestinal segments. These findings were supported by fluorescence microscopic observations. Uptake by Peyer's patches was specific for negatively charged liposomes as judged from competition studies.

Analysis of Variance↗

In vitro degradation of mitochondrial proteins by ATP-dependent protease in bovine adrenal cortex.

We have examined in vitro degradation of mitochondrial proteins by ATP-dependent protease in bovine adrenal cortex. Purified ATP-dependent protease degraded at least five proteins in vitro in the presence of ATP and Triton X-100 using mitochondrial fraction as a substrate. Two of the degraded proteins were identified as P-450scc and adrenodoxin reductase by immunoblotting. No degradation of P-45011 beta or adrenodoxin was detected. Purified P-450scc and adrenodoxin reductase were also degraded. By analyzing degradation products of P-450scc we identified 49 peptides and 59 cleavage sites. The size of the products was between 3 and 18 amino acid residues. The protease preferentially cleaved the carboxy-side of Leu, Phe, Ala, Val, Met, and some other amino acids. Since the protease (a matrix enzyme) is accessible to P-450scc and adrenodoxin reductase localized on the matrix side of inner membrane, the present results suggest that the protease might participate in the turnover of these two proteins and some other mitochondrial proteins.

ATP-Dependent Proteases↗

Failure characteristics of osteoporotic vertebral bodies monitored by acoustic emission.

The third lumbar vertebrae of nine elderly subjects (average age, 81.4 +/- 6.7 years) graded osteoporotic and the second to fifth lumbar vertebrae of a 37-year-old man graded as normal were used to investigate microdamage accumulation during quasi-static compression loading with an acoustic emission detection system. Mechanical parameters (apparent elastic modulus, stress, and strain) and acoustic emission event count rates were measured simultaneously. The normalized mean value of any mechanical parameters of normal group was significantly high with respect to that of osteoporotic group. The normalized mean value of cumulative acoustic emission event counts to maximum stress of the normal vertebrae was substantially small with respect to that of the osteoporotic vertebrae (p < 0.0005, z-test). Postloading microradiographs displayed fracture lines adjacent to the end plates in six vertebrae of osteoporotic group. These results are consistent with the hypotheses that microdamages of osteoporotic vertebral bodies are generated and accumulate at lower strains than those of normal vertebrae at a specific site.

Adult↗

Levels of complement regulatory molecules in lung cancer: disappearance of the D17 epitope of CD55 in small-cell carcinoma.

The levels of complement-regulatory molecules (complement receptor type one [CR1], decay-accelerating factor [DAF], membrane cofactor protein [MCP], and an inhibitor of membrane attack complex [CD59]) in lung cancer cells were analyzed to investigate the relation between their expression and histological subtypes, and the possibility of homologous complement deposition on cancer cells. In 25 cell lines (10 adenocarcinoma, 3 large-cell carcinoma, 7 small-cell lung cancer [SCLC], and 5 squamous cell carcinoma), flow cytometric analysis revealed that MCP was expressed in all cell lines, whereas none of the cell lines was CR1-positive. CD59 was detected in all cells. The DAF epitope defined by IA10 was expressed in all cells except one large cell carcinoma cell line. However, another epitope for anti-DAF monoclonal antibody, D17, was not detected in 5 (71.4%) SCLC and in 4 (22.2%) non-small-cell lung cancer. This disparity was seen in most cell lines, irrespective of histological subtypes. The loss of D17 reactivity seemed to be pertinent to malignant phenotype, because most of the normal pulmonary cells possessed the D17 epitope. Furthermore, a cell line lacking DAF (IA10-/D17-) allowed alternative pathway-mediated homologous complement (C3) deposition after pretreatment with anti-MCP antibody. This raises a new possibility for immunotargeting of cancer. These cell lines should be useful in studying the biology of lung cancer.

Antigens, CD↗