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Biomedical subjects

H Uno

Publications and source records attributed to H Uno.

At least 55 records · Page 3Linked to original sources

Clinical evaluation of serum prostate-specific antigen-alpha1-antichymotrypsin complex values in diagnosis of prostate cancer: a cooperative study.

BACKGROUND: We studied the clinical significance of serum prostate-specific antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay. METHODS: Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays. RESULTS: Serum PSA-ACT values ranged from less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/- SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. CONCLUSION: Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.

Disease Progression↗

A new candidate mutation (N528S) within the von Willebrand factor propeptide identified in a Japanese patient with phenotype IIC of von Willebrand disease.

Phenotype IIC of von Willebrand disease (vWD) is a subtype of type 2A vWD characterized by recessive inheritance and an impaired multimerization of von Willebrand factor (vWF) molecules beyond dimers. The 5 patients with phenotype IIC whose vWF gene defect has been characterized so far are either homozygous or double heterozygotes for mutations localized in exons 11, 12, 14 or 15. We report here the identification of a new candidate mutation in a previously described Japanese patient affected with phenotype IIC vWD. The propositus is homozygous for the A1833G nucleotide substitution, in exon 14 of vWF gene, responsible for the N528S mutation within the vWF propeptide. This finding is in agreement with the consanguineous origin of the propositus, whose parents are first cousins. Six patients' relatives who are asymptomatic were studied and found heterozygous for the N528S mutation. The screening of the whole vWF gene, either by SSCP or sequencing, did not reveal any other deleterious sequence alteration in the patient. Furthermore, the N528S nonconservative substitution identified is located in the vWF propeptide region, where the other phenotype IIC mutations described so far are clustered. The N528S candidate mutation characterized is, therefore, most probably responsible for the multimerization defect of vWF observed in this patient.

Adult↗

Sexing of carcass remains of the Sika deer (Cervus nippon) using PCR amplification of the Sry gene.

In order to determine the sex of carcass remains of the Sika deer (Cervus nippon), we improved a polymerase chain reaction (PCR) technique for amplification of the Sika deer Sry, a male-specific DNA region on the mammalian Y chromosome. From the nucleotide sequence of the Sry region obtained here, PCR primers, MT1 and MT2, capable of amplifying a shorter Sry region were newly designed, and a microsatellite locus was used as a positive control. Using these primers, 96 of 109 sex-unknown fawns (88%, 96/109) were successfully sexed (46 males and 50 females) regardless of the conditions of carcasses found in the field. The results and the methodology could greatly contribute to the study of the mortality pattern of the Sika deer population.

Animals↗

Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques.

The effect of androgen receptor transcriptional activation by RU58841, a nonsteroidal anti-androgen, was studied in the human prostate cancer PC3 cell line by cotransfection with wild-type androgen receptor (wt AR) and an androgen-responsive reporter (MMTV-ARE-CAT) construct. Anti-and rogens, hydroxyflutamide, and Casodex, and the antiestrogen, genistein, were studied in parallel for comparison with RU58841. The wt AR was activated only by the androgen dihydrotestosterone (DHT). Neither the anti-androgens nor antiestrogen can enhance AR transcriptional activity at 10(-11)-10(-7)M in PC3 cells. Hydroxyflutamide, RU58841, and Casodex, but not genistein, displayed competitively suppressive effects on DHT activation of wt AR. The potency of RU58841 was comparable to that of hydroxyflutamide. From this result, topical application of RU58841, which is considered to be a potential therapy for skin diseases, may induce systemic side effects. However, RU58841, on topical application, revealed a potent increase in density, thickening, and length of hair in the macaque model of androgenetic alopecia, whereas no systemic effects were detected. Together our results suggest that RU58841 may have potent antagonism to the wt AR and could be considered as a topically applied active anti-androgen for the treatment of androgen-dependent skin disorders, such as acne, androgenetic alopecia, and hirsutism.

Alopecia↗

CD45RO expression on peripheral lymphocytes as a prognostic marker for adult T-cell leukemia.

Adult T-cell leukemia (ATL) is an aggressive hematological malignancy etiologically linked to HTLV-I. The clinical subtype classification, age, performance status, serum calcium and LDH levels are major prognostic factors of ATL, but these criteria and factors do not always correlate with prognosis. CD45 is expressed on cells of the hematopoietic system, and plays a pivotal role in antigen-stimulated proliferation of T-lymphocytes. CD45RO is a very light weight isoform of CD45 expressed on activated T-cells. Recent studies have shown that peripheral lymphocytes show two patterns of CD45RO expression in HTLV-I infected individuals which appears to correlate with their clinical outcome. The acute type ATL patients have pattern A with CD45RO+ lymphocytes with intermediate expression (CD45ROint cells), and show a better prognosis than those who do not have any CD45ROint cells. Further studies demonstrated that CD45ROint cells were not infected with HTLV-I, and as a result we suggest that CD45RO expression be considered a marker of host immunity in acute type ATL clinical course, in contrast to the levels of WBC or LDH which are regarded as tumor markers and indicators of tumor mass.

Adult↗

[A case of pulmonary eosinophilic granuloma undergoing spontaneous remission].

A case of pulmonary eosinophilic granuloma that underwent spontaneous remission is presented. A 23-year old man presented with dry cough and fever. Chest X-ray film revealed diffuse reticulo-nodular infiltrates in the middle and upper lung fields. Chest CT and HRCT showed multiple cystic lesions with thick walls and small nodules predominantly in the inner zone. Based on radiographic findings, pulmonary eosinophilic granuloma was suspected. Bronchoalveolar lavage cell data showed lymphocyte and eosinophil alveolitis with no increase of CD 1 lymphocytes. The symptoms and radiographic findings improved markedly within 4 months after the onset of symptoms without treatment and upon cessation of smoking. Chest CT and HRCT showed that the cystic walls were thinner and that the small nodules had decreased. Thoracoscopic lung biopsy revealed granulomatous lesions consisting of CD 1 and S-100 protein positive histiocytes with infiltration of eosinophils and fibrous lesions. Pulmonary eosinophilic granuloma was diagnosed. There has been no recurrence for 1 year.

Adult↗

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

Adult↗

[Intraoperative CT imaging system using a mobile CT scanner gantry mounted on floor-embedded rails for neurosurgery].

Many neurosurgeons prefer to use intraoperative computed tomographic (CT) scanning, when possible, to check whether there is residual lesion or unexpected bleeding. We report a practical intraoperative CT imaging system using a high-speed CT scanner installed in the operating room along with a digitally controlled neurosurgical operating table. We designed a rail-track system to mobilize the CT gantry. The gantry is fixed onto a motorized carrier that can be moved smoothly on a rail-track embedded in the floor and with a maximum reach of 2.85 m from the room's wall to the operating table. The longitudinal motion of the operating table is easily adjusted by a foot switch from manual control to automatic control directly from the CT scanner's computer like an ordinary CT scanner bed in increments of 2, 5 or 10 mm during CT scanning. Either a carbon-made radiolucent head frame or carbon-made head plate is used as a headrest. Using this CT scanner system, pre- and intraoperative CT scannings were performed on 46 patients with brain tumors, cervical lesions or other intracranial lesions. We could operate on the patient with enough working space between the mobile CT gantry and the operating table for microneurosurgery. We could obtain intraoperative CT imaging of a patient on the operating table while the surgical wound remained open, the surgical drapes kept in place, and the surgical position unchanged, saving time in intraoperative CT scanning and preparation for further surgery when needed. This intraoperative CT imaging system installed in the operating room should be useful for neurosurgery.

Brain↗

Distinct phenotype of leukemic T cells with various tissue tropisms.

There is an emerging concept, the validity of which remains to be proven, that preferential expression of selective adhesion molecules on particular T cell subsets may result in tissue-specific migration. L-selectin, cutaneous lymphocyte-associated Ag (CLA), and integrin alpha4beta7 are proposed to be involved in selective migration of T cell subsets into peripheral lymph nodes, skin, and gastrointestinal mucosa, respectively. Adult T cell leukemia (ATL) is associated with lymphoid infiltration of tissues and secondary lymphoid organs. To clarify the role of these putative homing molecules in vivo, we assessed their expression on circulating ATL cells from patients with lymph node, skin, and gut involvement. L-selectin expression was significantly higher on peripheral ATL cells in patients with lymphadenopathy than in patients without it. CLA was highly expressed on peripheral ATL cells compared with normal T cells: its expression was also significantly higher on peripheral ATL cells from patients with skin involvement compared with cells from patients without it. beta7 was particularly highly expressed on peripheral ATL cells from patients with gastrointestinal involvement. In summary, the differential expression of beta7 and beta1 on peripheral ATL cells correlates with the presence of gastrointestinal involvement. Similarly, the presence of skin involvement is associated with the expression of CLA(high)beta7low on peripheral ATL cells. These results, which are consistent with the molecules CLA and alpha4beta7 mediating preferential T cell migration to the skin and gastrointestinal mucosa, respectively, may allow for a refinement of the classification of lymphoid neoplasms on the basis of differential expression of homing molecules.

Adult↗

Hypertrophic cranial pachymeningitis involving the pituitary gland: a case report.

BACKGROUND: As the use of magnetic resonance imaging (MRI) has become widespread, the reported cases of pachymeningitis have increased. Various inflammations are known to occur in the pituitary gland. However, an association between pachymeningitis and pituitary inflammation has not been recognized previously. CASE DESCRIPTION: This 56-year-old woman complained of incessant headache and deafness. MRI showed thickened dura at the right convexity and a dumbbell shaped pituitary enlargement, which was isointense to the gray matter (T1-weighted images) and homogeneously enhanced. Microscopic examination of the dura mater showed a marked increase of collagen fibers and various inflammatory cells. The anterior pituitary lobe was infiltrated with lymphocytes, and normal tissues were displaced by increased collagen fibers. CONCLUSION: Hypertrophic cranial pachymeningitis, a rare clinical entity, is a progressive lesion prone to include the dura mater at the skull base and can be fatal. We report a case of hypertrophic cranial pachymeningitis involving the pituitary gland, and discuss the possible etiology of the association.

Diagnosis, Differential↗

Nitric oxide stimulates prostaglandin synthesis in cultured rabbit gastric cells.

Both prostaglandins (PGs) and nitric oxide (NO) have cytoprotective and hyperemic effects in the stomach. However, the effect of NO on PG synthesis in gastric mucosal cells is unclear. We examined whether sodium nitroprusside (SNP), a releaser of NO, stimulates PG synthesis in cultured rabbit gastric mucus-producing cells. These cells did not release NO themselves. Co-incubation with SNP (2 x 10(-4), 5 x 10(-4), 10(-3) M) increased PGE2 synthesis, and SNP (10(-3) M) increased PGI2 synthesis in these cells. Hemoglobin, a scavenger of NO, (10(-5) M) eliminated the increase in PGE2 synthesis by SNP, but methylene blue, an inhibitor of soluble guanylate cyclase, (5 x 10(-5) M) did not affect the increase in PGE2 synthesis by SNP. 8-bromo guanosine 3':5'-cyclic monophosphate (8-bromo cGMP), a cGMP analogue, (10(-6), 10(-5), 10(-4), 10(-3) M) did not affect PGE2 synthesis. These findings suggest that NO increased PGE2 and PGI2 synthesis via a cGMP-independent pathway in cultured rabbit gastric cells.

Animals↗

Strategies for harmonic structure discrimination by zebra finches.

We trained zebra finches on a go/no-go operant conditioning procedure to discriminate between two harmonic structures that differed only by the presence or absence of the second harmonic. Test sessions revealed that the birds responded to probe stimuli based on the presence or absence of the second harmonic regardless of the other frequency components. Some of the birds also tended to use the fundamental frequency as a discriminative cue when the number of harmonics was few. These results indicate that birds use multiple strategies for this type of harmonic structure discrimination.

Acoustic Stimulation↗

Induction of tumor necrosis factor-alpha in the mouse hippocampus following transient forebrain ischemia.

To assess the role of tumor necrosis factor-alpha (TNF-alpha) in modulating the process of cerebral ischemic injury, we identified TNF-alpha-producing cells and studied the time course of TNF-alpha expression. Immunoreactivity for TNF-alpha appeared in white matter of the mouse hippocampus as early as 1.5 h following a 30-min global ischemic insult. Double staining for TNF-alpha and glial fibrillary acidic protein (GFAP) suggested that the TNF-alpha-positive cells are most likely microglia, not astrocytes. TNF-alpha immunostaining decreased at 6 and 24 h but increased again at 3 days, when pyramidal neurons showed degeneration. Adjacent-section staining for microglia and double staining with GFAP suggested that TNF-alpha-positive cells in the pyramidal cell layer were microglia and those in the white matter were astrocytes. By 5 days TNF-alpha immunostaining disappeared from these glial cells, while a number of microglia were accumulated in the degenerated hippocampal pyramidal layer. Pyramidal neurons never expressed TNF-alpha immunoreactivity. Western blotting confirmed biphasic TNF-alpha expression. Our findings suggest that early production of TNF-alpha by microglia may activate a cytokine network in post-ischemic brain resulting in TNF-alpha synthesis by astrocytes.

Animals↗

Involvement of capsaicin-sensitive sensory nerves in gastric adaptive relaxation in isolated guinea-pig stomachs.

We investigated the role of capsaicin-sensitive sensory nerves (CPSNs), nitric oxide (NO), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in gastric adaptive and receptive relaxation in isolated guineapig stomachs. Changes in intragastric volume and pressure were recorded simultaneously in isolated stomachs in baths containing atropine and guanethidine. Adaptive relaxation was induced by luminal distention, and receptive relaxation was induced by electrical vagal stimulation. We found that desensitization to capsaicin inhibited adaptive relaxation, but not vagally induced relaxation. Extraluminal capsaicin induced gastric relaxation. Adaptive relaxation and capsaicin-induced relaxation were reduced by both tetrodotoxin and NG-nitro-L-arginine (LNNA), but not by hexamethonium. The effect of LNNA was partially reversed by co-incubation with L-arginine. Neither CGRP(8-37) nor VIP(10-28) inhibited all responses of adaptive relaxation, vagally induced and capsaicin-induced relaxation. These findings suggest that activation of CPSNs may be involved in adaptive relaxation, and that NO, but not CGRP or VIP, may be involved in the mechanisms of adaptive relaxation and receptive relaxation.

Adaptation, Physiological↗

Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats.

The fuzzy rat, a genetic mutant between hairless and hairy albino rats, expresses androgen-dependent hypersecretion of sebum and hyperplastic sebaceous glands. Using this model for human acne, we examined the effects of inhibitors of human steroid 5 alpha-reductase isozymes, type I (MK 386) and type II (finasteride), and an androgen receptor blocker (RU58841) on regression of glandular and ductal hyperplasia. The above three agents, 1% weight volume, were dissolved into the vehicle (propylene glycol, alcohol and water) and applied on the backs of peripubertal male rats for 2 months. Control and castrate groups received vehicle alone. At 8 weeks, we examined the size the sebaceous glandular lobules and ducts in split epidermal preparations as well as in frozen sections of skin stained with osmium-potassium dichromate solution. The number of bromodeoxyuridine (BrdU)-positive cells was counted in the glandular lobes in split-skin tissues stained with BrdU immunochemistry. The results revealed that the sizes of both lobes and ducts in castrates were 40-60% smaller than in controls. RU58841 induced glandular and ductal regression equivalent to that in castrates. Finasteride induced a moderate degree of lobular and ductal reduction, whereas MK386 caused only ductal regression. Reduction of BrdU-positive cells in the sebaceous lobes was found in the skin treated with finasteride and RU58841. Serum concentrations of testosterone and dihydrotestosterone showed no significant changes in all drug-treated rats. The weight of the prostatic lobes was reduced significantly in rats treated with finasteride but not by the other two agents. RU58841 effectively counteracted endogenous androgens resulting in a suppression of growth of the sebaceous glands but not the prostate. This rodent model for androgen-dependent hyperplasia of the sebaceous glands is useful for the study of many pharmacological aspects comprising the rate of percutaneous absorption, stability and affinity to target organs of the testing compounds, and selection of adequate vehicle for topical application.

5-alpha Reductase Inhibitors↗

Inhibition of hair growth by testosterone in the presence of dermal papilla cells from the frontal bald scalp of the postpubertal stumptailed macaque.

Hair-follicle regression in the bald scalps of stumptailed macaques develops after puberty, which corresponds to an elevation of serum testosterone and dihydrotestosterone. Using the cultured cells from the pre- and postpubertal macaques, we examined the role of dermal papilla cells in testosterone-induced inhibition of outer root sheath cell proliferation. Testosterone showed no effects on proliferation of either dermal papilla cells or outer root sheath cells cultured alone. Testosterone-induced inhibition of outer root sheath cell proliferation occurred only in coculture with dermal papilla cells derived from the bald scalps of adult macaques but not with dermal papilla cells from the hairy occipital scalps of adult macaques or the prebald frontal scalps of juvenile macaques. Furthermore, RU 58841, an androgen receptor blocker, antagonized this testosterone-elicited inhibition. Together our data indicate that the inhibitory effect of testosterone on proliferation of epithelial cells is age dependent, and androgen may play an essential role in hair growth either by inducing repressor(s) from dermal papilla cells, which may then inhibit the growth of epithelial cells of the hair follicle, or by inducing growth factor(s) from dermal papilla cells, which, in turn, may trigger the induction of some repressors in epithelial cells, thereby inhibiting the epithelial cell growth. Our animal studies also showed that RU 58841 has a dramatic effect on hair regrowth in the bald frontal scalp of the stumptailed macaque, which may further support our in vitro culture studies showing that antiandrogens can antagonize testosterone-elicited hair growth. In summary, our studies may provide a model for further isolation of androgen-regulated repressor(s)/growth factors, which may help control hair growth and baldness.

Alopecia↗

New aspects of gastric adaptive relaxation, reflex after food intake for more food: involvement of capsaicin-sensitive sensory nerves and nitric oxide.

To accommodate the intake of food or liquid, gastric reservoir functions are important as the physiological reflex. There exist two major responses as a reservoir function of the stomach; adaptive and receptive relaxations. Adaptive relaxation is a reflex in which the fundus of the stomach dilates in response to small increases in intragastric pressure when food enters the stomach. Receptive relaxation is a reflex in which the gastric fundus dilates when food passes down the pharynx and the esophagus. The mechanisms of these two types of functional responses are to some extent different, although a nitric oxide (NO) dependent non adrenergic, non cholinergic neural pathway is involved in the both relaxation reflexes. Adaptive relaxation is an intragastric pressure induced reflex. Stretch of the gastric wall activates the mechanoreceptors in gastric mucosa (Mu), which generate impulses carried by the capsaicin-sensitive afferent sensory neuron. The sensory neuron can synapse on the inhibitory efferent neuron directly or activate it via interneurons of the myenteric plexus. This leads to the release of NO from the nitroxergic efferent neuron, which causes relaxation of circular muscle and hence of the fundus. Alternatively, an axon reflex causes the NO release from the sensory neuron, resulting in hexamethonium resistant gastric relaxation. Receptive relaxation is mediated by vagal motor fibers. In contrast with the pressure-induced adaptive relaxation, ganglionic nicotinic transmission is essential in the vagally induced relaxation. VIP and CGRP are important neurotransmitters of the inhibitory sensory neuron, which, however, may not mediate both adaptive and receptive relaxations. Disorders of these reservoir functions result in symptoms of early satiety and anorexia, which are the major symptoms of patients with functional dyspepsia.

Adaptation, Physiological↗

Progressive retinitis-encephalitis due to ganciclovir-resistant cytomegalovirus associated with aplastic anemia.

A 29-year-old woman with aplastic anemia who complained of visual disturbances and pain in the right eyeball was diagnosed as having cytomegalovirus (CMV) retinitis based upon the characteristic retinal changes and isolation of CMV. She received treatment with ganciclovir (GCV), and the retinitis initially responded for several months. However, the patient was found to have CMV lesions in the left eye followed by neurological symptoms. The CMV isolated just before her death was approximately 20 times more resistant to GCV than that isolated previously, suggesting that the GCV-resistant CMV had developed during the long-term treatment with GCV.

Adult↗