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Biomedical subjects

H Uno

Publications and source records attributed to H Uno.

At least 37 records · Page 2Linked to original sources

Indices for nutritional condition and thresholds for winter survival in sika deer in Hokkaido, Japan.

We derived fat indices for sika deer (Cervus nippon yesoensis) in eastern Hokkaido, Japan, and estimated the probability of over-winter survival with a logistic regression model using fat indices. Kidney fat mass (KFM) appears to be an adequate index of wide range of physical conditions before the onset of severe nutritional stress. When KFM values fell below 20 g, femur (FMF) and mandible cavity fat (MCF) indices declined sharply. FMF and MCF were useful indices for detecting malnourished deer. A logistic regression model describes survival thresholds in two bone fat indices for calves (45%) and three fat indices for adult females (FMF = 25%, MCF = 30%, KFM = 20 g). These models are useful for estimating the probability of winter survival in Hokkaido sika deer.

Adipose Tissue↗

Localization of trapping of 6-[(18)F]fluoro-L-m-tyrosine, an aromatic L-amino acid decarboxylase tracer for PET.

The purpose of this study was to address four major questions regarding 6-FMT, a noncatecholic PET tracer for AAAD: 1) Where is the specific uptake of 6-FMT? 2) Why does it accumulate where and to the degree that it does? 3) How does its uptake differ from that of fluoroDOPA globally? and 4) Does its regional uptake differ significantly from that of fluoroDOPA? High-resolution PET scans were obtained in three rhesus monkeys using 6-FMT and in two of them using fluoroDOPA. Anatomic distribution was analyzed visually and quantitative uptake of 6-FMT was compared with published regional decarboxylase activity and monoamine neurotransmitter concentrations. In addition to high uptake in the dopamine-rich striatal nuclei, there was specific uptake of 6-FMT in brain regions which have little dopaminergic innervation but which have other amines in significant concentration. 6-FMT uptake correlated best with regional AAAD activity (r = 0.97). It correlated slightly less well with the sum of catecholamine and indolamine neurotransmitter concentrations, but does not correlate with dopamine concentration. The uptake of 6-FMT is greater than that of fluoroDOPA, with only slight differences in their regional distributions. Radiolabeled analogs of DOPA are often implicitly or explicitly regarded as tracers for presynaptic dopaminergic function. However, localization of these tracers more broadly includes many regions with relatively high concentrations of norepinephrine and serotonin. This may be especially important in diseases or experimental states in which dopaminergic neurons are selectively reduced, and may allow for the study of nondopaminergic neuronal systems in vivo with this tracer.

Animals↗

Androgenetic alopecia: in vivo models.

Androgenetic alopecia is the most common form of balding in humans. There is great interest in finding a reliable animal model to study the pathogenesis and treatment of this abnormality. The sump-tailed macaque (Macaca artoides) has been the standard model and appears to be useful homologue. These primates are reasonably good predictors of compound efficacy. Due to reduced size and expense, rodent models have been sought. Testosterone inducible models require more development but offer potential. Xenografts of human skin to immunodeficient mice, notably nude or severe combined immunodeficiency, are small, relatively inexpensive, and easy to work with if a source of human tissue is available. Xenografts to double mutant mice for severe combined immunodeficiency and a number of hormone receptor null mutations offer new refinements to these xenograft models.

Alopecia↗

Alterations of calcium/calmodulin-dependent protein kinase II activity in ischaemia-induced neuronal death and neuronal protection against ischaemia in the gerbil hippocampus.

To clarify the relation between neuronal protection against ischaemia and calcium/calmodulin-dependent protein kinase II (CaM kinase II) activity, we investigated temporal alterations of the kinase activity in the hippocampus after transient forebrain ischaemia under neuroprotective conditions, employing the gerbil bilateral carotid artery occlusion model. The hippocampal CA1 neuronal density at 2 hours after 5 minutes of forebrain ischaemia was 214.7 +/- 25.8/mm (mean +/- S.D.), and did not differ from the control significantly; however, it decreased to 11.7 +/- 4.2/mm at 7 days after the ischaemia. The neuronal density at 7 days after the ischaemia was 185.1 +/- 18.5 under the hypothermic conditions, 128.7 +/- 19.6 with the brief ischaemic pretreatment, 65.0 +/- 13.4 with administration of MK-801, and 20.5 +/- 4.2 with the repetitive hyperthermic pretreatment, respectively. The Ca2+/calmodulin-dependent activity of CaM kinase II in the hippocampal cytosolic fraction was decreased to 47.5% of the control value at 2 hours after the ischaemia, when CA1 neuronal death was not observed. In contrast, the activity was 98.8% of the control under the hypothermic conditions, 91.4% with the brief ischaemic pretreatment, 71.2% with administration of MK-801, and 47.9% with the repetitive hyperthermic pretreatment, respectively. These results indicated that the preservation of the Ca2+/calmodulin-dependent activity of cytosolic CaM kinase II after ischaemia parallelled the neuroprotective effect in the gerbil hippocampus. Thus, it is suggested that the preservation of the activity may be involved in the mechanism of neuronal protection against ischaemia.

Animals↗

Determination of reference values for total PSA, F/T and PSAD according to prostatic volume in japanese prostate cancer patients with slightly elevated serum PSA levels.

BACKGROUND: For screening prostate cancer (CAP) using prostate-specific antigen (PSA), the indications of biopsies for patients showing slightly elevated PSA values are still controversial. Furthermore, the dependence of total PSA, free-to-total PSA ratio (F/T) and PSA density (PSAD) on prostatic volume in gray zone cases is unclear. METHODS: By analyzing 1913 patients with a serum total PSA ranging from 2.0 to 20 ng/ml, we evaluated the correlation between total PSA and age or prostatic volume and positive predictive value (PPV) in each range for total PSA, age and prostatic volume. Then suitable reference values for total PSA, F/T and PSAD were decided according to prostatic volume. RESULTS: There was no close correlation between PSA and age or volume. The PPV was high in the group with a prostatic volume of 10-30 ml. Prostatic volume was categorized into three groups, <20, 20-40 and > or =40 ml, and reference values for obtaining a sensitivity of 90% were proposed. The reference values of total PSA and PSAD were lowered and that of F/T was raised with increase in prostatic volume. The specificity was very low for the > or =40 ml group. The highest specificity of 36% in PSAD was obtained for the <20 ml group. CONCLUSION: The reference values for total PSA, F/T and PSAD must be changed according to prostatic volume in order to maintain a sufficient diagnostic sensitivity of CAP. Of these parameters, PSAD showed a high specificity in the group with a prostatic volume of <40 ml.

Adenocarcinoma↗

Comparative study of assays for prostate-specific antigen molecular forms.

BACKGROUND: The detection of prostate-specific antigen (PSA) molecular forms such as free PSA and PSA-ACT and the use of PSA molecular ratios, especially the percentage of free to total PSA, have been reported to improve the diagnostic accuracy of prostate cancer in the patients with slightly elevated serum PSA values. However, the correlation among the values of serum free PSA or PSA-ACT obtained in various assays remains unclear. METHODS: Serum free PSA and PSA-ACT values were detected with the following assays: Hybritech, DPC, EIKEN, Abbott, Roche and Can-Ag for free PSA and Dainippon, Chugai, EIKEN and Bayer for PSA-ACT. The data obtained with each assay were compared with Hybritech (free PSA) and Dainippon (PSA-ACT) as standards. RESULTS: The free PSA data obtained with the Hybritech, EIKEN, Abbott and Can-Ag kits were similar. The values obtained with the DPC and Roche kits showed a linear regression of y = ax + b with those obtained with the Hybritech, with a b value of zero and an a value of 1.20 and 1.57, respectively. The serum PSA-ACT values detected with the Dainippon and Chugai kits were identical. The equation for converting the data obtained with the EIKEN kits to the Dainippon value was 0.7636 x (EIKEN) + 0.1381. CONCLUSIONS: Serum free PSA and PSA-ACT values obtained with various assays were not necessarily the same. Some kits for the assay of free PSA and PSA-ACT gave the same serum values. The free PSA values obtained with the other kits could be converted using appropriate equations. The gamma-Sm values showed wide variations and were not considered suitable as a measurement of free PSA.

Humans↗

[Non-Hodgkin's lymphoma complicated by recurrent intractable generalized herpes zoster responsive to long-term acyclovir therapy].

A 34-year-old male with a history of chickenpox developed primary abdominal non-Hodgkin's lymphoma (diagnosed in August 1995). Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone achieved a partial remission. In July 1996, the disease recurred, and the patient received chemotherapy with carboplatine, etoposide, mitoxantrone, and prednisolone, but no response was noted. Involvement of the central nervous system and meninges was diagnosed on September 12, 1997. Blast cells were detected in the peripheral blood on September 26. Based on these findings, he was diagnosed as having leukemia. On September 27, painless vesicles developed on the left gluteal region. On October 13, the patient was hospitalized because the vesicles had spread over his entire body. Pathologic examination of the roofs of the blisters showed masses of inclusion bodies. Based on this, a diagnosis of varicella-zoster infection was made. Treatment with acyclovir (750 mg/day) for seven days failed to form crusts. New vesicles developed after the drug was discontinued, but crusts formed after acyclovir therapy was resumed. He died of interstitial pneumonia on December 21. Autopsy could not be performed. Histopathologic examination of pulmonary tissue obtained by necropsy did not reveal the presence of inclusion bodies characteristic of herpes simplex or varicella-zoster infection. Varicella-zoster virus (VZV) antigen was negative by an immunochemical staining method using monoclonal antibodies against VZV. Continuous long-term administration of acyclovir has been reported to be effective for non-Hodgkin's lymphoma complicated by recurrent intractable herpes zoster.

Acyclovir↗

Asymptomatic simian immunodeficiency virus infection decreases blood CD4(+) T cells by accumulating recirculating lymphocytes in the lymphoid tissues.

Declining blood CD4(+) T-cell counts mark the progress of simian immunodeficiency virus (SIV) disease in macaques and model the consequences of untreated human immunodeficiency virus infection in humans. However, blood lymphocytes are only a fraction of the recirculating lymphocyte pool, and their numbers are affected by cell synthesis, cell depletion, and distribution among blood and lymphoid tissue compartments. Asymptomatic, SIV-infected macaques maintained constant and nearly normal numbers of recirculating lymphocytes despite the decline in CD4(+) T-cell counts. Substantial depletion was detected only when blood CD4(+) T-cell counts fell below 300/microliter. In asymptomatic animals, changes in CD4(+) T-cell distribution were more important than lymphocyte depletion for controlling the blood cell levels.

Animals↗

Roles of testosterone in the growth of keratinocytes through bald frontal dermal papilla cells.

A coculture of dermal papilla cells (DPCs) from the bald frontal scalp of stumptailed macaques with keratinocytes derived from human neonatal foreskin revealed that testosterone inhibited keratinocyte proliferation, and that the antiandrogen RU58841 abolished this response. This testosterone-induced keratinocyte growth inhibition was not observed when either type of cells was cultured alone. We also examined conditioned media from the coculture system and demonstrated the identical testosterone-induced growth inhibition on keratinocytes, and this inhibitory effect was conditioned media concentration-dependent. These results suggested that the testosterone-mediated suppression on keratinocyte proliferation might proceed through some diffusible growth mediators in conditioned media. Differential display reverse transcriptase polymerase chain reaction allowed us to isolate several genes from frontal DPCs that can be either suppressed or induced by testosterone. Supervillin, a membrane-associated, F-actin-binding protein, was identified as one of the testosterone downregulated genes in frontal DPCs. Further characterization of these testosterone-target genes may reveal the mechanism by which testosterone inhibits the growth of follicular cells in androgenetic alopecia.

Alopecia↗

[Splenic lymphoma with villous lymphocytes expressing chromosomal abnormalities].

An 88-year-old Japanese woman with splenomegaly, but without lymphadenopathy, was admitted because of epigastric distress. Laboratory data disclosed an RBC of 310 x 10(4)/microliter, Hb of 10.1 g/dl, Ht of 30.6%, Plt count of 9.8 x 10(4)/microliter, and WBC of 4,470/microliter with 38% abnormal lymphocytes. Peripheral blood films revealed lymphocytes with thin, short cytoplasmic villi, condensed nuclear chromatin, and small nucleoli. The lymphocytes stained negative for tartrate-resistant acid phosphatase. Also, immunophenotyping was positive for expression of the cell surface markers CD19, CD20, IgG, kappa and HLA-DR, but not for CD5, CD10, CD11c, CD23, CD25, CD38, or CD103 antigens. Chromosomal analysis of peripheral blood cells disclosed the 46, XX, del(7), (q32) aberration. A splenectomy was performed simultaneously with partial colon resection because of a mucinous carcinoma found in the transverse colon. Histologic examination of resected spleen tissues revealed a distinctive pattern of white pulp infiltration by lymphoma cells. The histologic findings and clinical data were consistent with the features of splenic lymphoma with circulating villous lymphocytes. Our patient exhibited a relatively benign clinical course, and was being followed on an outpatient basis with no additional therapy.

Aged↗

Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA.

Aged↗

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation support in a patient with breast cancer metastasis to bone marrow: immunocytochemical monitoring of cancer-cell contamination].

A 32-year-old woman who 1 year earlier underwent a right mastectomy for stage II breast cancer with the histology of invasive ductal carcinoma (scirrhus type) was admitted due to recurrent, metastatic breast cancer in January 1997. She presented multiple metastatic lesions in the skin, lymph nodes, bone, lungs, liver, and spleen, and her bone marrow was replaced almost entirely by tumor cells. The patient was sequentially treated with 5 courses of cyclophosphamide (CPA) and adriamycin (ADM) (CA); 2 courses of CPA, ADM, and 5-fluorouracil; 5 caurses of docetaxel hydrate; and 1 course of CA. After recovery of the normal bone marrow by standard-dose chemotherapies, peripheral blood stem cells (PBSC) were then collected after mobilization with G-CSF. The number of breast cancer cells in bone marrow and PBSC samples was determined by immunocytochemical staining with an anti-cytokeratin monoclonal antibody. The number of tumor cells in PBSC sample was within the level for non-metastatic breast cancer. Complete remission was obtained with high-dose chemotherapy consisting of CPA and Thio-TEPA, and supported by autologous PBSC transplantation.

Adult↗

Liu-Jun-Zi-Tang, a kampo medicine, promotes adaptive relaxation in isolated guinea pig stomachs.

Some patients with dysmotility-like functional dyspepsia present impaired reservoir functions such as gastric adaptive relaxation. A traditional Chinese herbal medicine, Liu-Jun-Zi-Tang, has been identified as an effective drug against dyspeptic symptoms and is widely used for therapy in such patients. In this study, we examined the effects of this drug on the gastric adaptive relaxation in isolated guinea pig stomachs. The changes in intragastric volume and pressure were recorded in the presence of atropine and guanethidine. Gastric adaptive relaxation was induced by luminal distention. Liu-Jun-Zi-Tang (100 mg/ml) induced gastric adaptive relaxation at a lower intragastric pressure and increased the % volume of the gastric adaptive relaxation and the absolute intragastric volume. Metoclopramide (2 mg/ml), trimebutine (6 mg/ml) and cisapride (2 mg/ml) did not affect gastric adaptive relaxation. It was inhibited by means of the incubation of the stomach with NG-nitro-L-arginine (100 microM). Liu-Jun-Zi-Tang (100 mg/ml), but not gastroprokinetics overcame the effect of NG-nitro-L-arginine. These results suggested that Liu-Jun-Zi-Tang promoted gastric adaptive relaxation. This effect might, at least in part, contribute to the symptom relief in patients with functional dyspepsia.

Adaptation, Physiological↗

Colon cancer in aged captive rhesus monkeys (Macaca mulatta).

The age-related incidence of malignant neoplasia was surveyed from a total of 301 necropsy cases of rhesus monkeys ranging in age from 13-37 years performed in the Pathology Service Unit of the Wisconsin Regional Primate Research Center during the past 15 years. All our aged monkeys lived in indoor cages and were fed with monkey chow and supplemental fruits during the past decades. In this survey, we found a total of 51 malignant neoplasms, and among them 25 cases were colon cancer. The incidence of colon cancer increased with advancing age: 3.2% at 13-19 years, 9.2% at 20-25 years, 13.5% at 26-29 years, and 20.7% at 30-37 years. Most cancers were located in the cecum and transverse regions with a unicentric origin. Two multicentric cases were associated with chronic hypertrophic colitis. Precancerous polypous lesions were not found in all cases. Histologically, all cases were mucinous adenocarcinoma and had local invasion to the muscular wall. Metastasis to the mesenteric lymph nodes was found in only two cases. As in humans, colon cancer is a common outcome of aging in nonhuman primates.

Adenocarcinoma, Mucinous↗

Hypercalcemia associated with parathyroid hormone-related protein produced by B-cell type primary malignant lymphoma of the kidney.

A patient with primary non-Hodgkin's (B-cell type) lymphoma of the kidney developed hypercalcemia at the terminal stage of the disease. Although the plasma parathyroid hormone level was low, urinary cyclic AMP excretion was elevated. Serum osteocalcin (BGP) was suppressed and the plasma level of 1,25(OH)2D was within the normal range. Serum concentrations of PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) were elevated, and the tissue concentration of PRP-LI in the postmortem lymph node showed high level along with elevated serum PRP-LI, furthermore the production of PTHrP by the tumor was demonstrated by immunohistochemistry and Northern blotting analysis. These findings indicate that the hypercalcemia of the patient was caused by the PTHrP-producing B-cell lymphoma. Hypercalcemia was restored to normocalcemia by bisphosphonate treatment. Our case will add further information on humoral hypercalcemia in B-cell lymphoma, which rarely has been demonstrated to produce PTHrP.

Autopsy↗

Profile of endometriosis in the aging female rhesus monkey.

BACKGROUND: A retrospective analysis was conducted on necropsy records from a large rhesus monkey colony to evaluate the age-related prevalence of endometriosis. METHODS: A total of 314 records collected over a 15-year period were analyzed, yielding 66 monkeys with histologically verified endometriosis and 248 control subjects. RESULTS: The analyses demonstrated that the incidence of endometriosis increases progressively across the life span, ultimately impacting 21-45% of aged monkeys over 20 years of age. CONCLUSIONS: Because mild disease is often not diagnosed premortem, the endocrine and immune sequelae of endometriosis may be a potential confound in even nonreproductive research with aging primates. Prior research-related events influence the occurrence and severity of endometriosis in these long-lived animals, and specifically could have contributed to the high prevalence of endometriosis in this particular monkey colony.

Abdomen↗

Prostaglandin E1 antagonizes hypoxic pulmonary vasoconstriction but reduces systemic blood pressure in dogs.

OBJECTIVE: To investigate whether prostaglandin E1 (PGE1) directly inhibits hypoxic pulmonary vasoconstriction in dogs. DESIGN: Prospective, longitudinal study. SETTING: University research laboratory. SUBJECTS: Six mongrel dogs in vivo. INTERVENTIONS: The left thorax of anesthetized and ventilated dogs was opened and the left lower lobe was separately ventilated. The tip of the thermodilution pulmonary artery catheter was introduced into the left lower lobe pulmonary artery. The left lower lobe was ventilated with hyperoxic (95% oxygen and 5% CO2) or hypoxic (95% nitrogen and 5% CO2) gas. By manipulating the occluders placed on both pulmonary arteries, blood flow in the left lower lobe was regulated. Continuous pressure-flow plots for the left lower lobe were then obtained. MEASUREMENTS AND MAIN RESULTS: Measurements included continuous pressure-flow plot generation, thermodilution cardiac output and blood flow in the left lower lobe, and blood gas analysis. Alveolar hypoxia of the left lower lobe caused blood flow in the left lower lobe to decrease from 371.8 +/- 63.4 to 95.0 +/- 23.4 mL/min and shifted the pressure-flow plot to the right, with a decreased slope and with an increase in the pressure-axis intercept. Subsequently, systemic venous infusion of PGE1 at a rate of 0.3 microg/kg/min had no effect on the pressure-flow plot configuration, blood flow in the left lower lobe, pulmonary vascular resistance, systemic vascular resistance, and PaO2. However, there was a decrease in the pressure-axis intercept of the pressure-flow plot. Infusion of PGE1 at a rate of 3.0 microg/kg/min (high-dose) during hypoxia reduced pulmonary vascular resistance and systemic vascular resistance by 19% and 25%, respectively, and returned the pressure-flow plot toward normal while blood flow in the left lower lobe increased to 122.6 +/- 21.0 mL/min. Consequently, PaO2 decreased from 270 +/- 31 to 144 +/- 32 torr (36.0 +/- 4.1 to 19.2 +/- 4.3 kPa). CONCLUSION: High-dose PGE1 essentially inhibits hypoxic pulmonary vasoconstriction, at the expense of a deterioration in pulmonary gas exchange and systemic blood pressure in dogs.

Alprostadil↗