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Biomedical subjects

K Shinohara

Publications and source records attributed to K Shinohara.

At least 199 records · Page 11Linked to original sources

The levels of granulocyte colony-stimulating factor in the plasma of the bone marrow aspirate in various hematological disorders.

We developed a sensitive method of measurement of granulocyte colony-stimulating factor (G-CSF) by an enzyme-linked immunosorbent assay, which we applied in the plasma of the bone marrow aspirate in 70 patients with various hematological disorders. The lowest limit of detection by this method is 2 pg/ml. G-CSF was detected in all but two of the patients. Compared to the G-CSF level in normal healthy controls, those in non-Hodgkin's malignant lymphoma, aplastic anemia, agranulocytosis and multiple myeloma were significantly higher, while the level in refractory anemia was not different. The G-CSF level in acute myelogenous leukemia patients was either elevated or decreased regardless of the French-American-British subgroup. The level in acute lymphoblastic leukemia was not different from the normal value, as was that in refractory anemia with an excess of blasts, and that in chronic lymphocytic leukemia. A patient with chronic myelomonocytic leukemia showed initial elevation of G-CSF with normalization after entering complete remission. The G-CSF level in chronic myelogenous leukemia was significantly decreased, although one patient in hematological remission who was under alpha-interferon therapy showed normal levels. The level in polycythemia vera was not significantly different from the normal value. The G-CSF level for the entire group showed an inverse, although not statistically significant, correlation with the percentages of myeloid cells of the bone marrow (r = -0.174, p = 0.1703, n = 80). These results are thought to reflect the regulatory mechanism of granulopoiesis in the bone marrow in various hematological disorders, and it is concluded that this method may be of clinical use in the treatment of patients with these disorders and in the selection of candidates likely to benefit from G-CSF administration.

Agranulocytosis↗

Circadian modulation in photic induction of Fos-like immunoreactivity in the suprachiasmatic nucleus cells of diurnal chipmunk, Eutamias asiaticus.

Photic induction of immediate early genes including c-fos in the suprachiasmatic nucleus (SCN) has been well demonstrated in the nocturnal rodents. On the other hand, in diurnal rodents, no data is available whether the light can induce c-fos or Fos in the SCN. We therefore examined whether 60 min light exposure induces Fos-like immunoreactivity (Fos-lir) in the SCN cells of diurnal chipmunks and whether the induction is phase dependent, comparing with the results in nocturnal hamsters. We also examined an effect of light on the locomotor activity rhythm under continuous darkness. Fos-lir was induced in the chipmunk SCN. The induction was clearly phase dependent. The light during the subjective night induced strong expression of Fos-lir. This phase dependency is similar to that in hamsters. However, unlike in hamsters, the Fos-lir was induced in some SCN cells of chipmunks exposed to light during the subjective day. In the locomotor rhythm, on the other hand, the light pulse failed to induce the phase shift at phases at which the Fos-lir was induced. These results suggest that the photic induction of Fos-lir in the diurnal chipmunks is gated by a circadian oscillator as well as in the nocturnal hamsters. However, the functional role of Fos protein may be different in the diurnal rodents from in the nocturnal rodents.

Animals↗

Transition zone volume and transition zone ratio: predictor of uroflow response to finasteride therapy in benign prostatic hyperplasia patients.

OBJECTIVES: The aim of this study was to: (1) determine effects of finasteride on transition zone (TZ) volume, TZ ratio (TZ volume/total prostate volume), and total prostate volume; (2) analyze differences in TZ and total volume reduction among patients who improve peak urinary flow rates following finasteride therapy with those who do not; (3) investigate which parameters correlate with improvement in peak urinary flow rate and urinary symptom score; and (4) establish if there is any predictive value of these parameters for response to therapy. METHODS: Twenty-three patients with symptomatic benign prostatic hyperplasia (BPH) were treated with finasteride (5 mg/d) for 12 months and underwent transrectal ultrasound (TRUS) evaluation of total and TZ volume of prostate and measurement of peak flow rate and modified Boyarsky symptom score at baseline and at 12 months. Statistical analysis was done by unpaired t, Mann-Whitney, and Spearman rank correlation tests among responders (more than 3 cc/s improvement in peak flow rate) and nonresponders (less than 3 cc/s improvement in peak flow rate) to therapy. RESULTS: (1) Responders had substantial reduction in TZ volume (44.8% versus 16.05%; P < 0.03) and TZ ratio (25% versus 5% increase, P < 0.02) compared with nonresponders. (2) There was a significant correlation between reduction in TZ volume (r = 0.50; P < 0.03) and TZ ratio (r = 0.60; P < 0.006) with improvement in peak flow rates. No similar correlation was seen with total prostate volume changes. (3) Pretreatment TZ ratio helped in predicting peak flow improvement following finasteride therapy (r = 0.52; P < 0.01) and there was a 2.5-fold increased chance of improvement if baseline TZ ratio was more than 0.51. The modified Boyarsky symptom score decreased by 3.1 (mean), but there was no correlation with changes in peak urinary flow rate, total prostate volume, TZ volume, and TZ ratio. TZ ratio did not have significant predictive value for improvement in symptom score. CONCLUSIONS: This study provides data that simple measurable parameters are available which may be used prior to therapy to predict uroflow response to finasteride and similar agents.

Double-Blind Method↗

Photic information coded by vasoactive intestinal polypeptide and neuropeptide Y.

We investigated photic response of the concentration of vasoactive intestinal polypeptide (VIP) and neuropeptide Y in the rat suprachiasmatic nucleus (SCN) by enzyme immunoassay (EIA). The content of VIP in the SCN did not show circadian rhythms in constant darkness (DD). Under light-dark (LD) condition, VIP contents decreased over the course of the light period and then recovered during the dark period. When the light was continuously delivered to rats, VIP levels were monotonically decreased and did not return to the basal level. Accordingly, VIP in the SCN may code photic information on duration. On the other hand, there is a daily bimodal pattern in NPY content in the SCN under light-dark conditions. When rats were exposed to continuous light, the NPY level steadily increased and reached a peak in 2 h before returning to a basal level. The amount of increase did not depend on duration of light exposure. Thus, NPY in the SCN may code visual information on transitions, which is different from that conveyed by VIP. These results indicate that the two peptides act on a different stage of photic processing and may mediate distinct photic information to the circadian pacemaker.

Animals↗

The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostate-specific antigen, and biopsy Gleason score in prediction of final pathologic diagnosis in prostate cancer.

OBJECTIVES: To evaluate the role of ultra sound-guided systematic and lesion-directed biopsies, biopsy gleason score, preoperative serum prostate-specific antigen (PSA) as three objective and reproducible variables to provide a reliable combination in preoperative identification of risk of extraprostatic extension in patients with clinically localized prostate cancer. METHODS: The case records of 813 patients who underwent radical prostatectomy for clinically localized prostate cancer were analyzed. All had multiple systematic biopsies, two to three from each lobe, in addition to lesion-directed biopsies. Additionally, biopsies were done on seminal vesicles (SVs), if abnormal. Based on biopsy results, patients were classified as having stage B1 (T2a-T2b) or B2 (T2c) disease, depending on whether biopsies from one or both lobes were positive and stage C (T3) if there was evidence of SV involvement by biopsy of biopsies from areas of extracapsular extension as seen on transrectal ultrasound (TRUS) were positive. Logistic regression analyses with log likelihood chi-square test was used to define the correlation between individual as well as combination of preoperative variables and pathologic stage. RESULTS: On final pathologic examination, 473 (58%) patients had organ-confined disease, 188 (23%) had extracapsular extension (ECE), with or without positive surgical margins, and 72 (9%) had SV involvement. Eighty (10%) patients had pelvic lymph node metastases. Biopsy-based staging was superior to clinical staging in predicting final pathologic diagnosis. Logistic regression analyses revealed that the combination of biopsy-based stage, preoperative serum PSA, and biopsy Gleason score provided the best prediction of final pathologic stage. Probability plots constructed with these data can provide significant information on risk of extraprostatic extension in individual patients. CONCLUSIONS: This study demonstrates that TRUS-guided systematic biopsy in combination with preoperative serum PSA and biopsy Gleason score may provide a cost-effective approach for management decisions and prognostication in patients with prostate cancer.

Biopsy↗

High failure rate associated with long-term follow-up of neoadjuvant androgen deprivation followed by radical prostatectomy for stage C prostatic cancer.

OBJECTIVE: To evaluate whether neoadjuvant androgen deprivation before radical prostatectomy decreases tumour stage in patients with stage C prostatic cancer and to estimate the efficacy of cancer control achieved with this form of treatment. PATIENTS AND METHODS: Thirty men (mean age 65 years, range 52-74) with clinical stage C adenocarcinoma of the prostate were included in a phase II trial of neoadjuvant androgen deprivation (luteinizing hormone-releasing hormone agonist and an antiandrogen) before radical prostatectomy. The timing and extent of the changes in serum prostate specific antigen (PSA) levels and both prostate and cancer volume were recorded. Twenty-six men underwent radical prostatectomy with pelvic lymphadenectomy, two had pelvic lymphadenectomy alone, one had pelvic lymphadenectomy with radiotherapy and one refused additional treatment despite significant reductions in tumour volume and PSA while undergoing androgen deprivation. RESULTS: The toxicity of the treatment was low. Significant reductions in prostatic volume (mean 35%), tumour volume (mean 50%) and PSA concentrations (mean 96%) occurred in all patients, with the maximum reductions recorded during the first 2 months of androgen deprivation. However, despite significant physiological changes in prostate and tumour volume, tumour stage was reduced in only four patients. Of the patients who were surgically staged 41% were ultimately identified as having more advanced disease, including lymph node metastases in 21%. Overall, with a mean follow-up of 32.7 months, 72% of patients had evidence of disease recurrence, including detectable PSA. Of 26 patients who underwent radical prostatectomy, local recurrence occurred in five (19%), distant recurrence in one (4%) and both local and distant recurrence in one (4%). CONCLUSIONS: This study suggests that tumour stage reduction is uncommon in patients with stage C prostatic cancer treated with neoadjuvant androgen deprivation followed by radical prostatectomy. Furthermore, local and distant recurrences, as well as detectable levels of PSA, are common after such treatment.

Adenocarcinoma↗

The significance of prostatic intra-epithelial neoplasia.

OBJECTIVE: To investigate the relationship between the detection of prostatic intra-epithelial neoplasia (PIN) on initial prostate biopsy and subsequent invasive prostatic adenocarcinoma. PATIENTS AND METHODS: Thirty-six men (mean age 67 years, range 52-82) with PIN underwent digital rectal examination (DRE), serum prostate-specific antigen (PSA) measurement and transrectal ultrasonography (TRUS) before the initial biopsy and documentation of PIN. They were followed up with serial PSA, TRUS and a repeat biopsy every 6 months until either invasive carcinoma was identified or 2 years had elapsed. RESULTS: The initial biopsy revealed Grade I PIN in 33%, Grade II in 22%, and Grade III in 45% of the men. The repeat biopsy showed evidence of invasive carcinoma in 21 patients (58%; Group I), while 15 (42%) showed persistence of PIN (Group II). In Group I, 19 had had high-grade PIN (Grade II/III) on initial biopsy compared with one in Group II. The findings on DRE, and age, were no significantly different between groups. TRUS revealed a hypoechoic lesion in 15/21 patients in Group I compared with 7/15 patients in Group II. There was an increase in PSA level in 18 patients in Group I (from 8.4 to 11.6 ng/mL). CONCLUSIONS: PIN and invasive adenocarcinoma of the prostate were closely associated, and the likelihood for coexistence was higher in patients with high-grade PIN, increasing PSA level or positive findings on TRUS. We recommend that all patients who show high-grade PIN on prostate biopsy be followed very closely with serial PSA measurements and repeat biopsies from both the area of PIN and other areas of the prostate.

Adenocarcinoma↗

Assessment of the mutagenicity of extracts of TMV-coat-protein-gene induced transgenic tomato by the umu-test.

We examined the mutagenicity of extracts (juice and ethanol extract) from a transgenic tomato that was established by transfection of a gene encoding the coat protein of tobacco mosaic virus (TMV) to the F1 hybrid between Lycopersicon esculentum LA1000 and L. peruvianum PI128650, by the umu-test with Salmonella typhimurium TA1535/pSK1002 as the test organism. The extracts showed no detectable mutagenicity. The extracts from the above-mentioned F1 hybrids and wild tomatoes and cultivars (L. peruvianum PI128650, L. peruvianum PI126944, L. pimpinellifolium LS1524, L. pimpinellifolium LA722, L. hirsutum LS503, Mini-carol, Sun-cherry, Momotaro, Odoriko, Kagome77, and Ponderosa) also showed no detectable mutagenicity.

Capsid↗

Protein synthesis inhibitor phase shifts vasopressin rhythms in long-term suprachiasmatic cultures.

The effects of anisomycin, a protein synthesis inhibitor, on the circadian rhythm of arginine-vasopressin (AVP) release in organotypic slice cultures of the rat suprachiasmatic nucleus were examined. Anisomycin applied to the culture as a 6-h pulse shifted the phase of the AVP rhythm, depending on the circadian phase at which the pulse was given. The resultant phase-response curve consisted of a delay portion throughout the late subjective night and an advance portion in the middle of subjective day. The present findings suggest that protein synthesis is an important process which constitutes the circadian oscillation and/or the input pathway to the circadian pacemaker within the suprachiasmatic nucleus.

Animals↗

Circadian variations of neuropeptide Y-like immunoreactivity in the rat pineal gland.

Neuropeptide Y, which is present in the sympathetic nerves innervating pineal glands, has been shown to affect N-acetyltransferase activity and melatonin production. Using enzyme immunoassay, we measured daily patterns of neuropeptide Y (NPY) in rat pineal glands in light-dark cycles (LD) and in constant darkness (DD). NPY within rat pineal glands displayed daily rhythms in LD with a peak at zeitgeber time 16. Similar rhythms in the NPY content were also observed in DD. These rhythms have a similar phase-relationship to that of the rhythm of NAT activity, suggesting that NPY in rat pineal glands plays a role in circadian rhythms of NAT activity.

Animals↗

Circadian rhythms in the release of vasoactive intestinal polypeptide and arginine-vasopressin in organotypic slice culture of rat suprachiasmatic nucleus.

Temporal profiles of the amount of vasoactive intestinal polypeptide (VIP) were examined in the medium of organotypic suprachiasmatic nucleus (SCN) slice cultures over a 2-day period. Arginine-vasopressin (AVP) level was also measured in the same medium. The slices of the SCN were obtained from 7-8-day-old rats and cultured individually in tubes on a roller drum for 14 days. The VIP amount in the medium of SCN culture showed a circadian rhythm with a approximately 22-h period. Circadian rhythms with identical periods were also observed in AVP amount of the same culture. However, the peak time of the VIP rhythm was slightly ahead of that of the AVP rhythm. Furthermore, the total VIP amount in the medium over a 24-h period was six times as large as that of AVP. These results suggest that there is a circadian rhythm of VIP which is released from the ventrolateral SCN.

Animals↗

Transurethral evaporation of prostate (TUEP) with Nd:YAG laser using a contact free beam technique: results in 61 patients with benign prostatic hyperplasia.

OBJECTIVE: This prospective study was undertaken to evaluate the safety and efficacy of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser for treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 61 patients at a mean age of 71.6 years with symptomatic bladder outlet obstruction due to BPH underwent transurethral evaporation of prostate (TUEP) using Nd:YAG laser. Twelve of the patients were experiencing acute retention. Pre- and postoperative evaluation consisted of American Urological Association (AUA) symptom questionnaire and a sexual function questionnaire, uroflowmetry, postvoid residual urine, electrolytes, blood urea nitrogen, creatinine, hematocrit, and prostate volume estimation by transrectal ultrasound. TUEP was achieved by employing a side-firing Nd:YAG laser fiber with a durable quartz reflector and high-power density (Ultraline, Heraeus LaserSonics, Milpitas, CA) that was used in a contact mode. RESULTS: All patients have been evaluated for three months, 26 for six months, and 7 for twelve months. Mean prostatic size was 41.1 g. The mean improvement in symptom scores at one, three, six, and twelve months was 69.8 percent, 70.9 percent, 76.0 percent, and 70.9 percent, respectively (P = < 0.0001). The mean increase in maximum uroflow at one, three, six, and twelve months was 63.4 percent, 66.7 percent, 41.94 percent, and 164.52 percent, respectively (P = < 0.0001). There was no instance of significant fluid absorption or bleeding. The duration of postoperative catheterization was two days in 43 patients, three to seven days in 16 patients, and two to three weeks in 2 patients. There were no deaths. All patients evaluated by TRUS at six months had open channeling defects. Videocystoscopy performed in 16 patients at two to three months postoperatively revealed tissue slough. At repeat cystoscopy in these patients at six months, the prostatic fossa was completely healed with no evidence of tissue slough. CONCLUSIONS: It is concluded that the technique of TUEP using Nd:YAG laser is safe and, in preliminary results, appears apparently effective in the management of BPH.

Aged↗

Comparison of prostate specific antigen with prostate specific antigen density for 3 clinical applications.

We compared prostate specific antigen (PSA) to PSA density for 3 clinical uses: detection of nonpalpable prostate cancer, staging of clinically localized prostate cancer and prediction of PSA detectability following radical prostatectomy. Of 153 men with normal digital rectal examinations undergoing prostate biopsy 25% had prostate cancer. Analysis of receiver operator characteristic curves demonstrated that PSA density predicted the outcome of biopsy significantly better than did PSA (p = 0.0013). Pathological examination of 155 radical prostatectomy specimens revealed that 56% had pathologically uncontained disease. There was no difference between the ability of PSA and PSA density to predict the pathological findings (p = 0.2379). PSA data more than 1 year postoperatively were available in 96 of the 155 prostatectomy patients. Of these men 41% had postoperative PSA levels of 0.1 ng/ml. or more. Preoperative PSA and PSA density values were almost identical in the ability to identify these patients (p = 0.6776). While PSA density is superior to PSA for the detection of prostate cancer in patients with a palpably normal prostate, it does not offer any improvement over PSA for staging of prostate cancer or for the prediction of PSA detectability after radical prostatectomy.

Aged↗

Persistent infection with SIVmac chimeric virus having tat, rev, vpu, env and nef of HIV type 1 in macaque monkeys.

A chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu, env, and nef genes of human immunodeficiency virus type 1 was generated. The chimeric virus, NM-3n, grew competently in peripheral blood mononuclear cells from cynomolgus monkeys like the parental SIVmac. Two cynomolgus monkeys and one rhesus monkey inoculated with NM-3n raised antibodies to SIVmac Gag and HIV-1 Env. The antibodies raised in the cynomolgus monkeys persisted for at least 1.7 years. The antibodies contained virus neutralizing activity not only to the original chimeric virus but also to the parental HIV-1. Infectious viruses were isolated from one of the cynomolgus monkeys 37 and 63 weeks after inoculation and from the rhesus monkey continuously from 6 weeks after infection onward. The recovered virus maintained its chimeric structure but included several clones with mutations in the env V3 region. When the recovered virus was inoculated to another rhesus monkey, no difference in the frequency of virus recovery was seen from the originally infected monkeys. These carrier monkeys have so far shown no sign of the disease.

Animals↗

Fallout radioactivity in soil and food samples in the Ukraine: measurements of iodine, plutonium, cesium, and strontium isotopes.

To estimate the level and distribution of fallout attributable to the 26 April 1986 Chernobyl nuclear power station accident in the Ukraine, we sampled several kinds of substances at Korosten, Zhitomir and at Katyuzhanka, Vishgorod, Kiev in the Ukraine, and measured the radioactivity of 137Cs, 134Cs, 90Sr, 129I, 238Pu, 239,240Pu, and the density of 127I (stable). The substances investigated were soil, dry milk, wheat, rye, drinking water, and mushrooms. Except for the mushrooms collected, which were sampled at Katyuzhanka, Vishgorod, and at Kiev, all substances were at Korosten, Zhitomir. The activity of 137Cs, 134Cs, 90Sr, 238Pu, and 239,240Pu were all higher in soil and mushrooms than in the other four substances. The activity of 137Cs was 960 and 1,210 Bq kg-1 in the two soil samples and 6,110 Bq kg-1 in the mushrooms. The activity of 134Cs was approximately 15% of 137Cs in the two soil samples while < 3% of 137Cs in the mushrooms. The activity concentration level of 90Sr as compared to 137Cs concentration was 15-31% in food samples other than mushrooms but only 1.9% in mushrooms and 1.4 and 1.2% in the two soil samples. The radioactivity ratios, 238Pu: 239,240Pu and 239,240Pu: 137Cs, suggested that the proportion of cesium radioisotopes and 239,240Pu in the soil attributable to the Chernobyl accident was approximately 100% and 10-20%, respectively, while approximately 100% of 239,240Pu in the mushrooms was attributable to the accident. The activity of 129I was small but the ratio of 129I: 127I in the two soil samples was 4.3 x 10(-8) and 1.0 x 10(-7), which is approximately 10 times larger than that in the global fallout. These results suggest that the areas where the soil was sampled are iodine-deficient and were contaminated slightly by the Chernobyl accident.

Accidents↗