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Biomedical subjects

K Shinohara

Publications and source records attributed to K Shinohara.

At least 235 records · Page 13Linked to original sources

Selection of patients for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy: a decision analysis.

Indications for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy have not been established. Criteria to predict lymph node metastases were derived from the preoperative evaluations of 164 prostate cancer patients undergoing pelvic lymphadenectomy. Decision analysis was used to determine which criteria would be optimal indicators for laparoscopic pelvic lymphadenectomy prior to intended radical prostatectomy. Besides a digital rectal examination suggesting uncontained tumor, which was the best indication for laparoscopic pelvic lymphadenectomy, the most useful criteria were sonographic tumor volume > or = 3 cc and prostate-specific antigen (PSA) > or = 20 ng/mL. If either parameter was met, the sensitivity for identifying patients with pelvic lymph node metastases was 88 percent and the positive predictive value was 42 percent. When both were met, the sensitivity fell to 47 percent but the positive predictive value increased to 67 percent. A combination of Gleason biopsy score and PSA was the best criterion that was independent of transrectal ultrasonography. Using a PSA > or = 15 ng/mL for tumors with Gleason biopsy score > or = 7 or a PSA > or = 25 ng/mL for tumors with a Gleason biopsy score of 5-6 had a sensitivity of 71 percent and positive predictive value of 48 percent for identifying patients with pelvic lymph node metastases. In selecting patients for laparoscopic pelvic lymphadenectomy prior to radical retropubic prostatectomy, criteria with a positive predictive value greater than 39 percent maximize the utility of laparoscopic pelvic lymphadenectomy. Prior to radical perineal prostatectomy, laparoscopic pelvic lymphadenectomy will identify pelvic lymph node metastases that would otherwise be undetected by prostatectomy alone. The sensitivity of selection criteria, therefore, should be increased, as long as the positive predictive value remains above 20 percent.

Aged↗

Combined role of transrectal ultrasonography, Gleason score, and prostate-specific antigen in predicting organ-confined prostate cancer.

Prostate cancer staging is frequently inaccurate. By combining transrectal ultrasonography (TRUS) with a retrospectively derived grade-stratified prostate-specific antigen (PSA-GS) scale, we demonstrated 77 percent staging accuracy in 155 men with clinically localized prostate cancer undergoing radical prostatectomy. When used as the first step in a staging algorithm, PSA-GS (Score > or = 7: PSA > or = 4.0 ng/mL, uncontained; Score = 5 or 6: PSA > or = 8.0 ng/mL, uncontained; Score < or = 4: PSA > or = 16.0 ng/mL, uncontained) had a sensitivity of 75 percent and a specificity of 72 percent. The addition of TRUS to the staging algorithm, necessary only in patients with negative predictions by PSA-GS (46%), increased the sensitivity to 86 percent and the negative predictive value to 79 percent, while positive predictive value was unchanged at 77 percent. The combination of TRUS with PSA < 4 ng/mL or > or = 16 ng/mL identified subsets of patients with 85 percent and 88 percent likelihood of contained and uncontained disease, respectively. Our algorithm minimizes operator dependency by requiring TRUS in less than half of the patients. It produced improved staging, but the overall results were inaccurate in 23 percent of patients. Further refinements in prostate cancer staging are still necessary.

Aged↗

Processing of photic information within the intergeniculate leaflet of the lateral geniculate body: assessed by neuropeptide Y immunoreactivity in the suprachiasmatic nucleus of rats.

Entrainment of the circadian pacemaker in the suprachiasmatic nucleus is accomplished by two neural pathways, the retinohypothalamic and geniculohypothalamic tracts. The geniculohypothalamic tract, which originates from the intergeniculate leaflet and a portion of the ventral lateral geniculate nucleus, is composed of fibers immunoreactive to neuropeptide Y. To assess the processing of photic information by the geniculohypothalamic tract, neuropeptide Y immunoreactivity in the suprachiasmatic nucleus of rats kept under various external lighting conditions was determined by enzyme immunoassay of micropunched tissues. Neuropeptide Y levels in the suprachiasmatic nucleus steadily increased when rats were exposed to continuous light and reached a peak in 2 h before returning to basal level. The amount of increase did not depend on intensity and duration of light exposure. A light pulse as short as 5 min elicited a similar rise in neuropeptide Y, indicating that the response is due to the sudden transition from dark to light. This response, however, was only observed when the dark to light transition occurred at circadian time 0 (subjective dawn) of the pacemaker. A light pulse at circadian time 0, which effectively induces the increase in neuropeptide Y level, does not significantly shift the phase of the circadian rhythm. This observation indicates that the photic pathway utilizing neuropeptide Y may be functional only when the endogenous circadian rhythm is synchronized to external light and dark cycles. Administration of an excitatory amino acid antagonist (MK-801) blocked the increase of neuropeptide Y by light, while an agonist (N-methyl-D-aspartate) induced similar facilitatory effects to that of light on the neuropeptide Y level in the rat suprachiasmatic nucleus. These results suggest that the geniculohypothalamic tract processes photic information so as to facilitate distinction of the transition between light and darkness that occurs either at subjective dawn or dusk.

Animals↗

The value of prostate specific antigen and transrectal ultrasound guided biopsy in detecting prostatic fossa recurrences following radical prostatectomy.

The combination of prostate specific antigen (PSA) and transrectal ultrasonography was used to detect recurrent cancer in the prostatic fossa after radical prostatectomy. A total of 43 patients with persistently elevated PSA levels and negative bone scintigraphy following radical prostatectomy underwent digital rectal examination and transrectal ultrasonography. Ultrasound findings were considered suspicious if the scan showed any unusual hypoechoic tissue adjacent to the bladder neck, retro-trigone or peri-anastomotic site. Of 22 patients (51%) with biopsy proved cancer 21 (95%) had positive transrectal ultrasonography, while digital rectal examination was able to detect cancer in only 10 (45%). Among transrectal ultrasonography detected recurrences 15 (68%) were detected at the initial biopsy and 7 (32%) at repeat biopsies. Our study shows that the combination of PSA and transrectal ultrasonography provides a more effective method than digital rectal examination and PSA to detect biopsy proved cancer following radical prostatectomy.

Adenocarcinoma↗

Ultrasonic detection of non-palpable seminal vesicle invasion: a clinicopathological study.

In an effort to identify reliable criteria for detecting seminal vesicle invasion (SVI) with transrectal ultrasonography (TRUS) in patients with clinically localised prostate cancer, we reviewed the pre-operative sonograms in 230 patients who underwent radical retropubic prostatectomy; 49 patients (21%) had pathologically confirmed SVI. Conventional sonographic criteria for SVI (asymmetry, distension, atrophy, abnormal echogenicity and irregularity in outline) were present in 58 patients, but only 16 (28%) had pathologically confirmed SVI. On the basis of the results of a preliminary comparison of radical prostatectomy specimens and TRUS, we had revised our criteria for the recognition of SVI: (1) a hypoechoic lesion at the base of the prostate (within 10 mm of the seminal vesicle); (2) an "adhesion sign" resulting from the loss of the echo reflections from the normal fat plane between the prostate and the seminal vesicle; (3) "posterior convexity" of the seminal vesicles. When we reviewed the 230 sonograms retrospectively, we found a hypoechoic tumour at the base in 70 patients, of whom 37 had SVI (positive predictive value (PPV) 53%). An adhesion sign was found in 16 patients, 12 of whom had SVI (PPV 75%). Posterior convexity was present in 4 patients, all of whom had SVI. If any one of our sonographic signs was present, the overall accuracy (83%), sensitivity (90%) and positive predictive value (51%) were significantly better than with any one of the conventional criteria. Patients with SVI were also more likely to have a high serum prostate specific antigen (PSA) level. The PPV for SVI of a PSA level > or = 10 ng/ml was 38%. If the PSA was > 10 ng/ml and TRUS was positive (> or = 1 of our sonographic criteria), 16 (62%) of 26 patients had SVI. If the PSA was < 10 ng/ml and TRUS was negative, only 3 (3%) of 86 patients had SVI. It was concluded that the conventional criteria for detecting SVI on ultrasonography are not accurate in patients with early stage prostate cancer. There are, however, reliable criteria that predict SVI with reasonable accuracy and these criteria, combined with the serum PSA levels, can stratify patients into those with a low risk and those with a high risk of SVI.

Adult↗

Central nervous system complications after cardiac surgery: a comparison between coronary artery bypass grafting and valve surgery.

Central nervous system (CNS) complications (disturbance of consciousness, focal motor deficits, and seizures) after coronary artery bypass grafting (CABG) and cardiac valve surgery were studied retrospectively. The incidence of CNS complications was significantly more frequent in CABG (11%, 71/638) than in valve surgery (7%, 24/345). Major contributory factors of CNS complications were preexisting cerebrovascular disease and cardiopulmonary bypass time. In comparison to previous reports, older age, hypertension, diabetes mellitus, and cerebrovascular disease were more common in the patients undergoing CABG. The preexisting cerebrovascular disease and prolonged cardiopulmonary bypass time probably increase the risk of cerebral embolism and/or cerebral hypoperfusion. We conclude that patients undergoing CABG surgery are at greater risk for neurological damage in comparison to those undergoing valve surgery.

Aged↗

Myelodysplastic syndrome associated with myelofibrosis, a report of 3 cases.

Three cases of primary myelodysplastic syndrome (MDS) associated with myelofibrosis were initially diagnosed as refractory anemia by the presence of bicytopenia or pancytopenia and having normo- or hypercellular marrow with dysplastic features. The bone marrow aspiration of these patients showed dry tap a few months after admission, or on admission. Their bone marrow biopsy specimens revealed various grades of increased formation of reticulin fibers. One patient entered into complete remission in response to metenolone, while the other two patients died of cerebral hemorrhage several months after admission. These results indicate that this disease should be classified as a distinct subgroup of MDS.

Aged↗

Interphase death and reproductive death in X-irradiated MOLT-4 cells.

The killing effects of ionizing radiation on MOLT-4 cells were studied using colony formation assays, dye exclusion tests, and cell growth analysis. When MOLT-4 cells were exposed to X rays, the fraction of cells stained with erythrosin B increased markedly during the incubation after irradiation at 37 degrees C and reached a maximum within 24 h. In contrast, no such increase was observed for L5178Y cells or their derivative, radiosensitive mutant M10 cells, at a dose resulting in the same level of cell survival as measured by the colony formation assay. Detailed analysis of cell survival as measured by the dye exclusion test in comparison with that measured by the colony formation assay in MOLT-4 cells indicated that MOLT-4 cells are subject to interphase death as well as reproductive death. Analysis of subclones showed a wide variety of differences in the level of stained cells using the dye exclusion test. The results confirmed the population heterogeneity of MOLT-4 cells. Moreover, none of the subclones showed exactly the same cell survival when this was measured with the two assays. The present results strongly suggest that both modes of cell death may occur in single MOLT-4 cells. Possibly apoptosis is the mechanism accounting for both modes of death in these cells.

Adult↗

Photic regulation of peptides located in the ventrolateral subdivision of the suprachiasmatic nucleus of the rat: daily variations of vasoactive intestinal polypeptide, gastrin-releasing peptide, and neuropeptide Y.

We have determined, by enzyme immunoassay, daily and circadian patterns of the concentrations of three peptides, which are located in the ventrolateral subdivision of the suprachiasmatic nucleus (SCN): vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and neuropeptide Y (NPY). The contents of VIP and GRP, which are synthesized in the SCN, did not show circadian rhythms in constant darkness (DD). Under light-dark (LD) conditions, GRP content increased and VIP content decreased over the course of the light period and then gradually recovered during the dark period. Responsiveness of these peptides to light suggests that VIP and GRP may transmit visual information on duration of illumination. NPY, which is transported from the intergeniculate leaflet of the lateral geniculate body, showed a circadian rhythm with a peak at circadian time 12 hr in DD. This endogenous rhythm was remarkably modulated by photic stimulation. Under LD conditions, the NPY content in the SCN exhibited a bimodal rhythm with peaks at both the light-dark and dark-light transition points. Thus, NPY may convey visual information on the transitions. All these results indicate that the levels of VIP, GRP, and NPY are mainly regulated by light stimulation and suggest that peptides in the ventrolateral SCN are involved in the mediation of photic information to the pacemaker.

Animals↗

[Evaluation of lidocaine metabolite (monoethylglycinexylidide) as a liver function test].

In order to determine whether or not the lidocaine metabolism, monoethylglycinexylidide (MEGX) formation, could be used as a liver function test, we measured the serum levels of MEGX in 38 patients. There were significant correlations between values of MEGX (MEGX15, MEGX30, AUC15-30, AUC0-180) and conventional liver function tests (ICG R15, AT III, T. Bil). It appeared that value of MEGX 30 had maximum factor loading on conventional liver function tests by using principal component analysis. The advantage of adapting the MEGX formation as a liver function test of drug metabolism is simplicity of the method. MEGX formation could be useful index of the total liver function.

Evaluation Studies as Topic↗

Cell killing induced by decay of 125I during the cell cycle: comparison of 125I-antipyrine with 125I-bovine serum albumin.

The lethal effects induced by the decay of 125I in synchronized L5178Y cells were studied by suicide experiments. We used 125I-antipyrine, which is freely diffusible in cells, and 125I-bovine serum albumin (BSA), which remains outside the cells. Synchronized cells mixed with either 125I-antipyrine or 125I-BSA were frozen and stored at -196 degrees C for various periods to accumulate 125I decays. A clonogenic assay was used to measure the killing of these stored cells. Cells in G1-S and G2-M phases were more sensitive than those in late S phase for both 125I treatments. The ratio of survival in late S to that in G1-S (late S/G1-S) obtained by the decay of 125I-antipyrine, however, was much smaller than that obtained by the decay of 125I-BSA in the dose range examined. These results suggest that Auger electrons emitted from 125I-antipyrine cause a high-LET-type effect. The reason for the high-LET effect must be the intracellular localization of 125I-antipyrine and its closer contact with DNA.

Animals↗

[Clinical significance of urinary methylguanidine in non-dialyzed patients with chronic renal failure--prediction of progression rate of renal dysfunction].

To clarify a clinical significance of urinary methylguanidine (U-MG, micrograms/dl) in non-dialyzed patients with chronic renal failure, we measured U-MG, urinary creatinine (U-Cr, mg/dl) and serum creatinine (S-Cr, mg/dl), concurrently and continually in 36 out-patients whose S-Cr was over 4.0 mg/dl. Fresh urine sample was obtained and U-MG was measured by an enzymic method. S-Cr concentrations (mean +/- SD) at the initiation of dialysis therapy were comparable in non-diabetics and in diabetics, being 13.4 +/- 4.54mg/dl and 8.23 +/- 1.96mg/dl, respectively, with statistical significance (p < 0.01). U-MG/Cr (micrograms/mg. Cr) values were also different between them, being 9.28 +/- 4.97 in non-diabetics and 5.19 +/- 1.29 in diabetics, but with lesser statistical significance (p < 0.05) than S-Cr. U-MG/Cr correlated well with the terms till the initiation of dialysis therapy (r = 0.7189, p < 0.001), more significantly than S-Cr (r = 0.5506, p < 0.001) in parabolic regression analysis. U-MG/Cr were greatly varied among the 7 patients, although whose S-Cr was nearly the same level (6.0-6.9mg/dl). Most importantly, the tendency was found in these patients that the higher U-MG/Cr, the earlier the renal replacement therapy instituted. These results suggests that U-MG/Cr can be reliable parameter to predict the progression rate of renal failure and to help to know when renal replacement therapy should be instituted.

Adult↗

Synthesis and properties of mirror-image DNA.

We have investigated the conformations of the hexadeoxyribonucleotide, L-d(CGCGCG) composed of L-deoxyribose, the mirror image molecule of natural D-deoxyribose. In this paper, we report the synthesis of four L-deoxynucleosides and the L-oligonucleotide-ethidium bromide interactions. The L-deoxyribose synthon 9 was synthesized from L-arabinose with an over all yield of 28.5% via the Barton-McCombie reaction. The L-deoxynucleosides were obtained by a glycosylation of appropriate nucleobase derivatives with the 1-chloro sugar 9. After derivatization to nucleoside phosphoramidites, L-deoxycytidine and L-deoxyguanosine were incorporated into a hexadeoxynucleotide, L-d(CGCGCG) by a solid-phase beta-cyanoethylphosphoramidite method. This L-hexanucleotide was resistant to digestion with nuclease P1. The conformations of L-d(CGCGCG) were an exact mirror image of that of the corresponding natural one as described previously, and the conformations of the L-d(CGCGCG)-ethidium bromide complex were also the mirror images of those of the D-d(CGCGCG)-ethidium bromide complex under both low and high salt conditions. These results suggest that ethidium bromide prefers not a right-handed helical sense, but the base-base stacking geometry of the B-form rather than that of the Z-form. Thus, L-DNA would be a useful tool for studying DNA-drug interactions.

Chromatography, High Pressure Liquid↗

Fluctuations in serum cytokine levels in the patient with cyclic neutropenia.

The fluctuations of the levels of serum cytokines in a patient with cyclic neutropenia were studied. The greatest fluctuation was found in granulocyte colony-stimulating factor (G-CSF). Tumor necrosis factor-alpha level fluctuated inversely with fluctuation of G-CSF, and oscillation of interleukin (IL)-6 level preceded that in G-CSF level. It is likely that the variations of the levels of cytokines play a significant role in regulating hematopoiesis in cyclic neutropenia. Our results suggested that the stage of the granulocyte-committed stem cell is the major step of the defect, and the defect at the stage of the multipotent stem cell or bone marrow microenvironment was also suggested.

Adult↗

Absence of point mutation of N-ras oncogene in bone marrow cells with aplastic anemia.

Point mutation of N-ras oncogene at codons 12, 13 and 61 was studied in the bone marrow cells of patients with typical aplastic anemia using the polymerase chain reaction method for DNA amplification and dot blot hybridization to synthetic oligonucleotide probes. Point mutation was observed in none of the 15 patients studied. These findings indicate either that the pathogenesis of typical aplastic anemia is different from that of preleukemic states of myelodysplastic syndrome or acute leukemia in clonal evolution, or that the overlapping area sharing a common pathogenesis is much smaller than was presumed.

Anemia, Aplastic↗

Dual mode cytotoxicities of reactive oxygens on L5178Y radiosensitive mutant M10.

Cytotoxic effects of O2- and H2O2 on mammalian cells were investigated in comparison with the relative sensitivity of mouse L5178Y cells and its radiosensitive mutant M10. Both O2- and H2O2 exhibited two different modes of cytotoxic actions depending on their exposure rates: At a high exposure rate (4.3 nmol of O2-/mL/min), M10 was more sensitive to O2- than L5178Y normal type cell, in agreement with the case of X-rays; while at a low exposure rate (five times less than the high exposure rate), M10 became more resistant than L5178Y. Similar results were obtained with H2O2. Reactive species responsible for these two different cytotoxic actions were examined with special reference to the metal-catalyzed Haber-Weiss reaction, by using a metal chelator, 1,10-phenanthroline, and an .OH scavenger, dimethylsulfoxide (DMSO). Significant protection by 1,10-phenanthroline was observed, which indicates the presence of a metal-dependent process in both cytotoxic actions. DMSO showed a marked protective effect, except for the case of M10 exposed at the low exposure rate, in which DMSO showed no protection. The resistance of M10 to O2- and H2O2 observed at the low exposure rate suggests the possibility that reactive species other than .OH are involved in the cytotoxicity.

Animals↗