Biomedical subjects

J Nakashima

Publications and source records attributed to J Nakashima.

At least 55 records · Page 3Linked to original sources

PubMed1997

The value of serum carboxyterminal propeptide of type 1 procollagen in predicting bone metastases in prostate cancer.

PURPOSE: Carboxyterminal propeptide of type 1 procollagen (P1CP) is believed to be a marker of new bone formation. We investigated the possible application of serum P1CP as a biochemical marker for bone metastases in patients with prostate cancer. MATERIALS AND METHODS: Prostate specific antigen (PSA), prostatic acid phosphatase (PAP), P1CP and alkaline phosphatase were measured in 136 serum samples from 79 patients with untreated prostate cancer, 29 with stage D2 disease in remission and 28 with progressive stage D2 carcinoma. RESULTS: Serum P1CP and alkaline phosphatase were significantly elevated in untreated patients with a positive bone scan (278.9 +/- 61.9 ng./ml. and 826.5 +/- 176.3 international units per 1., respectively) compared to those with a negative bone scan (104.2 +/- 4.2 and 200.8 +/- 9.1, respectively, p <0.05). The areas under receiver operating characteristics curves were 0.86 for P1CP, 0.87 for alkaline phosphatase, 0.88 for PSA and 0.85 for PAP. The best accuracy rates for P1CP, alkaline phosphatase, PSA and PAP to predict bone lesions were 84, 87, 86 and 84%, respectively. P1CP provided a greater specificity and positive predictive value. These serum markers correlated significantly with the extent of disease on bone scan (p <0.05). The incidence of positive serum P1CP and alkaline phosphatase decreased significantly in response to endocrine therapy in patients with bone metastasis, and increased progressively in association with progression of the tumor (p <0.05) parallel to PSA and PAP. CONCLUSIONS: These findings suggest that serum P1CP is a useful indicator for predicting bone metastases.

Aged↗

PubMed1997

[Retinoic acid-induced cell growth inhibition and differentiation in testicular carcinoma cells in culture].

Testicular germ tumor cells could be differentiated spontaneously or by some chemotherapeutic compounds. However, the mechanism by which the cells are differentiating from the stem cell remains unclear. The KU-MT cells, which were newly established from lung metastasis of testicular carcinoma, have been continuously producing alpha fetoprotein (AFP). Retinoic acids are well-known to induce cellular differentiation in culture and have already been applied for a clinical usage against leukemia. In the present study, all-trans-retionic acid (ATRA) elevated the level of AFP and inhibited the growth of KU-MT cells in vitro. ATRA also arrested the cell cycle in G1 and reduced the percentage of the S phase cell in terms of wild type p53, leading to apoptosis in part. Retinoids, especially retinoic acid receptor (RAR)-alpha specific agonists induced laminin production, a marker of endodermal differentiation; whereas arotinoid, a retinoid not bound to RAR-alpha, did not affect laminin expression. In summary, retinoic acids could mediate cell growth and differentiation of testicular tumor through RAR-alpha.

Antineoplastic Agents↗

PubMed1996

Client self-determination and professional intervention: striking a balance.

Social workers find themselves caught in the cross fire between two imperatives: (1) outcome-oriented and competency-based practice requisites and (2) the principle of client self-determination. In this context, the authors hypothesize that social workers use a wide range of gradations along a continuum of practice directiveness. Furthermore, there is ethical justification for this diverse role repertoire. Directiveness modalities are influenced by specific conditional factors that guide practitioner behavior. A study is described that empirically explores and amplifies these hypotheses.

Adult↗

PubMed1995

Tumor necrosis factor and coagulopathy in patients with prostate cancer.

This study was undertaken to evaluate the relationship between serum tumor necrosis factor (TNF) and coagulopathy in patients with prostate cancer. TNF levels in 104 sera obtained from 101 prostate cancer patients were determined using an enzyme immunoassay. Serum levels of fibrin/fibrinogen degradation product E fragment (FDP) and plasma levels of fibrin degradation product D-dimer in patients with elevated serum TNF levels were 1221.95 +/- 375.94 ng/ml and 27.34 +/- 9.81 micrograms/ml, which were significantly higher than those (FDP, 94.35 +/- 13.17 ng/ml; D-dimer, 1.03 +/- 0.20 micrograms/ml) in patients with undetectable serum TNF levels (P < 0.01). In addition, patients with elevated serum TNF levels showed significant increases in plasma levels of thrombin-antithrombin-III complex and plasmin-alpha 2-antiplasmin inhibitor complex and a significantly higher incidence of positive plasma soluble fibrin monomer complex than did those with undetectable serum TNF levels. The percentage of prothrombin time was significantly decreased in the group with elevated serum levels of TNF. Serum levels of TNF were significantly elevated in patients with serum FDP levels of > or = 200 ng/ml than in those with serum FDP levels of < 200 ng/ml (3.91 +/- 0.45 versus 2.17 +/- 0.08 units/ml) and in patients with plasma D-dimer levels of > or = 2 micrograms/ml than in those with plasma D-dimer levels of < 2 micrograms/ml (3.82 +/- 0.48 versus 2.10 +/- 0.06 units/ml). These results suggest that TNF may be one of the pathogenetic factors that could explain the occurrence of coagulopathy in patients with prostate cancer.

Adenocarcinoma↗

PubMed1995

MRI evaluation of cavitation induced by laser prostatectomy.

Magnetic resonance images obtained by endorectal surface coils have shown histopathological changes in the prostate. In patients who underwent laser prostatectomy, MR imaging demonstrated how deeply the laser energy penetrated and how different changes were induced by the coagulation and vaporization techniques. Cavitation effects were quantitatively analyzed, and the processes of reepithelization after sloughing of necrotic tissues were observed in gadolinium-enhanced T1-weighted images.

Aged↗

PubMed1995

Establishment of a human cell line secreting neuron-specific enolase from a primitive neuroectodermal tumor of the retroperitoneal cavity.

Primitive neuroectodermal tumor (PNET) is one of the small round cell malignancies of presumed neural crest origin for which an effective treatment has not yet been established. In the present study, a human cell line, designated KU-9, was established from a 27-year-old male patient with PNET of the retroperitoneal cavity and has been successfully maintained in nude mice and in culture. On histological examination, the primary tumor was composed of poorly differentiated small round cells arranged in clusters showing a variety of mitotic changes, and contained Homer-Wright rosettes. The histopathological appearance of the KU-9 xenografts was similar to that of the primary tumor. Electron microscopy revealed neurosecretory granules and cytoplasmic processes in the xenograft. No significant amplification of N-myc gene was observed in the KU-9 cells. The KU-9 cells showed chromosome numbers ranging from 56 to 61 with consistent structural abnormalities being add(2)(q31), +add(11)(p11.2), +add(13)(p11.1), and +del(22)(q12). Cultured KU-9 cells grew exponentially with a doubling time of about 50 h and a time-dependent increase in medium levels of neuron-specific enolase (NSE) was noted. Serum levels of NSE in KU-9 tumor-bearing nude mice were significantly elevated and a linear relationship between the serum NSE levels and the tumor NSE content or tumor volume was observed, suggesting that serum levels of NSE may reflect the PNET tumor burden and tumor extent. These results indicate that the KU-9 cell line provides a reproducible model system which could be useful in gaining some insight into the histogenesis and oncogenesis of PNET and in establishing an effective treatment for PNET.

Adult↗

PubMed1995

Retroperitoneal Ewing's sarcoma.

We report a case of extraskeletal Ewing's sarcoma arising in the retroperitoneal cavity. The tumor was excised en bloc with the left kidney and infiltrated portion of the left ureter. Histological diagnosis was confirmed by both electron micrography and immunohistochemical staining using a newly developed mouse monoclonal antibody 5C11, which specifically reacts with Ewing's sarcoma. An adjuvant chemotherapy T-11 regimen has been successfully preventing the recurrence.

Adult↗

PubMed1995

[Clinical efficacy of methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy following radical surgery for locally invasive urothelial cancers: long-term results].

Determined were long-term results of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) adjuvant chemotherapy following radical surgery for locally invasive urothelial cancers. All cases at least histologically exhibited one of the following findings, a stage beyond pT3b (bladder cancer) or pT3 (upper tract urothelial cancer), lymph duct tumor involvement (ly +), venous involvement (V +), and/or regional lymph node involvement (N1) without any evidence of distant metastasis and/or residual tumors. Two cycles of M-VAC chemotherapy were given after radical surgery for each case. A total of 33 cases comprising 21 bladder cancers and 12 upper tract urothelial cancers following cystectomy and/or nephroureterectomy with partial cystectomy who had a mean follow-up period of 56.7 +/- 9.2 months could be analyzed. Overall actuarial survival rates of three- and five-years estimated by Kaplan-Meier method were respectively 41.9% and 31.6%. These results indicate that the postoperative outcome was extremely poor in patients with locally advanced urothelial cancer even after extensive adjuvant chemotherapy. Therefore, more effective modalities including optimal dose and scheduling of chemotherapy are needed to assure therapeutic improvement of locally invasive urothelial cancers.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Magnetic resonance imaging following microwave thermotherapy, laser ablation and transurethral resection in patients with BPH.

Morphologic changes in hyperplastic prostate tissue following three different treatments were analysed by MRI using an endorectal surface coil. In cases treated by TUMT, the MRI findings of the prostate showed hemorrhagic necrosis, which was absorbed in 12 weeks, and a widened prostatic urethra. In cases treated by laser ablation, the thermal effect went deep, causing necrotic changes, and it took more than 8 weeks for the tissue to be shed and re-epithelization completed. In TURP, degenerative changes were seen only near the surface following mass reduction of the hyperplastic tissue, and the capsule shrinkage resulted in normalization of the prostatic urethra. It is suggested that improvement of the other parameters, such as IPSS and peak flow, in patients with obstructive BPH basically depends on these morphologic changes shown by MRI.

Aged↗

PubMed1995

Enhancement of erythropoietin production by selective adenosine A2 receptor agonists in response to hypoxia.

The purpose of this study was to characterize the effects of two new adenosine A2 agonists, 2-(p-(2-carboxyethyl)phenethyl amino)-5'-N-ethylcarboxamidoadenosine (CGS-21680) and N6-(2(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)-adenosine (DPMA), on erythropoietin (EPO) production in vivo and in vitro. Intravenous injections of CGS-21680 (100 to 500 nmol/kg mouse/day) and DPMA (50 to 500 nmol/kg mouse/day) for 4 days produced significant increases in serum levels of EPO in exhypoxic polycythemic mice. CGS-21680 (10(-7) to 10(-6) mol/L) and DPMA (10(-8) to 10(-5) mol/L) also produced significant increases in medium levels of EPO in a cloned EPO-producing Hep3B hepatocellular carcinoma cell line after 18 hours of incubation in 1% O2. Both compounds also increased cellular cAMP levels significantly in a dose-dependent manner after 1 hour of incubation. A2 receptor binding assays with tritiated CGS-21680 revealed a single type of adenosine receptor binding site on Hep3B cell membranes with a dissociation constant of 132.9 nmol/L and a binding capacity of 270.6 fmol/mg protein. The Ki competition binding values versus tritiated CGS-21680 were 217 nmol/L for CGS-21680 and 86.8 nmol/L for DPMA. These results indicate that adenosine A2 receptor activation amplifies EPO production in response to hypoxia, both in vivo and in vitro.

Adenosine↗

PubMed1994

Adenosine A2 receptor modulation of erythropoietin secretion in hepatocellular carcinoma cells.

The present studies were undertaken using a cloned erythropoietin (Ep) producing hepatocellular carcinoma cell line (Hep3B) to attempt to correlate the receptor binding properties and biological activities of 5'-N-ethylcarboxamideadenosine (NECA), N6-cyclohexyladenosine (CHA) and N6-cyclopentyldenosine (CPA). Ep and cAMP levels in cultures of Hep3B cells in response to these adenosine analogues were measured by radioimmunoassay. Receptor binding affinities of the adenosine analogues were determined by measuring inhibition of binding of [3H] NECA to Hep3B cell membranes. Scatchard analysis of [3H]NECA to Hep3B cell membranes. Scatchard analysis of [3H]NECA binding to Hep3B cell membranes indicates a single class of binding sites with a dissociation constant of 431 nM and a binding capacity of 573 fmol/mg protein. The adenosine analogues tested produced a significant increase in Ep secretion and cAMP accumulation (ED50 for cAMP accumulation, NECA = 3.3 x 10(-7) M, CHA = 4.2 x 10(-6) M, CPA = 2.2 x 10(-6) M). In addition, NECA showed a higher binding affinity (Ki, 3.8 x 10(-7) M) for Hep3B cell membranes in comparison with CHA (Ki, 6.3 x 10(-6) M) and CPA (Ki, 3.9 x 10(-6) M). These results indicate that the rank order for potency for NECA, CHA and CPA in their binding to Hep3B cell membrane receptors correlates very well with their biological effects on Ep secretion and cAMP accumulation in Hep3B cells.

Adenosine↗

PubMed1994

Flow cytometric bromodeoxyuridine/deoxyribonucleic acid bivariate analysis for predicting tumor invasiveness of upper tract urothelial cancer.

We previously reported that flow cytometric bromodeoxyuridine/deoxyribonucleic acid (DNA) bivariate analysis can provide important information on the malignant potential of bladder cancer. Therefore, in the current study we further evaluated upper tract urothelial tumors to clarify whether DNA/bromodeoxyuridine bivariate analysis can provide additional prognostic information on patients with upper tract urothelial tumor. A total of 43 upper tract urothelial tumors that were resected by nephroureterectomy was analyzed. Flow cytometric DNA ploidy and bromodeoxyuridine labeling were determined by an in vitro bromodeoxyuridine labeling method. DNA diploid tumors were associated with an 85.9% 3-year survival rate compared to 36.5% for DNA aneuploid tumors. On the other hand, 11 high bromodeoxyuridine labeled tumors demonstrated a 16.4% 3-year survival rate compared to 82.4% for those with low bromodeoxyuridine labeled tumors. Multivariate survival analysis using the Cox proportional regression model was performed to identify the most informative factors for prognosis, with the single most important factor being histological tumor stage. Nearly as important and the next factor to be chosen was tumor grade, followed by bromodeoxyuridine labeling index status. DNA ploidy status did not influence clinical outcome. Thereafter, when actuarial 3-year survival rates according to the bromodeoxyuridine labeling index status in grade 3 tumors were estimated, 68.4% and 16.7% 3-year survival rates were observed in cases of low and high bromodeoxyuridine labeling index tumors, respectively. These results indicate that flow cytometric bromodeoxyuridine/DNA bivariate analysis may be useful in dividing patients with grade 3 upper tract urothelial carcinoma into 2 different prognosis groups.

Bromodeoxyuridine↗

PubMed1994

Primitive neuroectodermal tumor of the retroperitoneal cavity.

We report a case of primitive neuroectodermal tumor (PNET) arising from the retroperitoneal cavity. Because of infiltration, the tumor was excised en bloc with the left kidney. Despite postoperative adjuvant chemotherapy and local radiation therapy, the tumor recurred and the patient died of the disease 3 months postoperatively. Serum levels of neuron-specific enolase (NSE) correlated with those of lactate dehydrogenase (LDH), and it is suggested that monitoring NSE and LDH is useful in evaluating tumor recurrence. The clinical course and the treatment of this aggressive tumor are reviewed.

Adult↗

PubMed1993

Effects of 5'-N-ethylcarboxamideadenosine (NECA) on erythropoietin production.

The present studies were undertaken to assess the effects of 5'-N-ethylcarboxamideadenosine (NECA), an adenosine analogue, on erythropoietin (Epo) production. NECA (0.05 and 0.1 mumol/kg i.v.) produced significant increases in serum Epo levels (368.8 +/- 56.1 and 384.6 +/- 45.9 mU/ml, respectively) in exhypoxic polycythemic mice after a four hour exposure to hypoxia when compared with hypoxia controls (133.2 +/- 18.2 mU/ml). The hypoxic kidney Epo levels were 46.4 +/- 13.4 mU/kg kidney which were significantly higher than normoxic kidney Ep levels (< 1.24 mU/kg kidney). Theophylline (20 mg/kg i.p.), an adenosine receptor antagonist, significantly inhibited the stimulatory effects of NECA on serum Epo levels. In vitro cultures of an Epo producing hepatocellular carcinoma (Hep3B) cell line with NECA (> or = 10(-6) M) for 20 hours under hypoxic conditions (1% O2) produced significant increases in medium levels of Epo when compared with hypoxia controls. Hepatocellular carcinoma cells treated with NECA at a concentration range of 10(-7) M to 5 x 10(-5) M for one hour in a hypoxic atmosphere also had significantly higher cAMP levels than that of hypoxia controls. Scatchard analyses of [3H]NECA binding to membrane preparations of hepatocellular carcinoma cells showed low affinity binding sites with a dissociation-constant (Kd) of 0.44 microM and a binding capacity of 863 fmol/mg protein. These findings suggest that the increase in Epo production in response to NECA under hypoxic conditions can be attributed, at least in part, to stimulation of adenosine A2 receptors which is coupled to adenylyl cyclase activation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

In vivo and in vitro erythropoietin activities in cultures of a hepatocellular carcinoma cell line.

The present studies were undertaken to characterize erythropoietin (Ep) production in an Ep-producing hepatocellular carcinoma (Hep3B) cell line. Hep3B cells which had been maintained in culture were transplanted under the renal capsule and subcutaneously in nude mice. The Hep3B xenograft doubling time is approximately 7 days. The mean hematocrit value of the Hep3B tumor-bearing nude mice was 33.2 +/- 1.1% (n = 8), which was significantly lower than that of control nongrafted nude mice (40.8 +/- 1.7%, n = 5). The Hep3B tumor-bearing nude mice showed significantly higher Ep levels in the sera (37.5 +/- 5.5 munits/ml, n = 8) than control nude mice (13.5 +/- 2.7 munits/ml, n = 5). Ep levels in the sera were correlated (R = 0.714) with the total Ep in the tumor extracts, whereas no Ep was detectable in any of the kidney extracts. On the other hand, an inverse linear relationship (R = -0.811) between the hematocrit values and Ep levels in the sera was demonstrated in the Hep3B tumor-bearing nude mice. The Hep3B cells recultured after growing in the nude mice were capable of enhancing Ep production in response to hypoxia, very similar to the original Hep3B cells which had been maintained in culture during the same time period. In addition, 15-methyl-prostaglandin E1 at a concentration range of 4-400 ng/ml produced significant increases in Ep secretion and cAMP accumulation in Hep3B cultures under hypoxic conditions (1% O2). The Ep produced by Hep3B cells expressed 3.7 times higher in vitro bioactivity than immunoactivity. The bioactivity of Hep3B Ep was completely neutralized by an antibody to highly purified human recombinant Ep. In contrast, the in vivo bioactivity of the Hep3B Ep was less than one tenth of its immunoactivity. These results indicate that the Hep3B tumor-bearing nude mice and the in vitro Hep3B culture system may provide a reproducible model system which should be useful for studies of the mechanism of Ep production.

Animals↗

PubMed1993

A case of parameatal urethral cyst with calculi.

Parameatal urethral cyst is very rare. Although 15 cases have been reported in Japan, no case of parameatal urethral cyst with calculi has previously been reported. We report the first case of parameatal urethral cyst with calculi in a 22-year-old female patient.

Adult↗

PubMed1993

[Increase in erythropoietin secretion mediated by adenosine A2 receptors].

The present study was undertaken to assess the adenosine receptor regulation of erythropoietin (Ep) secretion in hepatocellular carcinoma cells (Hep3B) in response to hypoxia. In vitro cultures of Hep3B cells with N6-cyclohexyladenosine (CHA) at a concentration of 10(-5)M produced significant increases in cyclic AMP accumulation (142.43 +/- 13.31 pmole/10(6) cells) after 1 hr and Ep secretion (29.83 +/- 1.69 mU/ml) after 20 hr when compared with their respective hypoxia controls (cAMP: 3.05 +/- 0.26 pmole/10(6) cells, Ep: 19.41 +/- 1.41 mU/ml). The stimulatory effects of CHA on both Ep secretion and cyclic AMP accumulation were significantly inhibited by 8-phenyltheophylline (8-PT) at a concentration of 5 x 10(-7). No significant change in cell growth was observed at the CHA and 8-PT concentrations used in these experiments employing a spectrophotometric method. Incubation with 8-bromo cyclic AMP (10(-4)M) in response to hypoxia also produced a significant enhancement of Ep secretion (30.74 +/- 0.50 mU/ml) when compared with hypoxia controls (22.69 +/- 0.23 mU/ml), whereas no significant increase occurred in a normoxic atmosphere. CHA inhibited specific binding of [3H]5'-N-ethylcarboxamideadenosine (100 nM) to Hep3B cell membrane preparations in a dose-dependent manner in the displacement experiments and IC50 was 7.72 x 10(-6)M. These results indicate that Ep secretion is stimulated by adenosine membrane A2 receptors which are linked to adenylyl cyclase activation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

The role of hypoxia in renal production of erythropoietin.

Hypoxia is the fundamental stimulus for erythropoietin (EP) production. It is clear that hypoxia increases erythropoietin messenger RNA in a renal cell, which leads to the production of increased amounts of erythropoietin in the kidney. Hypoxia also increases external messenger substances that amplify the effects of hypoxia and increases erythropoietin messenger RNA to further accelerate erythropoietin production. Some of these messenger substances are adenosine, eicosanoids, oxygen-derived metabolites, and beta-2 adrenergic agonists that are postulated to act through the activation of cell membrane receptors and are coupled to an increase in a G stimulatory protein which activates adenylate cyclase. This leads to increased production of cyclic adenosine monophosphate (AMP) for the production of key phosphoproteins that are involved in the biosynthesis/secretion of erythropoietin. This paper considers the physicochemical properties of human erythropoietin, pharmacologic agents that increase and decrease erythropoietin production/secretion, serum erythropoietin levels in normal human subjects and in patients with several types of anemia, and a model for the role of adenosine and other external messenger substances in erythropoietin biosynthesis/secretion.

Adenosine↗