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Biomedical subjects

K Yoshikawa

Publications and source records attributed to K Yoshikawa.

At least 181 records · Page 10Linked to original sources
PubMed1999

Breast parenchymal activity on scintimammography: comparison between bone-seeking agents and 99mTc-sestamibi.

The aim of this study was to evaluate breast parenchymal activity on scintimammography with bone-seeking agents and 99mTc-MIBI. Scintimammography was performed with bone-seeking agents in 61 patients and with 99mTc-MIBI in 33 patients. Activity in the breast parenchyma contralateral to the suspected lesion was visually assessed by two independent observers. Increased breast parenchymal activity was shown in 19 of 61 patients examined with bone-seeking agents, while it was demonstrated in only two of 33 patients examined with 99mTc-MIBI. Breast parenchymal activity of bone-seeking agents was higher in patients aged 50 years or younger than in those older than 50. Increased parenchymal activity of bone-seeking agents may disturb visualization of primary breast cancer especially in relatively young patients. Low parenchymal activity is suggested to be a favorable characteristic of 99mTc-MIBI as a scintimammographic agent.

Adult↗
PubMed1999

Evaluation of flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells.

The estimation of intralesional haemodynamics is crucial in determining appropriate treatment for soft-tissue vascular malformations. The aim of this study was to develop a method to evaluate the flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells (99mTc-RBCs). Seventy-nine soft-tissue vascular malformations, including 20 arteriovenous malformations and 59 venous malformations, in 57 patients were examined. Following the intravenous injection of 99mTc-RBCs, dynamic imaging was performed for 30 min with the lesion in the field of view (99mTc-RBC flow study). A time-activity curve was generated for the lesion, and the lesion was categorized as a high-flow or low-flow lesion by visual inspection of the curve. In low-flow lesions, mean vascular transit time (MTT) was calculated by curve fitting based on a two-compartment model. Twenty-nine lesions in 19 patients were examined twice, and reproducibility was assessed. In 23 venous malformations in 16 patients, 99mTc-Sn colloid was percutaneously injected into the intravascular space of the lesion, and dynamic data of 5-min duration were acquired (direct puncture scintigraphy). MTT was estimated from the washout curve and compared with MTT estimated by 99mTc-RBC flow study. 99mTc-RBC flow study classified all 20 arteriovenous malformations as high-flow lesions and all 59 venous malformations as low-flow lesions. In the low-flow lesions, MTT estimated by 99mTc-RBC flow study ranged from 61.2 to 2174.9 s. In the reproducibility study, complete concordance in classification and high correlation in MTT were shown between the first and second examinations. MTT estimated by 99mTc-RBC flow study was significantly correlated with that estimated by direct puncture scintigraphy. In summary, 99mTc-RBC flow study provides a quantitative indicator of intralesional haemodynamics in low-flow lesions in addition to accurate distinction between high-flow and low-flow lesions. The results of this study suggest the feasibility of detailed evaluation of flow characteristics in soft-tissue vascular malformations using 99mTc-RBCs.

Adolescent↗
PubMed1999

Effect of 12-O-tetradecanoyl-phorbol ester and incisional wounding on neuropsin mRNA and its protein expression in murine skin.

The expression of neuropsin mRNA in vivo in mouse skin was examined by in situ hybridization and Northern blotting under stimulated conditions. Two kinds of epidermal stimuli, a topical application of a chemical tumor promoter and incisional wounding, were used. A single topical application of 12-O-tetradecanoyl-phorbol 13-acetate induced epidermal hyperplasia and simultaneously induced an extensive increase in neuropsin mRNA in the suprabasal cells. A full-thickness skin incision also induced a profound increase in neuropsin mRNA in the suprabasal cells surrounding the wound but not in actively proliferating basal cells. The increases in neuropsin mRNA occurred rather late and were limited to the site of drug application or around the incision. Interestingly, neuropsin mRNA was not expressed in the epithelial tongue migrating toward the wound during re-epithelialization. Thus, neuropsin might participate in accelerated epidermal differentiation rather than in the proliferation or migration of keratinocytes in the wound.

Animals↗
PubMed1999

Activation of monocytes in vivo causes intracellular accumulation of lipoprotein-derived lipids and marked hypocholesterolemia--a possible pathogenesis of necrobiotic xanthogranuloma.

Necrobiotic xanthogranuloma (NXG) is a rare histiocytic disease with generalized xanthomatosis. However, most cases with NXG are normolipidemic or hypolipidemic. The mechanism for the formation of xanthoma in NXG has not yet been clarified. We observed a case of NXG with severe hypocholesterolemia (total cholesterol: 1.69 mmol/l) and analyzed the function of monocytes in this case. Histological examinations by light microscopy revealed a large amount of lipid deposition in the patient's freshly isolated monocytes. The patient's monocytes showed a 3-fold increase in cholesteryl ester content and a 3-fold enhancement of acetyl low density lipoprotein (LDL) uptake compared with the control monocytes. However, no significant difference was noted in the expression of CD36 protein and the mRNA levels of scavenger receptor-class A (SR-A) between the monocytes of the patient and the control. The phagocytotic ability of the patient's monocytes was enhanced 1.5-fold compared with that of the control monocytes. These findings suggest that the activated monocytes may have degraded the modified LDL via a pathway other than CD36 or SR-A, and accumulated a great amount of lipids in vivo. In conclusion, the present study has demonstrated a possible pathogenesis of NXG that the activation of monocytes in vivo may contribute to the intracellular accumulation of lipoprotein-derived lipids leading to non-inherited xanthomatosis and the marked hypocholesterolemia.

Aged↗
PubMed1999

Muscarinic receptor occupancy by biperiden in living human brain.

Anticholinergic drug is often used to treat extrapyramidal symptoms. We measured muscarinic cholinergic receptor (mAchR) occupancy by the oral administration of biperiden in eight healthy subjects using positron emission tomography (PET) and [11C]N-methyl-4-piperidylbenzilate (NMPB). After the baseline scan each subject underwent one or two post-dose PET scans. mAchR occupancy was 10-45% in the frontal cortex three hours after the oral administration of 4 mg of biperiden. The occupancy correlated with the plasma concentration of biperiden in a curvilinear manner.

Adult↗
PubMed1999

Central nervous system symptoms in patients with Behçet disease receiving cyclosporine therapy.

OBJECTIVE: To investigate the association between the development of central nervous system (CNS) symptoms in patients with Behçet disease and medical therapy. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 317 patients with Behçet disease with ocular complications who visited Hokkaido University Hospital, Sapporo, Japan, between 1978 and 1994. MAIN OUTCOME MEASURES: The incidence of CNS symptoms in different medical therapies. RESULTS: Twenty-one (6.6%) of the 317 patients developed CNS symptoms, namely neuro-Behçet disease. Of the 21 patients, 12 were undergoing cyclosporine therapy. Of the 47 patients who underwent cyclosporine therapy, 12 (25.5%) developed CNS symptoms, whereas only 9 (3.3%) of 270 patients who did not undergo cyclosporine therapy developed CNS symptoms. CONCLUSIONS: Cyclosporine in the treatment of Behçet disease appears to cause neurotoxicity or to accelerate the development of CNS symptoms. Thus, neurologic complications appear to represent a major side effect of cyclosporine in the treatment of patients with Behçet disease.

Adult↗
PubMed1999

A new method for magnetoencephalography: a three-dimensional magnetometer-spatial filter system.

A novel three-dimensional magnetometer-spatial filter system was developed to study human brain activity with high spatiotemporal resolution. The system combines the high temporal resolution of magnetoencephalography with the high spatial resolution achieved by using three-dimensional magnetometers and spatial filters to measure the direction and intensity of magnetic fields generated during brain activity. Simulation and phantom studies indicate that the system is capable of mapping current sources of magnetic fields with a spatial resolution comparable to that of any other brain functional imaging technique while maintaining millisecond temporal resolution. Application of this system to the human brain resolved magnetoencephalographic responses evoked by motion stimuli on a millisecond scale into responses occurring in visual cortical areas V1, V2/3 and V5. It also revealed signals related to contextual modulation in V1 and V2/3. This system provides a new way of studying the dynamics of human brain function.

Brain↗
PubMed1999

Growth-stimulating effects of tumor necrosis factor-alpha on simian virus 40-transformed human keratinocytes is linked to phosphorylation of retinoblastoma protein.

In this report, we show that tumor necrosis factor-alpha (TNF-alpha) has a strong growth-stimulating effect on simian virus 40 (SV40)-transformed keratinocytes, while it exerts a potent growth-inhibitory effect on normal human keratinocytes. Addition of TNF-alpha to SV40-transformed keratinocytes stimulated cell growth by 216, 246, or 248% at 25, 50, or 250 ng/ml after 4 days culture compared with untreated cells, while addition to normal human keratinocytes reduced growth to 65, 38, and 32% at the same concentrations, respectively. Cell cycle analysis by flow cytometry showed that treatment of SV40-transformed keratinocytes with 250 ng/ml TNF-alpha for 48 h increased the S-phase cells from 19.8 +/- 0.3 to 49.7 +/- 2.4%. The percentage of G1/G0 phase cells decreased from 62.6 +/- 1.6 to 32.4 +/- 3.3%. We also demonstrated by immunofluorescent staining that SV40 large T antigen was enhanced by TNF-alpha incubation. Additionally, we examined the hyper and hypo-phosphorylated state of retinoblastoma protein (pRB), the cell cycle regulatory protein. TNF-alpha induced hyperphosphorylated pRB in SV40-transformed keratinocytes. On the other hand, TNF-alpha suppressed it in normal keratinocytes. We hypothesize that the enhancement of SV40 large T antigen and hyperphosphorylated pRB is involved in the mechanism of growth stimulation of SV40-transformed keratinocytes by TNF-alpha.

Cell Division↗
PubMed1999

Repeat-assessment of 1,4-dioxane in a rat-hepatocyte replicative DNA synthesis (RDS) test: evidence for stimulus of hepatocyte proliferation.

1,4-Dioxane is a nongenotoxic hepatocarcinogen but in our previous replicative DNA synthesis (RDS) studies with the [3H]thymidine (TdR)-technique, it failed to increase hepatocyte RDS values when given by gavage to male F344 rats as a single 2000 mg/kg body weight dose. However, in a current series of trials with TdR, it showed equivocal responses 24 or 48 hr following treatment with 2000 mg/kg in time-course experiments, and positive responses 24 hr following 1000, 1500 and 2000 mg/kg in dose-response experiments. An increased RDS incidence was also observed at the dose of 2000 mg/kg with data for 5-bromo-2'-deoxyuridine (BrdU)-incorporation. These present findings thus support the hypothesis that a capacity to induce cell proliferation may play a key role in 1,4-dioxane hepatocarcinogenesis.

Animals↗
PubMed1999

New lanostanoid glycosides from the fruit body of laetiporus versisporus

Four new lanostanoid glycosides, 3beta, 7alpha-dihydroxy-24-methylene-lanost-8-en-21-oic acid 7-O-beta-D-glucopyranoside (1), 3beta,7alpha-dihydroxy-lanost-8, 24-dien-21-oic acid 7-O-beta-D-glucopyranoside (2), 7alpha-hydroxy-3-keto-lanost-8,24-dien-21-oic acid 7-O-beta-D-glucopyranoside (3), and 7alpha-hydroxy-3-keto-24-methylene-lanost-8-en-21-oic acid 7-O-beta-D-glucopyranoside (4) were isolated from the fruit bodies of Laetiporus versisporus. Compounds 1-4 were named laetiposides A-D, respectively. Their structures were established by extensive NMR experiments and chemical methods.

Journal Article↗
PubMed1999

Antibacterial activity of multiple antigen peptides homologous to a loop region in human lactoferrin.

An 11-residue peptide (FQWQRNMRKVR) homologous to just over half the loop region of human lactoferricin is thought to be responsible for antimicrobial properties of human lactoferricin. Multiple antigen peptides (MAP) of the 11-residue peptide exerted significant antibacterial effects against a broad spectrum of bacteria including MRSA. More than eight branching was favourable for increasing its antibacterial activity. Our report shows a novel possibility for MAP to increase the activity of antibiotic peptides other than simply to stimulate antibody production, as reported so far.

Amino Acid Sequence↗
PubMed1999

MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas.

The monoclonal antibody G250 (mAbG250) raised against a human renal cell carcinoma (RCC) has been shown to react with a large number of RCCs. Recently, G250 antigen was isolated and found to be homologous to the MN/CA9 gene originally identified in HeLa cells. To determine whether G250 antigen (MN/CA IX/G250) could be a potential therapeutic target and a tumour marker, a total of 147 cases of RCC were investigated immunohistochemically as well as by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, total RNAs extracted from patients' peripheral blood samples were analysed for MN/CA9/G250 mRNA signals. Immunohistochemistry demonstrated strong expression in 128/147 (87.1%) of RCCs, in contrast to the lack of expression observed in normal tissues. RT-PCR analyses of frozen specimens resulted in the clear detection of MN/CA9/G250 mRNA signals in 137/147 (93.2%), and despite subtle differences the results were almost identical to those for immunohistochemistry. Although high-grade and -stage tumours exhibited significantly lower expression than low-grade and -stage tumours, a large proportion of tumours expressed MN/G250 protein as well as mRNA. RT-PCR analysis of patients' blood samples revealed the presence of circulating MN/CA9/G250 expressing cells. These findings suggest that this antigen may be a potential therapeutic target as well as diagnostic marker for RCCs.

Antigens, Neoplasm↗
PubMed1999

Expression of mRNA for androgen receptor, 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase in human dermal papilla cells.

In order to determine whether adrenal and gonadal weak androgens are utilized to form active androgens in human hair, we studied the expression of mRNA for androgen receptor (AR), 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in cultured dermal papilla cells (DPCs) from various body sites. AR mRNA was expressed in beard (Be) and axillary hair (Ax) DPCs from both sexes, but only at a low level in DPCs from occipital scalp hair (OS). Type I 5alpha-reductase mRNA was expressed by all DPCs. Type II 5alpha-reductase mRNA was identified in beard DPCs, but was absent from OS and Ax DPCs. Type II 17beta-HSD mRNA was strongly expressed in outer root sheath cells (ORSCs), while DPCs except for male Ax expressed no type II 17beta-HSD mRNA. In contrast, type III 17beta-HSD mRNA was strongly expressed in Be DPCs and Ax DPCs from both sexes; ORSCs showed a low level of expression. Expression of type III 17beta-HSD mRNA was not regulated by androgen in DPCs. These results suggest that the sensitivity of hairs to androgen is partially controlled by the site-specific expression of AR, 5alpha-reductase and 17beta-HSD in DPCs.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Preservation of pathological tissue specimens by freeze-drying for immunohistochemical staining and various molecular biological analyses.

Conditions of preserving DNA, RNA and protein in pathological specimens are of great importance as degradation of such macromolecules would critically affect results of molecular biological analysis. The feasibility of freeze-drying as a means of preserving pathological tissue samples for molecular analysis has previously been shown. In the present study, further tests on long-term storage conditions and analyses of freeze-dried samples by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, western blotting and immunohistochemistry are reported. Rat chromosomal DNA of freeze-dried samples stored for 4 years showed slight degradation while RNA degradation was more prominently seen at an earlier stage of storage. However, these 4 year DNA and RNA samples were still able to serve as a template for some PCR and RT-PCR analyses, respectively. Overexpression of c-erbB-2 and p53 protein was demonstrated by western blotting and immunohistochemical staining using freeze-dried human breast cancer tissues. Although macromolecules in freeze-dried samples degrade to some extent during the preservation period, they should still be of value for certain molecular biological analyses and morphological examination; hence, providing more convenient and inexpensive ways of pathological tissue storage.

Animals↗
PubMed1999

The significance of resections for residual masses after chemotherapy in metastatic testicular tumors.

BACKGROUND: After chemotherapy for metastatic testicular tumors, masses may remain, often in the metastatic sites. This study analyses the role of resections for the residual masses. METHODS: Seventy-seven patients with advanced (stage II, III) testicular tumors were treated. Of these, 38 patients, including eight with seminoma and 30 patients with non-seminomatous germ cell tumors, underwent resection of residual masses after chemotherapy and have been followed for a median of 41.5 months (range 2-138) after the resection. RESULTS: Residual masses were necrosis/fibrosis in 19 patients, mature teratoma in 11 and cancer in eight. The ratio of cancer in stage III (41.2%) was significantly higher than that in stage II (4.8%). Ten of 38 (26.3%) patients experienced recurrences in sites other than the resected sites, and five of 10 patients have died of cancer. Most recurrences (80%) occurred within two years. Recurrences after resection were detected in 4.8% of stage II patients, 52.9% of stage III, 16.7% of necrosis/fibrosis and mature teratoma, and 62.5% of cancer. The survival rate of patients with cancer was significantly lower in spite of adjuvant chemotherapy after surgery. CONCLUSIONS: Resection for residual masses after chemotherapy in metastatic testicular tumors was useful in confirming the tissue and in controlling the metastatic sites. Recurrences were often found in patients with cancer in the residual mass and the prognosis of patients with cancer was poor, therefore the development of more effective therapy for patients with cancer is required to improve the prognosis.

Adolescent↗
PubMed1999

Neoadjuvant therapy and bladder substitute for invasive bladder cancer: 20 years experience at Tohoku University.

BACKGROUND: Neobladder, using the intestine, was performed after neoadjuvant therapy and total cystectomy as a treatment for invasive bladder cancer. METHODS: Between January 1977 and April 1997, an ileocecal neobladder was used for 23 patients and a sigmoid neobladder was chosen for use in 32 patients. For the diagnosis of invasive bladder cancer and the evaluation of neoadjuvant therapy, we used whole-layer core biopsy (WLCB) of the bladder tumor and fine needle aspiration biopsy (FNAB) of pelvic lymph nodes after bipedal lymphography. For neoadjuvant therapy, two to four courses of internal iliac arterial infusion chemotherapy (IIA) were undertaken in 32 patients. Five patients were treated with IIA combined with 40 Gy irradiation to the pelvic space. RESULTS: Pretreatment WLCB revealed a tumor of stage T2b or greater in 10 patients. After neoadjuvant therapy, three patients were down-staged to pT0. In five patients, pretreatment FNAB revealed pelvic lymph node metastases that were not detected by computed tomography or magnetic resonance imaging. Fine needle aspiration biopsy post-neoadjuvant therapy revealed tumor stage N0 in all patients and lymph node dissection revealed pN0 in four patients. Of the five patients who received 40 Gy irradiation, none had any postoperative complications, such as intestinal fistula or urinary leakage. Four male patients (10%) had urethral recurrence, but all were successfully treated by transurethral resection. Two patients treated prior to 1985 experienced local recurrence. Neither was treated by neoadjuvant therapy. Eight patients who died after 1985 had metastatic cancer, but none had local recurrence. None of the patients who received a sigmoid neobladder required clean intermittent catheterization or had bilateral vesico-ureteral reflux. CONCLUSIONS: Neoadjuvant therapy seems to reduce local recurrence in invasive bladder cancer. The sigmoid colon may be suitable for neobladder.

Adult↗
PubMed1999

Regulation of keratin 9 in nonpalmoplantar keratinocytes by palmoplantar fibroblasts through epithelial-mesenchymal interactions.

Palms and soles differ from other body sites in terms of clinical and histologic appearance, response to mechanical stress, and the distribution of keratin 9. Because keratin 9 is exclusively expressed in the palmoplantar suprabasal keratinocyte layers, it is considered a differentiation marker of palms and soles. We studied palmoplantar mesenchymal influences on keratin 9 induction in nonpalmoplantar epidermis. Although palmoplantar keratinocytes when cultured alone continued to express keratin 9 mRNA in 12 (100%) of 12 cultures, nonpalmoplantar keratinocytes did not express it in 16 of 17 cultures. Although nonpalmoplantar keratinocytes did not express keratin 9 mRNA when cultured with nonpalmoplantar fibroblasts, they did express it within 2 h in cocultures with palmoplantar fibroblasts derived from papillary dermis. Grafting of these coculture sheets on severe combined immunodeficient mice resulted in an epidermis, which histologically showed hyperkeratosis and acanthosis and immunohistochemically expressed keratin 9. Furthermore, pure epidermal sheets from nonpalmoplantar skin grafted on the human sole wounds due to burn, injury, and the resection of acral lentiginous melanoma, demonstrated adoption of palmoplantar phenotype and expressed keratin 9. Our report indicates extrinsic keratin 9 regulation by signals from dermal fibroblasts. This is also the first to suggest the possibility of treating palmoplantar wounds with nonpalmoplantar epidermis, which is much easier to obtain and harvest.

Animals↗