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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 145 records · Page 8Linked to original sources

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis.

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Adolescent

Regional distribution of growth hormone-releasing hormone (GHRH) receptor mRNA in the rat brain.

We examined the tissue distribution of growth hormone-releasing hormone (GHRH) receptor mRNA in the rat brain because several lines of evidence have suggested that GHRH plays a functional role in the brain. GHRH receptor mRNA was detected in the hypothalamus as well as pituitary, but not in olfactory bulb, caudate putamen, cerebral cortex, hippocampus, cerebellum, or brainstem by RNase protection assay. To clarify the precise localization of GHRH receptor mRNA in the hypothalamus, reverse transcription-polymerase chain reaction (RT-PCR) was used. A PCR product of the predicted size (564 bp) was detected in the periventricular, arcuate, and ventromedial nuclei, and the anterior hypothalamic area, but not in the paraventricular nucleus in the hypothalamus. These areas where GHRH receptor mRNA was detected are possible sites of GHRH action. Another band, smaller in size than that of the predicted PCR amplification product, was detected in the anterior hypothalamic area and arcuate nucleus, respectively. Hybridization analysis with a cDNA probe for GHRH receptor demonstrated that the smaller bands as well as that of the predicted size corresponded to GHRH receptor cDNA. The role of the short form of the GHRH receptor remains unknown.

Animals

Effect of beat frequency on the velocity of microtubule sliding in reactivated sea urchin sperm flagella under imposed head vibration.

The heads of demembranated spermatozoa of the sea urchin Tripneustes gratilla, reactivated at different concentrations of ATP, were held by suction in the tip of a micropipette and vibrated laterally with respect to the head axis. This imposed vibration resulted in a stable rhythmic beating of the reactivated flagella that was synchronized to the frequency of the micropipette. The reactivated flagella, which in the absence of imposed vibration had an average beat frequency of 39 Hz at 2 mmol l-1 ATP, showed stable beating synchronized to the pipette vibration over a range of 20-70 Hz. Vibration frequencies above 70 Hz caused irregular, asymmetrical beating, while those below 20 Hz induced instability of the beat plane. At ATP concentrations of 10-100 mumol l-1, the range of vibration frequency capable of maintaining stable beating was diminished; an increase in ATP concentration above 2 mmol l-1 had no effect on the range of stable beating. In flagella reactivated at ATP concentrations above 100 mumol l-1, the apparent time-averaged sliding velocity of axonemal microtubules decreased when the imposed frequency was below the undriven flagellar beat frequency, but at higher imposed frequencies it remained constant, with the higher frequency being accompanied by a decrease in bend angle. This maximal sliding velocity at 2 mmol l-1 ATP was close to the sliding velocity in the distal region of live spermatozoa, possibly indicating that it represents an inherent limit in the velocity of active sliding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Free bile acids inhibit IgE production by mouse spleen lymphocytes stimulated by lipopolysaccharide and interleukins.

The interaction of IL-4, IL-5, and free bile acids with the immunoglobulin production by mouse spleen lymphocytes was studied to examine their immunoregulatory activity. In the absence of lipopolysaccharide (LPS), IL-4 enhanced the IgE and IgG production significantly and the IgA production weakly, but not the IgM production. On the other hand, IL-5 had an inhibitory tendency on the IgE and IgA production, though not significantly. In the presence of LPS, both IL-4 and IL-5 significantly enhanced the IgE production by mouse splenic lymphocytes. When the lymphocytes were cultured with the physiological concentration of free bile acids (10 microM) and LPS for 3 days, chenodeoxycholic acid inhibited the IgE production, but cholic and deoxycholic acids did not. In the presence of IL-4 or IL-5, these bile acids cancelled the stimulatory effects of interleukins and rather significantly inhibited the IgE production. These results suggest that these free bile acids act as an anti-allergic agent.

Animals

[Clinical study of renal cell carcinoma with brain metastasis].

Of 130 cases with renal cell carcinoma treated at Cancer Institute Hospital from January, 1981 to December, 1992, 14 (10.6%) developed brain metastasis, 12 of whom had had preceding pulmonary metastasis. Interval between the initial treatment of the primary lesion (nephrectomy in 13, embolization in 1) and the diagnosis of brain metastasis ranged 0 to 57 months with a median of 11 months. Twelve patients had clinical symptoms such as headache, vomiting, paralysis or disturbance of consciousness. Eleven patients were treated with external beam irradiation (30-60 Gy linear accelerator). Only 3 (30%) of 10 patients with measurable lesion on CT scan achieved PR but 6 (66.7%) of 9 had symptomatic improvement. Especially, chronic intracranial hypertension such as headache and vomiting disappeared in 5 (83.3%) of 6. Average survival period and one year survival after the diagnosis of brain metastasis were 5 months and 14.3%. Although most of the patients with brain metastasis died of the progression of other organ metastasis, radiation therapy for brain metastasis was useful to palliate the agonizing symptoms.

Adult

[Primary retroperitoneal pure choriocarcinoma].

A thirty-year-old clerk presented with a history of left supraclavicular lymph node swelling of a month duration and newly detected multiple lung and mediastinal tumors. Abdominal computed tomography showed two retroperitoneal masses, but no abnormality in both testes was found by physical and ultrasonographic examination. Biopsy of supraclavicular lymph nodes revealed pure choriocarcinoma. Furthermore, beta-subunit of human chorionic gonadotropin was elevated up to 700 ng/ml but alfafetoprotein was normal, resulting in the diagnosis of primary retroperitoneal pure choriocarcinoma. Two cycles of combination chemotherapy with etoposide (VP-16), ifosfamide and cisplatin (VIP) was given and followed by bleomycin, etoposide and cisplatin (BEP) (2 cycles) because of cystitis symptom due to ifosfamide. Since post chemotherapeutic evaluation revealed only partial response, we surgically removed all residual masses in the lung, mediastinum and retroperitoneum, which histologically proved to be necrotic fibrous tissue. He has remained disease-free 15 months after surgery without additional therapy. In order to improve prognosis of primary retroperitoneal pure choriocarcinoma, intense chemotherapeutic regimen like VIP should be given, regularly repeated and followed by aggressive surgical resection of residual masses.

Adult

[Leiomyosarcoma of the prostate: a case report of remission for 9 years by radiotherapy].

A 68-year-old-man with chief complaints of pollakisuria and lower abdominal discomfort was referred to our hospital on September 19, 1983. A histopathological study of the transrectal needle biopsy specimens revealed a malignant tumor of the prostate with spindle-shaped cells. The patient had been considerably improved by radiotherapy. However, 9 years later, the tumor recurred and the histopathological study showed the same findings as the initial biopsy and furthermore the recurrent tumor was diagnosed as a leiomyosarcoma of the prostate by immunohistochemical stain. He was unresponsive to chemotherapy and died 11 years after initial diagnosis.

Aged

[Intra-arterial chemotherapy with cisplatin, vincristine, methotrexate and adriamycin for recurrent penile cancer: a case report].

A 60-year-old man visited our hospital with a chief complaint of penile tumor on November 13, 1984. Circumcision of true phimosis was performed and biopsy of the 27 x 27 mm fixed tumor on the glans revealed well differentiated squamous cell carcinoma. Seventy Gy of electron irradiation to the penis revealed a complete response. On February 1, 1985 bilateral inguinal lymph node dissection was performed and revealed metastasis to a left inguinal node. In May 1990, erosive changes occurred on the irradiated region, and local recurrence was confirmed. Since 2 courses of MBD (methotrexate, bleomycin, cisplatin) chemotherapy was not effective, additional wedge dissection was performed. In January 1992, local recurrence was found. Four courses of intra-arterial chemotherapy (cisplatin, vincristine, methotrexate, adriamycin) was performed with a complete response. No evidence of disease has been recognized for more than two years after completion of the treatment.

Antineoplastic Combined Chemotherapy Protocols

[Chemosensitivity of cultured meningiomas].

Meningioma is one of the popular benign brain tumors. However, the recurrence of this tumor is not infrequently encountered. In an attempt to establish the useful adjuvant therapy for the recurrent meningioma, in vitro chemosensitivity study for meningioma was conducted. Among various chemotherapeutic agents tested here, cisplatin showed highest cytotoxicity on cultured meningioma cells. In conclusion, cisplatin may be useful in adjuvant chemotherapy for the recurrent meningioma.

Antineoplastic Agents

[Histological evaluation of bronchial tissue from elderly individuals with bronchial asthma].

We studied morphologic and morphometric characteristics of the bronchial walls in lungs obtained at autopsy form elderly patients who had had bronchial asthma. Thirteen patients (age at time of death 57 to 98 years; average, 81 years) were divided into three groups: AS, died of severe asthma attack (n = 4); AC, admitted with asthma symptoms but died of other diseases (n = 6); and NA, died of other diseases and had had no asthma symptoms in the year before death (n = 3). Lungs from ten non-smokers with no history of bronchial asthma or other lung disorders were used as control. Transverse sections of segmental and subsegmental bronchi were prepared, and four quantities were analyzed: 1) the ratio of total bronchial gland area to total area of the bronchial wall (Yamanaka index), 2) the thickness of the basement membrane, 3) the thickness of the smooth muscle bundle, and 4) the ratio of luminal area to total area of the bronchial wall (bronchial dilation ratio). In the AS group, the Yamanaka index and the thickness of the smooth muscle bundles and of the basement membrane were significantly greater than those in the control group at both the segmental and subsegmental levels, with massive eosinophil infiltration into the bronchial walls. Furthermore the bronchial dilation ratio at the subsegmental level correlated closely with the Yamanaka index. Thickness of the smooth muscle bundle seemed to be most representative of the severity of asthma symptoms. In conclusion, morphometric findings of bronchial walls in elderly patients with asthma symptoms seem to be similar to those in their younger counterparts.

Age Factors

Transfer of a constitutive viral promoter-cystic fibrosis transmembrane conductance regulator cDNA to human epithelial cells conveys resistance to down-regulation of cAMP-regulated Cl- secretion in the presence of inflammatory stimuli.

The expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can be down-regulated by inflammatory stimuli such as phorbol myristate acetate (PMA). Since the respiratory manifestations of cystic fibrosis (CF) are characterized by intense chronic airway inflammation very early in life, successful gene therapy for CF will require that expression of the transferred normal CFTR gene be resistant to down-regulation by inflammatory mediators. To evaluate the concept that a viral promoter--human CFTR cDNA unit would be resistant to this form of down-regulation, a retrovirus promoter (5' long terminal repeat of the Moloney murine leukemia virus)--human CFTR cDNA unit was transferred to T84 human colon carcinoma cell line using a retrovirus vector. Exposure of the retrovirus-modified T84 cells to PMA resulted in down-regulation of the endogenous CFTR mRNA transcripts (6.5 kb), but did not affect the level of exogenous CFTR transcripts (8.0 kb). Importantly, in parallel with the persistence of the exogenous CFTR transcripts, the modified cells still maintained cAMP-regulated CI- secretion in the presence of PMA. These in vitro data suggest that a constitutive viral promoter--CFTR cDNA unit should be resistant to modulation by inflammatory stimuli, a likely requirement for successful gene therapy for CF.

Blotting, Northern

Enhancer function of a 53-bp repetitive element in the 5' flanking region of the human neutrophil elastase gene.

Expression of the human neutrophil elastase (NE) gene is limited to the early stage of myeloid cell differentiation in bone marrow cells. While NE gene expression is controlled mainly at the transcriptional level during bone marrow cell differentiation, the mechanism of transcriptional control is not fully understood. One motif of interest in the 5' flanking region of the gene is the six tandem repeats of a 53-bp nucleotide sequence (REP53) containing a potential binding site for a basic helix-loop-helix protein located at -1032 to -716. The REP53 sequence can function as a non-cell specific transcriptional enhancer which is capable of augmenting heterologous promoter activity. When the single REP53 element was inserted into the pAZ1037 chloramphenicol acetyltransferase (CAT) expression vector immediately upstream of the chicken beta-actin promoter in either normal or inverted orientation and used to transfect K-562 erythroleukemia or HeLa cervical carcinoma cells, these modified vectors achieved 2 to 3-fold higher CAT activity than the parental pAZ1037 vector irrespective of orientation of the REP53.

Animals

Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: a multicenter randomized trial. Kobe University Urological Oncology Group.

A multicentric randomized trial was conducted for the purpose of investigating the prophylactic efficacy of intravesical epirubicin instillation following transurethral resection of superficial bladder cancer in comparison with the efficacy of doxorubicin. The patients were centrally randomized into 2 groups and received 19 intravesical instillations of epirubicin or doxorubicin at 30 mg/30 ml physiological saline twice a week for 4 weeks and then once monthly for 11 months. A total of 150 patients with Ta and T1 superficial bladder cancer were entered in the trial, and 114 were evaluable. The nonrecurrence rates determined for each group at 1 and 2 years by the Kaplan-Meier method were 92.8% and 88.6%, respectively, for the epirubicin group and 86.4% and 81.7%, respectively, for the doxorubicin group. The differences between the two groups were not statistically significant. The main side effects encountered in this study were symptoms of bladder irritation such as micturitional pain, pollakisuria, and hematuria. The respective frequencies of those symptoms were 10%, 15.0%, and 5.0% in the epirubicin group and 14.8%, 14.8%, and 0 in the doxorubicin group. These results suggest that epirubicin is a useful drug, comparable with doxorubicin, for intravesical instillation chemotherapy in the prophylactic treatment of superficial bladder cancer.

Administration, Intravesical

Gene transfer to freshly isolated human respiratory epithelial cells in vitro using a replication-deficient adenovirus containing the human cystic fibrosis transmembrane conductance regulator cDNA.

Cystic fibrosis (CF) results from mutations of the CF transmembrane conductance regulator (CFTR) gene and subsequent defective regulation of cAMP-stimulated chloride (Cl-) permeability across the apical membrane of epithelial cells. In vitro transfer of normal CFTR cDNA corrects this defect, and studies in experimental animals have shown successful gene transfer to airway epithelium in vivo using a recombinant adenoviral vector containing the human CFTR cDNA (AdCFTR), supporting the feasibility of in vivo AdCFTR-mediated gene therapy for the respiratory manifestations of CF. One step in applying this therapy to CF patients is to evaluate the safety and efficacy of AdCFTR-mediated gene transfer in the actual target for human gene therapy, human airway epithelium. The present study demonstrates that AdCFTR restores cAMP-stimulated Cl- permeability in human CF bronchial epithelial cells. In addition, the study utilizes freshly isolated human airway epithelial cells from the nose and/or bronchi of normal individuals and/or individuals with CF to demonstrate that after in vitro AdCFTR-mediated gene transfer: (i) AdCFTR DNA does not replicate as a function of dose and time; (ii) CF epithelial cells express AdCFTR-mediated normal human CFTR mRNA; and (iii) CF epithelial cells, including terminally differentiated ciliated cells (the most common airway epithelial cell type), express the normal human CFTR protein. Together, these data support the use of AdCFTR in human gene therapy trials and suggest that biologic efficacy should be achievable in vivo.

Adenoviridae

Langerhans cell histiocytosis presenting as a varicelliform eruption over the entire skin.

A boy with skin eruptions resembling varicella and specific for Langerhans cell histiocytosis (LCH) is reported. At his initial visit when he was four months old, vesiculopustular lesions were present over the entire body; these had first appeared on the third day post partus. Histopathological, immunohistochemical, and electron microscopical examination confirmed the Langerhans cell phenotype and Birbeck granules in the responsible cells. He also had hydronephrosis, recurrent fever, and cutaneous bacterial infections. His parents refused further medical treatment and he died of diarrhea with cachexia about two years later. LCH may present diagnostic difficulties by manifesting as a skin eruption which resembles varicella.

Chickenpox

Infantile granulomatous urachal abscess with acute localized peritonitis and appendicitis.

Infected urachal remnants in early childhood are occasionally seen. However, intraperitoneal penetration of an infected urachal remnant, resulting in acute peritonitis, is rare. We report a case of infantile granulomatous urachal abscess extending into the peritoneum and appendix. The diagnosis and treatment of urachal abscess in childhood are discussed.

Abscess

Human T lymphotropic virus type 1 uveitis after Graves' disease.

A distinct clinical entity of uveitis associated with human T lymphotropic virus type 1 (HTLV-I) has been reported previously. During the period between January 1989 and April 1992, 93 patients were observed with HTLV-I uveitis and a significant correlation was found between Graves' disease and HTLV-I uveitis. Sixteen of the 93 patients with HTLV-I uveitis (17.2%) had a previous history of Graves' disease. Fifteen patients were female (15/60, 25.0%) and one was male (1/33, 3.0%). Interestingly, uveitis occurred after the onset of Graves' disease in all cases. On the other hand, none of 222 patients with idiopathic uveitis who were seronegative to HTLV-I had a history of Graves' disease. Although the mechanisms by which HTLV-I causes the correlation between uveitis and Graves' disease are unknown, the present data suggest that immune mediated or autoimmune mechanisms are involved in HTLV-I uveitis.

Adult