PubMed HealthSearch

Biomedical subjects

H Takizawa

Publications and source records attributed to H Takizawa.

At least 19 recordsLinked to original sources

Interleukin 6/B cell stimulatory factor-II is expressed and released by normal and transformed human bronchial epithelial cells.

Airway epithelial cells have a potential to participate in local immune and inflammatory responses via releasing biologically active compounds. We studied the expression and release of interleukin 6 (IL-6), a multifunctional cytokine possibly involved in tissue immune responses. Primary culture of normal human bronchial epithelial cells and its transformed cell line BEAS-2B released significant amount of biologically and immunologically intact IL-6 into media. A protein synthesis inhibitor cycloheximide abolished the IL-6 release, suggesting a de novo synthesis. Northern blot analysis demonstrated the expression of the specific IL-6 mRNA. Human bronchial epithelial cells can produce IL-6 and contribute to the local activity of IL-6, suggesting that these cells may play a role in the regulation of airway immune responses.

Antibodies, Monoclonal

Resonance Raman study on the active-site structure of a cooperative hemerythrin.

Resonance Raman spectra were observed for the oxy and azidomet forms of a cooperative hemerythrin (Hr) isolated from Lingula unguis and a noncooperative Hr from Siphonosoma cumanense. The O-O stretching frequency of the oxy derivative of the L. unguis Hr was lower in the high-affinity form generated at pH 7.6 than in the low-affinity form generated at pH 6.2, while that of the S. cumanense Hr did not change at those two pH values. The Fe-O-Fe symmetric stretching mode of L. unguis azidomet-Hr exhibited a frequency shift between pH 7.6 and 6.2, while that of S. cumanense was not shifted. However, the corresponding band of the oxy form did not show a pH-dependent frequency change. Therefore, it is noted that the azidomet form is not a suitable model for studying a mechanism of cooperativity, contrary to the structural similarity between the oxy and azidomet forms. The Fe-O2 as well as Fe-N3 stretching frequencies were found to have no relation with the oxygen affinity. Upon exchange of solvent from H2O to D2O, the O-O and Fe-O2 stretching modes of L. unguis Hr were shifted to higher and lower frequencies, respectively, and their magnitudes were the same for the high- and low-affinity forms. The same frequency shifts were observed for S. cumanense Hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[The role of insulin on renal sodium handling and sympathetic nerve activity in overweight normotensive subjects].

Recently, it was suggested that the role of hyperinsulinemia on the hypertensive mechanism of essential hypertension might be related to renal sodium handling and sympathetic nerve activity, especially in obese hypertensive patients. However, the interrelationship between insulin, obesity, renal sodium metabolism and sympathetic nerve activity in normotensive subjects (NT) still remains unclear. The present study, therefore, was undertaken to clarify the role of insulin on renal sodium handling and sympatho-adrenal function in overweight NT. The study consisted of 24NT, who were divided into two groups of twelve non-obese (NNT) and twelve obese (ONT) subjects. NNT was categorized as a body mass index (BMI) less than, and ONT as a BMI equal to or more than 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance test. During the two-hour clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance(CCr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma immunoreactive insulin (IRI), plasma norepinephrine concentration (pNE), and plasma epinephrine concentration (pE) were determined. Although no significant difference was found in age, MAP, HR, pE, CCr or UNaV between the two groups, a significantly higher IRI (p less than 0.05) and lower FENa (p less than 0.05) were observed in ONT than in NNT. There was no significant correlation between IRI and UNaV, FENa or pE in ONT or in NNT. In addition, no significant correlation was shown between FENa and pNE or pE in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla

Species-specific restriction of complement by HRF20 (CD59) generated by cDNA transfection.

The 20-kDa homologous restriction factor (HRF20, CD59) is a phosphatidyl inositol-anchored membrane glycoprotein that inhibits the formation of human complement membrane attack complexes. The cDNA of HRF20 was transfected into Chinese hamster ovary (CHO) cells resulting in expression of human HRF20 protein on the cell surface anchored via glycosylphosphatidyl inositol. The transfected CHO cells were resistant to human complement-mediated cell killing. However, the cells remained sensitive to rat and guinea pig complement. Therefore, species specificity between HRF20 and complement is maintained in HRF20 generated on the CHO cells following transfection with HRF20 cDNA.

Animals

Serum-free culture of fractionated bovine bronchial epithelial cells.

Procedures for the serum-free culture of a density fractionated population of bovine bronchial epithelial cells have been established. Epithelial cells dispersed by protease digestion were fractionated by density equilibrium centrifugation, followed by plating of the small basal-like population on type I collagen-coated culture dishes. Two or three passages of 1:4 split enriched for a population of actively dividing cells, which could be stored in liquid nitrogen for subsequent use. Clonal growth assays revealed optimum proliferation using a 1:1 mixture of medium RPMI 1640 and LHC-9, a medium employed for human bronchial epithelial cells. Cellular growth rate, which was 0.6 to 1.3 doublings per day depending on the cell preparation, was conveniently decreased by supplementing LHC-9 medium with less than 50% RPMI. In contrast to airway epithelial cell cultures from other species, serum stimulated the growth of bovine bronchial epithelial cells in this system. Transforming growth factor beta 1, however, inhibited growth and induced differentiation into a squamous phenotype. Also in contrast with other systems, the bovine cells were resistant to growth inhibition by 100 nM tetradecanoyl phorbol acetate or 1 microM calcium ionophore A23187. Combination of phorbol ester with ionophore decreased mitotic activity, although induction of squamous morphology was not observed. Therefore, growth inhibition and squamous differentiation were not tightly coupled in this system. Finally, biologically synthesized matrix deposited by these cells stimulated growth rate. This culture system will therefore be useful in assessing the activities of both soluble and matrix-associated factors in the absence of serum.

Animals

Hypersensitivity pneumonitis in athymic nude mice. Additional evidence of T cell dependency.

We previously demonstrated that C57 Black/6 mice develop lung lesions similar to human hypersensitivity pneumonitis (HP) by repeated transnasal administration of Thermoactinomyces vulgaris (Tv) antigen. To elucidate the role of T cells in the development of this disease, Tv antigen (90 micrograms/day) was transnasally administered to athymic nude C57 Black/nu/nu (nu) mice and their littermates (+/nu) three times a week for 3 wk. The nude mice developed minimal lung lesions, whereas their thymus-intact littermates (+/nu) showed changes equivalent to those in C57 Black/6. Changes in local inflammatory cell responses were evaluated by bronchoalveolar lavage, and increases in the numbers of lymphocytes and macrophages were significantly less severe in the nude mice than in the +/nu mice. Interestingly, the increase in polymorphonuclear leukocytes 6 h after the last antigen inoculation was equivalently seen in both groups. When spleen-derived T cells (more than 95% Thy-1.2+) from the sensitized +/nu mice were adoptively transferred to nude mice, the HP-like lesions in the recipients were found after Tv antigen challenge. These results suggest that Thy-1.2+ T cell-mediated immunity was necessary for the development of HP in this murine model.

Alveolitis, Extrinsic Allergic

Transforming growth factor-beta stimulates the expression of desmosomal proteins in bronchial epithelial cells.

Transforming growth factor-beta 1 (TGF-beta 1) has been shown to induce squamous differentiation of cultured airway epithelial cells. It has also been shown to increase expression of matrix proteins and integrin receptors in cell culture of these and other cells. However, it is unknown if TGF-beta 1 affects expression of genes encoding intercellular junctional proteins. Therefore, we have investigated the effect of TGF-beta 1 on the expression of proteins and mRNAs for desmoplakins (DPs) I and II, desmosomal plaque proteins. Fibronectin, known to be induced by TGF-beta 1 was used as a positive control and tubulin as a negative control. Twenty-four hours after TGF-beta 1 stimulation, DP I and II mRNA levels assessed by Northern blotting analysis had increased significantly (DP I mRNA, 1.8-fold, P less than 0.05; DP II mRNA, 2.4-fold, P less than 0.04), thereby indicating pretranslational regulation of DP expression. By comparison, mRNA for fibronectin increased 8.1-fold whereas mRNA for tubulin was unchanged. Immunofluorescence using the monoclonal anti-DP I and II antibodies revealed dramatic increased expression of punctate DP structures after exposure to TGF-beta 1. Immunoblot analyses with polyclonal anti-DP I antibodies showed increased levels of both DP I (250 kD) and DP II (215 kD), with the DP I increase being more pronounced (DP I, 2.5-fold; DP II, 1.4-fold at 48 h relative to controls), suggesting translational regulation by TGF-beta 1. This study therefore demonstrates the ability of TGF-beta 1 to alter cellular phenotype by altering expression of proteins involved in intercellular junctions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[The effect of kallikrein and caffeine on the sperm survival of cryopreserved semen in patients with oligozoospermia].

Cryopreservation of semen from patients with oligozoospermia (sperm counts less than 20 million/ml) generally results in a severe decline in the percentage of motile spermatozoa after thawing in comparison with normozoospermia. We studied the effects of two metabolically active compounds, namely kallikrein and caffeine, on the survival of frozen-stored spermatozoa, in particular, from patients with oligozoospermia. A modified Ackerman's solution was used as the protective medium, and the specimens were frozen using a programmed freezer. We evaluated the post-thaw survival rate of spermatozoa by sperm counts on addition of agents. 1) When used the modified Ackerman's solution only, the post-thaw survival rate in the cases of oligozoospermia was significantly lower than that in the cases of normozoospermia. On the other hand, between these groups, there were no significant differences in the post-thaw activity rates of spermatozoa. 2) When added 1 KE/ml kallikrein and 7.5 mM caffeine (final volume) to the protective medium, the survival rate in the cases of oligozoospermia increased significantly, so that no significant differences were seen in the survival rates between the groups of oligozoospermia and normozoospermia. The effect of caffeine was better than that of kallikrein. 3) It was suggested that kallikrein and caffeine activated the non-motile live spermatozoa after thawing especially in the cases of oligozoospermia.

Adult

[Studies on the regulation of normal bronchial epithelial cell proliferation and proto-oncogene expression].

The regulatory mechanisms of proliferation and differentiation of normal airway epithelial cells seem important for the better understanding of lung carcinogenesis. We isolated bovine and human bronchial epithelial cells by enzymatic digestion of bronchi, and cultured them in serum-free growth factor-supplemented medium. To determine the role of growth factors in the proliferation of bovine bronchial epithelial cells, the effect of each of these additives was evaluated. Of these, fetal calf serum (FCS), bovine pituitary extract (BPE), insulin and insulin-like growth factor-1 (IGF-1) showed a significant stimulatory effect on cell growth. These four additives induced transient increases in c-fos, c-jun and c-myc proto-oncogene mRNA levels. Transforming growth factor beta (TGF beta) inhibited growth factor-induced cell proliferation, and also showed selective inhibition of c-myc induction. We also studied the effect of interleukin 6 (IL-6) on human bronchial epithelial cell proliferation. IL-6 showed a significant inhibitory effect on cell growth. These cells were capable of expressing and releasing IL-6 and had specific receptors for IL-6, suggesting an autocrine mechanism. These results suggest that TGF beta and IL-6 may play roles in the regulation of airway epithelial cell growth as inhibitory growth factors.

Animals

[Interleukin 6 receptors on human bronchial epithelial cells].

It has been suggested that a variety of cytokines may play important roles in the regulation of immune and inflammatory responses in the lung. The purpose of this study was to determine whether interleukin 6 (IL-6) could affect the cell growth of human bronchial epithelial cells via a specific receptor for IL-6. Human recombinant IL-6 inhibited the cell proliferation in a dose-dependent manner. Binding assay with radiolabelled IL-6 demonstrated that human bronchial epithelial cells had specific receptors for IL-6. Moreover, Northern blot analysis using digoxigenin-labelled IL-6R mRNA expression in these cells. Interestingly, proinflammatory cytokines IL-1 alpha and IL-6 upregulated IL-6R mRNA levels. These results suggest that IL-6 may affect the functions of bronchial epithelial cells via a specific receptor, and that its activity on cells may be regulated at the level of receptor-cytokine binding.

Bronchi

[An autopsy case of sarcoidosis associated with renal failure].

A 62-year-old woman presented with uveitis and abnormal chest X-ray (bilateral hilar adenopathy). Skin biopsy in 1983 had revealed non-caseating epithelioid cell granuloma consistent with sarcoidosis. Her serum biochemical investigations and exploratory laparoscopy suggested nodular liver cirrhosis, but biopsy was not performed. Both blood urea nitrogen (BUN) and serum creatinine values were within normal limits. She received prednisolone therapy of 15 mg daily initially, and later a maintenance dose of 5 mg daily. In 1985, she complained of skin itching and her laboratory data revealed severe renal insufficiency (BUN 97 mg/dl, serum creatinine 12.2 mg/dl) and hypercalcemia (corrected serum calcium level: 11.5 mg/dl). Prednisolone treatment (40 mg daily) resulted in a dramatic improvement of renal function as well as other clinical abnormalities due to sarcoidosis, without any significant changes in liver function. She died of cerebral infarction in 1989. Autopsy showed interstitial nephritis with tubular calcinosis and hyalinized glomeruli. It is postulated that hypercalcemia due to sarcoidosis contributed to the renal failure in this patient. This case suggests that renal damage due to sarcoidosis may be reversible with appropriate corticosteroid therapy.

Female

[A case of asymptomatic endobronchial lipoma followed for 4 years].

Bronchoscopy was performed on a 68-year-old male patient with pulmonary tuberculosis, and revealed a yellow smooth polypoid tumor in the lumen of the left upper division bronchus. The histopathological diagnosis of the biopsy specimen was endobronchial lipoma. Since the patient did not have any symptoms due to the lipoma, we performed treatment for tuberculosis and continued careful observation of the tumor. During the subsequent 4 years, the patient developed no complications such as obstructive pneumonia, and the size of the tumor under bronchoscopic observation did not change. Endobronchial lipoma is a very rare benign tumor. Almost all reported cases have undergone operation or endoscopic surgery. This case is the first that was followed over 4 years without surgical procedure. The findings of follow-up bronchoscopic examination suggest that the growth rate of endobronchial lipoma is very slow. Furthermore, we reviewed 36 cases of endobronchial lipoma in the Japanese literature, including our case. Smoking seems to have a strong relation to the occurrence of the tumor. It is noteworthy that 6 cases had separate malignancies, but the direct relationship between endobronchial lipoma and such malignancies is unclear.

Aged

[A case of new type scrub typhus (tsutsugamushi disease) presenting with acute respiratory failure and hemophagocytic syndrome].

A 47-year-old male was referred to our hospital with persistent high fever. He had received antibiotics (ASPC) for the diagnosis of acute infectious disease, which failed to respond, and subsequently developed marked lymphocytopenia and thrombocytopenia. During his hospitalization, hypoxic respiratory failure rapidly developed. A bone marrow aspiration revealed marked hemophagocytosis, leading to the tentative diagnosis of opportunistic respiratory infection associated with malignant histiocytosis. Treatment for suspected malignancy and Pneumocystis carinii pneumonia was commenced. However, because of the initial lack of response to ASPC, generalized skin rashes without an ordinary stick wound which had diminished before the hospitalization, and a history of working outdoors in a nearby mountain area, the possibility of new type tsutsugamushi disease was strongly suggested. Intravenous administration of minocycline promptly improved his symptoms and laboratory data. The diagnosis was confirmed by a significant increase in the titer of antibody to Rickettsia tsutsugamushi. The thrombocytopenia was considered to have been caused by co-existent hemophagocytic syndrome.

Acute Disease

Regulation of bovine bronchial epithelial cell proliferation and proto-oncogene expression by growth factors.

The proto-oncogenes are thought to play important roles in the regulation of cellular growth and differentiation. In order to evaluate the role of proto-oncogenes in the regulation of growth of bronchial epithelial cells, we studied steady-state levels of fos, jun, and myc transcripts in response to fetal calf serum, bovine pituitary extract, and insulin. Extensively quiescent populations of bovine bronchial epithelial cells in growth factor-free medium were stimulated to divide by each of these three additives. We observed rapid but transient increases of fos, jun, and myc expression in association with such growth stimulation. There were no changes in tubulin mRNA levels over the same time periods. Other "growth factors" (epidermal growth factor, hydrocortisone, epinephrine, triiodothyronine, and transferrin) were also studied and did not affect either cell growth or expression of fos, jun, or myc. We further examined the effect of transforming growth factor-beta1 (TGF-beta1) on the above stimulatory effects. TGF-beta1 consistently inhibited the growth induced by fetal calf serum, bovine pituitary extract, or insulin and, interestingly, reduced proto-oncogene myc mRNA level without altering that of fos and jun. In conclusion, proto-oncogenes fos, jun, and myc appear to play a role in the regulation of growth response in bovine bronchial epithelial cells. It is also possible that TGF-beta1 exerts its growth inhibitory effect, at least in part, through the processes that involve the regulation of proto-oncogene myc transcription in these cells.

Animals

A new series of antiallergic agents. I. Synthesis and activity of 11-(2-aminoethyl)thio-6,11-dihydrodibenz[b,e]oxepin derivatives.

A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin derivatives was synthesized and evaluated for antiallergic activity. Convenient methods for the preparation of sulfides from alcohols were developed. Structure-activity relationships are described. Compound 7, 11-[2-(dimethylamin)ethyl]thio-6,11-dihydrodibenz[b,e] oxepin-2-carboxylic acid hydrochloride, was the most potent in the rat passive cutaneous anaphylaxis test (ED50 = 0.92 mg/kg p.o.). It had a potent inhibitory effect on anaphylactic bronchoconstriction in guinea pigs (ED50 = 0.029 mg/kg p.o.) and H1 receptor antagonistic effect (Ki = 14 nM) with few central nervous system side effects. Additionally, an antagonistic effect against prostaglandin D2-induced contraction of isolated guinea pig trachea (pA2 = 5.73) was an attractive mechanism of action of the new antiallergic agent. Compound 7 was selected for further evaluation as KW-4994.

Animals

[Spontaneous disappearance of a middle fossa arachnoid cyst--a case report].

A case of a middle fossa arachnoid cyst which spontaneously disappeared is reported. A 16 year old boy visited our out-patient clinic complaining of headache after a blunt head trauma by a motorcycle accident. The neurological examination was negative except for mild neck pain on the flexion and extension of neck. Plain x-ray of skull and neck were negative. CT scan demonstrated an arachnoid cyst in the left Sylvian fissure. It was planned to follow up the patient by CT scan. After 10 months, he was examined by CT scan, which revealed the spontaneous disappearance of the arachnoid cyst and some dilatation of the anterior horn of the lateral ventricle. The patient did not have any additional trauma or infection during the interval between two examinations. Spontaneous disappearance of arachnoid cyst was extremely rare as only 4 cases were reported previously. The basic mechanism of this natural cure was considered to be rupture of outer or inner membrane of arachnoid cyst which would facilitate absorption of its content.

Adolescent