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Biomedical subjects

M Kita

Publications and source records attributed to M Kita.

At least 91 records · Page 5Linked to original sources

Radical radiotherapy for medically inoperable non-small cell lung cancer in clinical stage I: a retrospective analysis of 149 patients.

PURPOSE: In order to obtain the standard treatment results of medically inoperable non-small cell lung cancer (NSCLC) in Stage I in the post-CT scan era, a retrospective analysis of patients who were treated by radical radiotherapy was performed. METHODS AND MATERIALS: 149 cases treated between 1980 and 1989 were accumulated from ten large hospitals in Japan. All patients received a total dose of 55-75 Gy (mean 64.7 Gy) with conventional fractionation. For evaluation of treatment results, complete response (CR) rate, median survival period and long-termed survival rates were used. RESULTS: The median survival of the all cases was 27.2 months and the actuarial 3- and 5-year survival rates were 34.2% and 22.2%, respectively. CR was obtained in 57 cases (38%). The CR rate was strongly correlated with the long-term survival (5-year survival rate in CR group: 35.1% compared with PR + NC group: 14.1% (P < 0.0001)). The size of tumor was also of prognostic importance. In 116 patients who died within 5 years after treatment, 66 patients (57%) died of local tumor regrowth. CONCLUSION: Although the medically inoperable NSCLC patients in Stage I should be offered curative radiation therapy, development of some new steps to increase the CR rate and local control rate is urgently needed.

Aged↗

Influence of the sensory retina on healing of the rabbit retinal pigment epithelium.

PURPOSE: To compare the healing process of the retinal pigment epithelium (RPE) with and without the overlying sensory retina. METHODS: A dome-shaped retinal detachment was created in the pigmented rabbit eye by injecting balanced salt solution into the subretinal space. The detached retina was partially removed with a vitrector; in some eyes, the detached retina was removed completely. RPE about 1.5 mm in diameter was removed from Bruch's membrane and aspirated through the retinal break. All eyes were examined morphologically. RESULTS: Independent of the sensory retina, 4 days postoperatively the RPE wound was covered by immature RPE cells that gradually formed an epithelial-like sheet by 2 weeks postoperatively. In eyes with overlying sensory retina, regenerated RPE cells similar to normal RPE cells formed a monolayer in most areas. The RPE-photoreceptor outer segment interface gradually organized. In eyes with no sensory retina, the regenerated RPE cells were longer, mounded, and their microvilli were shorter and disorganized. The RPE cells were multilayered in some areas and often had a tubuloacinar structure. CONCLUSIONS: The RPE wounds healed rapidly, independent of the presence of the overlying sensory retina, up to 2 weeks after RPE removal. Reconstruction of the RPE monolayer and the apical morphology of regenerated RPE cells were influenced by the sensory retina.

Animals↗

Cytokine expression in the alkali-burned cornea.

PURPOSE: This study investigated the cytokine expression profile in alkali-burned mouse corneas, in order to elucidate the mechanisms of corneal damage and repair. METHODS: The cytokines expressed in alkali-burned corneas were identified by polymerase chain reaction (RT-PCR), then quantitated using ELISA. Based on the ELISA results, immunohistochemical analyses were performed to localize cytokine expression. RESULTS: Among the ten cytokines examined, IL-1 (IL-1 beta), IL-6, IL-10 and TNF-alpha mRNA were expressed in alkali-burned corneas. Quantitation revealed that IL-alpha and IL-6 were strongly induced in the early stages of alkali burn, peak production of IL-1 alpha (53.2 pg/cornea) and IL-6 (23.6 pg/cornea) occurring at days 3 and 7, respectively. The production of IL-10 and TNF-alpha was not significantly elevated during the 42 day period after burn. Immunohistochemical analyses revealed that both IL-1 alpha and IL-6 were mainly localized in regenerating epithelial basal cells. CONCLUSIONS: IL-1 alpha and IL-6 levels in the cornea are dramatically elevated in the regenerated epithelium during the early stages of alkali burn, and may play an important role in associated corneal damage and repair.

Alkalies↗

Determination of interferon-alpha2 allele composition in the genomic DNA from healthy volunteers and leukemic patients in Japan.

The three interferon-alpha2 (IFN-alpha2) sequences identified to date differ from each other in just two nucleotide positions, both of which result in changes in amino acids. Thus, the mature IFN-alpha2a protein product is characterized by a lysine residue at position 23 (AAA) and a histidine at position 34 (CAA), IFN-alpha2b has an arginine at position 23 (AGA) and histidine at position 34 (CAT), and IFN-alpha2c has arginine residues at both positions 23 (AGA) and 34 (CGT). These nucleotide variations in the DNA sequence can be distinguished by selective restriction enzyme analysis. We studied the distributions of the three IFN-alpha2 variants by analyzing chromosomal DNA from 103 Japanese volunteers and 33 patients with hematologic disorders. Fragments of 238 bp and 617 bp of the IFN-alpha2 gene containing codons 23 and 34 were amplified by PCR using specific primers, and the PCR products were analyzed with specific restriction nucleases to identify the IFN-alpha2 variant sequences. Only IFN-alpha2b gene was detected in normal volunteers, and no IFN-alpha2a gene was detected in Japanese subjects. However, IFN-alpha2c was detected in 4 of 33 (12.1%) patients with leukemia.

Adult↗

An 11-year-old girl with reflex sympathetic dystrophy successfully treated by thoracoscopic sympathectomy.

We report on an 11-year-old girl with reflex sympathetic dystrophy (RSD) complaining of severe pain in her right upper extremity. Oral administration of narcotics or non-steroid anti-inflammatory drugs gave no relief in pain. Thoracoscopic electrocauterization of the thoracic sympathetic ganglion at the level of T3 was performed 3 months after the start of symptoms, and brought complete resolution of pain.

Arm↗

Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains.

BACKGROUND: Helicobacter pylori strains possessing the cagA gene are thought to induce interleukin 8 (IL-8) in gastric mucosa. However, it is still unclear whether a relation exists between the cagA gene and the expression patterns of cytokines other than IL-8. AIMS: To investigate the relation between the cagA gene and the production of various cytokine proteins using an enzyme linked immunosorbent assay (ELISA). PATIENTS AND METHODS: In 184 patients, the cagA gene was detected by polymerase chain reaction (PCR), and levels of production of IL-1 beta, IL-6, IL-7, IL-8, IL-10, and tumour necrosis factor alpha (TNF-alpha) in antral biopsy specimens were measured by ELISA. RESULTS: Mucosal levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were significantly higher in H pylori positive than in H pylori negative patients. Furthermore, the mucosal levels of IL-1 beta and IL-8 were significantly higher in specimens infected with cagA positive strains than in those infected with cagA negative strains. In H pylori positive patients, the mucosal level of IL-8 was closely correlated with that of IL-1 beta (p < 0.0001), and the mucosal level of IL-6 was closely correlated with that of TNF-alpha (p < 0.0001). CONCLUSION: These findings suggest that the ability to induce cytokines differs among the strains; cagA+ strains induce various kinds of cytokines and may cause severe inflammation, whereas cagA- strains induce IL-8 and IL-1 beta only weakly and may cause only mild inflammation. However, as most patients infected with the cagA+ strains have gastritis, these strains may not be equivalent to ulcerogenic strains.

Adult↗

Expression of 47 kDa heat shock protein (HSP47) during development of mouse cornea.

The 47-kDa heat shock protein (HSP47) is assumed to be a molecular chaperone specific to collagen. We examined and compared the expression patterns of HSP47 and alpha 1(I) collagen in the developing mouse cornea. Expression of HSP47 and alpha 1(I) collagen mRNAs was assessed by Northern blot analysis and in situ hybridization, and that of HSP47 protein was determined by Western immunoblotting and immunohistochemistry. HSP47 mRNA and protein were expressed strongly in early embryonic ocular tissues and were developmentally down-regulated during ocular development. Both were distributed in the mesenchymal cells (presumptive corneal stroma, sclera and choroid) and hyaloid blood vessels until post-natal day 14. The level of alpha 1(I) collagen mRNA increased during ocular development, was maximally expressed in the three days after birth, and was detected in mesenchymal cells. HSP47 expression is regulated developmentally toward completion and plays an important role during ocular development especially in corneal morphogenesis. We discuss here the relation between expression of HSP47 and alpha 1(I) collagen.

Animals↗

Staphylococcal enterotoxin B-specific adhesion of murine splenic T cells to a human endothelial cell line.

The presence of a putative autoantigen of autoimmune disorder in a target organ may cause accumulation of specific T cells in the inflammatory region. One of the mechanisms of such accumulation involves the migration of specific-circulating T cells through the endothelial cells into the target lesion. The presence of only a few specific T cells responsive to a putative autoantigen has hampered the investigation of specific migration of circulating T cells to the target organ. We used a superantigen to investigate specific T-cell adhesion to endothelial cells, because it stimulates a large proportion of T cells with particular V beta elements and adhesion of T cells to the endothelium is a vital step in the migration process. Adhesion of murine T cells to the human endothelial cell line, EA.hy926, was specifically increased in the presence of staphylococcal enterotoxin B (SEB). The increase was interferon-gamma (IFN-gamma)-dependent, and consisted mainly of CD4+ T cells. V beta 8.1,2+ T cells preferentially adhered to endothelial cells in the presence of SEB compared with V beta 6+ T cells. Pretreatment of endothelial cells with SEB increased the adherence of V beta 8.1,2+ T cells, while anti-human leucocyte antigen (HLA)-DR and -DQ antibodies inhibited the increased adherence of V beta 8.1,2+ T cells. Our results demonstrate that increased T-cell adhesion to endothelial cells is SEB specific, and that the specificity is dependent on major histocompatibility complex (MHC) class II molecules expressed on endothelial cells and on the recognition of the SEB-MHC class II complex by V beta 8.1,2+ T cells.

Animals↗

Impaired production of interferon-alpha in whole-blood cultures from patients with renal cell carcinoma.

OBJECTIVE: To determine the immune status of patients with renal cell carcinoma (RCC) by estimating the production of interferon-alpha (IFN-alpha) in whole-blood cultures from these patients and from healthy subjects. PATIENTS, SUBJECTS AND METHODS: Peripheral blood (2 mL) was collected from 30 untreated patients (23 men and seven women, mean age 59 years, range 35-78) with RCC and 30 healthy subjects (23 men and seven women, mean age 62 years). The patients with RCC comprised 17 with low-stage (stage I, II) and 13 patients with high-stage (stage III, IV) RCC. Sendai virus was added to the samples and incubated at 37 degrees C for 20 h, the supernatants collected and the activity of IFN-alpha determined by a conventional cytopathic-effect inhibition assay performed in microtitre plates with FL cells and challenged with vesicular stomatitis virus. RESULTS: The production of IFN-alpha was suppressed significantly in patients with high-stage RCC compared with that in the control subjects (P < 0.05), but there was no significant difference when compared to patients with low-stage RCC. CONCLUSION: This study demonstrated that the immune status of patients with high-stage RCC was impaired significantly and exogenous IFN-alpha therapy might be beneficial clinically for this group.

Adult↗

Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa.

BACKGROUND & AIMS: Helicobacter pylori strains possessing the cagA gene are thought to be associated with gastroduodenal diseases. Furthermore, some cytokines are considered to play a role in gastric mucosal inflammation. The aim of this study was to investigate the relationship between cagA gene and cytokine messenger RNA (mRNA) expression in gastric mucosa. METHODS: In 160 patients, the cagA gene was detected using polymerase chain reaction, and interleukin (IL) 1 beta, IL-6, IL-7, IL-8, IL-10, and tumor necrosis factor (TNF) alpha mRNA were detected using reverse-transcription polymerase chain reaction. RESULTS: Specimens infected with cagA gene-positive strains (cagA-positive specimens) had significantly more severe infiltration of polymorphonuclear leukocytes and mononuclear cells than those infected with cagA gene-negative strains (cagA-negative specimens). Levels of expression of IL-6, IL-7, IL-8, IL-10, and TNF-alpha mRNA were significantly higher in H. pylori-positive than H. pylori-negative patients. Furthermore, the level of IL-8 mRNA expression was significantly higher in cagA-positive than cagA-negative specimens. CONCLUSIONS: cagA-positive strains induce the expression of IL-8 mRNA, suggesting that IL-8 may play important roles in the pathogenesis of gastroduodenal diseases associated with H. pylori infection.

Adult↗

MR imaging of liver cirrhosis.

PURPOSE: The objective of this study was to identify the factors affecting the visualization of regenerating nodules in cirrhotic liver by MR imaging. MATERIAL AND METHODS: MR images from patients with liver cirrhosis and normal subjects were studied, and signal intensity within the liver was measured and correlated with histologic findings. A reference phantom was also used as a standard. RESULTS: The signal intensity of the liver on T2-weighted (T2WI) spin-echo (SE) images was significantly increased in patients with liver cirrhosis. Multiple ring-like or reticular high-intensity areas (RHAs) were demonstrated on T2WI SE images in 44 of 125 cirrhotic livers. Histologic examination in 44 cases revealed various degrees of inflammatory changes in fibrous septa surrounding regenerative nodules in all specimens, vascular dilation in fibrous septa in 4 specimens, and no hemosiderin deposition in some specimens. The results of linear discriminant analysis showed that inflammatory changes in fibrous septa were significantly more pronounced in cases with RHAs on MR. CONCLUSION: RHAs seen on T2WI SE images may correspond to fibrous septa with inflammation. The signal intensity of fibrous septa surrounding regenerative nodules on T2WI SE images may be increased in liver cirrhosis due to inflammation or vascular dilation, contributing to the visualization of regenerating nodules as relatively low-intensity regions on MR.

Adult↗

MR imaging of the parotid gland in Sjögren's syndrome: a proposal for new diagnostic criteria.

OBJECTIVE: Because classic diagnostic techniques for sjögren's syndrome (SS) are invasive and require radiation exposure, a noninvasive diagnostic method might benefit patients with SS. The purpose of this study was to determine whether quantitative analysis of MR images of the parotid gland can differentiate patients with SS from normal subjects. SUBJECTS AND METHODS: We performed quantitative analysis of MR images of the parotid gland for 40 patients with definite and probable SS, for 30 normal subjects matched by age and sex to the SS patients, and for 10 patients with parotid inflammation. MR images of teh parotid gland were assessed by calculating standard deviations (SD) of signal intensity. RESULTS: SD of signal intensity exclusively (p < .0001) separated MR images of the parotid glands of patients with definite SS from those of normal subjects. SD of signal intensity for the parotid glands of patients with probable SS also were significantly higher (p < .001) than those of normal subjects. Changes in signal intensity were specific for SS and did not occur with parotid inflammation. Tentative categorization on the basis of signal intensity patterns on MR images of the parotid glands of SS patients showed a high correlation with the results of labial gland biopsy (r = .834) and sialography (r = .936). CONCLUSION: Taken together, these results conclusively indicate that quantitative analysis of MR images for SD of signal intensity is useful method for diagnosing SS and can replace classic methods, which are invasive.

Adolescent↗

[Untoward effects of low dose methotrexate therapy in rheumatoid arthritis].

Sixty patients with rheumatoid arthritis who were administered weekly low dose methotrexate (MTX) were retrospectively analyzed for their untoward effects of MTX by interviewing to the patients and by the medical records. Cough and sputa were the most frequent symptoms (23.3%) and gastrointestinal symptoms were the next (20%). Five of 60 patients (8.2%) showed liver function test abnormalities, and four (6.7%) exhibited transient exacerbation of arthralgia for several hours to a few days after MTX administration. Three patients (5%) suffered from interstitial pneumonitis. Hair loss was seen in 3 patients (5%), and headache, leucocytepenia, fever, skin eruption, abnormal taste, hemorrhagic cystitis, and flashing were experienced in a patient, respectively. Three (5%) suffered from fungal infection, and herpes zoster, sepsis, and osteomyelitis were experienced in each one patient, respectively. MTX was withdrawn in three patients (5%) because of cough and sputa the drug was withdrawn in other three patients because of the interstitial pneumonia, and was drawn in another three patients because of transient exacerbation of arthralgia. The drug was withdrawn in each one patient, because of nausea and vomiting, skin eruption, osteomyelitis, and sepsis, respectively. Overall, MTX were withdrawn in 21 patients (35%), and, of those, 13 patients (21.7%) because of untoward effects and 8 patients (13.3%) because of the lack of efficacy.

Adult↗

Ixodid tick salivary gland extracts inhibit production of lipopolysaccharide-induced mRNA of several different human cytokines.

Extracts prepared from the salivary glands (SGE) of partially fed adult female Rhipicephalus appendiculatus ticks reduced the expression by human peripheral blood leukocytes 9PBLs) of lipopolysaccharide (LPS)-stimulated cytokine mRNA. Treatment with SGE had no obvious effect on cytokine mRNA production when compared with untreated PBLs. LPS treatment induced or increased mRNA production for IFN alpha, TNF-alpha, IL-1 alpha, IL-1 beta, IL-5, IL-6, IL-7 and IL-8. All the LPS-stimulated cytokine mRNAs were reduced when treated with a mixture of LPS and SGE. The results indicate the potential of ticks in modulating the cytokine network of their vertebrate hosts, possibly to facilitate blood feeding.

Animals↗

Enhancing effect of platelet-derived growth factors on migration of corneal endothelial cells.

To investigate the role of platelet-derived growth factor (PDGF) in corneal wound healing, we examined the effect of human natural PDGF, recombinant PDGF-BB, and PDGF-AA on the migration of rabbit corneal endothelial cells. In a modified Boyden chamber in fetal bovine serum-free conditions, natural PDGF and PDGF-BB, at a concentration of 1-3 or 10 ng/ml, enhanced the migration of endothelial cells, whereas at a higher concentration (10 or 30 ng/ml), this enhanced migration was suppressed; the optimal concentration range for enhancing migration was 3-10 ng/ml. PDGF-AA did not enhance the migration. Natural PDGF and PDGF-BB activity was found for up to 6 h after the beginning of culture, and was completely blocked by anti-PDGF neutralizing antibodies. A checkerboard assay demonstrated that PDGF-BB had a chemotactic effect on the corneal endothelial cell migration. These results suggest that natural PDGF and PDGF-BB, but not PDGF-AA, are involved in corneal wound healing by stimulating the migration of corneal endothelial cells.

Animals↗

Effect of Kawasaki disease on migration of human umbilical vein endothelial cells.

Kawasaki disease, which is characterized by systemic vasculitis causing coronary arterial involvement in childhood, shows a variety of immunoregulatory abnormalities. Especially the direct or indirect deleterious effects on endothelial cells of cytokines and anti-endothelial cell antibodies (AECA) are considered to be involved in the mechanism responsible for production of vasculitis. Intravenous administration of high doses of gamma-globulin (IVGG) has been used as an effective therapy for Kawasaki disease. To examine the behavior of endothelial cells affected by cytokines and IVGG in Kawasaki disease, we studied the effects of interferon (IFN), IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha on the migration of human umbilical vein endothelial cell line (tHUE01) by a modified Boyden chamber method. Plasma from patients with acute Kawasaki disease markedly enhanced the migration of tHUE01 cells. Cytokines, with the exception of TNF-alpha, also enhanced the migration of tHUE01 cells in a dose-dependent manner. Anti-IFN antibody inhibited the migratory activity in response to not only IFN-gamma but also to the plasma from patients with Kawasaki disease. Rabbit AECA (rAECA) also significantly stimulated the migration of tHUE01 cells. Plasma from patients treated with IVGG did not affect the migration of tHUE01 cells. Addition of gamma-globulin significantly inhibited the migration of tHUE01 cells induced by the cytokines or rAECA. These results suggest that cytokines and AECA are important in restructuring and destroying vessel walls in Kawasaki disease by enhancing the migration of endothelial cells, and that IVGG may be therapeutically effective for this disease by suppressing this endothelial cell migration.

Animals↗

Exacerbation of rheumatoid arthritis after removal of adrenal adenoma in Cushing's syndrome.

A 46-year-old woman with rheumatoid arthritis had been on non-steroidal antiinflammatory agents for eighteen years until she developed cushingoid features and hypertension resistant to antihypertensive drugs. She had high plasma cortisol and 24 h urinary 17-hydroxycorticosteroids (17HCS) which were not suppressed by 8 mg dexamethasone per day for two days. The circadian rhythm of plasma cortisol was absent and plasma ACTH concentrations were suppressed before and after intravenous administration of CRH. Abdominal computed tomography demonstrated a tumor (3.0 x 3.0 x 2.3 cm) in the right adrenal gland and a 131I-6 beta-19-nor-methylcholesterol scan revealed marked uptake on the same side. The patient underwent a right adrenalectomy and the diagnosis of a cortisol secreting benign adenoma was histologically confirmed. Blood pressure declined and cushingoid features regressed, but three months after the operation and while the patient was on replacement, she complained of pain on motion, marked tenderness and swelling of fingers, wrists, elbows, knees and foot joints, and had very high rheumatoid factors. Treatment with immunosuppressive drugs and oral and intraarticular administration of glucocorticoids were necessary to relieve the clinical symptoms of rheumatoid arthritis. In summary, we report a patient with rheumatoid arthritis and Cushing's syndrome due to an adrenal adenoma, in whom rheumatoid arthritis was exacerbated after curing the Cushing's syndrome. This suggests that it is imperative to follow the development and/or course of autoimmune diseases after the treatment of Cushing's syndrome.

17-Hydroxycorticosteroids↗

Expression of cytokine mRNA in gastric mucosa with Helicobacter pylori infection.

BACKGROUND: We have studied the cytokine production patterns in gastric mucosal biopsy specimens with and without the Helicobacter pylori infection, using a reverse transcription-polymerase chain reaction (RT-PCR) method capable of detecting low levels of specific mRNA. METHODS: Total RNA was prepared from biopsy specimens with the acid guanidinium thiocyanate-phenol-chloroform method. cDNA was synthesized by M-MLV RTase and amplified using the oligonucleotide primers specific for interleukin-1 beta (IL-1beta), IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-beta, and IFN-gamma by PCR methods. RESULTS: Although IL-1 beta and IFN-gamma mRNA were detected in most specimens, IL-2, IL-3, IL-4, IL-5, IL-9, TNF-alpha, and IFN-beta mRNA were not detected at all. The expressions of IL-7 and IL-8 mRNA were significantly higher in H. pylori-positive gastritis than in H. pylori-negative normal controls. There was a significant correlation between the expression of IL-8 mRNA and the severity of gastritis both in the antrum and in the corpus. On the other hand, there was a significant correlation between the expression of IL-7 mRNA and the severity of gastritis only in the corpus. CONCLUSIONS: These findings suggest that some cytokines, especially IL-7 and IL-8, play some roles in H. pylori-associated gastritis.

Adult↗