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Biomedical subjects

K Sugisaki

Publications and source records attributed to K Sugisaki.

At least 19 recordsLinked to original sources
PubMed1998

Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions.

To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL-1beta, TNF-alpha, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN-gamma, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive. In general, MCP-1 and TNF-alpha proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response.

Animals↗
PubMed1998

Clinicopathologic characteristics of the lungs of patients with human T cell lymphotropic virus type 1-associated myelopathy.

Lung autopsy specimens were evaluated histologically in the six patients with human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). The results revealed two histologic changes. First, lymphoid infiltrates were distributed widely in peribronchiolar and perivascular regions, subpleural regions, and the alveolus. Lymphoid infiltrates were also observed in bronchial mucosal glands in relatively large bronchi, in which the acinar epithelium was sometimes degenerated. Second, chronic inflammatory changes, such as smooth muscle hypertrophy, fibrosis, or squamous cell metaplasia, were increased significantly in the membranous bronchioles of HAM patients compared with specimens from lung cancer control patients. Such histologic changes were subclinical in most cases, but one case had an abnormal chest shadow, and two cases had recurrent pneumonia. In HAM patients, high levels of HTLV-1-specific cytotoxic T lymphocytes are believed to attack the HTLV-1-bearing cells in the lung, resulting in inflammatory reactions.

Aged↗
PubMed1996

Rabbit vascular endothelial adhesion molecules: ELAM-1 is most elevated in acute inflammation, whereas VCAM-1 and ICAM-1 predominate in chronic inflammation.

Activation of the microvasculature is a major component of the inflammatory response. During inflammation the vascular endothelium not only becomes more permeable to plasma proteins but also develops adhesion molecules that initiate the local immigration of leukocytes. We describe herein the in vivo changes in the three major vascular adhesion molecules during the development and healing of two types of rabbit dermal inflammatory lesions: (1) acute lesions produced in rabbits by the topical application of 1% sulfur mustard (SM, the military irritant/toxicant); and (2) chronic (immune-mediated) lesions produced in rabbits by intradermal injections of Mycobacterium bovis (BCG), the vaccine strain of tubercle bacillus. In each case, frozen tissue sections were made from lesions of various ages and stained immunohistochemically for von Willebrand (vW) factor to measure the total functional microvasculature. The sections were also stained immunohistochemically for the vascular endothelial adhesion molecules ICAM-1, ELAM-1 (E-selectin), and VCAM-1, and for the leukocyte ligands for ICAM-1: LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). Infiltrating monocytes and lymphocytes expressed the LFA-1 ligand and infiltrating PMN expressed the MAC-1 ligand. The area of stained microvasculature per square millimeter of tissue section was determined with the use of a computerized image analyzer. Edema and cell infiltration spread apart the microvessels, changing the number of microvessels per square millimeter of tissue section. Three methods of assessing such changes are presented. In SM lesions, endothelial ICAM levels were decreased from normal by about 50% at 1 and 2 days (when the lesions reached their peak size) and returned to normal at 3 and 6 days (during the healing process). ELAM rose in peak SM lesions and remained high during healing. VCAM levels, however, were only elevated in the 6-day (almost healed) lesions. In BCG lesions the levels of endothelial ICAM and VCAM (and to a lesser extent ELAM) were increased at 9 days and remained so as the size of the lesions peaked at 23 days. During the healing phase at 37 days, the elevated ICAM and VCAM levels decreased but the slightly increased ELAM levels persisted. These findings indicate that ELAM plays a major role in acute inflammation and that VCAM and ICAM play major roles in chronic inflammation. VCAM is known to be monocyte and lymphocyte selective.

Acute Disease↗
PubMed1996

The cytokines NAP-1 (IL-8), MCP-1, IL-1 beta, and GRO in rabbit inflammatory skin lesions produced by the chemical irritant sulfur mustard.

Developing and healing dermal inflammatory lesions were produced in rabbits by the topical application of dilute sulfur mustard (SM), the military vesicant. In tissue sections of such lesions, cells containing the mRNA of important cytokines were identified with in situ hybridization techniques. These cytokines were neutrophil attractant/activation protein-1 (NAP-1 (also called IL-8), monocyte chemoattractant (activating) protein 1 (MCP-1), interleukin 1 (beta) (IL-1 (beta)), and GRO (a growth factor and chemokine). Mononuclear cells (mainly macrophages and activated fibroblasts) contained the mRNA of all four of these cytokines. A higher percentage of cytokine-producing mononuclear cells (macrophages and activated fibroblasts) was present in lesions at 2 days (their peak size) than at 6 days, when they were almost healed. Granulocytes emigrated from the bloodstream, passed through the lesions, and were the major constituent of the protective crust. This sequence correlated with the distribution of cells able to produce NAP-1: At 2 days and 6 days, the mononuclears that contained messenger RNA for this granulocyte chemoattractant were found mainly in the upper part of the dermis. At 2 days and 6 days, cells containing the mRNA of IL-1, a primary cytokine, were also found predominantly in the upper dermis, i.e., nearest the site of injury. In contrast, mononuclears containing the mRNA of MCP-1 (a monocyte chemoattractant), and the mRNA of GRO (a granulocyte chemoattractant) were more equally distributed throughout the dermis. SM stimulated hair follicle epithelial cells to up-regulate GRO mRNA and, to a lesser degree, NAP-1 mRNA. Apparently, the irritation produced by SM directly or indirectly induces such epithelial cells to manufacture these growth factors. In the rabbit, hair follicles are known to be the main source of new epithelial cells after the covering epithelium has been destroyed. Therefore, GRO is probably a major autocrine-paracrine stimulus for such repair. A brief review of the role of cytokines in dermal inflammation is presented.

Animals↗
PubMed1996

Soft-X-ray damage to biological samples.

X-ray damage to biological samples was investigated in the wavelength region of 2.7-5 nm, which overlaps the so-called 'water-window', the wavelength range of 2.4-4.3 nm usually used in X-ray microscopy. Yeast cells and myofibrils were chosen as representatives of whole cell samples and motile protein systems, respectively. The samples were exposed to X-rays using an apparatus composed mainly of a laser-plasma X-ray source, a Wolter mirror condenser, and a sample cell. The yeast cells lost their dye exclusion ability when the X-ray flux was higher than 1 x 10(6) photons micron-2, while the myofibrils lost contractility when the X-ray flux was higher than 4 x 10(5) photons micron-2. These X-ray fluxes are lower than the flux required for the X-ray microscope observation of biological samples at a resolution higher than that of light microscopes.

Animals↗
PubMed1996

Cavitary tuberculosis produced in rabbits by aerosolized virulent tubercle bacilli.

Liquefaction of solid caseous tuberculous lesions and the subsequent cavity formation are probably the most dangerous processes in the pathogenesis of human pulmonary tuberculosis. In liquefied caseum, the tubercle bacilli grow extracellularly for the first time since the onset of the disease and can reach such large numbers that mutants with antimicrobial resistance may develop. From a cavity, the bacilli enter the bronchial tree and spread to other parts of the lung and also to other people. Of the commonly used laboratory animals, the rabbit is the only one in which cavitary tuberculosis can be readily produced. This report is the first to describe and analyze the complete course of cavitary tuberculosis, produced by aerosolized virulent bovine-type tubercle bacilli in commercially available New Zealand white rabbits. After the inhalation of 220 to 880 bacillary units, all of the rabbits were overtly well until they were sacrificed at 33 weeks. After the inhalation of 3,900 to 5,800 bacillary units, half of the rabbits died of progressive tuberculosis between 5 and 9 weeks and the other half lived until they were sacrificed at 18 weeks. Pulmonary cavities developed in both low- and high-dose groups, some beginning as early as 6 weeks. Bacilli from primary cavities sometimes caused nearby secondary cavities, but more frequently, they ascended the bronchial escalator, were swallowed, and caused secondary tubercles in the lymphoid tissue of the appendix and ileocecal junction. Histologically, and by culture, the number of bacilli found in the liquefied caseum varied from many to comparatively few. Strong tuberculin reactions at 4 weeks after infection were associated with fewer primary lesions, while strong tuberculin reactions at 33 weeks were associated with more cavitary lesions. In the tuberculous granulation tissue surrounding caseous and liquefied pulmonary foci and cavities, we found many mature epithelioid macrophages that contained high levels of the proteinase cathepsin D. Therefore, cathepsin D probably plays a major role in the liquefaction of solid caseous material and in the subsequent cavity formation.

Aerosols↗
PubMed1996

Sarcoidosis presenting as bilateral hydronephrosis.

We report an unusual case of sarcoidosis associated with bilateral hydronephrosis. The patient was a 53-year-old Japanese woman who presented with dysuria and urinary incontinence. Computed tomography of the abdomen showed bilateral hydronephrosis caused by a retroperitoneal mass, surrounded by enlarged retroperitoneal lymph nodes. Histological examination of the mass demonstrated noncaseating epithelioid cell granulomas involving the retroperitoneal lymph nodes. Corticosteroid therapy led to complete resolution of the retroperitoneal mass and hydronephrosis. This case emphasizes that sarcoidosis should be included in the differential diagnosis of a retroperitoneal mass.

Diagnosis, Differential↗
PubMed1995

A case of acute eosinophilic pneumonia caused by inhalation of Trichosporon terrestre.

We present the diagnostically challenging case of an 18-yr-old Japanese woman who presented with fever, nonproductive cough, and acute respiratory distress. Her chest radiograph showed diffuse interstitial infiltrates and bilateral pleural effusions. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and transbronchial lung biopsy. She was treated with minocycline, and was discharged in 2 wk. However, within 3 h of returning home, she experienced a recurrence. She showed positive immediate, Arthus, and delayed-type skin reactions and positive lymphocyte stimulation test to an antigen derived from Trichosporon terrestre, which was isolated from dust in her home. In addition, a bronchoprovocation test with the same antigen caused a nonproductive cough with fever, hypoxemia, and peripheral eosinophilia. We concluded that T. terrestre was the causal agent of the acute eosinophilic pneumonia.

Acute Disease↗
PubMed1995

Characterization of distribution of T lymphocyte subsets and activated T lymphocytes infiltrating into sarcoid lesions.

We studied the relationship between various T lymphocyte functions and granuloma formation in 5 lung tissue and 4 lymph node tissue samples from patients with sarcoidosis by immunohistological methods. In the lesion of sarcoidosis, T cells were positive for alpha beta TCR, but gamma delta TCR-positive T cells were rarely observed. The results of analysis of functional subsets showed that T cells in the internal area of granuloma were predominantly helper/inducer subset (CD4+CD45RA-). On the other hand, cytotoxic T cells (CD8+CD45RA-CD11b-) were present in abundance in the outer boundaries of granuloma. In addition, suppressor-inducer T cells (CD4+CD45RA+) were present in the surrounding areas. However, T cells of various subsets were present sporadically outside the granulomas. We also studied the distribution of T cells expressing activation-related antigens. The results showed that T lymphocytes in the internal area of granulomas more frequently had these antigens than did T lymphocytes in the external area. These findings suggested that T cells infiltrating into the sarcoidosis lesion demonstrated a layer-like distribution based on functional subsets. These findings also confirm that activated T cells were more abundantly distributed in the internal area of sarcoid granuloma than in the external area.

Antibodies, Monoclonal↗
PubMed1994

A case of malignant hemangiopericytoma: an immunohistochemical and ultrastructural study.

We report one case of malignant hemangiopericytoma which started with a tumor in the lower jaw and multiple nodules in the lung. The tumor quickly metastasized to the brain and chemotherapy was not at all effective. Hemangiopericytoma is generally diagnosed by its histological characteristics. Recently, however, electron microscopy and immunohistochemical methods have been used for its diagnosis. In our case, electron micrograph showed the growth of hemangiopericytoma cells around immature endothelial cells. In addition, the tumor cells reacted positively only with anti-vimentin antibodies, and the endothelial cells in the tumor tissue were positive for antifactor VIII antibodies. The observed features were consistent with the characteristics of hemangiopericytoma.

Antibodies, Monoclonal↗
PubMed1994

[A case of pulmonary sarcoidosis with circulatory insufficiency of segmental and subsegmental branches of pulmonary arteries].

A 50-year-old woman was admitted to our hospital on April 4, 1992, because of progressive worsening of dry cough and exertional dyspnea. Moderate hypoxemia and obstructive ventilatory impairment were present. Her chest roentgenogram and CT films showed thickened bronchovascular bundles in the absence of significant parenchymal fibrosis. Transbronchial lung biopsy revealed the formation of noncaseous epithelioid cell granulomas. Pulmonary perfusion scintigraphy showed multiple perfusion defects predominantly in the upper lung fields. Pulmonary ventilation scintigraphy showed a normal pattern. After administration of prednisolone for 3 months, her chest roentgenogram and CT films demonstrated marked decrease of infiltrates, but there was no improvement of hypoxemia and perfusion defects on pulmonary perfusion scintigraphy. Pulmonary angiography revealed multiple stenoses and occlusions of segmental and subsegmental branches of pulmonary arteries. Long-term steroid treatment will be necessary for this rare form of pulmonary sarcoidosis to prevent the development of pulmonary hypertension.

Female↗
PubMed1993

[A case of chronic asthma with emphysematous change in a middle-aged woman].

A 32-year-old woman with chronic asthma is presented. She had suffered from dyspnea and breathlessness on exertion for 7 years. Her chest X-ray film on admission showed marked emphysematous changes and chest CT scan revealed low attenuation areas, however she was a non-smoker and had no previous childhood respiratory problems. She was administered prednisolone to treat the wheezing attack and hypoxemia. After treatment, her lung function and hypoxemia improved, but low attenuation areas of the chest CT scan remained unchanged. These facts suggest the possibility that bronchial asthma which is controlled poorly for a long time, may cause emphysematous change of the lung.

Adult↗
PubMed1990

[Immunohistochemical analysis of T-lymphocyte subsets on the sarcoid lymph nodes using the computerized analytic system for the light microscopic figures: the relation to the histological maturation stages of the lymph nodes].

Lymph nodes obtained from 19 patients with sarcoidosis were classified into four groups according to their histological maturation stages, which were the early stage, the former mature stage, the late mature stage and the healing stage. Immunohistochemical analysis of CD4 positive cells and CD8 positive cells were performed using monoclonal antibodies to these lymph nodes. Then the number of the positive cells per square millimeters of a granuloma was estimated using a computerized analytic system for light microscopic figures. The number of CD4-positive cells per square millimeter of a granuloma was almost constant from the early stage to the mature stage, but inclined to decrease in the healing stage; on the other hand, the number of CD8-positive cells per square millimeter of granuloma decreased extremely in the mature stage, compared with the early stage and the healing stage. Moreover the CD4/CD8-positive cell ratio in granulomas, calculated from these data, was elevated in the mature stage, compared with the early and the healing stages. From the above results, the CD4/CD8-positive cell ratio in a granuloma was demonstrated to be a valuable index for evaluating the histological activity of the granuloma of sarcoid lymph nodes. Furthermore, the decrease of CD8-positive cells in mature stage granuloma was considered to be related to the maturation of the epithelioid cell granulomas in sarcoidosis.

Computers↗
PubMed1989

Effects of gene dosage on the expression of human growth hormone cDNA in Escherichia coli.

Gene dosage effects on the foreign protein production in Escherichia coli have been analyzed with the expression vectors containing one, two and four tandemly arranged human growth hormone cDNAs under various culture conditions. In a limited synthetic culture medium, a proportional relationship was observed between the number of the integrated cDNA and the amount of human growth hormone produced. With a culture medium rich in the nutrients, however, no such relationship was observed. These results suggest that, under the limited culture conditions, high-level expression of a foreign gene can be achieved by tandemly joined multiple copies of cDNA.

Blotting, Western↗
PubMed1989

[Non-aromatizing androgen 19-hydroxylase in human fetal organs].

19-hydroxyandrostenedione (19-OH A), known for many years as an obligatory intermediate of estrogen biosynthesis, has recently been found to be an amplifier of aldosterone action and in itself a hypertensinogenic steroid (J. Steroid Biochem., 16; 329, 1982). To search the presence of a non-aromatizing andorgen 19-hydroxylase in fetal organs, metabolism of labeled androstenedione(A) in fetal adrenal, liver, lung, brain and kidney was studied. 19-hydroxylase activity was calculated by the amounts of 19-OH A formed from A. The tissue homogenate was incubated with [4-14C]A and NADPH for different periods of time under air. The product, [4-14C] 19-OH A with added carrier standard [6,7-3H] 19-OH A was separated and purified by TLC, acetylation and TLC to constant 3H/14C ratio. The identity of the product was established by C.C.D. and by GC-MS analysis of purified product 19-AcOA in a larger scale adrenal incubation of non-labeled A. 19-hydroxylase activity was 0.9 pmol/min/mg protein for adrenal, but there was a negligible quantity of 19-OH A in lung, brain and kidney. Estrogen production was also assayed by 3H-water method using [1 beta-3H, 4-14C] A (3H/14C = 69.9). No detectable amount of estrogen was found in incubation of any homogenate except for liver. These results indicate that the non-aromatizing 19-hydroxylase activity in fetal adrenal gland is much higher than that in other organs. This is the first report to demonstrate the presence of 19-hydroxylase in human fetal adrenal tissue. It is suggested that 19-OH A secreted from fetal adrenal may also be associated with serum concentration of fetal circulation.

Adrenal Glands↗
PubMed1989

Primary structure of chicken pituitary prolactin deduced from the cDNA sequence. Conserved and specific amino acid residues in the domains of the prolactins.

The perform of chicken prolactin (PRL) deduced from the cDNA sequence contains a signal peptide of 30 amino acid residues followed by a mature PRL of 199 residues. Chicken PRL shows 77, 68, 67, 58, and 31% identity of amino acid sequence with whale, human, ovine, rat, and salmon PRLs, respectively. Elucidation of the primary structure of avian PRL enabled extended analysis of the specific and conserved amino acid residues and domains of the PRL molecules. The mammalian, teleostean, and avian PRLs share 32 common residues, and these conserved residues are observed to cluster in four distinct domains (PD1 to PD4), corresponding to four of five conserved domains of the growth hormones. Of the 32 residues, 8 residues in the PD2 and PD4 domains, including 4 cysteines, are conserved by other members of the growth hormone family, which indicates that these 8 residues may be essential for common structural features of the gene family. On the other hand, 13 other residues distributed among all four domains are conserved almost exclusively in the PRLs, suggesting that these residues are indispensable for specific binding of the PRLs to their receptors.

Amino Acid Sequence↗