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Biomedical subjects

H Mitani

Publications and source records attributed to H Mitani.

At least 55 records · Page 3Linked to original sources

Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells.

Peripheral blood monocytes are common precursor cells of dendritic cells (DCs) and macrophages. We have searched for factors with the potential to regulate the differentiation of monocytes to DCs and macrophages. When CD14+ monocytes are cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL) 4, the CD14+CD1a- population, which consists of macrophages, was found in the serum-containing cultures but not in the serum-free cultures. Addition of IL-6 receptor-neutralizing monoclonal antibody (mAb) or gp130-neutralizing mAb to the serum-containing cultures resulted in a decreased population of CD14+CD1a- cells. An increase in the CD14+CD1a- population with reduction in CD14-CD1a+ DCs was observed with the addition of IL-6 to cultures, whereas IL-11, leukaemia inhibitory factor, oncostatin M or macrophage colony-stimulating factor did not affect the differentiation of monocytes in the presence of GM-CSF plus IL-4. This effect of IL-6 was blocked by tumour necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), IL-1beta, CD40 ligand (CD40L) and transforming growth factor beta1 (TGF-beta1). Among these factors, TNF-alpha was most potent in interfering with the action of IL-6. These results suggest that IL-6 inhibits the differentiation of monocytes to DCs by promoting their differentiation toward macrophages, which is modulated by factors such as TNF-alpha, LPS, IL-1beta, CD40L and TGF-beta1.

Adult↗

A detailed linkage map of medaka, Oryzias latipes: comparative genomics and genome evolution.

We mapped 633 markers (488 AFLPs, 28 RAPDs, 34 IRSs, 75 ESTs, 4 STSs, and 4 phenotypic markers) for the Medaka Oryzias latipes, a teleost fish of the order Beloniformes. Linkage was determined using a reference typing DNA panel from 39 cell lines derived from backcross progeny. This panel provided unlimited DNA for the accumulation of mapping data. The total map length of Medaka was 1354.5 cM and 24 linkage groups were detected, corresponding to the haploid chromosome number of the organism. Thirteen to 49 markers for each linkage group were obtained. Conserved synteny between Medaka and zebrafish was observed for 2 independent linkage groups. Unlike zebrafish, however, the Medaka linkage map showed obvious restriction of recombination on the linkage group containing the male-determining region (Y) locus compared to the autosomal chromosomes.

Animals↗

Novel cerebral lesions in the Eker rat model of tuberous sclerosis: cortical tuber and anaplastic ganglioglioma.

The Eker rat is a model for human tuberous sclerosis (TSC) caused by a mutation in the Tsc2 gene. We describe here histological and immunohistochemical findings of the brain lesions in Eker rats, with emphasis on 2 novel lesions found in this study: a cortical tuber and an anaplastic ganglioglioma. The rat cortical tuber resembled those of humans, and further confirmed the value of this animal model as a tool for investigating the molecular pathology of tuberous sclerosis. On the other hand, the rat anaplastic ganglioglioma had features of a malignant neoplasm that are absent from human subependymal giant cell astrocytomas.

Animals↗

Fluvastatin suppresses atherosclerotic progression, mediated through its inhibitory effect on endothelial dysfunction, lipid peroxidation, and macrophage deposition.

Fluvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts an inhibitory effect on intimal thickening after mechanical injury in normocholesterolemic rabbit artery at a dose not enough to elicit a known action of lipid lowering. This study was designed to determine whether atherosclerotic progression triggered by hypercholesterolemia can be inhibited by fluvastatin under conditions without its hypocholesterolemic effect. Rabbits were fed a 0.5% cholesterol diet or normal diet for 17 weeks and were treated with either fluvastatin (0.3-2 mg/kg/day, p.o.) or pravastatin (2 mg/kg/day, p.o.). Atherogenic features manifested in the cholesterol-diet group, compared with the normal-diet group; they were the increase in serum lipid peroxide level, in the intraluminal lesion area of the aorta, and in macrophage content of the aortic cross-sectional lesion area; the attenuation of endothelium-dependent relaxing response to acetylcholine in the femoral artery; and the increase in serum lipid level. Treatment with fluvastatin, but not pravastatin, inhibited the manifestation of the atherogenic features without a serum lipid-lowering effect. Thus fluvastatin is likely to reduce the risk of atherosclerotic progression, to which endothelial dysfunction, lipid peroxidation, and macrophage accumulation in the vasculature may contribute, irrespective of changes in serum lipid levels.

Animals↗

Effective arterial elastance of irregular beats during atrial fibrillation in canine left ventricle.

Effective arterial elastance (E(a)) was originally defined as the end-systolic pressure (ESP)/stroke volume (SV) ratio of the left ventricle (LV). E(a) combined with LV contractility (E(max)), E(a)/E(max), proved to be powerful in analyzing the ventriculo-arterial coupling of normal and failing hearts in regular beats. However, E(a) sensitively changes with LV E(max), preload, and afterload widely changing among irregular beats. This has discouraged the use of E(a) during arrhythmia. However, we hypothesized that E(a) could serve as the effective afterload (not always arterial) elastance against ventricular ejection under arrhythmia. We tested this hypothesis by analyzing beat-to-beat changes in E(a) of irregular beats during electrically induced atrial fibrillation (AF) in normal canine in situ hearts. We newly found that during AF in each heart: 1) E(a) changed widely among irregular beats and became markedly high in weak beats with small SVs; 2) E(a) and E(a)/E(max) distributed non-normally with large skewness but 1/E(a) distributed more normally; 3) 1/E(a) correlated closely with end-diastolic volume, E(max) and preceding beat intervals; and 4) the reciprocal of mean 1/E(a) closely correlated with mean ESP/mean SV. These results support our hypothesis that E(a) can serve as the effective afterload elastance against ventricular ejection on a per-beat basis during AF. E(a)/E(max) can also quantify the ventriculo-afterload (not arterial) coupling on a per-beat basis. This study, however, warns that mean E(a) and mean E(a)/E(max) of irregular beats cannot necessarily represent their averages during AF.

Animals↗

Bcl-2 in cell-cycle regulation of hematopoietic cells by transforming growth factor-beta1.

We reported that several growth factors regulate the doubling time of hematopoietic progenitor cells by modulating the time required to pass through the G1 phase. As recent studies revealed the link between cell death and cell-cycle progression, we asked if cell death regulators such as Bcl-2 play a role in regulating the cell-cycle of hematopoietic cells by growth factors. Among growth factors, transforming growth factor-beta1 (TGF-beta1), a negative regulator of hematopoiesis, was chosen. When a large number of cells was required for analysis, we used IL-3-dependent Ba/F3 cells instead of primary hematopoietic progenitor cells because the response of Ba/F3 cells to TGF-beta1 was similar to that of primary hematopoietic progenitor cells. TGF-beta1 decelerated the cell-cycling of hematopoietic cells by inducing a delay in G1 to S phase transition, an event associated with increase in the level of Bcl-2 as well as p27, a cyclin/cyclin-dependent kinase inhibitor. In experiments using Ba/F3 cells with the potential to produce Bcl-2 in an inducible manner, Bcl-2 apparently functions upstream of p27. The effects of TGF-beta1 on Bcl-2 and p27 expression as well as cell growth were abrogated by c-kit ligand. These findings suggest that Bcl-2 plays a crucial role in regulating the cell-cycle of hematopoietic progenitor cells.

Animals↗

[Treatment strategy for cervical node metastasis from squamous cell carcinoma of the oropharynx].

The purpose of this study is to ascertain the role of neck surgery and radiation therapy for cervical lymph node metastasis in oropharyngeal cancer patients. We reviewed 217 previously untreated patients with squamous cell carcinoma of the oropharynx who were treated at the Cancer Institute Hospital in Tokyo between 1971 and 1995. The N stage distribution was; N0: 83(38.2%), N1: 42(19.4%), N2a: 23(10.6%), N2b: 27(12.4%), N2c: 33(15.2%), and N3: 9(4.2%). A predominance of cervical node metastases in level II and III was revealed and there were no skip metastases outside of level II and III. The control rate of cervical metastasis for each N stage was; N0: 96.9%, N1: 90.0%, N2a: 76.5%, N2b: 62.5%, N2c: 50.0%, and N3: 0%. Definitive irradiation provided sufficient treatment for small nodes, when the primary tumor growth was well controlled by radiation therapy. Neck dissection was necessary for more advanced neck metastases. Selective limited neck dissection (level II and III) is recommended for N0 and N1 patients, and modified or classical RND is considered to be better for most cases with N2 and N3.

Adult↗

[Ultrasonographic evaluation of metastatic cervical lymph nodes in head and neck cancers].

This study evaluates the use of ultrasonography (USG) to diagnose metastatic cervical lymph nodes. Three-hundred and one lymph nodes were removed from 58 patients with squamous cell carcinomas of the head and neck. None of the patients had received any preoperative treatments for cancer. The lymph nodes were then histopathologically examined: 139 metastatic lymph nodes and 162 non-metastatic nodes were found. USG was then used to evaluate the size, internal echo, and margin of each lymph node. Size was found to be the best criteria for distinguishing metastatic lymph nodes from non-metastatic lymph nodes in all cervical regions (78% accuracy). Superior internal jugular lymph nodes and submandibular lymph nodes larger than 7 mm and mid and inferior internal jugular lymph nodes larger than 6 mm were regarded as metastatic. Internal echoes were classified into five patterns: homogeneous hypoechoic, homogeneous hyperechoic, heterogeneous, eccentric hyperechoic, and centric hyperechoic. Homogeneous hyperechoic and heterogeneous patterns were characteristic of metastatic nodes, while eccentric hyperechoic patterns were characteristic of non-metastatic nodes. Homogeneous hypoechoic patterns were observed in both metastatic and non-metastatic nodes. Regular margins were found in 81% of the metastatic nodes. Of the 22 lymph nodes with irregular margins, however, 91% were metastatic. Evaluations using a combination of USG and clinical feature criteria were compared with evaluations using only thickness as a criterium. Although thickness is the single most important factor in diagnosing metastatic nodes, the combination of USG and clinical feature criteria improved the accuracy of diagnosis to 83%. Thus, diagnostic methods involving a combination of several criteria are more accurate than methods involving only a single criterium.

Carcinoma, Squamous Cell↗

Effects of cyclosporin A on refractory B-cell chronic lymphocytic leukemia.

This report details the effects of cyclosporin A (Cs-A) on the clinical course of B-cell chronic lymphocytic leukemia (B-CLL) with an increase in circulating T cells that express CD3, CD8, CD25, CD45RO, and T-cell receptor alpha beta chain. Cs-A was used for treatment of a female patient with refractory B-CLL and was shown to increase dramatically the number of leukemic B cells in association with a simultaneous increase in T cells in vivo. To study this effect more precisely, CD19+ (B cells) and CD3+ (T cells) cells were isolated from the patient and cultured in the presence or absence of Cs-A. When Cs-A was added to the culture, no cell stimulation was seen. However, CD3+ cells from the patient underwent cell death, relative to those from healthy donors. On the other hand, CD19+ cells from the patient were more resistant to Cs-A than those from healthy donors. Because in vitro experiments cannot explain this phenomenon of Cs-A increasing leukemic cells (not only B-CLL cells but also T cells), care should be exercised in the clinical use of Cs-A in B-CLL patients.

Antigens, CD19↗

[A surgical case of adult Bochdalek hernia assisted by thoracoscopic surgery].

A case of adult Bochdalek hernia in a naturally healthy 49-year-old woman is described. She was seen at our hospital because of cough lasting for about one month. The chest X-ray film revealed a gastrointestinal gas image in the left thoracic cavity. In addition, the CT scan and upper gastrointestinal series showed prolapse of the stomach, small intestine and a part of transverse colon. Operation was performed through a mini-thoracotomy using a thoracoscope assistedly. No hernia sac was observed and the diaphragmatic defect was 6 x 5 cm in size. After the organs was restored, the defect was closed with continuous over-and-over suture and the diaphragm was enhanced by PROLEN MESH.

Endoscopy↗

An incident involving blood sucking by a tick in a suburb in Japan.

We encountered a patient whose blood was sucked by Haemaphysalis longicornis in the suburb of a business city in Tokushima prefecture in Japan. The tick, which had been attached to the lower limb of the patient for one week, measured 10 mm in length. There were no notable objective or subjective findings after the complete extirpation of the tick. The area had not been known in recent history to be a habitat of ticks, and, thus, this case is of importance in terms of predicting future trends of tick-borne diseases in Japan.

Aged↗

[Estimation of sympathetic skin response using DC servo-amplifier].

The aims of this paper are to make clear the characteristics of sympathetic skin response(SSR) wave. The records of SSR wave were obtained using a DC servo-amplifier with the frequency response of DC to 30 Hz and drift level of 10 microV/10 min. The SSR from the palm of 10 normal control subjects(6 males and 4 females, age range 21-25 yrs) were elicited by electrical stimulation of the median nerve at upper arm. The results that the peak latency and the duration of SSR were approximately 6.32 +/- 2.5 s and 47.5 +/- 7.5 s respectively were obtained experimentally with the amplifier, though the results of AC recordings with time constant of 0.3 s were about 1.0 s and 2.0 s respectively. It can be considered that exact peak latency and duration of SSR are much longer than those data of previous studies. These findings suggest that electric stimulation should be applied at longer intervals than 60 s for rejection of the remaining potential level of SSR and the habituation.

Action Potentials↗

Long-term dentofacial stability after bimaxillary surgery in skeletal Class III open bite patients.

The purpose of this study was to evaluate long-term dentofacial stability after bimaxillary surgery in skeletal Class III open bite patients. Twenty-three Japanese adults (5 males, 18 females) were randomly selected as the experimental group from the files of Tohoku University Dental Hospital according to the following criteria: (1) skeletal Class III malocclusion with anterior open bite, (2) simultaneous Le Fort I and sagittal split ramus osteotomies, and (3) complete set of cephalograms taken at predetermined intervals until 5 years after debonding. Based on the manner of maxillary surgical repositioning, they were divided into the following 2 groups: (1) impaction group of 13 subjects (2 males, 11 females) who had maxillary superior repositioning without rotation of the palatal plane, and (2) rotation group of 10 subjects (3 males, 7 females) who had maxillary repositioning with clockwise rotation of the palatal plane. These patients were compared to a control group of 11 adults (1 male, 10 females) with skeletal Class III malocclusion without open bite who underwent bimaxillary surgery by the same techniques. Our data showed that overbite stability in the rotation group was better than that in the impaction group. This suggests that clockwise rotation of the palatal plane, which moves the anterior maxillary structures down, is an effective way to produce a reasonably stable correction of the anterior open bite. In contrast, superior repositioning of the maxilla that significantly rotates the mandible in the closing direction should be applied with caution.

Adolescent↗

Quantitative alterations of hyaluronan and dermatan sulfate in the hairless mouse dorsal skin exposed to chronic UV irradiation.

The quantitative alterations of hyaluronan and dermatan sulfate in the upper dermis (fibrous tissue) and the lower dermis (adipose tissue) of the hairless mouse skin chronically exposed to the UV irradiation as solar-simulating irradiation (lambda(max) 352 nm, UV distribution: 300-310 nm, 0.9%; 310-320 nm, 2.0%; 320-420 nm, 97.1%) were evaluated. Hyaluronan and dermatan sulfate contents in each part of dermis were determined as follows: skin sections on a glass slide prepared by histological technique were processed into the upper dermis and the lower dermis with a small surgical knife, and treated with chondroitinase ABC and ACII in the presence of bacterial collagenase. The resulting unsaturated disaccharides were determined by HPLC method. By applying this method to the UV-irradiated hairless mouse skin, it was found that the chronic UV irradiation increased dermatan sulfate in the upper dermis, whereas an increase of hyaluronan content was not statistically significant. In the lower dermis, on the contrary, both hyaluronan and dermatan sulfate contents remarkably increased as compared with the control mice. Furthermore, the histological study showed the accumulation of the collagen fibers in the lower dermis of the UV-irradiated hairless mouse skin following the disappearance of adipocytes. These findings indicate that the increases of glycosaminoglycan contents in the UV-irradiated skin are related to the accumulation of the extracellular matrix components in the lower dermis.

Animals↗

Expression, secretion, and inhibition of angiotensin-converting enzyme in cultured human bronchial epithelial cells.

The purpose of this study was to determine whether angiotensin-converting enzyme is present in cultured human bronchial epithelial cells and which types of epithelial cells possess this enzyme. It is well known that serum promotes squamous differentiation of airway epithelial cell culture in vitro. We found that whole-cell homogenates of both basal (serum-untreated) and squamous-differentiated bronchial epithelial cells degraded hippuryl-L-histidyl-L-leucine, a synthetic substrate for angiotensin-converting enzyme. Analysis of RNA expression by reverse transcription-polymerase chain reaction (RT-PCR) showed the presence of mRNA for angiotensin-converting enzyme in both types of cells. In addition, we found that squamous cells secreted the enzyme into the culture medium more than basal cells did. Angiotensin-converting enzyme inhibitors (imidaprilat, enalaprilat) inhibited the enzyme activity in bronchial epithelial cells with an IC50 of 0.9-3.6 nM. Exogenously added bradykinin was degraded to bradykinin-(1-5), an inactive fragment, in the squamous cell cultures. Our data indicate the presence of angiotensin-converting enzyme in cultured human bronchial epithelial cells and also that the enzyme is secreted by squamous differentiated cells.

Angiotensin Receptor Antagonists↗

Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice.

Germ-line mutations of the human TSC2 tumor suppressor gene cause tuberous sclerosis (TSC), a disease characterized by the development of hamartomas in various organs. In the Eker rat, however, a germ-line Tsc2 mutation gives rise to renal cell carcinomas with a complete penetrance. The molecular mechanism for this phenotypic difference between man and rat is currently unknown, and the physiological function of the TSC2/Tsc2 product (tuberin) is not fully understood. To investigate these unsolved problems, we have generated a Tsc2 mutant mouse. Tsc2 heterozygous mutant (Tsc2+/-) mice developed renal carcinomas with a complete penetrance, as seen in the Eker rat, but not the angiomyolipomas characteristic of human TSC, confirming the existence of a species-specific mechanism of tumorigenesis caused by tuberin deficiency. Unexpectedly, approximately 80% of Tsc2+/- mice also developed hepatic hemangiomas that are not observed in either TSC or the Eker rat. Tsc2 homozygous (Tsc2-/-) mutants died around embryonic day 10.5, indicating an essential function for tuberin in mouse embryonic development. Some Tsc2-/- embryos exhibited an unclosed neural tube and/or thickened myocardium. The latter is associated with increased cell density that may be a reflection of loss of a growth-suppressive function of tuberin. The mouse strain described here should provide a valuable experimental model to analyze the function of tuberin and its association with tumorigenesis.

Animals↗

Mast cell degranulation in rat mesenteric venule: effects of L-NAME, methylene blue and ketotifen.

Mast cells are present in proximity to the microvessels, and on stimulation with inhibition of NO synthesis, are a rich source of numerous inflammatory mediators. A microcirculatory study was undertaken to clarify whether nitric oxide (NO) and activation of guanylate cyclase is involved in degranulation of perivascular mast cells in the rat mesenteric venule, and whether oral administration of ketotifen suppress the degranulation. Intravital microscopy was used to monitor the rates of adherence and extravasation of leukocytes in single unbranched venules with diameters between 25 and 35 microm of rat mesentery. Leukocyte rolling velocity, red blood cell velocity, vessel diameter and blood pressure were also measured. Mast cell degranulation was quantified within 30 microm from the venule. NG-nitro-L-arginine methyl ester (L-NAME) at an intravenous dose of 30 mg kg-1 increased the number of degranulated cells, while its enantiomer, D-NAME at the same dose had no effect. Superfusion with methylene blue (MB), an inhibitor of soluble guanylate cyclase, at 50 microm elicited similar degranulation of the mast cells. The degranulation was associated with increased adhesion of leukocytes to the endothelium and the slowed rolling. Pretreatment with ketotifen at an oral dose of 1 mg kg-1 inhibited mast cell degranulation in responses to either L-NAME or MB. It is conceivable that guanylate cyclase for NO production pathway in endothelial and/or mast cells is involved in the mast cell degranulation process, and the process or subsequent action of NO may be preserved by ketotifen, eliciting down-modulation of mast cell activation.

Animals↗