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Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 271 records · Page 15Linked to original sources

Expression of mucin carbohydrates and core proteins in carcinomas of the ampulla of Vater: their relationship to prognosis.

We examined the expression of carbohydrate antigens which are associated with the earliest steps in mucin glycosylation (Tn and sialosyl-Tn) and the expression of the mucin core protein antigens associated with MUC1 gene product (DF3 antigen) as well as MUC2 gene product (intestinal-MRP antigen) in tissues from 38 patients with carcinoma of the ampulla of Vater, in order to determine whether these mucin antigens are available as tumor markers or not, and to evaluate whether their expression is correlated with the biological behavior of the carcinomas or not. DF3 antigen showed a relatively high expression rate (61%) in the carcinoma tissues, but was rarely expressed in the non-neoplastic epithelium around the carcinomas in the region of the ampulla of Vater. Tn and sialosyl-Tn antigens showed high expression rates in the carcinoma tissues (86% and 84% each), whereas they showed rare or no expression in the non-neoplastic epithelium around the carcinomas, except for highly restricted expression in the duodenal villous epithelium. The patients with positive DF3 expression in the carcinoma showed significantly poorer survival than those with negative DF3 expression (P < 0.05), whereas the patients with positive intestinal-MRP expression in the carcinoma showed significantly more favorable survival than those with negative intestinal-MRP expression (P < 0.05). The expression rate of DF3 antigen was significantly higher in the cases with deep invasion into the pancreas (89%) than in those with no or minimal invasion (52%) (P < 0.05). In contrast, the expression rate of intestinal-MRP antigen was significantly higher in the cases with no or minimal invasion into the pancreas (38%) than in those with deep invasion (0%) (P<0.05). In conclusion, the expression of DF3, To and sialosyl-Tn antigens is an effective histopathological indicator for carcinomas in the area of the ampulla of Vater, and the expression of DF3 and intestinal-MRP antigens is a useful indicator of the prognosis of the patients.

Adult↗

Mammary hamartoma: immunohistochemical study of two adenolipomas and one variant with cartilage, smooth muscle and myoepithelial proliferation.

Three cases of mammary hamartoma were investigated immunohistochemically and are described. Case 1 was a 42 year old woman with an elastic hard tumor, 1.5 cm in diameter, in her left breast. Case 2 was a 49 year old woman with a semisoft tumor, 5 x 2 cm, in her right breast. Case 3 was a 47 year old woman with a hard tumor, 5 cm in diameter, in her left breast. In each case, mammography and ultrasonography revealed a benign-looking, well-circumscribed mass without calcification. Histologically, the tumors were composed of adipose tissue, mammary glands, and fibrous and/or fibromuscular tissue. The tumor in case 3 also contained small islands of hyaline cartilage. Immunohistochemical analysis was performed, and epithelial and mesenchymal components were discretely and differentially immunostained except that the smooth muscle component seemed to be derived from myoepithelial cells. Cartilage formation might be the result of metaplasia, and 'metaplastic variant of the mammary hamartoma' or 'choristoma' may be an appropriate term for cartilage-containing mammary hamartoma. Using proliferating cell nuclear antigen (PCNA)-immunostaining, we observed that each component of the tumors had an individual growth rate. This finding may reflect one aspect of the biological characteristics of hamartoma.

Adenoma↗

Immunoexpression of the alpha subunit of a guanine nucleotide-binding protein (Go) in pulmonary neuroendocrine cells and neoplasms.

The alpha subunit of a GTP-binding protein, Go, was investigated in pulmonary neuroendocrine neoplasms and fetal tissues of the lung by an immunohistochemical method. Positive immunostaining for the alpha subunit of Go (Go alpha) was found predominantly on the cell membrane and found occasionally in the cytoplasm. Typical carcinoids were all positively stained (9/9), and small cell carcinoma showed weaker and less frequent staining (5 positive cases in 10). Atypical carcinoids were variously stained (3/4). The tendency for obvious neuroendocrine differentiation to be immunohistochemically determined in typical carcinoids and not in small cell carcinoma is also true of staining for neuron specific enolase (NSE), chromogranin A (CG-A) and synaptophysin. In the lung, Go alpha-immunostaining was positive not only in nerve tissues but also in the airway epithelium. In the fetal lung, serial sections immunostained for NSE, CG-A and Go alpha confirmed that Go alpha-immunoreactive cells belong to the neuroendocrine cell population. The biological significance of Go alpha is unclear in normal and neoplastic lung tissues, but Go alpha is a useful marker of neuroendocrine cells and neoplasma of the lung.

Adult↗

Ammonia response to exercise in patients with congestive heart failure.

OBJECTIVE: To assess energy depletion in skeletal muscle in patients with congestive heart failure by measuring blood purine metabolites during exercise and, at the same time, determine the implications of the ammonia response to exercise in these patients. SETTING: Tottori University Hospital, Yonago, Japan. PATIENTS: 49 heart failure patients (New York Heart Association (NYHA) grades I-III) and 16 normal subjects. MAIN OUTCOME MEASURES: Blood lactate, ammonia, and hypoxanthine levels were measured during exercise with expired gas analysis. RESULTS: In normal exercising subjects as well as in each heart failure subgroup, the ammonia threshold was significantly higher than both the lactate threshold [control: 21.8 (SD 5.3) v 17.4 (3.3) ml/kg/min; NYHA class I: 18.9 (3.8) v 15.5 (2.6); class II: 14.8 (2.5) v 12.7 (2.4); class III: 13.5 (2.6) v 11.8 (2.5)] and the ventilatory threshold (P < 0.01). The difference between the ammonia and lactate thresholds was noted in all normal subjects and in all heart failure patients. The ammonia threshold, however, was significantly lower in heart failure patients than in normal subjects and it decreased with increasing NYHA class (P < 0.01). Maximum ammonia levels were lower in the heart failure group and decreased further with higher NYHA classifications [control: 198 (52) mg/dl; NYHA class I: 170 (74); class II: 134 (58); class III: 72 (15); P < 0.01]. There were significant correlations between maximum ammonia values and maximum lactate, oxygen consumption, and hypoxanthine levels (r = 0.74, 0.48, and 0.87, respectively; P < 0.001). CONCLUSIONS: The ammonia threshold may reflect the onset of ATP depletion in exercising skeletal muscles, as opposed to the onset of anaerobic respiration. It seems therefore that energy depletion in skeletal muscles during exercise occurs after attaining the anaerobic threshold. Both aerobic and anaerobic capacities of skeletal muscle are reduced in patients with congestive heart failure.

Adenosine Triphosphate↗

Immunohistochemical study of CA 19-9 and SPan-1 in cases of hydronephrosis.

Although the serum level of carbohydrate antigen (CA) 19-9 is reportedly increased in patients with hydronephrosis, virtually no immunohistochemical studies of this condition have been performed. Therefore, we examined immunohistochemically 11 hydronephrotic kidneys and 3 normal control kidneys using antibodies against CA 19-9 and SPan-1, another sialylated carbohydrate antigen. Immunoreactivity for CA 19-9 was seen in the transitional and tubular epithelia in most of the hydronephrotic kidneys (9 of the 11 cases), and also detected in 2 of the 3 control specimens, although there the distribution appeared to be limited. SPan-1 immunoreactivity showed the same trend. CA 19-9 and SPan-1 immunoreactivity in hydronephrosis appeared to be more widely distributed than in controls, although its mechanism remains unclear.

Adult↗

Glomerular capillary regeneration and endothelial cell apoptosis in both reversible and progressive models of glomerulonephritis.

In summary, angiogenetic capillary regeneration with endothelial proliferation occurred among mesangiolytic lesions in Thy-1 GN, and the damaged glomerulus recovered its normal structure with the reconstruction of the capillary network. In anti-GBM GN on WKY rats, the damaged glomerulus showed rare capillary regeneration and progressed to global sclerosis. In Thy-1 GN, endothelial cell apoptosis was found in the regenerated capillaries with endothelial cell hypercellularity. On the other hand, in anti-GBM GN on WKY rats, the number of endothelial cell apoptosis increased during the evolution of glomerular sclerosis. We have concluded that glomerular capillary regeneration plays an essential role in the recovery of damaged glomeruli. Moreover, apoptosis is indispensable in regulating the number of intrinsic endothelial cells. We also found that endothelial apoptosis is important in progression of glomerular sclerosis.

Animals↗

The intercalated disc of monkey myocardial cells and Purkinje fibers as revealed by scanning electron microscopy.

The intercalated discs of working myocardium and Purkinje fibers of the monkey heart were examined by scanning and transmission electron microscopy. The NaOH/ultrasonication technique resulted in the digestion of connective tissue and a separation of the intercellular junctions of intercalated discs, such that these could be visualized three-dimensionally. The intercalated discs of ventricular myocytes, atrial myocytes and Purkinje fibers vary considerably in number and configuration, as do the intercalated discs of the three different layers of the ventricular myocardium. Myocytes in the subepicardial, middle and subendocardial layers of the ventricle have 1-3, 4-5 and 5-6 intercalated discs at the end of these cells, respectively. Those in the endocardial layer are characterized by the presence of small laterally-placed intercalated discs. Atrial myocytes and Purkinje fibers usually only have 1-2 intercalated discs. Individual intercalated discs in ventricular myocytes have complicated stairs with 10-30 steps and corresponding risers, while those of atrial myocytes and Purkinje fibers have simple stairs with 1-3 steps and risers. Steps equivalent to the plicate segments are characterized by densely-packed microplicae and finger-like microprojections which greatly increase surface area in ventricular myocytes. Microprojections in atrial myocytes and Purkinje fibers are sparse by comparison. Risers equivalent to the interplicate segments containing large gap junctional areas are most numerous in left ventricular myocytes, followed by right ventricular myocytes, Purkinje fibers and atrial myocytes in decreasing order. The geometric arrangement of the various types of myocytes may be related with impulse propagation. Large intercalated discs of cell trunks and series branches may participate in longitudinal propagation, while small laterally-placed ones may be the site of transverse propagation.

Animals↗

Effect of mizoribine on pulmonary lesions in MRL/lpr/lpr mice.

The present study was made to investigate the effect of mizoribine (MZR), an imidazole nucleoside immunosuppressant, on pulmonary lesions and immunological mode of action of MRL/lpr/lpr mice. Four-week-old female MRL/lpr/lpr mice were injected subcutaneously with 20 mg/kg body weight of MZR every other day. For control, mice were given phosphate-buffered saline (PBS) every other day. MZR caused the delay in the histological development of peribronchial and perivascular lymphocytic infiltrations in the lungs of MRL/lpr/lpr (MRL/lpr) mice. And then, MZR suppressed the number of immunoglobulin (Ig) (IgG and IgM) secreting B cells and anti-DNA-secreting B cells in the spleen of MRL/lpr/lpr mice. The above data indicate that MZR could be useful for the treatment of pulmonary lesions associated with autoimmune disorders such as systemic lupus erythematosus (SLE).

Animals↗

[A clinical study of radial prostatectomy].

BACKGROUND: The objective of this study is to evaluate the efficacy of radical prostatectomy for patients with organ-confined prostate cancer. METHODS: From 1990 to 1994, a total of 50 patients with prostate cancer underwent radical retropubic prostatectomy. RESULTS: Eleven patients were in state A2, 34 in stage B and 5 in stage C according to clinical stage. Extended disease was observed pathologically in 45%, and 59% of patients in clinical stages A2 and B, respectively. Preoperative serum PSA levels were closely correlated with pathological extension of the disease. The disease-free rates for organ-confined disease, extended disease without lymph node metastasis and stage D1 disease were 75% (3 years), 82% (2 years) and 80% (3 years), respectively. Four patients had rectal injuries, and three of these underwent temporary colostomy diversion. Two patients had bladder neck contracture and received internal urethrotomy. Urinary incontinence improved in 60% of patients during the first 6 post-operative and in 90% of patients within 12 post-operative months. Urinary incontinence tended to improve earlier in patients with nerve-sparing than those without it. The erectile capacity in nerve sparing patients recovered good. CONCLUSION: Our results indicate that radical prostatectomy is a safe and temporarily satisfactory treatment for the patient with organ-confined prostate cancer.

Adenocarcinoma↗

Apoptosis in progressive crescentic glomerulonephritis.

Recent studies in the experimental proliferative glomerulonephritis (GN) indicate that apoptosis is the major mechanism that mediates the resolution of glomerular hypercellularity during the repair process of experimental GN. The role of apoptosis during progressive GN, however, has not yet been well understood. We have, therefore, examined the role of apoptosis during the progression of experimental crescentic GN to end-stage renal failure. A progressive model of antiglomerular basement membrane GN was induced in Wistar-Kyoto rats with a single injection of anti-rat glomerular basement membrane antibody. Renal function and histologic studies were performed chronologically from Day 0 to Week 8 after disease induction. The incidence of apoptosis in glomeruli as well as glomerular crescents was examined during the progression of crescentic GN to end-stage kidney disease. Many leukocytes infiltrated glomeruli from the early phase of GN, and severe necrotizing and mesangiolytic glomerular damage was observed from Day 5 to Week 3. After glomerular damage, mesangial hypercellularity with mesangial cell proliferation and extracellular matrix accumulation began with crescent formation. Thereafter, glomerular inflammation continued with marked extracellular matrix accumulation until Week 4, and the renal function deteriorated. The proliferative glomerular lesions subsequently progressed to sclerotic lesions and eventually to chronic renal failure in Week 8. Although the number of proliferating cells and infiltrating leukocytes slowly decreased, glomerular inflammation resolved with scar formation as mesangial sclerosis. Significant apoptosis was present from Day 7 (mean +/- SEM, 0.53 +/- 0.12 cells/glomerular cross-section) and gradually increased in number with the proliferating lesions as glomerular inflammation continued. Moreover, apoptosis increased during the resolution of the glomerular inflammation, and many apoptotic cells were present in the sclerotic lesions in Week 8 (1.97 +/- 0.27 cells/glomerular cross-section). As glomerular inflammation subsided, cellular crescents progressed to fibrous crescents with a reduction of cellularity by Week 8, and apoptosis increased significantly within these lesions. These findings indicate that apoptosis plays an essential role in the resolution of intra- and extraglomerular inflammation and in the elimination of glomerular cells within the scarring regions for progressive crescentic GN. The regulation of the apoptotic phenomenon during crescentic GN may be important in the progression of glomerular inflammation and the development of pathologic glomerular sclerosis.

Animals↗

Angiotensin I-converting enzyme insertion/deletion polymorphism: potential significance in nephrology.

Angiotensin I-converting enzyme (ACE) plays a pivotal role in cardiovascular homeostasis and by activating angiotensin I into angiotensin II and inactivating bradykinin. These two peptides play antagonistic roles on the cardiovascular system by regulating vascular tone and vascular smooth muscle cell proliferation. Identification of the ACE gene as a genetic marker for various forms of cardiovascular disease is a recent result of the progress made in molecular biology and genetics. The insertion/deletion (ID) polymorphism of the ACE gene defined by the presence or absence of the 287 base pair Alu sequence situated in intron 16 has been investigated as a possible genetic marker for a variety of cardiovascular disease including myocardial infarction, essential hypertension, cardiomyopathy, and diabetic vascular complications. This paper reviews prior reports and briefly describes our recent study on the association of the ACE I/D polymorphism and antiproteinuric effect of ACE inhibitors in patients with proteinuria.

Cardiovascular Diseases↗

[Acute appendicitis caused by mucorales in a patient with severe aplastic anemia: report of an autopsy case].

A male patient with severe aplastic anemia was admitted for bone marrow transplantation. While waiting for a donor, high doses of methylprednisolone, anabolic steroid and granulocyte colony stimulating factor were given without response. Deferoxamine was administered for prophylaxis of hemochromatosis because of high level of ferritin. Acute right lower abdominal pain and pyrexia developed. A diagnosis of acute appendicitis was made and appendectomy was performed. The histopathological examination of the resected appendix revealed necrotizing hemorrhagic appendicitis with numerous hyphae of Mucorales. Though anti-fungal agent (amphotericin B) administration was continued, he subsequently developed ileo-cecal abscess and eventually died due to myoglobinuric nephropathy caused by extensive necrosis of the iliopsoas muscle. Autopsy revealed dissemination of hyphae of Mucorales in lungs, kidneys, large vessels and muscle of the bilateral lower limbs. Systemic vascular invasion and embolization of fungal hyphae were also observed. However, culture of exudate sampled from ileocecum yielded no Mucorales. It was emphasized that antemortem diagnosis and effective anti-fungal treatments are essential for the management of intestinal mucormycosis. The relation ship between mucormyocosis and deferoxamine was also discussed.

Acute Disease↗

[Successful treatment of interstitial pneumonitis with cyclosporin A in a patient with rheumatoid arthritis accompanied by acute interstitial nephritis].

A 49-year-old male was admitted to our hospital because of acute renal failure. He had been treated by a local doctor for rheumatoid arthritis (RA) during the past eight years. We treated him with steroid pulse therapy, because of suspected acute interstitial nephritis. We confirmed this diagnosis by renal biopsy and steroid pulse therapy markedly improved his renal dysfunction. Immunohistochemical studies revealed that interstitial infiltrating leukocytes consisted mainly of polymorphonuclear leukocytes (PMNs), macrophages and B lymphocytes, while T lymphocytes were less predominant. ELAM-1 and GMP-140 were expressed in the peritubular capillaries. These findings suggest that endothelial activation of the peritubular capillaries may cause interstitial infiltration of PMNs and macrophages, resulting in the development of acute interstitial nephritis. Four months later, he developed severe interstitial pneumonitis, and his symptoms were not improved by high-dose steroid pulse and cyclophosphamide pulse treatment. Eight weeks after the second admission, cyclosporin A (Cy A) was started. Three weeks after starting Cy A, he was free from symptoms and his chest radiograph was normalized. Renal function was also improved by Cy A. These observations suggest that endothelial activation by adhesion molecules may play an important role in RA-related autoimmune diseases and that Cy A might be efficacious in such cases.

Acute Disease↗

Role of neutrophil elastase in the development of renal necrotizing vasculitis.

To assess the pathogenetic mechanisms of renal vasculitis, we performed immunohistochemical studies using renal biopsy specimens which were obtained from a patient with microscopic polyangiitis during both the acute and the convalescent phase. Intense infiltration and aggregation of neutrophil elastase positive (NE+) cells were observed especially in the periglomerular and perivascular areas in the first biopsy in which vascular necrosis, rupture of Bowman's capsule, and necrotizing glomerulonephritis were present. In addition to intracellular NE expression, NE was also expressed extracellularly in both segmental glomerular tufts and the interstitium. Intensity of NE immunoreactivity in the glomeruli was closely correlated with the development of glomerular necrotizing lesions and crescents, but no such correlation was detected with the infiltration of macrophages, T cells or B cells. In the second biopsy (convalescent phase), patchy intracellular NE expression was present in the interstitium, but no aggregation of NE+ cells or extracellular NE expression was detected in either the glomeruli or the interstitium. These findings suggest that recruitment of polymorphonuclear leukocytes in perivascular and periglomerular areas as well as in glomerular tufts, and subsequent extracellular release of NE in situ may play an important role in the development of renal vasculitis characterized by vascular necrosis, rupture of Bowman's capsule, and tuft necrosis.

Biopsy, Needle↗