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Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 757 records · Page 42Linked to original sources

A long-term survivor of ruptured hepatocellular carcinoma after hepatic resection.

We treated a patient who had previously undergone a hepatic resection for ruptured hepatocellular carcinoma (HCC) but developed a solitary peritoneal recurrence at the site of the incision 8 years and 9 months later. Since no other recurrence was evident, we resected the tumour. The primary tumour was 2.5 cm in size and histological examination revealed HCC without any histological risk factors for intrahepatic recurrence. The peritoneal tumour consisted of less differentiated cancer cells than those found in the primary tumour. The positive rates of Ki-67 were 10% in the primary tumour and 23.3% in the peritoneal recurrence. The DNA indexes in both tumours were considered to be identical. The comparison between the primary and peritoneal tumours suggested that the histological differentiation and proliferation activity can change after recurrence, in spite of consistent DNA ploidy contents. Clinically, a patient who undergoes a hepatic resection for ruptured HCC can survive for a long time, such as 10 years, if they have good liver function and small HCC without any histological risk factors for intrahepatic recurrence. However, since late recurrence is possible, a follow up for as long as 10 years is recommended.

Aneuploidy↗

Stimulatory effect of nitric oxide on bicarbonate secretion in bullfrog duodenums in vitro.

The effect of nitric oxide (NO) on HCO-3 secretion was examined in vitro using an isolated preparation of bullfrog duodenum. The tissue was bathed in unbuffered Ringer's solution gassed with 100% O2 on the mucosal side and HCO-3 Ringer's solution gassed with 95% O2-5% CO2 on the serosal side. The HCO-3 secretion was measured by the pH-stat method using 2 mmol/l HCl as the titrant to keep the mucosal pH at 7.4. (+/-)-(E)-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamine (NOR3) was used as a NO donor and added to the serosal solution. To analyze the NOR3 action on HCO-3 secretion, the effects of dibutyryl adenosine-3',5'-cyclic monophosphate (dbcAMP), dibutyryl guanosine-3',5'-cyclic monophosphate (dbcGMP), methylene blue, and indomethacin on the HCO-3 response were also examined. NOR3 (1x10(-4) and 3x10(-4) mol/l) caused an increase in HCO-3 secretion in a dose-dependent manner, and this effect appeared with an about 30-min time lag, reaching the level of 1.5-2.5 times greater than basal values at 1-2 h later. Both dbcAMP (1x10(-3) mol/l) and dbcGMP (1x10(-3) mol/l) also caused a significant increase in HCO-3 secretion in bullfrog duodenums in vitro, although the onset of the HCO-3 response to dbcGMP was delayed as compared to the former. The stimulatory action of NOR3 on duodenal HCO-3 secretion was significantly attenuated by methylene blue (5x10(-5) mol/l) and indomethacin (1x10(-5) mol/l), the latter also inhibiting the HCO-3 response to dbcGMP. The release of prostaglandin E2 in the serosal solution was significantly increased after addition of NOR3 (3x10(-4) mol/l) and dbcGMP (1x10(-3) mol/l) in an indomethacin-sensitive manner. These results suggest that the NO donor increases duodenal HCO-3 secretion in vitro, and this action of NO donor is cGMP-dependent and mediated by endogenous prostaglandins. Duodenal HCO-3 secretion may be regulated locally by NO/cGMP in addition to prostaglandin/cAMP.

Animals↗

Evidence for TGF-beta-mediated 'defense' of the glomerulus: a blackguard molecule rehabilitated?

Transforming growth factor beta (TGF-beta) has been regarded as a 'blackguard molecule' that induces glomerular diseases. During the process of glomerulonephritis, upregulated TGF-beta stimulates the production of extracellular matrix and inhibits its degradation, leading to excessive matrix deposition. On the other hand, TGF-beta has the potential to be anti-inflammatory via inhibition of mitogenesis and production of inflammatory mediators by glomerular cells. This molecule strongly inactivates infiltrating cells, especially macrophages, which play a pivotal role in the generation of glomerular injury. The aim of this article is to summarize the potentially beneficial action of TGF-beta in the glomerulus and to address its 'bright side' in glomerular inflammation.

Animals↗

Gene transfer into the adult kidney for unravelling disease processes.

Insights into the pathogenesis of human disease must be based on an understanding of the molecular mechanisms that regulate the structure and function of individual organs. For this purpose, gene transfer technologies provide powerful and attractive tools. In principle, two different approaches are feasible to identify pathophysiological roles of certain genes: 'gain-of-function', and 'loss-of-function'. The former examines consequences of overexpression of an exogenous gene, and the latter investigates the outcomes of inhibition of a particular molecule via antisense, decoy, ribozyme and dominant-negative strategies. Gene transfer to specific renal structures allows evaluation of in vivo effects of certain molecules on the structure and function of each nephron segment. It would also be useful for therapeutic intervention in renal diseases through introduction of therapeutically relevant genes into affected sites. This article summarizes current experience with renal gene transfer and addresses its potential impacts on the understanding of renal function in vivo.

Adult↗

Transgene regulation by the tetracycline-controlled transactivation system.

The tetracycline-controlled transactivation system is one of the most powerful tools for modifiable expression of exogenous genes. This system enables selective, stringent and quantitative regulation of transgenes in vitro and in vivo. By combining with antisense genes, ribozymes or genes encoding dominant negative mutants, it is also feasible to control certain endogenous gene functions. Combination with transgenic or 'gene knockout' technologies enables the generation of mice in which a certain gene function is conditionally reinforced or deleted. These sophisticated methods are useful for investigation of gene function during embryogenesis and in adult organs and for well-controlled gene therapy approaches. This article briefly outlines the concept of the tetracycline-regulated gene expression systems and addresses the current experience in kidney research.

Animals↗

Transfer of genetically engineered cells to the glomerulus.

In the rat, cultured cells injected into the renal circulation are entrapped in the glomerulus. This peculiar property allows to create chimeric glomeruli in which genetically engineered cells are populated. Using glomerular cells engineered in vitro, it is feasible to generate glomeruli that produce recombinant gene products. This approach would be useful for identification of local function of a certain gene product in the glomerulus and for therapeutic intervention in glomerular disease. Transfer of activated leukocytes to the glomerulus is useful to elucidate pathologic actions of infiltrating cells on the glomerular structure and function. Use of leukocytes in which certain gene function is selectively reinforced or deleted should enable to disclose exact roles of leukocyte-associated genes in glomerular pathophysiology. Transfer of engineered leukocytes also allows to investigate how resident cells modulate the activity of infiltrating cells in normal and pathologic circumstances. This article summarizes current experience with adoptive transfer of engineered cells to the glomerulus and addresses its potential application to kidney research.

Animals↗

Immunohistochemical analysis of estrogen receptors in 313 paraffin section cases of human thyroid tissue.

Three hundred and thirteen cases of human thyroid tissues, comprising 39 nodular goiters from 34 females and 5 males, 130 adenomas from 93 females and 37 males, and 144 carcinomas from 99 females and 45 males were used for the present immunohistochemical assessment of estrogen receptor (ER) expression. Thirty-three cases of follicular carcinoma, 115 cases of papillary carcinoma and 6 cases of anaplastic carcinoma were included in the malignant tumor group. Incidences of ER-positive cases were 23/39 (58.9%) for nodular goiter, 44/130 (33.8%) for adenoma and 26/144 (18.0%) for cancer. In the individual carcinoma categories, 7/23 (30.4%) follicular, 19/115 (16.5%) papillary and 0/6 (0%) anaplastic lesions were judged as positive cases. Thus, the incidence of ER-positive cases tended to decrease with the degree of malignancy; this trend being similar in both sexes. Moreover, the average ages of ER-positive cases were lower than those of ER-negative cases for all types of thyroid carcinoma except the follicular variety in males. It was thus suggested that ER expression may be related to prognosis and tumor growth at early stage. Since the incidence of ER does not significantly differ between females and males, the observed sex differences regarding thyroid tumor incidence may reflect the higher estrogen serum content in females.

Adenoma↗

Antigen immunohistochemistry of renal cell adenomas in autopsy cases: relevance to histogenesis.

Eighty-three kidneys from autopsy cases, all more than 60 years of age, were used in the present studies. Three millimeter-thick step slices from all kidneys were embedded in paraffin, and serial sections from all blocks used for the immunohistochemical demonstration of Leu M1 (leukocyte membrane antigen) and LTA (Lotus tetragonolobus agglutinin) in cells of proximal convoluted tubular origin, and PNA (peanut agglutinin) and EMA (epithelial membrane antigen) in cells of distal convoluted tubular origin. The ABC staining method was used in all cases. A total of 65 renal cell adenomas found in 31 of the 83 kidneys consisted of 40 papillary, 20 tubular and 5 solid type lesions. The sizes of these renal cell adenomas were from 0.6 to 5 mm in diameter and compression of neighboring tissues was characteristic. Papillary renal cell adenomas were positive in their cytoplasms for Leu M1 and LTA in 7 cases and at their cell membranes for PNA and EMA in 33 cases. The respective figures for tubular renal cell adenomas were 6 cases for Leu M1 and LTA and 14 cases for PNA and EMA. All solid renal cell adenomas were positive in their cytoplasms for PNA and EMA. The immunohistochemical results thus indicated 13 of 65 lesions to have a proximal convoluted tubular cell origin and 52 to be possibly derived from distal convoluted tubules or collecting ducts. A role for metaplasia, however, could not be ruled out.

Adenoma↗

Major basic protein and topical administration of ketotifen in pollinosis under natural allergen provocation.

In this study we investigated the potential relation among subjective symptoms, blood eosinophil counts and the levels of major basic protein (MBP) in serum throughout the pre- to postpollen season. In addition, we compared the effects of topical administration of ketotifen on these parameters between the prophylactic treatment group (n = 10) and the postsymptomatic treatment group (n = 10). We found that (1) the levels of MBP in serum during the season were significantly higher than those before the season and (2) the levels of the above three parameters in the prophylactic treatment group were significantly lower than those in the postsymptomatic treatment group during the season. It was concluded from these results that the action of MBP may be involved in the pathogenesis of allergic rhinitis. Furthermore, for the first time we provided evidence that topical ketotifen administration could suppress the systemic upregulation of the blood eosinophil count and MBP level in subjects with pollinosis.

Administration, Topical↗

Effect of methimazole on rat renal carcinogenesis induced by N-ethyl-N-hydroxyethylnitrosamine.

The effect of methimazole on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal lesions was investigated in a medium-term initiation/promotion bioassay in male Wistar rats. EHEN-initiated rats underwent unilateral nephrectomy of the left kidney and subsequent addition of the renal tumor promoters trisodium nitrilotriacetate (NTA), potassium dibasic phosphate (PDP), or hydroquinone (HQ), alone or in combination with methimazole, to the diet for 20 wk. The addition of methimazole reduced the severity of simple and adenomatous renal hyperplasias induced by NTA, PDP, and HQ, but had no effect on the number of renal cell tumors that arose in EHEN+NTA groups. Methimazole also decreased the bromodeoxyuridine (BrdU) labeling indices, but had little effect on the expression of alpha 2u-globulin in treated kidneys as compared to controls. It appears that methimazole exhibits antagonistic properties to nongenotoxic nephrotoxins, protecting against renal damage but not against tumorigenesis, probably arising from genotoxic insult.

Adenoma↗

Promoting effect of monosodium aspartate, but not glycine, on renal pelvis and urinary bladder carcinogenesis in rat induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Although the incidences were relatively low, hyperplasias of the renal pelvis and the urinary bladder have been observed in Fischer-344 (F-344) rats after both sodium aspartate and glycine treatments in long-term 2-yr bioassays. In the present study, the effects of these amino acids on development of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary lesions were investigated in male and female F-344/DuCrj rats. F-344 rats of both sexes, 6 wk old at the commencement, were given 0.05% BBN for 4 wk and then treated with one of the amino acids at a level of 5.0% in the drinking water for the following 36 wk. Proliferative lesions in the renal pelvis often associated with necrosis and mineralization were increased in the group treated with BBN followed by sodium aspartate, but not by glycine, in both sexes. The same group demonstrated higher incidences of urinary bladder tumors with increased urinary pH and sodium concentration and decreased creatinine and uric acid, but not accompanying crystallization. These results showed a clear promoting effect of sodium aspartate for urinary carcinogenesis in rats. The mechanisms of the effect on the renal pelvis and urinary bladder might be different.

Animals↗

Significance of p53 protein expression in growth pattern of esophageal squamous cell carcinoma.

The significance of intraepithelial carcinoma concomitant with esophageal squamous cell carcinoma during carcinogenesis and progression of the tumor has been discussed diversely. The purpose of the current study was to elucidate the relation between p53 protein expression and the growth pattern of the squamous cell carcinoma of the esophagus with attention to coexistence of intraepithelial carcinoma. Seventy cases with squamous cell carcinoma of the esophagus surgically resected without preoperative adjuvant therapy, including 49 cases with intraepithelial carcinoma contiguous to the invasive lesion, were analyzed immunohistochemically for p53 expression. Positive immunoreactivity of p53 was found in 36 (51.4%) of 70 cases. The frequency of p53 protein expression in cases with intraepithelial carcinoma (65.3%; 32/49) was significantly higher than that (19.0%; 4/21) in cases without intraepithelial carcinoma (p<0.001). The value of invasion coefficient, which indicates a ratio of the area of invasive cancerous lesion occupied in the whole lesion, in the cases with p53 protein expression was significantly smaller than that in the cases without p53 protein expression (p<0.001). In conclusion, p53 protein expression was found to be significantly related to the coexistence and spreading of intraepithelial carcinoma contiguous to squamous cell carcinoma of the esophagus.

Carcinoma, Squamous Cell↗

Concentrations of vascular endothelial growth factor in the sera of gastric cancer patients.

VEGF (vascular endothelial growth factor) is known to play crucial roles in tumor angiogenesis. In 281 gastric cancer patients, aberrant increase of VEGF level was observed in 36 patients (12.8%). In 14 recurrent patients, 8 showed an increase of VEGF. The serum VEGF levels of stage IV cancer were significantly higher than those of stage I. The serum levels of recurrent patients were significantly higher than those of stage I, II and III. VEGF levels of patients with serosal invasion were significantly higher than those of patients without serosal invasion. In depth of invasion (t-factor), VEGF levels of t4 cancer were significantly higher than those of t1-t3. In venous infiltration of tumors, VEGF levels of v3 were significantly higher than v0 and v1. There was no significant difference with respect to H-factor and P-factor status. In eleven recurrent or advanced gastric cancer patients, serum VEGF was sequentially examined between pre- and post-chemotherapy. All of them showed a decrease of serum VEGF concentration after partial response by chemotherapy. The patients who had progressive disease after chemotherapy showed an increase of VEGF levels. Serum VEGF levels were closely related to the extent of gastric cancer and the response of chemotherapy.

Biomarkers, Tumor↗

HLA-DR antigen expression in squamous epithelial dysplasia and squamous cell carcinoma of the esophagus: an immunohistochemical study.

To clarify the biologic significance of esophageal squamous epithelial dysplasia, especially the similarity to carcinoma in situ, immunohistochemical investigation of HLA-DR antigen expression and lymphocyte infiltration was performed. HLA-DR antigen was expressed in 12 of the 35 invasive carcinomas (34.4%), 23 of the 38 intraepithelial carcinomas (60.5%), 21 of the 50 areas of dysplasia (42.0%) and only 2 of the 625 specimens of non-cancerous squamous epithelium (0.3%). The HLA-DR-positive rate of dysplasia localized continuous to HLA-DR-positive carcinoma was 68.4%, which was significantly higher than that for HLA-DR positive dysplasia localized continuous to HLA-DR negative cancer (11.1%) (p<0.05). In areas of dysplasia and intraepithelial carcinoma, T cell infiltration was significantly increased at the sites of HLA-DR antigen expression (P<0.01). B cell infiltration was also more common in areas of positive expression. These results suggest that HLA-DR antigen is associated with the local immune response to squamous epithelial dysplasia, and that HLA-DR antigen expression may prevent tumor invasion similarly to its role in intraepithelial carcinoma.

Adult↗

[Predictive factor for TESE (testicular sperm extraction)--ICSI (intracytoplasmic sperm injection) for non-obstructive azoospermia].

BACKGROUND: TESE-ICSI has been used very successfully in the treatment of the patients with non-obstructive azoospermia but its indication is still controversial. We performed retrospective study concerning parameters to predict successful recovery of testicular sperm from the patients and outcomes of ICSI. PATIENTS AND METHODS: 44 patients with non-obstructive azoospermia who underwent TESE-ICSI from July, 1997 to September 1999 were studied retrospectively. RESULTS: 1) Testicular sperm were retrieved from 32 patients (72.7%). ICSI was performed in 29 patients and the partner of 15 patients (46.9%) got pregnant. From 10 patients with histology of Sertoli-cell-only, we could retrieve sperm in 3 patients (30%). 2) Testicular volume, Johnsen's score count (JSC), and FSH were significant parameter to predict the recovery of testicular sperm from the patients, but if we see only the patients with JSC less than 7, there were no significant parameter. Chromosomal abnormality was not a significant parameter. 3) The partner's age, motility of recovered sperm and testicular volume correlated with fertilization rate. Chromosomal abnormality was not significant parameter to predict fertilization. CONCLUSIONS: There was no absolute parameter to predict the recovery of testicular sperm from the patients with non-obstructive azoospermia. All patients with non-obstructive azoospermia can be the indication of TESE-ICSI.

Adult↗

Ileus with incarceration of Spigelian hernia.

An 85 year-old female with ileus due to incarceration of Spigelian hernia, which was diagnosed pre-operatively with the findings of the abdominal computed tomography and plain radiographic pictures, is reported. A simple hernioplasty was made by suturing the internal oblique and transverse muscles to the rectus sheath. The post-operative condition is satisfactory without any recurrence of hernia.

Abdominal Muscles↗

Carcinoid tumor of the ileum with intestinal obstruction.

An 83 year-old female presenting with intestinal obstruction due to a carcinoid tumor of the small intestine is herein reported. The intra-operative findings revealed a stenotic lesion and ischemic changes of the ileum. A segmental jejunotomy was performed and a submucosal tumor was recognized as a causal lesion. Histopathological investigation demonstrated the features of carcinoid tumor.

Aged↗