Biomedical subjects

N Shikata

Publications and source records attributed to N Shikata.

At least 55 records · Page 3Linked to original sources

PubMed1996

Histopathological changes in rabbit uterus carcinoma after transcatheter arterial embolization using cisplatin.

The effects of chemoembolization with cisplatin on gynecological malignancy were investigated using rabbit uterine tumors. A group of 20 rabbits were subjected to inoculation of the uterus with 5 x 10(7) VX2 carcinoma cells and 4 weeks later were divided into four groups, each consisting of five rabbits: an untreated control group, a group given cisplatin intraarterially (IA), a group subjected to transcatheter arterial embolization (TAE) with Gelfoam particles and a group subjected to transcatheter chemoembolization (TACE) with Gelfoam particles plus 1 mg/kg cisplatin. All groups were examined histologically 2 days after treatment. The untreated control group was further investigated 4 weeks after inoculation. In the untreated control group, the tumor cell nuclei varied in size and were irregular in form, and multiple nuclei and nuclear division were also observed. No necrotic zones were found up to 4 weeks after inoculation. The IA group showed no necrosis, but a few apoptotic cells were scattered throughout the tumor. In the TACE group, necrosis was observed in the center of the tumors, but proliferating cells persisted at the periphery. In the TACE group, necrosis was observed in the central part with many apoptotic cells surrounding the necrotic region in layers. The proliferating cell nuclear antigen (PCNA) index was 95.88% in the untreated control group, 86.6% in the IA group, and 8.62% in the TACE group, indicating a significant reduction in cell proliferation in the TACE group. These findings suggest that TACE results in more effective cytotoxicity than the other two treatments in uterine cancer tumor transplants.

Animals↗

PubMed1996

Liver apoptosis after dimethylnitrosamine administration in shrews.

Female house musk shrews (Suncus murinus, Insectivora) were given a single i.p. dose of 30 mg/kg dimethylnitrosamine (DMN) at 8 weeks of age which was lethal 36 to 48 hrs after dosing. Liver tissues were collected from shrews killed 3, 6, 16, 24 and 36 hrs after treatment, and the sequential development of the lesions was characterized. DMN induced acute centrilobular cell injury. In 6 hrs, a few cells became apoptotic in the centrilobular area; the number increased at 16 hrs and 24 hrs, and was prominent at 36 hrs. There was no inflammatory reaction or necrosis and hemorrhage was not obvious. These apoptotic cells as well as normal appearing cells in the centrilobular area were labeled by the TUNEL method. In both hepatocytes and endothelial cells, apoptosis was confirmed electron microscopically as nuclear chromatin condensation at the periphery with no mitochondria swelling. When an i.p. dose of 10 mg/kg DMN was given twice at 8 and 9 weeks of age, no acute toxicity was induced, and the liver of shrews surviving for 50 weeks of age was normal with no tumor formation. These findings indicate that a single i.p. administration of 30 mg/kg DMN induced severe and fatal toxicity on liver tissues in shrews due to apoptosis, whereas 2 x 10 mg/kg DMN had no carcinogenic effect.

Animals↗

PubMed1996

Pigmentary degeneration induced by N-methyl-N-nitrosourea and the fate of pigment epithelial cells in the rat retina.

Pigmentary degeneration of the retina was induced by a single intraperitoneal injection of 75 mg/kg of N-methyl-N-nitrosourea (MNU) in female Brown-Norway colored rats at 50 days of age, which were then observed at 24, 48 and 72 h and 7, 21, 35 and 150 days after the treatment. MNU-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanism 24 h after the treatment, and the destruction was completed by day 7. During the photoreceptor cell degeneration, proliferation of Müller cells and infiltration of macrophages was prominent 72 h and 21 days after the treatment, respectively. Müller cell proliferation and macrophage infiltration corresponded to degenerative photoreceptor cell phagocytosis, and proliferating Müller cell processes responded to stabilize the damaged retina. Pigment epithelial cell detachment from the Bruch's membrane was seen 72 h after the treatment, and migration within all layers of the retina was seen at day 7 when photoreceptor cells were lost. At 21, 35 and 150 days after the treatment, lack of photoreceptor cells and deposition of pigment epithelial cells within the retina but not in contact to vascular endothelial cells were characteristic. MNU-induced photoreceptor apoptosis followed by Müller cell and macrophage reaction then pigment epithelial cells deposition within the retina partially resembles retinitis pigmentosa in humans.

Animals↗

PubMed1996

Fas-independent apoptosis of photoreceptor cells in C3H mice.

The morphogenesis of the photoreceptor cells in the retinas of C3H mice carrying the rd gene and C57BL mice carrying the normal gene was compared, and retinas of the C3H mutants (C3H-lpr/lpr, -lprcg/lprcg, and -lpr/lpr-gld/gld) defective in apoptosis through the Fas system were examined. In the C57BL retina, the inner and outer nuclear layers were separated at 8 days of age, and the photoreceptor inner and outer segments began to grow between 8-11 days after birth with their most rapid growth occurring between 14-17 days of age. In the C3H retina, the development was comparable to that of the C57BL retina at 8 days of age but the reduction in thickness of the outer nuclear and photoreceptor layers was noted at 11 days of age, and the outer nuclear layer became reduced to only a few nuclei in thickness at 14 days, being completely missing or reduced to a single row of cells at 20 days. The degeneration was by an apoptotic mechanism as confirmed morphologically and by the TUNEL method. In all the C3H mutant retinas examined over 24 days of age, the complete depletion of the outer nuclear layer or reduction to a single row comparable to 20-day-old C3H mice was seen. The rd gene action is therefore independent of Fas/Fas ligand-medicated apoptosis.

Animals↗

PubMed1996

Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N-nitrosourea in the rat retina.

Retinal degeneration was induced by a single intraperitoneal injection of N-methyl-N-nitrosourea in female Sprague-Dawley albino rats at 50 days of age by two dose regimens, which were observed sequentially at 24, 48, and 72 hours and 7, 21, and 35 days after the treatment. After a dose of 75 mg/kg, methylnitrosourea evoked progressive retinal degeneration in all treated rats whereas a dose of 50 mg/kg was less effective. The 75-mg/kg-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanism, as confirmed morphologically and by the terminal dUTP nick end labeling method. Apoptosis had already started at 24 hours after the treatment and was completed by day 7. During the photoreceptor degeneration, proliferation of glial fibrillary acidic protein and vimentin-positive Müller cells as detected by proliferating cell nuclear antigen labeling appeared at 48 hours and was prominent 72 hours after the treatment, and macrophage infiltration within the retina as recognized by ED1 positivity was maximal 7 and 21 days after the treatment. Retinal degeneration was also induced in female Brown-Norway colored rats in a similar dose-dependent manner. Pigment epithelium was discontinuous above Bruch's membrane, and migration of the swollen pigment epithelium toward the inner nuclear layer was seen 7 days after the treatment. Therefore, as also confirmed electron microscopically, the most striking change was the destruction of photoreceptor cells by the apoptotic process, followed by Müller cell proliferation, pigment epithelium migration, and macrophage infiltration for cell debris phagocytosis, resulting in a thin remnant of retina with attenuated inner nuclear cells in direct contact with Bruch's membrane or with the pigment epithelium and/or with the Müller cells 35 days after the treatment.

Animals↗

PubMed1995

Immunohistochemical staining patterns of keratins in normal oesophageal epithelium and carcinoma of the oesophagus.

To clarify the keratin staining patterns of invasive carcinoma of the oesophagus, 22 cases of formalin-fixed paraffin-embedded surgical specimens were examined immunohistochemically with the labelled streptavidin biotin method using a panel of six different monoclonal anti-keratin antibodies. The antibody reacted adequately when antigen was retrieved in a microwave oven, and the relationship between morphological characteristics and keratin reaction patterns was analyzed in carcinomas and compared with adjacent histologically normal epithelium. In the normal oesophageal epithelium, AE3 and CK8.12 labelled all layer of cells, KS-1A3, E3 and KL1 labelled suprabasal cells, and LL002 selectively labelled the basal cells. In squamous cell carcinomas, AE3, CK8.12, KL1 and LL002 labelled almost all the tumour cells regardless of their differentiation, E3 only labelled keratinized cells, while marked decrease or loss of KS-1A3 staining was seen in all cases examined. Therefore, the characteristic profile of squamous cell carcinoma was a strong and diffuse expression of keratin 14 and 16, strong but localized expression of keratin 17, and loss of keratin 13 expression. Undifferentiated carcinoma totally lacked all keratin reactivity. The findings suggested that the neoplastic epithelial cells showed different keratin reactivity and distribution compared to normal oesophageal epithelium. In addition, histologically normal epithelium, dysplasia and carcinoma-in-situ adjacent to or overlying carcinoma expressed keratin 14.

Antibodies, Monoclonal↗

PubMed1995

Expression of androgen receptors in skin appendage tumors: an immunohistochemical study.

Androgen receptor (AR) expression was examined in normal skin and in 52 cases of various skin appendage tumors using a monoclonal antibody (F39.4.1) raised against the N-terminal domain of human AR. Microwave oven heating in citrate buffer solution followed by immunostaining with the labeled streptavidin biotin (LSAB) method was applied to formalin-fixed paraffin-embedded sections. Immunoreactive AR was restricted to the nuclei. In normal skin, AR was consistently localized in seboblasts and in some differentiated sebocytes, and variable expression was seen in luminal epithelial cells of eccrine and apocrine glands in the secretory portion. Hair follicles and epidermis showed no reactivity. In sweat gland tumors, AR was identified focally in inner layer cells of the tubuloglandular component of ten of thirteen chondroid syringomas but the remaining tumors were nonreactive. In sebaceous gland tumors, benign tumors with mature sebaceous elements (sebaceous nevi and sebaceous adenomas) showed AR expression, but the sebaceous epitheliomas and sebaceous carcinomas lost their expression. No AR expression was observed in hair follicle tumors, except in AR-positive mature sebaceous glands incorporated into the cyst wall of steatocystomas.

Apocrine Glands↗

PubMed1995

Improved lipid visualization with a modified osmium tetroxide method using ultrasonic treatment and intensification with imidazole or triazole.

Formalin fixed autopsy tissue containing lipids were cut into 1-5 mm thick blocks, washed well, then postfixed in 2% OsO4 in 0.03 M veronal acetate buffer for 30, 60, 90, 120, or 180 min with or without ultrasonic treatment. Tissues exposed to ultrasound for 90 min showed superior penetration of OsO4 and well preserved histological architecture. Tissues also were immersed for 1 hr in veronal acetate buffer (pH 7.4) containing 0.5% imidazole or triazole and compared with untreated controls. Paraffin sections, 4 microns thick, were examined under a light microscope with an image analyzer. Both intensity and percentage area of osmium blackening were significantly higher in samples immersed in imidazole or triazole than in untreated controls. No difference was observed between imidazole- and triazole-immersed samples. The OsO4 method, modified by ultrasound treatment and imidazole- or triazole-immersion, can be applied to routine formalin fixed autopsy materials for improved lipid visualization.

Fatty Liver↗

PubMed1995

Experimental models for carcinogenesis in the house musk shrew, Suncus murinus, Insectivora.

Animal carcinogenicity studies have mainly been performed on rodents. From the phylogenetic point of view, animals closer to humans must be included in these studies. Insectivora are considered to be the most primitive placental mammals and much closer to the early primates than rodents. Among the insectivora, the house musk shrew (Suncus murinus, family Soracidae), has been bred under laboratory condition. This animal is small having a short life span, and a comparatively low incidence of spontaneous tumor provides a useful animal model for tumor induction studies. We have examined the carcinogenicity of several chemicals known to produce tumors in rodents and found shrews, in general, to be sensitive to these chemicals but often showed different targets compared to rodents, and some chemicals tested were demonstrated not to be carcinogenic. Here we describe the carcinogenic studies performed in our laboratory and review other works including the occurrence of spontaneous tumors in shrews. Shrew carcinogenesis may fill up the gap of knowledge existing between the rodents and human beings.

Animals↗

PubMed1994

Tenascin expression in normal human adult skin and skin appendage tumours.

The expression and distribution of tenascin, an extracellular matrix glycoprotein, was investigated immunohistochemically using an anti-human tenascin monoclonal antibody (RCB 1) in formalin-fixed paraffin-embedded tissues obtained from 79 patients with skin appendage tumours, and compared with adjacent normal skin. Tissue specimens were pretreated with actinase and processed by the labelled streptavidin-biotin method. In normal skin, tenascin immunoreactivity was consistently found around the ductal portion of the sweat glands, around the lower part of the hair follicle and hair bulbs, and around or within blood vessels. Immunoreactivity was also observed variably around secretory coils of the sweat glands, and below the epidermis. No immunoreactivity was seen around the sebaceous glands. Tumours originating from sweat glands and hair follicles expressed tenascin around the tumour cells nests, while sebaceous gland tumours were immunonegative. Thus, tenascin expression in skin appendage tumours generally resembled that in corresponding normal tissue.

Cell Adhesion Molecules, Neuronal↗

PubMed1994

Immunohistochemical reaction patterns of keratins in MNNG-induced shrew oesophageal carcinomas.

The distribution of keratins in N-methyl-N'-nitro-N-nitrosoguanidine-induced oesophageal carcinomas in shrews was tested immunohistochemically, using a panel of seven different monoclonal antibodies. The studies were done on methacarn-fixed paraffin-embedded tissue, using the labelled streptavidin biotin method, and the relationship between morphological characteristics and keratin reaction patterns in carcinomas was analysed and compared with that in adjacent "normal" oesophageal epithelium. In the normal oesophageal epithelia, KL1, AE1, AE3, CK8.12, and CK4.62 stained suprabasal cells, 312C8-1 reacted to basal cells, and KS-1A3 labelled all epithelial cells. In squamous cell carcinomas, almost all the cancer cells were labelled strongly by 312C8-1 and weakly by KS-1A3, while a few cells in the centres of the keratinized foci were stained by KL1, AE1, AE3, CK8.12, and CK4.62. Like human oesophageal carcinomas, shrew oesophageal carcinomas maintain expression of human keratin 14, as determined by 312C8-1. The expression of human keratin 13, as determined by KS-1A3, was down-regulated.

Animals↗

PubMed1992

Breast carcinoma in patients receiving neuroleptic therapy. Morphologic and clinicopathologic features of thirteen cases.

We report 13 cases of breast carcinoma in patients treated with neuroleptics (prolactin-releasing drugs). Twelve of the patients were female and one was male. Nine patients had unicentric carcinoma, one had multicentric tumors arising synchronously, and three had bilateral tumors (synchronous in one case and metachronous in two cases). Thirteen tumors in ten patients were invasive ductal carcinomas, two tumors in one patient were mucinous carcinomas, and the two other patients had lipid-secreting carcinomas. Immunohistochemical staining showed alpha-lactalbumin (alpha-LA) in the lipid-secreting carcinomas at sites exhibiting active lipid secretion. A precise cause-effect relationship is difficult to elucidate, since the patients ranged in age from 40 to 64 years (mean: 51 years) when cancer was first diagnosed. However, the relatively high incidence of multiple tumors and the production of lipid and alpha-LA by the cancer cells were unusual features suggesting an association with neuroleptic therapy.

Adult↗

PubMed1992

A mixture of paraphenylenediamine and imidazole: its effect on the extraction of lipid droplets during electron microscopy staining.

To prevent extraction of lipids during a double staining procedure for electron microscopy, the tissue slices, double fixed with glutaraldehyde and osmium tetroxide to preserve microvesicular lipid droplets in the cytoplasm, were immersed for 2 hr in veronal buffer (pH 9.0) containing 0.5% p-phenylenediamine and 0.5% imidazole immediately after postfixation. The stained sections of the immersed tissue slice showed blackened, well circumscribed lipid droplets similar to those in corresponding unstained sections. Moreover, highly contrasting features of the cellular architecture could be visualized with the double stained, as well as routinely prepared sections.

Adrenal Cortex↗

PubMed1991

Induction of tumors in the Japanese house musk shrew, Suncus murinus (Insectivora), by dimethylbenz[a]anthracene.

The carcinogenic effect of 7,12-dimethylbenz[a]anthracene (DMBA) was examined in the virgin female Japanese house musk shrew, Suncus murinus (family: Soricidae, order: Insectivora). Leukemia, musk gland tumors, pilosebaceous tumors and sarcomas were induced in the DMBA-treated shrews, whereas none of the controls developed any tumors up to 50 weeks of age. DMBA emulsion was administered i.p. at a dose of 1.25 or 2.5 mg once a week, with either four or eight doses being given from 8 weeks of age. Leukemia developed in 100% (9/9), 50% (5/10), 56% (5/9) and 0% (0/10) of the animals treated with a total dose of 20 mg (8 x 2.5 mg), 10 mg (8 x 1.25 mg), 10 mg (4 x 2.5 mg) and 5 mg (4 x 1.25 mg) of DMBA respectively. Leukemia was of the lymphatic and/or mast cell type, and the spleen was the organ invariably involved. A dose-dependent effect of DMBA was not observed for pilosebaceous and musk gland tumors. When 1 mg of DMBA powder was dusted into the subcutaneous tissue at 4 weeks of age, sarcomas developed at the dusted site (69%; 9/13).

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1990

Microvesicular fatty liver in rats with resembling Reye's syndrome induced by 4-pentenoic acid.

To produce an animal model of Reye's syndrome (RS), 20 adult male Wistar rats were given 10 repeated i.p. injections of 50 mg/kg 4-pentenoic acid (PA) each separated by an 8-h interval. Then, 90 min after the tenth dose, they were given a final i.p. injection of 150 mg/kg PA. Thirteen control animals were injected with vehicle only using the same time schedule. More than half the animals in each group were fed a common diet, but the others were fasted during the terminal 10-h stage. All rats were sacrificed 30 min after the last injection. At the terminal stage, in comparison with the vehicle-injected controls, hypolipemia, hypoglycemia and high titers of serum ammonia and urea N were estimated significantly in the PA-treated rats fed throughout the whole period. Hypolipemia and hypoglycemia were more prominent in the terminally fasted group than the group fed continuously. Only in the PA-treated rats fed throughout the whole period moderate morphological signs of microvesicular fatty liver were exhibited. Ultracytochemical findings and biochemical determinations showed that the major lipids in the microvesicular fatty livers were triglycerides. Morphometric analysis revealed distinct hepatic mitochondrial swelling in the PA-treated rats. Therefore, the above treatment with PA was able to induce microvesicular fatty liver in rats with resembling RS, which were fed throughout the treatment procedure, but not in the terminally fasted rats.

Animals↗

PubMed1990

[An autopsy case of extra-adrenal malignant pheochromocytoma].

An autopsy case of an extra-adrenal malignant pheochromocytoma in a 34-year-old woman is reported. On laparotomy, many advanced stage malignant tumors originating from the paraganglia along the abdominal aorta were found to have invaded the lumbar vertebrae. After a partial resection, Co60 radiation therapy of the paraganglia was instituted, as well as of the metastatic lesions, with little effect. It was found that alpha-methyl-tyrosine was effective in controlling the plasma catecholamine, but had to be discontinued because of an untoward effect (anxiety). The patient subsequently developed intractable hypertension and a paralytic ileus from excess catecholamine secretion. As an alpha 1 adrenergic blocker was not effective, we had to use large doses of phentolamine to control these complications. Despite various intensive therapies, however, the patient died of heart failure resulting from 4 years of severe hypertension.

Adult↗

PubMed1990

[An autopsy case of multiple myeloma accompanied by extensive nodular infiltration into the extraskeletal tissue].

Discussed is the case of a 41-year-old Japanese man dead at 4 months after start of his clinical course of multiple myeloma of the Bence-Jones protein lambda type of the skull. Autopsy findings revealed that atypical plasmacytes had infiltrated extensively into the testes, the retroperitoneum, including the pancreas and the renal pelvis, the bilateral pleura, the right subclavian soft tissue, and the meningism, but not to the liver, spleen, and lymph nodes. In both testes, which weighted 120 g and 100 g, respectively, myeloma cells were found disseminated throughout the testicular tissue. Such a testicular involvement in cases of a multiple myeloma is extremely rare. The pertinent literature also is reviewed.

Adult↗

PubMed1989

[21-hydroxylase deficiency associated with adrenal tumor: case report of two brothers].

Described herein are two brothers with 21-hydroxylase deficiency (21-OHD) associated with adrenal tumors, and these possible mechanisms are discussed. A 34-year-old male was admitted on Jan. 9, 1984 because of an enlarged and tender left breast. Physical examination revealed short stature (152 cm, 76.5 kg), gynecomastia and shortening of metacarpal bone. His testes were small (2.6 X 1.6 X 1.9 cm). Urinary excretion of 17-OHCS was within normal range (5.9 mg/day), but those of 17-KS, 17-KGS and pregnanetriol were markedly increased (44.4, 110 and 22.6 mg/day, respectively). Plasma concentrations of progesterone and ACTH and urinary excretions of estrone, estradiol and estriol were also increased. Urinary excretions of 17-KS were decreased to 11.7 mg/day and 17-KGS to 22.3 mg/day after the ingestion of 2 mg/day dexamethasone for two days. The computed tomography and a scintigraphy with 131I-Adosterol revealed a tumor in the left adrenal gland, and the adrenal arteriography revealed a neovascularity and a tumor stain in the tumor. These data indicated that the patient was suffering from both 21-OHD and the left adrenal tumor. At this point, adenoma or adenocarcinoma of the adrenal gland was suspected. The left adrenal tumor (85 g) was resected on April 10, 1984, and the pathological diagnosis was adrenal adenoma. The patient's endocrinological abnormalities, however, did not improve after the operation. Urinary excretions of 17-KS and KGS were increased to 57.9 and 108.5 mg/day, respectively, in the patient's elder brother, and 63.3 and 127.9 mg/day, respectively, in his younger brother, indicating that they also had 21-OHD. Interestingly, an adrenal tumor was diagnosed by abdominal computed tomography in the elder brother who had the same HLA typing as the present case. The three brothers had 21-OHD, and two of them had both 21-OHD and adrenal tumor. To our knowledge, this is the first report documenting the co-existence of adrenal tumors in brothers with 21-OHD. This suggests that adenoma can be one of the complications of 21-OHD, probably due to the chronic stimulation by ACTH, and that a possible linkage to HLA may exist in such cases.

Adenoma↗