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Biomedical subjects

K Asanuma

Publications and source records attributed to K Asanuma.

At least 19 recordsLinked to original sources

Macroscopic extranodal invasion is a risk factor for tumor recurrence in papillary thyroid cancer.

Papillary thyroid cancer patients, upon whom curative operation was performed, were investigated to clarify whether or not macroscopic extranodal invasion is a risk factor for recurrence. They were divided into three groups: group A, patients whose primary tumor showed extrathyroidal invasion (n=31); group B, those whose metastatic lymph nodes showed extranodal invasion (n=6); group C, those who showed both extrathyroidal and extranodal invasion (n=9). Recurrence was significantly higher in groups B and C than in group A (P<0.05). It was concluded that macroscopic extranodal invasion to the adjacent structures was a risk factor for recurrence in patients with papillary thyroid cancer.

Adult↗

The rate of tumour growth does not distinguish between malignant and benign thyroid nodules.

OBJECTIVE: To clarify whether or not the rate of tumour growth is a useful measure for distinguishing papillary thyroid cancer from benign nodules. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: Fourteen patients with 27 nodules (<20 mm) followed up for 20 months or more. INTERVENTIONS: High resolution ultrasonography (US). MAIN OUTCOME MEASURE: Growth rate. RESULTS: There were 15 papillary thyroid cancers and 12 benign nodules. The median tumour diameters at the first and the last US examination were 9.0 mm (range 6-19) and 9.0 mm (range 5-21) in papillary thyroid cancers followed up for 37 months (range 21-85), and 11.5 mm (range 4-19) and 11.5 mm (range 5-23) in benign nodules followed up for 38 months (range 20-84), respectively. CONCLUSION: The rate of growth of thyroid nodules as documented by ultrasound did not prove to be useful in distinguishing between malignancy and benign disease of small thyroid nodules (<20 mm).

Adult↗

The likely transformation of papillary thyroid carcinoma into anaplastic carcinoma during postoperative radioactive iodine-131 therapy: report of a case.

We report herein a case of papillary carcinoma which appeared to transform into anaplastic carcinoma during postoperative radioactive iodine-131 (131I) therapy. A 67-year-old man who was diagnosed as having papillary thyroid carcinoma with bilateral neck lymph node involvement and multiple lung metastases underwent total thyroidectomy prior to 131I therapy. Immediately after a second course of 131I therapy, the patient complained of right neck pain and swelling, and a biopsy of the swollen neck lymph node was taken. Histologic examination of this biopsy specimen revealed anaplastic carcinoma. With p53 immunohistochemical staining, both the primary tumor and the biopsy specimen were positive. We speculate that first, some DNA damage in tumor cells was induced by the initial 131I therapy, but neither DNA repair nor cell apoptosis occurred because the p53 gene was already mutated; then further DNA damage was induced by the second 131I therapy, leading to anaplastic transformation.

Aged↗

Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion.

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.

Adult↗

Clinical recurrence of papillary thyroid cancer in the remnant lobe.

OBJECTIVE: To find out which factors predict recurrence of cancer in the remnant after unilateral thyroid lobectomy for patients with papillary cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: One hundred thirty-three patients with a clinically solitary papillary thyroid cancer who had unilateral lobectomy for the primary disease between 1966 and 1990 and were followed up for more than 60 months. Twelve patients had developed recurrences in the remnant gland by the time of the second operation and 121 patients had not as judged by a second operation, an ultrasound examination, or by palpation. RESULT: The primary tumour size in those who developed recurrences was significantly larger than in those who did not (p < 0.0001), and clinical signs of regional lymph node involvement or distant metastases were also significantly more common (p = 0.006). No patient died of their cancer. CONCLUSION: Size of the primary tumour is an important prognostic factor for recurrence of solitary papillary thyroid cancer in the remnant after unilateral lobectomy. Such recurrences are unlikely to be lethal.

Adolescent↗

Survivin as a radioresistance factor in pancreatic cancer.

We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy.

Caspase 3↗

Role of human telomerase reverse transcriptase and telomeric-repeat binding factor proteins 1 and 2 in human hematopoietic cells.

Telomerase, an enzyme that adds hexameric repeats of 5'-TTAGGG-3', termed telomeres, to the ends of chromosomal DNA, has been implicated in cellular immortalization and cellular senescence. Recently several relevant genes have been cloned, including those encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1). Also important are genes encoding human telomeric-repeat binding factor proteins (TRF) 1 and 2. We compared 10 human malignant hematopoietic cell lines, 19 samples from patients with acute leukemia and normal granulocytes and monocytes to study telomerase activity and expression of these various genes using a reverse transcription-polymerase chain reaction (RT-PCR). In all 10 malignant cell lines with telomerase activity, hTR, hTERT mRNA, and TEP1 mRNA were expressed, while in normal monocytes and granulocytes without telomerase activity, expression of hTR, but not hTERT mRNA was detected. TEP1 mRNA was expressed in normal monocytes, but not granulocytes. Expression of TRF1 and TRF2 mRNAs was greater in the normal cells than in human malignant hematopoietic cell lines and in 16 samples of patients with acute leukemia. When differentiation of the malignant hematopoietic cell line HL-60 was induced using tumor-necrosis-factor 471 and all-trans retinoic acid (ATRA), telomerase activity decreased gradually during differentiation. Of the three telomerase components, only hTERT mRNA expression showed changes paralleling telomerase activity, becoming undetectable with differentiation. In contrast, initially low expression of TRF1 and TRF2 mRNAs increased during differentiation. Not only hTERT, but also TRF1 and TRF2 are important regulators of telomerase activity that represent potential targets for gene therapy against cancer.

Adolescent↗

Multiple branchial cleft-like cysts in a female patient with Hashimoto's thyroiditis.

We report a case of branchial cleft-like cysts (intrathyroidal lymphoepithelial cysts) associated with Hashimoto's thyroiditis. Palpation did not detect any nodules. Multiple cystic lesions were detected in the lateral side of the thyroid bilateral lobes by imagings of an I-123 scintigram, Tl-201 scintigram, sonography, and computerized tomography. Sonography displayed multiple cysts with strong echogenic spots in the cystic fluid. Repeated fine needle aspiration biopsies of the cysts consistently revealed only normal lymphocytes. Although these lesions could not be given diagnosis, subtotal thyroidectomy leaving the intact isthmus was performed. Microscopic findings revealed multiple branchial cleft-like cysts lined by flattened epithelial cells. Surrounding the epithelial lining were dense lymphoid follicles with large, reactive germinal centers. The remaining thyroid parenchyma showed Hashimoto's thyroiditis. Multiple branchial cleft-like cysts should be considered when sonographic examination reveals multiple cysts in the lateral side of the bilateral lobes, and fine needle aspiration biopsy displays only normal lymphocytes. To our knowledge, this is the first case of branchial cleft-like cysts associated with Hashimoto's thyroiditis reported in Japan.

Adult↗

Acinic cell carcinoma of the palate: case report and immunohistochemical observation.

We report a rare case of acinic cell carcinoma of the palate in a 63-year-old Japanese woman. Clinical examination demonstrated a firm, mobile mass without regional lymph-adenopathy. Histopathologically, the tumor was composed of large, polyhedral or round cells with basophilic granular cytoplasm (serous acinar-like cells) and reticular or clear cytoplasmic cells. These tumor cells were positive for the periodic acid-Schiff reaction, but negative for alcian blue. The tumor nests were separated by thin vascular tissue and incompletely encapsulated. Immunohistochemically, the tumor cells exhibited positive reactivity for alpha-amylase, lactoferrin, secretory component, S100 protein, and epithelial membrane antigen, but were negative for actin, glial fibrillary acidic protein, keratin, and carcinoembryonic antigen. These results suggest that this tumor is well differentiated into serous acinar cells and that the reticular and clear cytoplasmic cells are a modified form of these cells.

Biomarkers, Tumor↗

Three point mutations of human butyrylcholinesterase in a Japanese family and the alterations of three-dimensional structure.

Three different mutations at codons 330 (TTA to ATA), 365 (GGA to AGA) and 515 (CGT to TGT) of human butyrylcholinesterase (hBChE) were identified in a Japanese family. We correlated alterations in in the patient's hBChE activity with possible structural alterations in the three-dimensional structure of hBChE caused by the point mutations. This study was performed using the published computer-generated three-dimensional structure of hBChE based on the structure of acetylcholinesterase. The amino acid substitution at L330I was adjacent to hydrophobic residues that form the channel domain of the active center. This side chain faced the side opposite the active center. The amino acid substitution at G365R was located at the position most remote from the active center, and this substitution site was exposed to the surface of the BChE protein. Alpha-helical structure was present to the active center, and the guanidyl residue of native Arg 515 was hydrogen-bonded to the carboxyl group of Asp 395 in the alpha-helix. These point mutations may cause steric effects on the present patient's hBChE activity. This is the first report of three-dimensional structural analysis performed on the L330I, G365R, and R515C mutations of hBChE.

Adult↗

Smooth muscle layer-specific variations in the autonomic innervation of bovine myometrium.

1. To clarify the autonomic innervation regulating longitudinal muscle (LM) and circular muscle (CM) motility in the bovine uterus, functional (nerve stimulation, adrenergic drug responsiveness) and biochemical studies (catecholamine content, radioligand binding) were conducted on parous luteal-phase myometrium. 2. Electrical field stimulation (EFS; 60 V, 0.5-msec duration) caused tetrodotoxin (1 microM)-sensitive contractions in a frequency-dependent manner (0.5-20 Hz) in both LM and CM layers. 3. The EFS-induced LM contractions were potentiated by propranolol and conspicuously decreased by phentolamine, yohimbine, idazoxan or guanethidine, but were unaffected by prazosin or atropine. 4. On the other hand, CM contractions were only slightly decreased by phentolamine, idazoxan, yohimbine and guanethidine, but were insensitive to propranolol, prazosin or atropine. 5. The noradrenaline content in LM was about five times higher than that in CM. 6. Noradrenaline, adrenaline, clonidine, xylazine, UK14,304 and phenylephrine caused concentration-dependent contractions of both smooth muscle layers. 7. Clonidine, UK14,304 and xylazine were more potent contractile agents than noradrenaline and phenylephrine. 8. The contractile response to noradrenaline was competitively antagonized by yohimbine, but not by prazosin. 9. Binding studies using [3H]-prazosin and [3H]-rauwolscine revealed that the bovine myometrium contained both alpha1- and alpha2-adrenoceptors, but the alpha2-type receptor was dominant in both LM (94% of alpha-adrenoceptors) and CM (88%) layers. 10. The distribution of alpha-adrenoceptors was muscle layer-specific; that is, the concentration of alpha1-receptors in LM was the same as in CM, but the concentration of alpha2-receptors in LM was 2.6 times higher than that in CM. 11. The results of the present study indicate that there are layer-specific variations in the functional innervation of the parous bovine myometrium (exclusive adrenergic innervation in LM and adrenergic [minor] plus nonadrenergic, noncholinergic innervation [major] in CM), and that alpha2-adrenoceptors, which were responsive to the excitatory response of endogenous and exogenous noradrenaline, were dominant in both muscle layers of the bovine myometrium.

Adrenergic alpha-Agonists↗

[Subacute motor neuronopathy associated with myasthenia gravis and thymoma].

We reported a 63-year-old woman, suffered from myasthenia gravis with thymoma who later developed subacute motor neuronopathy after thymectomy. She noticed distally dominant muscle weakness and atrophy of bilateral upper extremities without sensory loss 4 month after thymomectomy. Her muscle weakness did not improve by intravenous administration of anti-cholinesterase (Tensilon test). Electrophysiological examinations showed no decremental response of examined muscles during repetitive nerve stimulation, nor motor nerve conduction block nor demyelination of affected peripheral nerves. Laboratory study demonstrated positive anti-acetylcholine receptor, anti-nuclear and SS-A antibodies. On immunohistochemistry, the patient's sera positively stained human and rat anterior horn cell cytoplasm as well as axoplasm of spinal white matter and root nerve axon, suggesting the presence of anti-axon antibody, possibly against neurofilament or tubulin components. The biopsied muscle specimen showed neurogenic muscle changes, but with no evidence of vasculitis nor cellular infiltration. Therapeutic trial of plasmapheresis was effective for her muscle weakness. Further recovery of weakness and muscle atrophy of hand muscles was obtained by combined therapy of intravenous and oral corticosteroid administration and plasmapheresis. These clinical, electrophysiological and histological findings suggested that antibodies against neuronal component might be responsible for her motor neuronopathy associated with myasthenia gravis. The findings of our case study may support the idea that some cases of motor neuron disease are caused by auto-immune mechanism.

Autoantibodies↗

Mutagenicity of p-aminophenol in E. coli WP2uvrA/pKM101 and its relevance to oxidative DNA damage.

It was recently reported that p-aminophenol (p-AP) induces DNA cleavage in mouse lymphoma cells, CHO cells and human lymphoblastoid cells. The mutagenicity of p-AP has not, however, been detected by reverse mutation assays. The purpose of this study was to assess the mutagenicity of p-AP by reverse mutation assay using Escherichia coli WP2uvrA/pKM101, which has a spectrum for detecting mutations different from those of other strains in the family with an AT base pair at the mutation site and has higher sensitivity to certain oxidative mutagens as compared to other strains. We found that p-AP was mutagenic to E. coli WP2uvrA/pKM101. The mutagenic activity of this compound was suppressed with the addition of dimethylsulfoxide or catalase, suggesting the involvement of active oxygen species in the mutagenic process induced by p-AP. To further elucidate the underlying mechanism, we used isolated DNA for the following experiments. It was revealed, by gel electrophoretic analysis, that p-AP induced DNA cleavage in the presence of Fe(III). However, p-AP alone did not induce this cleavage. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by p-AP in calf thymus DNA was also detected in the presence of Fe(III) by HPLC with an electrochemical detector. ESR-spin trapping experiments using DMPO detected the production of hydroxyl radical (.OH) in the solution of p-AP with Fe(III). Both p-AP mediated DNA damages and .OH production by p-AP in the presence of Fe(III) were completely inhibited by .OH scavengers (ethanol, mannitol, sodium formate, dimethylsulfoxide) and catalase. These results suggest that .OH derived from the reaction between H2O2 and Fe(III) (Fenton reaction) participates in the oxidative DNA damage. Accordingly, the same mechanism might be working in E. coli WP2uvrA/pKM101 during induction of the mutation by p-AP.

Adenosine Triphosphatases↗