Intrathyroid thyroglossal duct cyst simulating a thyroid nodule.

A case of intrathyroid thyroglossal duct cyst is reported. A 50-year-old woman presented with a right lateral neck mass that was clinically indistinguishable from a thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) revealed normal-looking squamous cells. Right thyroid lobectomy was performed and microscopic examination revealed a cyst lined by squamous epithelium that was consistent with a thyroglossal duct cyst. The lesion was completely surrounded by normal thyroid tissue. Our experience suggests that intrathyroid thyroglossal duct cyst should be remembered in the differential diagnosis of a thyroid nodule. Detection of benign squamous cells by US-FNAB may be useful for ruling out the possibility of a cystic thyroid tumor.

Long-term role of nitric oxide in the enteric nervous system of the transplanted rat intestine.

We investigated the long-term changes of the nitric oxide (NO)-related neural component after syngeneic total small bowel transplantation in rats. In the present study, the NO-related neural component was examined using the electrophysiological and NADPH-diaphorase histochemical technique. The rats were divided into four groups: an untreated young adult control group, an untreated 2-year-old control group, a group killed 1 month after transplantation, and a group killed 2 years after transplantation. A superfusion apparatus was used to evaluate the response of jejunal strips to electrical transmural stimulation. In the presence of adrenergic and cholinergic blockade, the inhibitory effect of L-N(G)-nitro arginine (L-NNA; a nitric oxide synthesis inhibitor) on nonadrenergic, noncholinergic (NANC) relaxation was expressed as a L-NNA-sensitive component. The L-NNA-sensitive component accounted for 41.6 +/- 4.6% (mean +/- SE), 43.1 +/- 3.5%,54.6 +/- 4.1%, and 55.8 +/- 3.5% in the young control group, 2-year control group, 1-month transplant group, and 2-year transplant group, respectively, being significantly higher in the transplant groups (p < 0.05). The actual strength of the L-NNA-sensitive component was 0.24 +/- 0.03 (mean +/- SE), 0.26 +/- 0.02, 0.44 +/- 0.04, and 0.46 +/- 0.04 mg of tension per mg of wet weight, respectively, also being significantly higher in the transplant groups (p < 0.001). In addition, the percentage of NADPH-diaphorase-positive fibers was 24.1 +/- 1.1% (mean +/- SE), 25.5 +/- 1.4%, 31.0 +/- 1.6%, and 30.9 +/- 2.0%, respectively, being significantly higher in the transplant groups (p < 0.05). These results suggest that NO neurons in the intrinsic jejunal nervous system have an adaptive role in maintaining intestinal graft motility.

Initial steps in lymph node metastasis formation in an experimental system: possible involvement of recognition by macrophage C-type lectins.

We used histological observations and experiments with fluorescent cell tracers to investigate the roles of tissue macrophages in recognition through a galactose/N-acetylgalactosamine-specific C-type lectin (mMGL) in lymph node metastasis formation by mouse ovarian tumor OV2944-HM-1 (HM-1) cells. Lymph node metastasis from subcutaneous sites was shown to be initiated by the entry of tumor cells into the subcapsular sinus of lymph nodes where mMGL-positive cells were mainly located. To investigate whether mMGL-positive cells contributed to host resistance against lymph node metastasis, we repeatedly treated mice bearing transplanted tumors with an mMGL-blocking monoclonal antibody that was known to inhibit mMGL binding to its ligands. The number of HM-1 cells recovered from lymph nodes 2 weeks after subcutaneous injections was significantly greater when the mice were treated with the blocking anti-mMGL antibody. These results suggested that mMGL-positive macrophages contributed to the host's defense against lymph node metastasis.

Diagnostic value of ultrasound-guided fine-needle aspiration biopsy, core-needle biopsy, and evaluation of combined use in the diagnosis of breast lesions.

BACKGROUND: To investigate whether ultrasound-guided core-needle biopsy (US-CNB) has more diagnostic value for breast tumors than ultrasound-guided fine-needle aspiration biopsy (US-FNAB) and to evaluate their combined use in patients with breast tumors. STUDY DESIGN: US-FNAB was carried out in 233 patients with breast tumors (254 lesions); both US-FNAB and US-CNB (combined biopsy) were performed in 81 of these patients (82 lesions). The diagnosis obtained by US-FNAB and US-CNB was compared with the surgical findings and the diagnostic value of US-CNB and combined biopsy were retrospectively evaluated. RESULTS: The sensitivity of US-FNAB was 86.9%, the specificity was 78.6%, and the accuracy was 84%. In contrast, the sensitivity of US-CNB was 86.2%, the specificity was 95.8%, and the accuracy was 89%. The specificity of US-CNB was significantly higher than that of US-FNAB and the inadequate biopsy rate of US-CNB was significantly lower than that of US-FNAB. For combined biopsy, the sensitivity, specificity, and accuracy were all 100%. The sensitivity, specificity, and accuracy of combined biopsy were significantly higher than those of US-FNAB. CONCLUSIONS: These findings suggest that US-CNB is more useful than US-FNAB, and that a combination of US-CNB and US-FNAB can markedly improve the preoperative diagnosis of breast cancer.

[Evaluation of amrubicin with a 5 day administration schedule in a mouse model].

It was reported that amrubicin hydrochloride (9-aminoanthracycline SM-5887), showed a higher therapeutic activity than doxorubicin against human tumor xenografts implanted into nude mice with a single treatment schedule. In order to find a more effective treatment schedule, the efficacy, toxicity and pharmacokinetic properties with a 5 consecutive day treatment schedule were investigated. The total amount of the maximum tolerated dose and tumor growth inhibiting activity with a 5 day schedule was found to be higher than with a single administration. High levels of amrubicinol, the active metabolite of amrubicin, was detected in the tumor tissue. It was thus assumed that the improved efficacy with the 5-day schedule resulted from the high accumulation of amrubicinol. Bone marrow suppression at the MTD with the 5 day schedule was severer than with a single dose, but recovery was rapid, similar to that following a single dose. In conclusion, it was demonstrated that a 5 day treatment schedule was more effective than a single administration.

Uptake and intracellular distribution of amrubicin, a novel 9-amino-anthracycline, and its active metabolite amrubicinol in P388 murine leukemia cells.

Amrubicin, a 9-aminoanthracycline anti-cancer drug, and its C-13 hydroxyl metabolite amrubicinol, were examined for growth-inhibitory activity as well as cellular uptake and distribution in P388 murine leukemia cells and doxorubicin-resistant P388 cells. Also discussed are the differences in the mechanisms of action among amrubicin, amrubicinol and doxorubicin in terms of their cellular pharmacokinetic character. In P388 cells, amrubicinol was about 80 times as potent as amrubicin, and about 2 times more potent than doxorubicin in a 1-h drug exposure growth-inhibition test. A clear cross-resistance was observed to both amrubicin and amrubicinol in doxorubicin-resistant P388 cells, though the resistance index was lower for amrubicin. The intracellular concentration of amrubicinol was about 6 times and 2 times higher than those of amrubicin and doxorubicin, respectively. Compared to doxorubicin, amrubicin and amrubicinol were released rapidly after removal of the drugs from the medium. A clear correlation was found between the growth-inhibiting activity and the cellular level of amrubicin and amrubicinol in P388 cells. About 10 to 20% of amrubicin or amrubicinol taken up by the cells was detected in the cell nuclear fraction, whereas 70 to 80% of doxorubicin was localized in this fraction. These results suggest that amrubicin and amrubicinol exert cytotoxic activity via a different mechanism from that of doxorubicin.

Ultrasound-guided fine-needle aspiration biopsy for breast tumors: needle guide versus freehand technique.

BACKGROUND: We retrospectively studied whether a needle guide is necessary when performing ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in patients with breast tumors. METHODS: A total of 47 patients (50 lesions) with breast tumors underwent US-FNAB with a needle guide and 127 patients (143 lesions) underwent the procedure without a needle guide (freehand biopsy). The diagnoses obtained by US-FNAB were compared with the surgical findings. RESULTS: The sensitivity of freehand biopsy for tumors < 3 cm in diameter was significantly higher than that of the needle guide technique. CONCLUSIONS: We recommend performing US-FNAB without a needle guide (freehand biopsy) in order to maximize the correct preoperative diagnosis rate, especially in patients with tumors < 3 cm in diameter.

Accessory breast cancer: a case report and review of the Japanese literature.

The case of a 31-year-old woman with accessory breast cancer in the left axilla is described. She had noticed a swelling in the left axilla during her three pregnancies. The preoperative diagnosis of accessory breast cancer was made on the basis of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) and clinical history. She was treated by wide local resection and regional lymph node dissection. Although cancer originating from accessory breast tissue has been reported very rarely, knowledge of this disorder may facilitate the correct diagnosis of axillary tumors. US-FNAB is a useful and simple technique for the tissue diagnosis of axillary tumors.

In vivo efficacy and tumor-selective metabolism of amrubicin to its active metabolite.

The tissue distribution of a novel antitumor anthracycline antibiotic, amrubicin, was studied using seven human tumor xenografts implanted into nude mice, in order to identify the principal factors determining its therapeutic efficacy. We found a good correlation between the level of the metabolite amrubicinol in the tumor and the in vivo efficacy. High metabolic activity of amrubicin to amrubicinol was detected in tumor tissue homogenates, especially in cell lines highly sensitive to amrubicin in vivo. In contrast to amrubicin, the administration of amrubicinol showed less tumor-selective toxicity in these human tumor xenograft models. These data indicate that the tumor-selective metabolism of amrubicin to amrubicinol resulted in a tumor-selective disposition of amrubicinol, leading to good efficacy in in vivo experimental therapeutic models.

Tumor-selective distribution of an active metabolite of the 9-aminoanthracycline amrubicin.

It has been reported that the 9-aminoanthracycline amrubicin shows good efficacy in human tumor xenograft models. We studied the disposition and metabolism of amrubicin in mice, in comparison with those of doxorubicin. Amrubicinol, a 13-hydroxy metabolite of amrubicin, which is 10 to 100 times more cytotoxic than amrubicin, was detected as a major metabolite in blood and tissues, and aglycones of amrubicin were also detected. A pharmacokinetic study revealed that amrubicin had a smaller distribution volume and a shorter half-life than doxorubicin. In several normal tissues, the levels of amrubicin and amrubicinol were lower than those of doxorubicin. In contrast, the tumor levels of amrubicinol in the mice treated with amrubicin were higher than those of doxorubicin in the mice treated with that drug, in tumors that are sensitive to amrubicin. These results suggest that the potent therapeutic activity of amrubicin is caused by the selective distribution of its highly active metabolite, amrubicinol, in tumors.

Cytotoxicity of amrubicin, a novel 9-aminoanthracycline, and its active metabolite amrubicinol on human tumor cells.

Amrubicin, a completely synthetic 9-aminoanthracycline derivative, was previously shown to have potent antitumor activities against various human tumor xenografts. In this study, the in vitro activities of amrubicin and its major metabolite, amrubicinol, were examined using 17 human tumor cell lines. Amrubicinol was 5 to 54 times more potent than amrubicin, and as potent as doxorubicin, in inhibiting the growth of the cells following 3-day continuous drug exposure. Amrubicinol closely resembled doxorubicin in its profile of activities on the 17 human tumor cell lines. Cells were incubated with the drugs for 1 h, and the intracellular drug concentration and cell growth inhibition after 3 days were determined. Amrubicinol attained similar intracellular concentrations at lower medium concentrations compared to amrubicin, and the intracellular concentration of amrubicinol necessary to produce 50% cell growth inhibition was 3 to 8 times lower than that of amrubicin in 4 cell lines tested. Amrubicinol has a higher activity level inside the cells than does amrubicin. When cells were incubated with amrubicin for 5 h, a substantial amount of amrubicinol, more than 9% of that of amrubicin, was found in cells in 4 of the 8 cell lines tested. Amrubicinol may contribute to the in vitro growth-inhibitory effect of amrubicin on these cells. The results suggest that amrubicinol plays an important role in the in vivo antitumor effect of amrubicin as an active metabolite.

Thyroid cancer in uremic patients.

BACKGROUND: The combination of thyroid cancer and secondary uremic hyperparathyroidism has thus far been reported in only 25 cases. METHODS: Here we report our experience of 19 patients with secondary hyperparathyroidism who underwent parathyroidectomy. RESULTS: Thyroid nodules were present in five patients (26.3%), including one with a benign nodule and four with papillary thyroid cancer (21.1%). CONCLUSION: Our experience suggests that, in order to make a correct diagnosis, clinicians should consider the possibility of thyroid cancer in uremic patients with secondary hyperparathyroidism.

Psychobehavioral factors involved in the isolated office hypertension: comparison with stress-induced hypertension.

OBJECTIVE: To investigate the psychobehavioral factors involved in the isolated clinic blood pressure elevation and hypertension induced by mental stress. DESIGN AND METHODS: We studied 73 untreated patients with essential hypertension defined as World Health Organization stage I or II (28 men and 45 women, mean age 55 +/- 11 years). The amount of isolated clinic blood pressure elevation was examined in terms of the difference between clinic and daytime ambulatory blood pressures. Blood pressure (measured using a Finapres device) and R-R interval (measured electrocardiographically) were continuously monitored with subjects at rest and under mental stress (counting backward) to examine the cardiovascular response to the stress. Psychobehavioral characteristics such as anger, anxiety, tension, type A behavior pattern, and nervousness were evaluated and scored using structured interviews and self-reporting questionnaires. RESULTS: The anger score was inversely correlated to the clinic-ambulatory blood pressure difference for the systolic (r = -0.308, P < 0.01) and diastolic (r = -0.233, P < 0.05) blood pressures. The score for type A behavior pattern tended to be inversely correlated to the clinic-ambulatory blood pressure difference for diastolic blood pressure (r = -0.209, P < 0.1). The nervousness score was positively correlated to stress-induced increase in the systolic (r = 0.249, P < 0.05) and diastolic (r = 0.232, P < 0.05) blood pressures. The clinic-ambulatory blood pressure difference was not related to the blood pressure rise induced by mental stress (r = 0.170 for systolic blood pressure; r = 0.112 for diastolic blood pressure). CONCLUSION: The isolated clinic blood pressure elevation and hypertension due to mental stress were related to different psychobehavioral factors.

Comparison of variant expression of estrogen receptor mRNA in normal breast tissue and breast cancer.

To investigate whether estrogen receptor abnormalities are associated with resistance of breast cancer to endocrine therapy, we compared estrogen receptor mRNA between normal breast tissue and carcinoma. Using the RT-PCR, paired cancer and normal breast tissue specimens from 15 patients were analyzed. Exon-deleted variants were found in both tumor and normal tissue, with differences of variant expression between normal and tumor tissue being observed. One patient showed multiple deletions in the hormone-binding domain. Alterations in the amount and/or kind of variant ER expression may be important in determining the response of breast cancer to endocrine therapy.

Evaluation of ultrasound-guided fine-needle aspiration biopsy for thyroid nodules.

BACKGROUND: We retrospectively studied whether ultrasound-guided fine-needle aspiration biopsy (US-FNAB) showed improved sensitivity in patients with palpable thyroid nodules. METHODS: A total of 70 patients (72 lesions) with thyroid nodules underwent US-FNAB and 94 patients (94 lesions) underwent FNAB guided by manual palpation (standard FNAB). The diagnoses obtained by US-FNAB were compared with the surgical findings. RESULTS: The sensitivity of US-FNAB for palpable thyroid nodules was 62% the specificity was 74% the accuracy was 68% the positive predictive value was 100%, the negative predictive value was 70% and the inadequate biopsy rate was 17%. In contrast, the sensitivity of standard FNAB was 45%, the specificity was 51%, the accuracy was 48% the positive predictive value was 96, the negative predictive value was 55, and the inadequate biopsy rate was 30%. The accuracy of US-FNAB was significantly higher than that of standard FNAB. For tumors < or = 2 cm in diameter, the sensitivity and accuracy of US-FNAB were both significantly higher than those of standard FNAB. CONCLUSION: These findings suggest that US-FNAB can improve the preoperative diagnosis of thyroid cancer, especially in patients with tumors < or = 2 cm in diameter.

Tumor site-selective localization of an adoptively transferred T cell line expressing a macrophage lectin.

CTLL-2 cells were transfected with an expression vector that contained cDNA of a mouse macrophage galactose/N-acetylgalactosamine-specific calcium-type lectin (MMGL) and a stable transfectant (CTL-ML) was established. These cells and mock transfectant cells (CTL-CEP) were labeled with a long-term fluorescent cell tracer, DiI. The labeled cells were intravenously injected into mice that contained established lung metastases produced by OV2944-HM-1 ovarian tumor cells. Analyses with fluorescence microscopy of a series of frozen lung sections from the recipient mice revealed that CTL-ML preferentially accumulated in the lung metastatic nodules, whereas CTL-CEP did not. Time course studies showed that the preferential accumulation was evident 3 days after adoptive transfer. We also found that OV2944-HM-1 cells bound peanut agglutinin and Vicia villosa agglutinin B4, whose sugar specificity overlaps with the specificity of MMGL. These results suggested that MMGL molecules expressed on CTLL-2 cells contributed to their selective trafficking or retention in tumor foci possibly through recognition of tumor-associated cell surface carbohydrate antigens. These results also suggested that MMGL could be used for the selective targeting of effector cells in adoptive immunotherapy.

The stability of truncated epidermal growth factor receptor mRNA is higher than that of the full-length receptor mRNA in rat hepatoma cells.

Truncated and full-length epidermal growth factor (EGF) receptors are produced in rat liver cells. The truncated EGF receptor mRNA is almost identical to the full-length EGF receptor mRNA except for the lack of a 3' region of the full-length receptor mRNA. To understand the stability of rat EGF receptor mRNAs, we analyzed the expression of EGF receptor mRNAs in the hepatoma cell line, AH66 and liver cells. Ten, 7 and 5 kb full-length and 2.7 kb truncated EGF receptor mRNAs were detected in both of them. The half-lives of the 10 and 2.7 kb EGF receptor mRNAs were determined in AH66 cells using a transcriptional inhibitor, 5,6-dichlororibofuranosylbenzimidazole. The half-lives of the 10 and 2.7 kb mRNAs were 1.2 and 11 h, respectively. These results indicated that the truncated mRNA is 4 times more stable than the full-length mRNA in rat cells. As for the stability, the role of a sequence of 3'-untranslated region of the EGF receptor mRNA was discussed.

Effects of bright artificial light on subjective mood of shift work nurses.

The effects of bright artificial light on the subjective mental state of 10 female nurses working shifts at a university hospital were assessed. We investigated two series of five consecutive workshifts rotations comprising one normal, two night and two evening shifts, using two self-administered rating scales. The subjects were exposed to artificial light, brighter than 3,000 lux, for a total of 30 min during each workshift of the second series, whereas they worked under normal lighting conditions (approximately 250 lux) during the first series. A three-way layout ANOVA, with repeated measures, revealed that bright light tended to improve eagerness and reduce tension, and improved vigor, eagerness, appetite and impairment (the latter only on the second night) significantly or nearly significantly during night, but not evening, shifts. These results suggest that bright artificial light affects the mental state of nurses during night, but not evening, shift work.