Atypical medullary carcinoma of the breast with cartilaginous metaplasia in a patient with a BRCA1 germline mutation

We examined a 34-year-old premenopausal woman who had noticed a left-breast lump a month previously. She had no past history of malignancies but had a family history of breast and ovarian cancers. Her mother had suffered from ovarian cancer when aged 47 years and had died of the disease at age 52. The younger two of the patient's four aunts had developed breast cancer when they were 37 and 48 years old. A physical examination showed an ill-defined mass, 1.5 cm in diameter, located in the upper outer quadrant of the patient's left breast. Mammography revealed diffuse microcalcification in both breasts but ultrasonography revealed an irregular tumorous lesion only in the left breast. Aspiration breast cytology revealed adenocarcinoma of the left breast. Modified radical mastectomy of the left breast and excision of a biopsy specimen from the right breast were carried out simultaneously. Histopathologically the left-breast tumor was an atypical medullary carcinoma with cartilaginous metaplasia, of histological grade 3, and the right-breast specimen showed fibrocystic changes with atypical ductal hyperplasia. Estrogen receptors were positive, but progesterone receptor was not detected on the tumor cells, which were immunopositive for nuclear p53 although c-erbB-2 overexpression was not observed. A nonsense germline mutation of the BRCA1 gene (exon5) was detected. The patient has been well since the operation (10 months). These findings may provide useful information about the carcinogenesis and biological behavior of BRCA1-associated breast cancers.     

Quantification of regional cerebral blood flow using 99mTc-HMPAO SPECT and intravenous 133Xe injection method]

We converted an absolute value of 133Xe-CBF (initial slope index, ISI) to the three dimensional CBF-SPECT using the intravenous 133Xe injection technique and 99mTc-HMPAO SPECT according to the microsphere model (method A), and the three compartment model described by Lassen et al. (method B): [formula: see text] [formula: see text] where f = flow in the region of interest (ROI), fr = flow in the reference region, C = count density of 99mTc-HMPAO SPECT in the ROI, Cr = count density of 99mTc-HMPAO SPECT in the reference region, and alpha = conversion to clearance ratio of HMPAO. We used alpha value of 1.5, and the whole cerebrum as a reference region. Four asymptomatic subjects and 15 patients with ischemic cerebrovascular disease were entered the study. In method A, excellent correlation was seen between ISI and SPECT-CBF in both of the cerebral hemisphere (r = 0.993; p < 0.001, n = 38) and the cerebellar hemisphere (r = 0.901; p < 0.001, n = 38). When back diffusion of HMPAO was corrected by method B, correlation coefficient of SPECT-CBF with ISI was equivalent to that in method A in the cerebrum (r = 0.978; p < 0.001, n = 38), while the correlation coefficient ih the cerebellum was lowered (r = 0.726; p < 0.001, n = 38) although high flow to low flow ratio was increased. Reproducibility of rCBF assessed 1 week apart from the first CBF-SPECT was highly reproducible in all of the brain regions; correlation coefficient ranged from 0.757 to 0.910 with a mean correlation coefficient of 0.834 (n = 11). The slope and intercept of the linear regression line between 2nd rCBF versus 1st CBF were 0.889 (range, 0.791-1.141) and 5.5 (range, -9.1-13.4), respectively. Regional CBF measured by method B was approximately 20% increase from that measured by method A. However, there was no significant difference in the reproducibility of rCBF between the two methods. Our results indicate that rCBF can be simply and noninvasively quantified using 99mTc-HMPAO SPECT and absolute unit of CBF measured by 133Xe injection technique. SPECT-CBF offers high resolution images and may be applicable for various cerebrovascular disorders in routine clinical use.     

Effects of goniopora toxin on bullfrog atrial muscle are frequency-dependent

Summary When goniopora toxin (GPT), a marine toxin isolated from coral, was applied to the bullfrog atrial muscle, the duration of action potential (APD) was prolonged, and a positive inotropic effect was produced. Such effects of GPT were influenced by stimulus frequency. At lower frequencies of 0.1 Hz, GPT (10 to 100 nmol/l) produced a moderate prolongation of APD and positive inotropic effect. At higher prequencies (1.0 Hz), however, the effects of GPT on both APD and contraction were suppressed. In contrast, APD and duration of contraction were prolonged with long intervals of stimulation (1–3 min), in the presence of GPT. The rested-state contraction was also markedly increased and prolonged by GPT. When the membrane potential was conditioned by voltage clamp pulses, the prolonged action potential in GPT-treated muscle was shortened in proportion to the increase in conditioning depolarization. However, the shortening effect of conditioning depolarization was attenuated by lengthening the resting period after the conditioning depolarization. These results, in conjunction with our previous results, suggest that the frequency-dependent effects of GPT on APD and contraction reflect time-and membrane potential-dependent changes of the toxin-modified sodium channels.This work was supported in part by a Grant-in Aid for Special Project Research from the Ministry of Education, Science and Culture of Japan to M. F. (No. 59104007)     

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose of 3000 rad was performed. On the 11 th day, tumor cells and mononuclear cells, which were separated from the low-dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunotherapy.     

Mode of action of ticlopidine in inhibition of platelet aggregation in the rat.

Ticlopidine, when orally administered to rats, resulted in activation of basal and prostaglandin E1 (PGE1)-stimulated adenylate cylase activity through increase in affinity of the cyclase in platelet membrane to PGE1, although it failed to affect adenosine- or sodium fluoride-stimulated activity of the enzyme. In washed platelets, Ticlopidine also activated basal and PGE1-stimulated activity of the cyclase and prevented reduction in the cyclase activity caused by low concentrations of PGE2. Furthermore, Ticlopidine inhibited malondialdehyde formation in platelets induced by thrombin but failed to inhibit that caused by exogenous arachidonic acid. Adenosine 3',5'-cyclic monophosphate (c-AMP): phosphodiesterase activity of platelet lysate was not significantly affected by Ticlopidine treatment. These findings indicate that Ticlopidine inhibits platelet aggregation and prostaglandin synthesis from endogenous substrate through activating basal and PGE1-stimulated activity of the cyclase, preventing PGE2-induced depression of the cyclase activity and thus increasing platelet c-AMP level.     

Serial change in airway lumen and wall thickness at thin-section CT in asymptomatic subjects

PURPOSE: To retrospectively analyze serial changes in airway lumen and wall thickness (WT) at multi-detector row computed tomography (CT) in asymptomatic subjects. MATERIALS AND METHODS: Institutional review board did not require its approval or informed patient consent. Airway dimensions were analyzed in 52 patients (30 men and 22 women) without known cardiopulmonary disease. Contiguous 2-mm CT sections were obtained after reconstruction, extending from origin of right posterior basal segmental bronchi to posterior subsegmental bronchi. Following parameters were determined with semiautomatic image-processing program: luminal area (LA), total airway area (TA), short axis of lumen (LSD), and short axis of total airway (TSD). In airways in which adjacent vessel or branching of small bronchus abutted boundary of airway, extrapolated line was traced by one radiologist. Airway wall area (WA) was calculated as TA - LA, and WT was calculated as (TSD - LSD)/2. Relative WA (WA% = [WA/TA] . 100) and ratio of airway WT to total diameter (D) (WT/D = WT/TSD) were calculated. Linear regression analysis and Spearman rank correlation were used to evaluate relationship between airway parameters (LA, WA%, and WT/D ratio) and distance from origin of segmental bronchi. RESULTS: LA decreased as CT proceeded from hilum to periphery (r = -0.765, P < .001). In 308 (32.7%) of 943 bronchi, however, LA increased as CT proceeded from hilum to periphery. LA increased by 10% or more in 101 (10.7%) of 943 bronchi. Mean changes in WA% and WT/D ratio between two contiguous sections were 0.66 +/- 5.05 (standard deviation) and 0.003 +/- 0.024, respectively. WA% changed by more than 5% between two contiguous sections in 274 (29.0%) of 943 bronchi. WT/D ratio changed by more than 0.02 between two contiguous sections in 338 (35.8%) of 943 bronchi. CONCLUSION: Variation of airway lumen and WT is found in asymptomatic subjects without known cardiopulmonary disease.     

Decreased Activity and Expression of Intestinal Oligopeptide Transporter PEPT1 in Rats with Hyperthyroidism in Vivo

PURPOSE: To examine the effect of thyroid hormone status on PEPT1 in vivo, the activity and expression of PEPT1 in the small intestine were examined in euthyroid and hyperthyroid rats. METHODS: Hyperthyroidism was induced by treating rats with L-thyroxine (12 mg/L) in the drinking water for 21 days. Transport activity was measured by everted small intestinal preparations and in situ intestinal loop technique. Expressions of PEPT1 mRNA and protein were evaluated by competitive polymerase chain reaction and Western blotting, respectively. RESULTS: The uptake of [14C]glycylsarcosine by everted small intestinal preparations was significantly decreased in hyperthyroid rats, whereas that of methyl-alpha-D-[14C(U)]-glucopyranoside was not altered. Kinetic analysis showed that the Vmax value for [14C]glycylsarcosine uptake was significantly decreased in hyperthyroid rats, whereas the Km value was not affected. The mean portal vein concentrations after intrajejunal administration of [14C]glycylsarcosine were also decreased in hyperthyroid rats. Moreover, hyperthyroidism caused a significant decrease in the expression of PEPT1 mRNA in the small intestine, whereas the expression of Na+/glucose cotransporter (SGLT1) mRNA was not changed. The level of PEPT1 protein was also decreased in the small intestine of hyperthyroid rats. CONCLUSIONS: These results indicate that in hyperthyroid rats, the activity and expression of PEPT1 were decreased in the small intestine.     

Bioelectrical impedance analysis for assessment of severity of illness in pediatric patients after heart surgery

OBJECTIVE: To investigate whether perioperative changes in bioelectrical impedance reflect the severity of illness in pediatric patients after heart surgery. DESIGN: Prospective, controlled study. SETTING: University-affiliated children's hospital. PATIENTS: A total of 107 patients admitted to a pediatric intensive care unit after congenital heart surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Single frequency (50 kHz) bioelectrical impedance was measured in the lower extremities before surgery and immediately, 16 hrs, and 40 hrs after admission (D0, D1, D2) to the pediatric intensive care unit. Postoperative changes in bioelectrical impedance were assessed by calculating values relative to the preoperative data (bioelectrical impedance ratio). These bioelectrical impedance ratios at D0 in both the nonsurviving and surviving patients were 0.84 +/- 0.06 and 0.85 +/- 0.01 (mean +/- SE), respectively, indicating that the initial decrease caused by surgical stress itself was not directly related to the prognosis. The bioelectrical impedance ratio showed an increase toward preoperative values in surviving patients (0.94 +/- 0.02) at D1, and they showed a sustained decrease (0.70 +/- 0.06) in nonsurviving patients. Patients with a bioelectrical impedance ratio at D1 of < 0.8 showed a higher mortality (25%) compared with those patients with a day-1 bioelectrical impedance ratio of > or = 1.0 (0%). The duration of the stay in the pediatric intensive care unit, mechanical ventilation, and inotropic support were all significantly longer in the patients with the lower bioelectrical impedance ratio. CONCLUSIONS: Measurement of the relative changes in postoperative bioelectrical impedance, which reflects perioperative alterations in body composition, provides a quantitative estimation of the critical illness in pediatric patients after heart surgery.