Primary neuroendocrine carcinoma of the breast: Report of a case

Primary neuroendocrine carcinoma (NEC) of the breast appears to be a rare neoplasm. Due to the limited number of the cases, a definitive therapeutic option for the disease has not yet been established. We herein report the case of a 57-year-old female patient with primary NEC of the breast who underwent a surgical resection and for whom the suitable adjuvant therapy is now being considered.     

Losartan Normalizes Endothelium-Derived Hyperpolarizing Factor–Mediated Relaxation by Activating Ca2+-Activated K+ Channels in Mesenteric Artery From Type 2 Diabetic GK Rat

Ca²⁺-activated K⁺ (K _Ca ) channels are important for endothelium-derived hyperpolarizing factor (EDHF) signaling. Since treatment with angiotensin II receptor blockers (ARBs) improves vasculopathies in type 2 diabetic patients, we asked whether the EDHF-type relaxation and its associated K _Ca channels [small (SK _Ca )–, intermediate (IK _Ca )–, and large (BK _Ca )–conductance channels] are abnormal in mesenteric arteries isolated from Goto-Kakizaki (GK) rats at the chronic stage of type 2 diabetes (34 – 38 weeks) and whether an ARBs (losartan, 25 mg · kg^?1 · day^?1 for 2 weeks) might correct these abnormalities. Although the acetylcholine chloride–induced EDHF-type relaxation in mesenteric arteries from GK rats was reduced versus the Wistar controls, it was significantly restored by losartan treatment. The SK _Ca-blocker apamin or the IK _Ca-blocker 1-[(2-chlorophenyl)diphenylmethyl]-1 H-pyrazole (TRAM-34) inhibited such relaxations in the losartan-treated or -untreated Wistar groups and in the losartan-treated GK group, but not in the losartan-untreated GK group. The BK _Ca-blocker iberiotoxin had a significant inhibitory effect in only one of these groups, the losartan-treated GK. The relaxations induced by the SK _Ca /IK _Ca acti-vator NS309 and the BK _Ca activator NS1619, which were impaired in GK rats, were normalized by losartan treatment. We conclude that losartan improves EDHF-type relaxation in GK rats at least partly by normalizing SK _Ca /IK _Ca activities and increasing BK _Ca activity.     

Neurologic sequelae and MRI in low-birth weight patients

Periventricular hyperintensity was detected using long repetition and echo time on spin-echo magnetic resonance imaging in 24 of 32 children with birth weights less than 2,500 gm. Functionally, 11 children were normal, 6 mildly handicapped, 7 moderately handicapped, and 8 severely handicapped. The functional handicaps were correlated to the degree of periventricular hyperintensity observed on magnetic resonance imaging when periventricular hyperintensity was divided into 4 grades; therefore, the extent of periventricular hyperintensity observed on magnetic resonance imaging has been proved to be of value in the clinical assessment of low-birth weight infants and children and may contribute to the prediction of later functional deficits.     

SPONTANEOUS RUPTURE OF THE SPLEEN IN ACUTE MYELOID LEUKEMIA

The results of an autopsy of an 80-year-old Japanese male with acute myeloid leukemia who died of spontaneous rupture of the spleen are reported. The patient was admitted because of anorexia, fatigue, weight loss, and multiple skin eruptions. Hematological examinations indicated a rapid increase in myeloblasts. The patient collapsed on the 28th hospital day, immediately after complaining of severe epigastralgia and vomiting. He died ten hours later. The autopsy revealed extensive leukemic infiltration of the bone marrows, spleen, lymph nodes, skin, and other internal organs. The spleen was enlarged and was ruptured in places at the hilar portion. Massive intraperitoneal hemorrhage from the rupture was the direct cause of death. The mechanisms of splenic rupture are discussed.     

Antidromic identification of neurons in the ventrolateral part of the medulla oblongata with ascending projections to the preoptic and anterior hypothalamic area (POA/AHA)

Seventy neurons in the ventrolateral medulla oblongata were antidromically activated by electrical stimulation of the preoptic and anterior hypothalamic area (POA/AHA) in female rats under urethane anesthesia. These identified cells were located within and adjacent to the nucleus reticularis lateralis and could be readily distinguished into at least two types of neurons, designated as ‘fast’ and ‘slow’ cells, on the basis of their waveform and conduction velocity.     

Flow-induced endothelium-dependent vasoreactivity in rat mesenteric arterial bed.

We studied rat mesenteric arterial beds to determine the relationship between the effects of flow-induced shear stress and agonists on mesenteric vasoreactivity. When beds were perfused at gradually increasing flow rates, perfusion pressure was flow rate-dependently increased. The flow rate-mediated increase in perfusion pressure was significantly enhanced by N(G)-nitro-L-arginine (L-NOARG) plus methylene blue (MB) and slightly enhanced by treatment with tetraethylammonium (TEA). In the presence of L-NOARG, MB, TEA, and indomethacin, the flow rate-induced increase in perfusion pressure was significantly enhanced, but this enhancement was significantly inhibited by combined treatment with BQ-123 plus BQ-788 (ET(A)- and ET(B)- receptor antagonists, respectively). The ET-1 content of the perfusate was significantly increased following combined pretreatment with L-NOARG, MB, TEA, and indomethacin at a high flow rate. The methoxamine-induced contraction was significantly enhanced by NOS inhibition in both high- and low- flow-treated groups. The released nitrite level was significantly greater in high-flow-loaded than in the low-flow-loaded beds. We conclude that in this model, the response of vascular tone to flow stimulation is subtly regulated by endothelium-derived factors (especially, NO, endothelium-derived hyperpolarizing factor, and ET-1), and that these factors interact with each other.     

MaxiK channel-triggered negative feedback system is preserved in the urinary bladder smooth muscle from streptozotocin-induced diabetic rats.

MaxiK channel, the large-conductance Ca2+-sensitive K+ channel, facilitates a negative feedback mechanism to oppose excitation and contraction in various types of smooth muscles including urinary bladder smooth muscle (UBSM). In this study, we investigated how the contribution of MaxiK channel to the regulation of basal UBSM mechanical activity is altered in streptozotocin-induced diabetic rats. Although the urinary bladder preparations from both control and diabetic rats were almost quiescent in their basal mechanical activities, they generated spontaneous rhythmic contractions in response to a MaxiK channel blocker, iberiotoxin (IbTx). The effect of IbTx on the mechanical activity was significantly greater in diabetic rat than in control animal. Similarly, the basal mechanical activity was increased with apamin, an inhibitor for some types of small conductance Ca2+-sensitive K+ channels, and this effect was more pronounced for diabetic rat. However, in both control and diabetic animals, IbTx action was stronger than that of apamin. Diabetes also enhanced the responses to BayK 8644, an L-type Ca2+ channel agonist. The extent of this enhancement in diabetic bladder vs. control was, however, almost the same as that attained with IbTx. Expression levels for MaxiK channel as well as apamin-sensitive K+ channels and L-type Ca2+ channel were not altered by diabetes, when determined as their corresponding mRNA levels. These results indicate that diabetes can potentially increase the basal UBSM mechanical activity. However, in diabetic UBSM, the main negative-feedback system triggered by MaxiK channel is still preserved enough to counteract the possible enhancement of this smooth muscle mechanical activity.     

Diabetes-related changes in contractile responses of stomach fundus to endothelin-1 in streptozotocin-induced diabetic rats.

The contractile response of the stomach fundus to endothelin-1 (ET-1) was examined in streptozotocin (STZ)-induced diabetic rats. In STZ-diabetic rats (versus age-matched control rats) (a) ET-1 caused a longer-lasting contraction of stomach fundus strips, and (b) in the dose-response curve, the ET-1-induced contraction was significantly greater for a given concentration (3 x 10(-7) to 10(-7) M). Although repeated application of ET-1 led to desensitization, the desensitization was less pronounced in STZ-diabetic rats than in the controls. The density of the binding sites for [(125)I]-ET-1 was increased in the diabetic stomach fundus (versus the controls), but Kd values were similar between the two groups. The ET(B) receptor mRNA expression level was significantly increased in the diabetic stomach fundus. These results suggest that the diabetes-related enhancement of the ET-1-induced contraction of the stomach fundus may be due to an increase in the ET(B) receptor population.