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Biomedical subjects

M Sasa

Publications and source records attributed to M Sasa.

At least 127 records · Page 7Linked to original sources

Juvenile gigantomastia: report of a case.

Juvenile gigantomastia in a 12-year-old girl was treated by a bilateral reduction mammoplasty with free transplantation of the areolae and nipples and the removal of 3,980 g of breast tissue. Regrowth of the residual breast tissue has been suppressed by the administration of tamoxifen, an antiestrogen drug, since the surgery. This case was positive for estrogen receptors (ER) by the dextran-coated charcoal method, while tissue staining for ER and estradiol resulted in a darker staining of the epithelial contents, especially of fibroadenoma-like nodules, using an immunocytochemical assay. It is thus suggested that the etiology of this disease might be related to a local hypersensitivity to estrogen.

Breast Diseases↗

The coexistence of lobular carcinoma in a fibroadenoma with a malignant phyllodes tumor in the opposite breast: report of a case.

It is very unusual for a carcinoma of the breast to coexist with a phyllodes tumor, or for a carcinoma to arise within a fibroadenoma. We present herein an extremely rare case of lobular carcinoma in situ arising in a fibroadenoma, associated with a malignant phyllodes tumor in the opposite breast. A 49-year-old woman was admitted to our hospital with a large mass in the right breast and a small mass in the left breast. Microscopic examination of biopsy materials revealed a malignant phyllodes tumor in the right breast and a fibroadenoma in the left breast, for which a right standard radical mastectomy and left lumpectomy were performed. Microscopic findings of the material excised from the left breast showed the presence of multiple lobular carcinoma in situ within the tumor mass of the fibroadenoma. However, histological examination did not detect any metastasis to the bilateral axillary lymph nodes. To our knowledge this is the only such case ever to be reported in Japan.

Adenofibroma↗

Frequency of spontaneous p53 mutations (CpG site) in breast cancer in Japan.

Sixty-five tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method and sequencing analysis. In total, 16 samples (24.6%) showed p53 gene alteration. Sixteen of these alterations were evaluated by sequencing analysis, and 15 showed missense point mutations while one showed a 9-base pair deletion. In the 15 point mutations, G:C to A:T transitions constituted the majority (53%), and five tumors (33%) had a transition at the CpG site, which are mutational patterns not commonly found in breast tumors from Europe and America. On the other hand, there were no G:C to T:A transversions in our cases, which were frequently observed transversions in Europe and America. These p53 mutation patterns in breast cancer in Japan are not similar to those in Europe and America reported by Hollstein et al. and Coles et al.. These findings suggest that there are some differences between mechanisms of breast cancer in Japan and in Europe and America.

Adult↗

The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

A pharmacological study using monkeys, in which parkinsonism was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was undertaken to elucidate the mechanism underlying urinary bladder dysfunctions in Parkinson's disease. Under ketamine anesthesia, cystometrograms showed that, in MPTP-treated monkeys, a contraction of the urinary bladder was induced with smaller bladder volume than that in normal monkeys. In MPTP-treated monkeys, subcutaneously injected SKF 38393, a dopamine D1 receptor agonist, significantly increased the bladder volume and pressure thresholds for inducing the micturition reflex without affecting those in normal monkeys. In contrast, subcutaneous injections of quinpirole, a dopamine D2 receptor agonist, and apomorphine, a dopamine D1 and D2 receptor agonist, slightly, but significantly reduced the volume threshold of the bladder for the micturition reflex in both normal and MPTP-treated groups. These results indicate that, in parkinsonism, the degeneration of dopaminergic neurons in the substantia nigra leads to the detrusor hyperreflexia, probably due to a failure of activation of dopamine D1 receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

A mechanism underlying dopamine D1 and D2 receptor-mediated inhibition of dopaminergic neurones in the ventral tegmental area in vitro.

1. An intracellular recording study was performed to elucidate the mechanism underlying D1 and D2 receptor-mediated inhibition of neuronal activities of dopaminergic neurones in the ventral tegmental area (VTA) using slice preparations of the rat brain. 2. VTA neurones were classified into type I and type II neurones according to the shape of the action potential, which correspond to dopaminergic and non-dopaminergic neurones, respectively. 3. Addition of dopamine (10 microM) and quinpirole (1-100 microM) to the bath hyperpolarized the membrane of the type I neurones concomitantly with an increase in membrane conductance and an inhibition of action potentials which occurred spontaneously and were elicited by depolarizing pulses applied to the cell. However, quinpirole (10 microM) had no effect on the threshold for action potentials induced by a depolarizing pulse. 4. These quinpirole (10 microM)-induced effects were antagonized by simultaneous application of domperidone (5 microM), a D2 receptor antagonist. 5. The amplitude of quinpirole (10 microM)-induced hyperpolarization was decreased by increasing the potassium concentration in the perfusing fluid or simultaneous application of tetraethylammonium (10 microM). 6. SKF 38393 (10 or 100 microM), a D1 receptor agonist, had no effect on the resting membrane potential or action potential firing induced by a depolarizing pulse applied to the cell. However, when SKF 38393 (10 microM) was applied simultaneously with quinpirole (10 microM), the threshold for action potential generation was elevated by 5-6 mV, although there was no enhancement of hyperpolarization induced by quinpirole. 7. The elevation of the threshold for action potentials induced by SKF 38393 in the presence of quinpirole was antagonized by simultaneous application of SCH 23390 (5 microM), a D1 receptor antagonist.8. Dopamine (10 microM), quinpirole (10 or 100 microM) and SKF 38393 (10 or 100 microM) had no effect on the resting membrane potential or spontaneously occurring action potentials in type II neurones.9. These findings suggest that activation of dopamine D2 receptors of dopaminergic neurones in the VTA increases potassium conductance, thereby hyperpolarizing the membrane and eventually inhibiting neuronal activities. They also suggest that simultaneous activation of both D1 and D2 receptors enhances the D2 receptor-mediated inhibitory effects by elevation of the threshold for action potential generation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Enhancement of D2 receptor agonist-induced inhibition by D1 receptor agonist in the ventral tegmental area.

1. A microiontophoretic study was performed on chloral hydrate-anaesthetized rats to examine the role of D1 receptors in the ventral tegmental area (VTA) neurones, which are inhibited by autoreceptor and D2 receptor agonists. 2. Inhibition by microiontophoretic application of quinpirole (a D2 agonist) of antidromic spikes elicited by stimulation of the nucleus accumbens in dopaminergic neurones of the VTA, was significantly enhanced by simultaneous application of SKF 38393 (D1 agonist), although SKF 38393 alone had little effect on the neurones. 3. In addition, quinpirole-induced inhibition was antagonized by iontophoretic application of domperidone (D2 antagonist), but was not affected by SCH 23390 (D1 antagonist). 4. Furthermore, SKF 38393-induced enhancement of inhibition by quinpirole was antagonized by simultaneous application of SCH 23390. 5. These results suggest that activation of D1 receptors located on the VTA dopaminergic neurones or on non-dopaminergic nerve terminals is not essential for inducing inhibition of the dopaminergic neurones, but enhances D2 receptor-mediated inhibition directly or indirectly via inhibitory neurones.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Effects of protein kinase C on the muscarinic excitation of rat adrenal chromaffin cells.

The role of protein kinase C (PKC) in the muscarinic excitation of chromaffin cells freshly isolated from rat adrenal medullae was examined by the patch-clamp recording method. Acetylcholine and McN-A-343, a M1-receptor agonist, depolarized the cell and induced action potentials. Phorbol 12,13-dibutyrate (PDBu), an activator of PKC, increased acetylcholine-induced firing concomitant with a persistent depolarization. Under voltage-clamp recording, both McN-A-343 and PDBu decreased the cesium-sensitive K+ current, which was induced by shifting the membrane potential between -140 mV and -40 mV. These results suggested that the stimulation of muscarinic M1-receptors by cholinergic drugs activated phospholipase C to degrade phosphoinositide, consequently producing diacylglycerol, and diacylglycerol activates PKC to induce excitation of adrenal chromaffin cells.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Blockade of retinal NMDA receptors by sodium nitroprusside is probably due to nitric oxide formation.

Effects of a nitric oxide (NO)-producing agent, sodium nitroprusside, on N-methyl-D-aspartate (NMDA) receptor activation in the cultured retinal neurons of rats were examined. NMDA in a Mg(2+)-free medium evoked inward currents at the resting membrane potential. Inward currents were also evoked by kainate. Sodium nitroprusside markedly reduced the NMDA-induced currents without affecting those induced by kainate. These results suggest the possible existence of a negative feed back system of NO which serves to regulate the activation of NMDA receptors in retinal neurons.

Animals↗

Release of sympathetic neurotransmitter evoked by electrical stimulation is increased in the chronically decentralized artery.

The present study was performed to confirm our previous proposal that the increase in neurotransmitter release is responsible for the supersensitivity of chronically decentralized artery to transmural nerve stimulation (TNS) in the rabbit. The ear artery was decentralized unilaterally by removing the preganglionic fiber proximal to the superior cervical ganglion (SCG), and the ear arteries and SCG were dissected 8 weeks after the operation. The increase in the tritium overflow induced by TNS from the chronically decentralized artery, which had been incubated with 3H-noradrenaline (NA) for 1 hr, was markedly increased at lower frequencies (0.1 and 0.2 Hz) than that from the control artery, whereas there was no difference at higher frequencies (> 0.5 Hz). No difference was observed in the neuronal uptake of 3H-NA during incubation for 1 hr between the control and decentralized arteries. There was also no change in the contents of catecholamines in both the artery and SCG after chronic decentralization, when assayed by a radioenzymatic procedure. In conclusion, the results obtained indicate that the supersensitivity to TNS after chronic decentralization is not due to the deranged catecholamine uptake and storage mechanisms in adrenergic nerve terminals and augmented transmitter biosynthesis, but due to the increased release of transmitter in response to low frequencies of TNS.

Animals↗

Relatively immediate relaxant effects of cholera toxin on isolated rabbit blood vessels.

A study was made on the relatively immediate relaxant effect of cholera toxin (CTX) on the isolated ear artery, thoracic aorta and saphenous vein of the rabbit. Both preparations of CTX, containing sodium azide (NaN3) and azide-free, showed no effect on the non-precontracted artery, but CTX containing NaN3 relaxed the moderately precontracted blood vessels with methoxamine promptly, i.e., with a time course of min order. However, the immediate relaxation produced by CTX containing NaN3 was attributed mainly to NaN3. Azide-free CTX, on the other hand, at 1-10 micrograms/ml gradually produced concentration-dependent relaxation of the precontracted vessels. The relaxant effects of CTX on the vessels were slow and long-lasting, i.e., with a time course of 10 min order. The relaxation induced by CTX was not influenced by the removal of endothelium nor by pretreatment with 10 microM indomethacin, 3 microM atropine or 3 microM propranolol. Activation of protein kinase C by a phorbol ester inhibited the relaxant effect of CTX. These results indicate that CTX relaxes the blood vessels by directly acting on the smooth muscles, without mediation by known endogenous relaxing factor, such as endothelium-derived relaxing factor (EDRF = NO) or prostaglandin I2 (prostacyclin) and by muscarinic receptor or beta-adrenoceptor.

Animals↗

Ifenprodil prevents glutamate cytotoxicity via polyamine modulatory sites of N-methyl-D-aspartate receptors in cultured cortical neurons.

Neuroprotective effects of ifenprodil, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, against glutamate cytotoxicity were examined in cultured rat cortical neurons. The viability of the cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 60 min. Ifenprodil and its derivative SL 82.0715 dose-dependently prevented cell death induced by glutamate. The NMDA antagonists MK-801 and 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid also prevented glutamate cytotoxicity with a potency similar to that of ifenprodil. Ifenprodil as well as MK-801 prevented NMDA-induced cytotoxicity, but did not affect kainate-induced cytotoxicity. Glutamate cytotoxicity was inhibited by removing extracellular Ca++ during and immediately after glutamate exposure. Ifenprodil and MK-801 reduced NMDA-induced Ca++ influx measured with rhod-2. Either spermidine, a polyamine modulatory site agonist, or glycine, a strychnine-insensitive glycine site agonist, potentiated NMDA- and glutamate-induced cytotoxicity. The protective effects of ifenprodil against NMDA- and glutamate-induced cytotoxicity were significantly reduced by spermidine, but not by glycine. These findings indicate that ifenprodil protects cortical neurons against glutamate cytotoxicity by selective antagonism of the polyamine modulatory site of the NMDA receptor complex.

Animals↗

Antiepileptic effects of CNK-602A, a novel thyrotropin-releasing hormone analog, on absence-like and tonic seizures of spontaneously epileptic rats.

The effects of CNK-602A (N-[(6-methyl-5-oxo-3-thiomorpholinyl) carbonyl]-L-histidyl-L-prolinamide), a novel thyrotropin-releasing hormone related analog, were investigated on absence-like seizure and tonic convulsion in the spontaneously epileptic rat (SER), which is a genetically defined double-mutant. When CNK-602A of 0.2-1 mg/kg was given intravenously to the animal, there were no changes in the background EEG except for an increase in low-voltage fast waves concomitant with behavioral alertness. However, CNK-602A suppressed absence-like seizure and tonic convulsion in a dose-dependent manner for over 1 h. These antiepileptic effects of CNK-602A on both seizures were antagonized by pretreatment with haloperidol (1 mg/kg, i.p.). It was found, using a brain in vivo microdialysis method, that CNK-602A at a dose of 1 mg/kg, which inhibits the seizures, increased the release of dopamine in the caudate nucleus. These results suggest that CNK-602A inhibits the seizures of SER in a similar manner to thyrotropin-releasing hormone (TRH), probably by increasing the release of dopamine in the central nervous system. In addition, the antiepileptic effects of CNK-602A were more potent and lasted longer than those of TRH.

Animals↗

A rare case of fibroadenoma in a tubular adenoma of the breast.

We report herein a case of a 31 year old housewife who underwent an excisional biopsy for a well-circumscribed lump in her breast. The lump contained 2 histological patterns, namely, fibroadenoma and tubular adenoma. These patterns had no transitional zone, were distinct and changed abruptly. This case was histologically diagnosed as "a fibroadenoma in tubular adenoma of the breast, benign", with no other such case ever having been reported in Japan. The histological findings of this case, convinced us that tubular adenoma is closely related to fibroadenoma.

Adenofibroma↗

[Inhibitory effects of Hachimijiogan on micturition reflex via the locus coeruleus].

Pharmacological studies were undertaken to elucidate the role of Hachimijiogan in the micturition reflex via the locus coeruleus, using alpha-chloralose-anesthetized cats. Rhythmic contractions of the urinary bladder induced by continuous infusion of saline into the bladder were dose-dependently inhibited by intravenous injection of Hachimijiogan (10, 30 and 90 mg/kg), as well as flavoxate hydrochloride (1 and 3 mg/kg). In contrast, contraction of the urinary bladder elicited by electrical stimulation of the locus coeruleus was significantly suppressed by intravenous injection of flavoxate, but not affected by that of Hachimijiogan. These results suggest that Hachimijiogan acts on the afferent pathway from the urinary bladder to the locus coeruleus, thereby inhibiting the micturition reflex, while it has no effects on the efferent pathway from the locus coeruleus to the urinary bladder.

Animals↗

The characteristics of interval breast cancer in mass screening.

To investigate the characteristics of interval breast cancer in mass screening, comparisons were made of the following three groups: interval group (21 interval breast cancer cases), mass screening group (87 breast cancer cases detected by mass screening) and outpatient group (266 breast cancer cases diagnosed at outpatient clinics). There were no differences among the three groups in terms of the case distribution by age or obesity, but significant differences in the case distribution according to nodal involvement and tumor size. Histological grading of the malignancy of the primary tumors disclosed that the incidence of breast cancer showing frequent mitoses was high in the interval group compared to the mass screening and outpatient groups. The 7-year cumulative disease-free survival rate was 75.3% in the interval group, 90.0% in the mass screening group and 83.1% in the outpatient group. The mean tumor size of the interval cases at the time of mass screening, back-calculated on the basis of the estimated tumor doubling time, was 1.5 cm in diameter, smaller than that of the mass screening group. It is surmised that interval breast cancer is characterized by marked proliferation of the tumor cells and has a poorer prognosis than the other group cases. These findings might be due to the marked proliferation of interval breast cancer rather than because of cases having been overlooked at the time of the last screening.

Adult↗

[A comparative analysis of interval breast cancer with breast cancer detected by mass screening or in outpatient clinics].

To investigate the characteristics and the prognosis of interval breast cancer, 21 interval cases were reviewed and compared with a total of 87 patients with breast cancer detected by mass screening and 266 found in outpatient clinics on the basis of the clinicopathological features. The postoperative cumulative 7-year disease-free rates were 61.1%, 81.4% and 69.0% in the interval cases, mass screening cases and outpatient clinic cases, respectively. The percentage of cases showing frequent mitoses in cancer cells was statistically higher for interval cancer than for the other breast cancers. The average tumor size of the interval cases calculated from the speculated tumor doubling times, was 1.51 cm. It is surmised that interval breast cancer is characterized by a marked proliferation of tumor cells and has a poorer prognosis than the other breast cancers. This might be due to the marked proliferation of interval breast cancer rather than under-counting because there were no malignant findings at the time of the last screening.

Adult↗