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Biomedical subjects

M Sasa

Publications and source records attributed to M Sasa.

At least 109 records · Page 6Linked to original sources

Significant Correlation between the Presence of Type W Collagen in the Duct Wall and the Development of Wide Intraductal Cancerous Extension in Breast Cancer.

To identify the characteristics of cases with an wide intraductal cancerous extension (WICE), we examined the relationship between WICE and type IV collagen distribution, and the relationship between WICE and the content of the proliferation-associated proteins in human breast cancer. The immunohistochemical distribution of type IV collagen and proliferating cell nuclear antigen (PCNA) were investigated in formalin-fixed tissue sections from 21 breast cancer cases. We demonstrated a significant correlation (p=0.014) between the presence of WICE and immunostaining of type IV collagen in the cancerous ducts (ducts occupied by cancer cells) in the central invasive area of breast cancer. However, no correlation was found between the presence of WICE and the PCNA index (percentage of positive cells per 1000 tumor cells). These findings suggest that the lack of the process of the loss of type IV collagen in the duct wall is more important than the nature of the tumor cells in the development of WICE.

Journal Article↗

5-HT1A receptor-mediated inhibition of lateral vestibular nucleus neurons projecting to the abducens nucleus.

Electrophysiological studies were performed using cats anesthetized with alpha-chloralose, to elucidate the 5-hydroxytryptamine (5-HT) receptor subtypes involved in the 5-HT-induced inhibition of the lateral vestibular nucleus (LVN) neurons projecting to or through the abducens nucleus. The effects of 5-HT receptor subtype agonists and antagonist were examined in polysynaptic neurons activated by stimulation of the ipsilateral abducens nucleus (IAN) antidromically, since these neurons are sensitive to 5-HT as shown in our previous study. Iontophoretic application of 5-HT and 8-hydroxy-2-(di-n-propylamino)tetrain (8-OH-DPAT), a selective 5-HT1A agonist, inhibited orthodromic spikes elicited by vestibular nerve stimulation in the majority of polysynaptic neurons activated by stimulation of ipsilateral IAN antidromically. There was a good correlation between the effects of 5-HT and 8-OH-DPAT. Iontophoretically applied 5-HT and 8-OH-DPAT also inhibited glutamate-induced firing in these neurons. Simultaneous application of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190), a 5-HT1A agonist/antagonist, significantly antagonized the 8-OH-DPAT-induced inhibition of glutamate-induced firing, although NAN-190 alone also caused weak suppression of glutamate-induced firing. Microiontophoretically applied 1-(3-chlorophenyl)piperazine (mCPP), a 5-HT1B agonist inhibited the orthodromic spike elicited by vestibular nerve stimulation and glutamate-induced firing in only a small number of the LVN neurons. 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, rarely affected these neurons. We postulate that postsynaptically located 5-HT1A receptors are mainly involved in the 5-HT-induced inhibition of polysynaptic neurons projecting in the region of the IAN.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice.

The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system.

Acoustic Stimulation↗

p53 alteration correlates with negative ER, negative PgR, and high histologic grade in breast cancer.

Seventy tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the RT-PCR-SSCP method. Sixty-five samples (92.9%) were investigated in the regions of codons 101-200 and 201-300. In total, 16 samples (24.6%) showed p53 gene alteration. We found that p53 gene alteration showed a correlation with (1) a negative ER status, (2) a negative PgR status, and (3) a high histologic grade (especially numerous mitotic figures) of the tumor. However, we found no correlation between p53 gene alteration and the lymph node status or clinical stage. Thus, p53 gene alteration in breast cancer may occur in highly malignant breast cancer other than advanced clinical stage cancer or node-positive cancer.

Adult↗

Excitation by talipexole, a dopamine D2 agonist, of caudate nucleus neurons activated by nigral stimulation.

An electrophysiological study using cats anesthetized with alpha-chloralose was performed to elucidate whether or not talipexole (B-HT 920 CL2: 6-allyl-2-amino -5, 6, 7, 8-tetrahydro-4H-thiazolo [4, 5 -d] -azepine-dihydrochroride), a dopamine D2 agonist, acts on postsynaptic dopamine receptors in the caudate nucleus (CN) neurons receiving excitatory input from the pars compacta of substantia nigra (SN). Extracellular neuron activities were recorded in the CN using a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette, each of which was filled with talipexole, quinpirole (dopamine D2 agonist), domperidone (dopamine D2 antagonist), glutamate and 2M NaCl. These drugs were microiontophoretically applied to the immediate vicinity of the target neuron. In the same neurons in which the spikes elicited by the SN stimulation were blocked by microiontophoretically applied domperidone, microiontophoretic application of talipexole and quinpirole induced a dose-dependent increase in spontaneous firing. This increase in firing by talipexole and quinpirole was blocked during simultaneous application of domperidone, although glutamate-induced firing remained unaffected by domperidone. In the CN neurons, in which the SN stimulation-induced spikes were not blocked by domperidone, spontaneous firing was not affected by talipexole or quinpirole. These findings suggest that talipexole activates CN neurons receiving a dopaminergic input from SN via D2 receptors, as does quinpirole.

Action Potentials↗

LTP of mossy fiber-stimulated potentials in CA3 during learning in rats.

The study was done to determine whether long-term potentiation (LTP) of the potentials occurs at mossy fiber (MF)-CA3 synapses with the advance of learning in unrestrained and unanesthetized rats. The rats were divided into two groups, the test and control groups. The test group was given daily learning tasks in the radial arm maze, whereas the control group was similarly handled without learning tasks. Complete acquisition of learning was observed in the test group on day 5, and the learning was maintained over 3 days. Under freely moving conditions, a significant increase in population spikes (PS) elicited by MF stimulation with the progress in learning was observed in the test group, and the PS potentiation remained stable after day 4. Furthermore, on day 7, when MF stimulation-induced PS in the test group were compared with that in the control group in pentobarbital-anesthetized rats, the responses were comparatively higher in the former. As the training-induced PS potentiation in CA3 occurred with the advance of learning, these findings suggest that LTP in CA3 induced by learning may be related to memory storage.

Animals↗

High detection rate of breast cancer by mass screening using mammography in Japan.

A trial of mass screening for breast cancer using both mammography and physical examination (independently) was carried out in women over 50 years of age in Tokushima Prefecture. Breast cancer was detected in eight of a total of 950 examinees by mammography alone, and no cases of breast cancer were detected by physical examination. The detection rate of breast cancer was 0.84%, which is very much higher than that obtained by conventional mass screening using physical examination alone. The detection rate increased especially in the sixth and seventh decades of life. All eight detected breast cancers were in the early stage. Based on these results, it is recommended to employ mammography in breast cancer screening for asymptomatic women aged over 50 years.

Adult↗

Inhibitory effects of 7-OH-DPAT, dopamine D3-receptor agonist, on nucleus accumbens neurons.

Effects of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine D3-receptor agonist, on neuronal activities of the nucleus accumbens (Acc) were examined in chloral hydrate-anesthetized rats. Spikes elicited by stimulation of the parafascicular nucleus were dose-dependently inhibited by microiontophoretic application of dopamine and 7-OH-DPAT. Glutamate-induced firing was also inhibited by these drugs. These findings suggest that D3 receptors are also involved in the postsynaptic inhibition of Acc neuron by dopamine.

Animals↗

Evidence for the excitatory cholinergic innervation in the rabbit portal vein.

We examined the possible existence of excitatory cholinergic innervation in isolated rabbit portal vein. Longitudinal strips of the vein in the presence of both phenoxybenzamine, an alpha-adrenoceptor antagonist, and NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, exhibited a small contraction in response to transmural electrical stimulation (ES). The contractile response to ES was augmented by physostigmine, an anticholinesterase agent, and inhibited by atropine. These findings indicate the existence of an excitatory cholinergic innervation in addition to the known adrenergic and non-adrenergic, non-cholinergic innervations in the rabbit portal vein.

Animals↗

Protective action of dopamine against glutamate neurotoxicity in the retina.

PURPOSE: The electrophysiologic study using patch-clamp techniques demonstrated that NMDA-induced currents had properties similar to those recorded in the brain. METHODS: Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. Immunocytochemical and electrophysiologic studies were done to identify the cultured cells. The neurotoxic effects of glutamate or N-methyl-D-aspartate (NMDA) on the retinal cultures were quantitatively assessed using the trypan blue exclusion method. RESULTS: The immunocytochemical study revealed that the major component of the rat retinal cultures was neurons including amacrine cells. The electrophysiologic study using patch-clamp techniques demonstrated that exposure to NMDA-induced currents with properties characteristic of those recorded in the brain. Brief exposure of these neurons to glutamate or NMDA induced delayed cell death. Glutamate neurotoxicity was prevented by the application of dopamine and forskolin. The protective action of dopamine was antagonized by a D1 receptor antagonist (SCH 23390) but not by D2 receptor antagonists (domperidone and sulpiride). A D1 receptor agonist (SKF 38393) protected glutamate-induced neurotoxicity in a concentration-dependent manner, whereas a D2 receptor agonist (quinpirole) did not affect it. CONCLUSIONS: These findings demonstrate that dopamine protects retinal neuronal cells against NMDA receptor-mediated glutamate neurotoxicity via D1 receptors.

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

[Improvement of clinical symptoms by UFT and TAM and a case of bone metastasis from breast carcinoma during pregnancy].

At age 35, the patient was diagnosed with left breast carcinoma (T4bN0M0, Stage IIIb) during her first pregnancy, and underwent mastectomy of the left breast and bilateral oophorectomy. Although CPA was administered as adjuvant chemotherapy after the operation, left pelvic pain developed about a year after the operation, and bone metastasis was detected from the imaging diagnosis. Then, the therapy was switched to UFT (600 mg/day) and tamoxifen (20 mg/day), which markedly relieved the pain along with bone scintiscan (NC) and simple X-P (NC). Five years have passed since the operation, and the progress is excellent. There is neither increase of pain nor adverse reactions to drugs. Furthermore, the patient received breast reconstruction operation at her strong insistence in the third year after operation, and has achieved a high quality of life (QOL).

Adult↗

[Early detection of breast cancer by mass screening using mammography].

A mass screening trial for breast cancer using mammography was carried out in Tokushima Prefecture, either itinerant screening in the communities or center screening at the workplace. Craniocaudal and lateral oblique imagings of the breast using two-view film mammography were performed at the first stage of screening. In addition, physical examination of the breast was also performed on subjects independently. A total of 8 cases with breast cancer were found in these trials by mammography alone, and no cases with breast cancer were detected by physical examination. The detection rates were 0.19% in itinerant screening, and 0.92% in center screening, respectively. This was much higher than the level (0.10%) obtained by mass screening using physical examination alone in Japan. Moreover, in elderly patients (age over 50 years), the detection rates were higher (0.54%, 1.21%). The number of clinical stage for cases with breast cancer detected by these screening were 5 cases in TIS and 3 in stage I. Thus, all cases were patients with early-stage breast cancer. From these results, mass screening using mammography should be mandatory for elderly women (over 50 years) with asymptomatic breasts.

Adult↗

Local cerebral glucose utilization in the interictal state of the spontaneously epileptic rat (SER).

Local cerebral glucose utilization (LCGU) in spontaneously epileptic rats (SER) and in their parent strains, zitter (ZI) and Kyoto-Wistar (KW) rats was studied by autoradiography with [14C]2-deoxyglucose. Compared to the LCGU in age-matched KW rats, LCGU in 8-week-old SERs, which had not yet exhibited epileptic seizures, was low in all brain regions examined, and there were no significant differences among the regions. Moreover, there were no differences in LCGU among all regions examined in both SERs and in ZI rats. By contrast, the interictal LCGU in 13-week-old SERs, which did exhibit epileptic seizures, was generally lower than in the other two strains, particularly in the hippocampus and amygdala. These findings suggest that the epileptogenic focus in SERs may lie in the hippocampus and amygdala.

Animals↗

Cancerous residue in breast-conserving surgery.

Local tumor extension was studied using a continuous series of multiple blocks of mastectomy specimens to assess malignancy remaining after breast-conserving surgery for early-stage breast cancer. In this study, 183 cases were chosen, consisting of 6 noninvasive ductal carcinoma cases and 177 invasive ductal carcinoma cases. The histopathology in 59 (32%) of the 183 cases corresponded to that showing extensions of more than 2.6 cm from the tumor margin. These wide extensions were also seen in 17% of breast cancers with a tumor size of less than 2 cm. The incidence of wide extension was higher in younger patients with cases of noninvasive ductal carcinoma. Extension to the nipple-areola was seen in 14% of cases with a tumor size of less than 2 cm. Breast cancers with multicentric development accounted for 3% of those with a tumor size under 2 cm. These findings suggest that if lumpectomy is performed with a margin of 2 cm for tumors with a size of 2 cm or less, a cancerous residue would be found in the surgical margin of 15-20% of the cases. The actual incidence was 23% of cases after breast-conserving treatment in our study. On the basis of the data, breast-conserving treatment with only local resection of the primary lesion showed cancerous residue such as intraductal cancerous extension in about 20% of cases. Therefore, it was concluded that, as part of breast-conserving therapy of early-stage breast cancer, radiation therapy of the whole breast should be performed after surgery with clear margins to control local recurrence.

Adult↗

Tumor progression accompanied by increase in proliferation rate in breast cancer: a preliminary report.

Forty consecutive cases with invasive ductal carcinoma of the breast (samples of both the primary invasive area and the involved node were available for 19 cases, multiple sections of breast tissue including both the primary invasive area and forefront intraductal cancerous area were available for 15 cases; and multiple sections of breast cancerous tissue and the involved node were available for six cases) were examined by immunohistochemical analysis for evaluation of their proliferation rate. In this study, we selected the PCNA index as a marker of the proliferation rate of the tumor cells. We demonstrated that the PCNA index of the primary invasive area was significantly higher than that of the forefront intraductal area (P = 0.0017), and the PCNA index of the involved nodes was significantly higher than that of the primary invasive area (P = 0.0004). These preliminary findings suggest that the progression from the tumor cells of the intraductal cancerous area to the metastatic tumor cells must be accompanied by two phases of increase in the proliferation rate.

Breast Neoplasms↗

Abnormal excitability of hippocampal CA3 pyramidal neurons of spontaneously epileptic rats (SER), a double mutant.

The spontaneously epileptic rat (SER:zi/zi, tm/tm), a double mutant, shows both tonic convulsions and absence-like seizures characterized by low-voltage fast waves and by 5-7 Hz spike and wave-like complexes in the cerebral cortical and hippocampal EEG, respectively. Characteristics of hippocampal CA3 pyramidal neurons were examined to determine whether these neurons are abnormally excitable. When a single stimulus was given to the mossy fiber, there was repetitive firing and a depolarization shift in neurons of mature SER (over 12 weeks old), in which epileptic seizures had fully developed. However, in young SER (7-8 weeks old) and littermates (zi/zi, tm/+), which did not show any seizures, only a single spike was elicited with each single stimulation of the mossy fiber. Intracellular recording showed that the resting membrane potential was not significantly different among young and mature SER and littermates, but a long-lasting (100-200 ms) depolarizing shift accompanied by repetitive firing was observed following a single stimulation of the mossy fiber in half of the CA3 neurons of mature SER. Furthermore, the input impedance of the CA3 neurons in mature SER was lower than that in young SER and in littermates. These results indicate that SER hippocampal CA3 neurons become abnormally excitable in conjunction with the development of epileptic seizures.

Animals↗

The quality of mass screening for breast cancer by physical examination.

Mass screening for breast cancer using physical examination alone has been carried out since 1983 in Zentsuji, Kagawa Prefecture, Japan. Over a 7-year period, breast cancer was detected in 11 of a total 8,271 examinees, the detection rate being high at 0.13%. The detected cases included a few early-staged breast cancers, suggesting that mass screenings are of slight efficacy. Seven cases of interval cancer were found by breast self-examination after the mass screenings, supporting the value of breast self-examination. A relatively large number of interval breast cancers was detected in 1985 and 1986, when the rates of required further examination remained under 1%. The sensitivity and specificity of this screening were 61.1% and 94.5%, respectively, indicating a low sensitivity. These results suggest that the qualitative diagnoses made from the first screening by physical examination alone were often revealed to be false negatives. Therefore, the existing diagnosis should be employed in the first screenings. It is recommended that mammography be introduced to detect breast tumors which are nonpalpable or undetectable by physical examination alone.

Adult↗