A novel and facile racemization of chiral 1,1'-biaryl-2,2'-dicarboxylic acids.
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Journal Article↗
Biomedical subjects
H Hiramatsu
Publications and source records attributed to H Hiramatsu.
Capabilities of liposomes for topological transformation.
Dynamic behaviors of liposomes caused by interactions between liposomal membranes and surfactant were studied by direct real-time observation by using high-intensity dark-field microscopy. Solubilization of liposomes by surfactants is thought to be a catastrophic event akin to the explosion of soap bubbles in the air; however, the actual process has not been clarified. We studied this process experimentally and found that liposomes exposed to various surfactants exhibited unusual behavior, namely continuous shrinkage accompanied by intermittent quakes, release of encapsulated liposomes, opening up, and inside-out topological inversion.
Lipids↗
A rare case of advanced ovarian carcinoma who developed difficulty walking 25 days after treatment with weekly paclitaxel.
Although taxol has shown significant activity in advanced ovarian cancer, peripheral neuropathy is likely to become the major dose-limiting toxicity. We describe a case of advanced ovarian carcinoma who developed difficulty walking because of marked pain in the lower extremities and loss of proprioception 25 days after treatment with weekly taxol (80 mg/m(2)x3).
Antineoplastic Agents, Phytogenic↗
Sentinel lymph node biopsy using tin colloid RI and blue dye method.
Axillary dissection has been considered essential for breast cancer staging because nodal metastasis is the most powerful predictive factor for recurrence. On the other hand, morbidity, such as lymphedema and shoulder dysfunction, may occur. Sentinel node biopsy is a good way to avoid unnecessary axillary dissection. We used tin colloid as a carrier of Tc99m tracer together with the blue dye method. The detection rate of the sentinel node was 27 cases out of 29 (90%) for the blue dye method, 10 cases out of 19 (53%) for the RI method, and 27 out of 33 (82%) for the combined method. The detection rate of the RI method was improved after adding the subcutaneous injection over the tumor from 45% before adding the subcutaneous injection to 82% after adding it. The false negative rate was 11% for the blue dye method, 0% for the RI method, and 10% for the combined method. This yields a sensitivity of 89% for the blue dye method, 100% for the RI method, and 90% for the combined method. Specificity was 100% for all three methods. Accuracy was 96% for the blue dye method, 100% for the RI method, and 96% for the combined method. There were two false negative cases. The average number of sentinel lymph nodes was 2.12 for the dye method, 1.66 for the RI method, and 1.95 for the combined method. There were three of 49 cases with identified parasternal lymph nodes by RI imaging. Lymphatic mapping using tin colloid may be useful for detecting sentinel nodes.
Adult↗
[MRI of ductal carcinoma in situ of the breast: patterns of findings and evaluation of disease extent].
Ten cases of ductal carcinoma in situ (DCIS) or DCIS with microinvasion were reviewed in order to evaluate the characteristic findings of DCIS and to evaluate the extent of disease on MRI. A 1.5Tesla Signa or Horizon (GE Medical Systems) unit was used with a dedicated receive-only breast coil. The pulse sequence based on RARE was used with the fat suppression technique. After examining both breasts with a large FOV (30 cm), the affected breast alone was examined with a smaller FOV (18 cm) and larger matrix (512 x 384) with and without Gd-enhancement. DCIS showed several types of findings on MRI: linear, spotty enhancement; gathering of linear enhancement; enhanced area or mass without distortion of the surrounding tissue; and well-circumscribed mass mimicking intraductal papilloma. Compared with typical findings of invasive carcinoma, DCIS tended to be enhanced slowly. After performing MR examination in addition to mammography and ultrasonography, a more accurate diagnosis of disease extent was possible in 6 of 10 patients. MRI was useful in providing more precise information on the disease extent of DCIS, and it is considered useful in planning the type of surgery. Further study using larger series and precise pathological correlations are necessary.
Adult↗
[Prolactinoma in a child showing high MIB-1 labeling index: a case report].
We report a very rare case of a prolactin secreting pituitary tumor (prolactinoma) which occurred in a 12-year-old boy. The tumor showed an extremely high MIB-1 index. The clinical implication in the postoperative management of childhood prolactinoma is discussed. The patient showed right third nerve palsy, and MRI revealed a pituitary tumor invading the right cavernous sinus. Preoperative hormonal evaluation showed a very high prolactin level (2800 ng/ml). The patient underwent transsphenoidal surgery, and the third nerve palsy disappeared just after the procedure. MIB-1 index obtained by using immunostaining was 18.9%. Postoperative prolactin level remained high (2200 ng/ml), and the patient was treated with 10 mg/day of bromocriptine. Prolactinomas in children with high MIB-1 index show resistance to treatment with bromocriptine. In the postoperative management of a childhood prolactinoma, it should be considered how to control sufficiently high serum prolactin level to expect sexual development while preserving other normal residual pituitary functions. If control with bromocriptine, fails radiation treatment should be adopted with careful observation of the increase in height and the progress of sexual development of the patient.
Bromocriptine↗
[Dynamic MRI and tumor angiogenesis of breast cancer].
The purpose of this study was to clarify the mechanism underlying early enhanced MR images of breast cancer by dynamic MR imaging from the aspect of tumor angiogenesis. The images depicted by dynamic MR imaging of breast cancer were divided into the following two groups: a marginal strong enhancement (MSE) pattern and a variable pattern without marginal strong enhancement (non-MSE). Twenty patients with invasive ductal carcinoma (maximum diameter < 2 cm) were examined by dynamic MR imaging, and the histological materials were submitted to two-dimensional computer image analysis with immunohistochemistry and histochemistry; morphological microvessel characteristics and microvessel density were examined; and the expression of vascular endothelial growth factor (VEGF) was investigated. In the MSE cases, vessel wall irregularity of capillaries and venules in the peripheral area adjacent to the tumor correlated (p < 0.001) with the enhancement pattern, and the total microvessel density (especially of arterioles with a maximum diameter less than 50 microns) of the peripheral area adjacent to the tumor was significantly higher than that of the tumor area. However, in the non-MSE cases, total microvessel density showed no significant difference between the peripheral area adjacent to the tumor and the tumor area, whereas the capillary density of the tumor area was four times greater than that of the peripheral area adjacent to the tumor. The expression of VEGF was strongly positive for the tumor nest adjacent to the capillaries. These results suggest that the enhanced images of the MSE pattern depend on abundant blood supply from arterioles and that the images of the non-MSE pattern might be reflective of angiogenic activity including variable VEGF expression of tumor cells. Thus the mechanism underlying early dynamic MR images of breast cancer was a complex result of tumor angiogenesis and the microcirculatory environment.
Adolescent↗
Genetic risk factors for coronary artery spasm: significance of endothelial nitric oxide synthase gene T-786-->C and missense Glu298Asp variants.
BACKGROUND: We recently identified two endothelial nitric oxide synthase (eNOS) gene polymorphisms, Glu298Asp and T-786-->C, which are independently associated with coronary spasm. eNOS gene intron 4b/a polymorphism is also reported to be involved in smoking-dependent coronary artery disease. The genetic linkage among these polymorphisms remains unknown. Also, it is unclear which variant is most responsible for coronary spasm. In the present study, we first examined the genetic linkage among these three variants. Next, we studied the risk factors of coronary spasm by using all significant genetic and conventional risk factors in a large-scale study. METHODS: The genotype and allele frequencies for the T-786-->C, intron 4b/a, and Glu298Asp variants were assessed in 423 randomly selected DNA samples to examine their genetic linkages. The relative capacities of all risk factors to predict coronary spasm were then analyzed using multiple logistic regression in 201 patients with coronary spasm and 345 volunteers. RESULTS: Comparison of allele frequencies revealed that the eNOS intron 4a allele was significantly linked to the T-786-->C mutation (P < 0.00001), whereas there was not a linkage between the intron 4a allele and the Glu298Asp variant (P = 0.1437) or between the Glu298Asp variant and the T-786-->C mutation (P = 0.1996). Multiple logistic regression revealed that the most predictive independent risk factor for coronary spasm was the T-786-->C mutation (P < 0.001), followed by cigarette smoking (P < 0.001), hypertension (P = 0.004), and the Glu298Asp variant (P = 0.028). CONCLUSIONS: We found that the T-786-->C mutation and the intron 4a allele are in linkage disequilibrium. We previously showed that the T-786-->C mutation reduced eNOS gene promoter activity. In that context, our results strongly suggest that the T-786-->C mutation underlies the functional characteristics of the intron 4a allele. Further, multiple logistic regression analysis revealed that the T-786-->C mutation is the most predictive risk factor for coronary spasm, followed by cigarette smoking. Given that those effects are potentially additive, patients carrying the eNOS gene variants should be strongly cautioned against smoking.
Adult↗
Hyperinsulinism-hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics.
Hyperinsulinism-hyperammonemia syndrome (HHS) is a recently identified genetic disorder characterized by hyperinsulinemic hypoglycemia with concomitant hyperammonemia. In patients with HHS, activating mutations in the glutamate dehydrogenase (GDH) gene have been identified. GDH is a key enzyme linking glutamate metabolism with the Krebs cycle and catalyzes the conversion of glutamate to alpha-ketoglutarate. The activity of GDH is controlled by allosteric inhibition by GTP and, so far, all the mutations of HHS patients have been located within the GTP-binding site. Characteristically, GDH from these individuals have therefore normal basal activity in conjunction with a loss of GTP inhibition. In this study, however, we have identified a novel variant GDH in a patient with a more severe form of HHS. The mutation is located outside the GTP-binding site and the patient's GDH shows consistently higher activity, even in the absence of allosteric effectors. These results further support the hypothesis that the activating mutation of GDH is the cause of HHS. The mechanism leading to the activation of GDH, however, is not always related to the loss of GTP inhibition as was originally suggested.
Adenosine Diphosphate↗
TMC-171A,B,C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282.
Four new antibiotics, TMC-171A (2), B (3), C (4) and TMC-154 (5) have been isolated from the fermentation of fungal strains Gliocladium sp. TC 1304 and TC 1282, respectively. Spectroscopic and degradation studies have shown that TMC-171s and TMC-154 were new members of the TMC-151 class of antibiotics, unique polyketides modified with a D-mannose and a D-mannitol or a D-arabitol. These compounds showed moderate cytotoxicity to various tumor cell lines.
Anti-Bacterial Agents↗
[Endovascular treatment of ruptured intracranial aneurysms using platinum coils in patients over 80 years of age].
Endovascular treatment of intracranial aneurysms using plantinum coils was performed in 10 patients over 80 years of age. The patients ranged in age from 81 to 96 years. Preoperative Hunt and Kosnik grading revealed one patient in grade I, 4 in grade II, 3 in grade III, and 2 in grade IV. The aneurysms were located in the internal carotid artery in 6 patients, in the anterior communicating artery in 1, and in the middle cerebral artery in 3 respectively. Intra-aneurysmal occlusion was accomplished in 8 patients with total or subtotal occlusion in 6 and partial occlusion in 2. In one patient with a peripheral middle cerebral artery aneurysm, the parent artery was occluded just proximal to the aneurysm. In the remaining one patient in grade III, an aneurysm associated with wide neck could not be occluded because of coil protrusion into the parent artery. In 9 patients who were successfully treated, all five patients in grade I or II and one in grade III resulted in good outcome, but the other three patients in grade III and IV showed poor outcome. No evidence of recurrent hemorrhage was noted during the follow-up period ranging from 2 months to 4 years. Endovascular coil embolization is a useful therapeutic alternative for treating ruptured intracranial aneurysms in patients over 80 years of age, especially those in Grade I or II.
Aged↗
Use of Modern Radiation Therapy Following Surgery for Invasive Breast Cancer.
Radiation therapy has long been used in the treatment of breast cancer. However, it is still very difficult to state with certainty whether or not radiation therapy is truly beneficial for patients with breast cancer, mainly because breast cancers are very heterogeneous in their clinical behavior, and because radiation therapy has undergone significant change in the methodology. We extensively reviewed the literature, and determined that radiation therapy increases the survival of some patients, particularly in conjunction with surgery and systemic therapy. Although the total proportion of such patients seems to be small, appliedto the general population of breast cancer patients, the absolute number of women who might benefit from radiation therapy may be quite large.
Journal Article↗
Cases of two patients whose food aversions disappeared following severe traumatic brain injury.
Following traumatic brain injury (TBI) the complete disappearance of food aversions was observed in the cases of two patients. In one of the cases, a young female, this change in her food aversion was manifested several months after the TBI, from the time when she was able to eat normally. The other patient, a young man, exhibited the disappearance of his food aversion immediately after recovery from his unconscious state following TBI. These results indicate that the disappearance of food aversions was a consequence of TBI.
Adult↗
The Role of Contrast-Enhanced High Resolution MRI in the Surgical Planning of Breast Cancer.
The role of contrast-enhanced high resolution MRI for planning surgery in breast cancer was evaluated. Of 72 patients examined, 57 patients had invasive ductal carcinoma, 2 had mucinous carcinoma, 1 had medullary carcinoma, 7 had invasive lobular carcinoma, 2 had ductal carcinoma in situ (DCIS) and 3 had Paget's disease. A 1.5 T Signa imager (GE Medical Systems, Milwaukee, WI) was used with a dedicated breast coil. The pulse sequence based on RARE(rapid acquisition with relaxation enhancement) was used with a fat suppression technique. After examining both breasts, the affected breast alone was examined with Gd enhancement. Linear and/or spotty enhancement on MRI was considered to suggest DCIS or intraductal spread in the area surrounding the invasive cancer. Of 72 patients, 50 showed linear and/or spotty enhancement on MRI and 41 of those 50 patients had DCIS or intraductal spread. In contrast, 22 of 72 patients were considered to have little or no intraductal spread on MRI and 17 of the 22 patients had no or little intraductal spread on pathological examination. The sensitivity, specificity and accuracy for detecting intraductal spread on MRI were 89%, 82% and 81%, respectively. Discrepancies in the estimated extent of intraductal spread were less than 2 cm in 90% of the patients according to pathological mapping. High resolution MRI was considered useful in detecting intraductal spread and in estimating its extent, however, larger study using precise correlation with pathology is necessary.
Journal Article↗
Dynamic MR Imaging and Tumor Angiogenesis in DMBA-Induced Rat Breast Cancer: Three Dimensional (3D) Reconstructed Image Analysis of Tumor Microvessels by Confocal Laser Scanning Microscopy.
We investigated the correlation between dynamic magnetic resonance imaging (MRI) findings in breast cancer and tumor angiogenesis in a dimethylbenz(a)anthracene(DMBA)-induced rat breast cancer model. In this study, we clearly demonstrated the three-dimensional (3D) architecture of tumor microvessel networks(MN)by confocal laser scanning microscopy (CLSM)and also investigated the hyperpermeability of tumor microvessels. Dynamic MRI findings were closely related to tumor angiogenesis. Three-dimensional reconstructed image analysis by CLSM revealed that the depicted images were dependent on microvessel density as well as microvessel permeability. It should be emphasized that dynamic MRI may have the potential to evaluate the tumor angiogenic activity in human breast carcinoma.
Journal Article↗
Estrogen receptor is not primarily responsible for altered responsiveness of ovalbumin mRNA induction in the oviduct from genetically selected high- and low-albumen chicken lines.
The role of estrogen receptor on ovalbumin mRNA induction by steroid hormones was investigated in primary cultures of oviduct cells from estrogen-stimulated immature chicks of genetically selected high- and low-albumen egg laying lines (H- and L-lines). In experiment 1, the extent of ovalbumin mRNA induction and changes in estrogen and progesterone receptors were compared between the oviduct cells from H- and L-lines with or without steroid hormones in the culture medium. In experiment 2, the effect of estrogen receptor gene transfection on the induction of ovalbumin mRNA was studied in the oviduct cells from the L-line chicks. The results showed a close correlation of the changes in ovalbumin mRNA with the numbers of nuclear and total estrogen receptors in the oviduct cells but not with the numbers of nuclear and total progesterone receptors. Estrogen receptor gene transfection induced ovalbumin mRNA to a moderate extent in the absence of the steroid hormones. To our surprise, however, estrogen receptor gene transfection apparently suppressed the ovalbumin mRNA responsiveness to estrogen to a considerable extent. It was concluded, therefore, that the extent of estrogen receptor expression might not be primarily responsible for the differences in responsiveness to steroid hormones of oviduct cells from genetically selected H- and L-line chickens.
Animals↗
Enhancement of antitumour activity of cisplatin by N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine. HCl in human ovarian cancer cells with intrinsic or acquired resistance to cisplatin.
This study was designed to the elucidate sensitising effects of the intracellular histamine antagonist, N,N-diethyl-2[4-(phenylmethyl)phenoxy] ethanamine HCl (DPPE) on the antitumour activity of cis-diamminedichloroplatinum (II) (CDDP) using human ovarian cancer cell lines with different sensitivities to CDDP (KF, sensitive) KFra (acquired CDDP resistant derived from KF), and KK and MH, intrinsically CDDP resistant. The KF cells were most sensitive to CDDP among cell lines used in this study and followed by MH, KK and KFra showing approximately 3.5, 4.0 and 9.1-fold IC50 values to KF, respectively. The acquired CDDP resistant KFra cells were approximately 6.1-fold more sensitive to DPPE than the parent KF cells, while MH and KK cells were more than 10-fold more resistant to DPPE than the KF cells. With regard to the inhibition of human ovarian cancer cell proliferation, phenyltoloxamine and L-histidinol were 5-2500-fold less cytotoxic than DPPE. Analysis of flow cytometry (FCM) revealed that with concentrations based on the IC50 to KF and KFra cells, DPPE resulted in G2-M accumulation in the KF (but not KFra) cells in a time-dependent manner during the course of 48 h incubation time. In addition, from a median effect analysis, DPPE seemed to have additive and somewhat synergistic effects on the antitumour activity of CDDP in KK and MH cells with intrinsic CDDP resistance, while minor antagonism in KFra cells with acquired CDDP resistance was observed. Although DPPE alone did not significantly inhibit the tumour growth of nude mice bearing KF cells, combinations of DPPE with CDDP resulted in improved survival compared with treatment with only CDDP. Adverse side-effects, as confirmed by monitoring haematocrit and the body weight were not observed during the experimental period. These results suggest that DPPE may be of clinical use for the treatment of intrinsically refractory ovarian carcinoma when combined with CDDP.
Adjuvants, Pharmaceutic↗