Core and valence photoelectron spectroscopy of a series of substituted disulfides.

The valence and core photoelectron spectra of three substituted disulfide systems, α-lipoic acid, trans-4,5-dihydroxy-1,2-dithiane, and di-Boc-cystamine, are presented alongside detailed theoretical analysis based on equation-of-motion coupled-cluster singles doubles for ionization potentials and the nuclear ensemble approach. A comparison of the linear and five- and six-membered ring cyclic structures reveals that the energetic separation of the non-bonding sulfur orbitals can be used to calculate a reliable estimate of the C-S-S-C dihedral angle, even for substituted disulfides, and that the sulfur 2p, oxygen 1s, and valence band photoelectron spectra are a useful site-specific probe of hydrogen bonding.

Frontier orbital stability of nitroxyl organic radicals probed by means of inner shell resonantly enhanced valence band photoelectron spectroscopy.

We have investigated the frontier orbitals of persistent organic radicals known as nitroxyls by resonant photoelectron spectroscopy (ResPES) under inner shell excitation. By means of this site-specific technique, we were able to disentangle the different atomic contributions to the outer valence molecular orbitals and examine several core-hole relaxation pathways involving the singly occupied molecular orbital (SOMO) localized on the nitroxyl group. To interpret the ResPES intensity trends, especially the strong enhancement of the SOMO ionized state at the N K-edge, we computed the Dyson spin orbitals (DSOs) pertaining to the transitions between the core-excited initial states and several of the singly ionized valence final states. We found that the computed vertical valence ionization potentials and norms of the DSOs are reasonably reliable when based on the long-range corrected CAM-B3LYP density functional. Thanks to their unpaired electrons, nitroxyls have recently found application in technological fields implying a spin control, such as spintronics and quantum computing. The present findings on the electronic structure of nitroxyl persistent radicals furnish important hints for their implementation in technological devices and, more in general, for the synthesis of new and stable organic radicals with tailored properties.

Revealing the electronic properties of the B-B bond: the bis-catecholato diboron molecule.

The electronic properties of a diboron molecule, namely bis(catecholato)diboron (2-(1,3,2-benzodioxaborol-2-yl)-1,3,2-benzodioxaborole) (B2Cat2), have been studied by comparing the results of photoemission (XPS) and near edge X-ray absorption spectroscopy (NEXAFS) experiments with the outcome of DFT calculations. The B 1s, C 1s and O 1s K-edges have been investigated for both the isolated gas phase molecule and the adsorbed one on the Au(111) surface. The main features of the polarized NEXAFS spectra at each of the three edges considered are not significantly affected by the presence of the substrate, with respect to the isolated molecule, indicating that the molecule-gold interaction is weak. Moreover, the comparison between the observed dichroism in the NEXAFS spectra of the adsorbed B2Cat2 and that in the NEXAFS spectra of the isolated molecule has confirmed the orbital symmetry assigned in the gas phase absorption spectra. The transitions to π(B-B) bonding and π*(B-B) anti-bonding final states represent the most relevant probe of the chemistry of the B2Cat2 molecule. We show that their theoretical description requires that the treatment of the relaxation changes among different excited state configurations, which we successfully implemented by using ΔSCF-DFT (ΔSCF) calculations.

Electronic structure investigation of biphenylene films.

Photoelectron Spectroscopy (PS) and Near-Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy have been used to investigate the occupied and empty density of states of biphenylene films of different thicknesses, deposited onto a Cu(111) crystal. The obtained results have been compared to previous gas phase spectra and single molecule Density Functional Theory (DFT) calculations to get insights into the possible modification of the molecular electronic structure in the film induced by the adsorption on a surface. Furthermore, NEXAFS measurements allowed characterizing the variation of the molecular arrangement with the film thickness and helped to clarify the substrate-molecule interaction.

Relationship between epidemiologic and endocrinologic aspects of cervical cancer.

In search of etiologic relevancy of the steroid deviations in urine, we compared the reproductive activities of patients having cervical cancer with those of normal controls. A premenopausal patient experienced the birth of her first child significantly earlier than did the urban control of corresponding age, despite their similarity of age at menarche. However, when the same patient was compared with the premenopausal rural control, this differences was not found. The same parameter also failed to differentiate a postmenopausal patient from the corresponding control of urban origin. The premenopausal patient who was indistinguishable from the rural control by age at first delivery was distinguished from the rural control by reduced excretions of adrenal steroids including 11-deoxy-17 ketosteroids and some corticosteroid metabolites. The spectrum and the degree of deviation of urinary steroids for a patient coincided with the spectrum and the degree of age dependency of the urinary steroids for a normal woman during and after adolescence. These findings indicated that the inability of the reproductive parameter to discriminate a patient was associated with growth retardation in a population, and a maturation deficiency of the adrenal gland (arrest of adrenarche) was implicated in the genesis of cervical cancer.

Ectopic adrenocorticotropin syndrome caused by lung cancer that responded to corticotropin-releasing hormone.

ACTH responses to corticotropin-releasing hormone (CRH) were studied in three patients with the ectopic ACTH syndrome caused by lung cancer. Plasma ACTH responded to synthetic CRH in two of three patients. Tumor tissues obtained from these two patients contained CRH and ACTH. In one patient, tumor ACTH secretion was stimulated by CRH in vitro. Tumor CRH was immunologically, chromatographically, and biologically similar to hypothalamic CRH. In addition, multiple forms of immunoreactive beta-endorphin were present in plasma and the tumor extracts. From these results, we conclude that some patients with the ectopic ACTH syndrome have tumors that produce both ACTH and CRH and that CRH can stimulate ACTH secretion by such tumors. Other patients with the ectopic ACTH syndrome do not have ACTH responses to CRH. Therefore, procedures other than CRH testing are needed to differentiate patients with Cushing's syndrome due to ectopic ACTH/CRH production from those with Cushing's disease, since the latter also usually have ACTH responses to CRH.

Presence of multiple HIV type 1 subtypes among mothers and children in Japan.

We collected blood samples from 70 HIV-1-infected pregnant women and 76 babies born to HIV-1-infected women in Japan, from 1989 to 1999. To analyze the genetic diversity of HIV-1 among mothers and children, we sequenced the C2-V3 regions of HIV-1 gp120. Phylogenetic tree analysis of these regions revealed that multiple HIV-1 subtypes, A, B, D, E, and G, were circulating among mothers and children in Japan. Thus, the genetic heterogeneity of HIV-1 among mothers and children in Japan is steadily increasing, although the number of cases remains small. Perhaps the longest term survivor, an 11-year-old child with a vertical HIV-1 subtype G infection in Japan, is one of our subjects.

Does surgical stress cause tumor metastasis?

The purpose of this study was to test the validity of our working hypothesis that the stress of radical surgery may affect the prognosis of a cancer patient by precipitating hematogenous tumor metastasis, and that enhancement of this type of tumor metastasis is mediated by an increase of glucocorticoid activity that is induced in a cancer patient by surgical stress. Practically, we looked for the presence of glucocorticosteroid excess in cervical cancer patients in the course of radical surgery, and also tested the possible impact of glucocorticoid excess on the development of tumor metastasis in mice with i.v. inoculated Ehrlich ascites clone 1 tumor cells. The results obtained indicated that: 1) a state of glucocorticoid excess was observed in cancer patients at an early stage of postoperative convalescence. 2) Development of lung metastasis of blood-borne Ehrlich ascites tumor cells was facilitated in mice by hydrocortisone pretreatment--a substitute for surgical stress conditioning. 3) In the enhancement of lung metastasis, the hormone was found to induce constriction of the lung capillary lumen on the one hand, and acceleration of microvillus growth of the tumor cell surface on the other hand two morphological changes that may facilitate intrapulmonary retention of tumor cells. 4) Cyclophosphamide, as tested in a series of adjuvant chemotherapy experiments, was effective in either retarding or arresting the progress of tumor metastasis in hydrocortisone-conditioned mice. The possible impact of surgical stress on the spread of blood-borne tumor cells to the lung and liver, as well as on the therapeutic effect of cyclophosphamide for the prevention of postoperative micrometastasis, is discussed in the light of glucocorticoid actions on its target tissues.

Relation between the hormonal and epidemiological aspects of ovarian cancer patients in Japan.

We compared the hormonal and epidemiological aspects of ovarian cancer patients in search of the etiology of this neoplasia. Case-control studies of Japanese women with and without cancer were conducted in parallel, with regard to both the excretion of 14 urinary steroids and the pertinent physical and physiological parameters. The results obtained are as follows: 1) premenopausal ovarian cancer patients before and after radical ovariectomy and postmenopausal-postoperative patients were associated with a specified steroid deviation profile characterized by a combination of general depression of androgens, progestins and corticosteroids with sole rescue of tetrahydrocortisol (THF) in urine. 2) The deviation profile of postmenopausal-preoperative cancer patients was distinguished from the 3 partner profiles by its preservation of normalcy in the excretions of androgen and progestin in urine. 3) Ovarian cancer patients were associated with growth retardation, when compared with urban healthy controls and patients with either breast cancer or endometrial cancer by the age-matching method. Ovarian cancer patients were also less fertile than age-matched normal controls, and were as infertile as age-matched patients with either breast cancer or endometrial cancer. 4) Epidemiological evidence was presented to suggest that the incidence of ovarian cancer in Japan was increasing in parallel with the recent increase of social tension in Japan. The possible relevance of the hormonal characteristics of ovarian cancer patients to both the epidemiological characteristics of the same cancer patients and the genesis of this neoplasia is discussed in the light of the 2-step carcinogenesis theory.

Interrelation between Western type cancers and non-Western type cancers as regards their risk variation in time and space. IV. Hormonal transition of Japanese women from the pro-cervical cancer age through the pro-endometrial cancer age to the pro-hypogonadism age.

Chronological trend of urinary steroid excretions in Japanese women was investigated during the period of June 1972 to August 1986 using healthy women of urban and rural origins, patients with breast cancer and patients with either cervical cancer or endometrial cancer. The excretions of 14 neutral steroids were estimated by gas liquid chromatography, and the obtained data were tentatively correlated with the epidemiological backgrounds. In the course of the chronological transition from the 1st stage (1972-1974) to the 2nd stage (1975-79), the urinary steroid pattern of Japanese women with and without cancer experienced a common change to produce specific deviations that were in agreement with the hormonal characteristics of a pill user or of an endometrial cancer patient. At the 3rd stage (1980-86), patients with either cervical cancer or endometrial cancer were distinguished from 1st stage controls by non-specific depression of all androgens, progestins and corticosteroids in urine. Throughout the whole period, both the risk for cervical cancer and the reproductive activity (birth rate) were found to decrease continuously in Japanese women. Evidence was presented to suggest that the above deterioration of the hormonal environment in Japanese women could be related to the stress of modern life rather than to defects in the diet. On the basis of the above findings, the 1st, 2nd and 3rd stages of our investigation were tentatively termed the pro-cervical cancer age, the pro-endometrial cancer age and the pro-hypogonadism age. The relation between the chronological change of urinary steroids and that of the epidemiological background was analyzed from the view point of population ecology.

The regularity of intersteroidal relations in urine as related to the law of mass action.

The relation between 14 urinary steroid excretions was investigated by intersteroidal regression analysis with urine from 59 follicular stage women, 135 luteal stage women and 5 female patients with adrenal disorders. The regularity of intersteroidal relation in urine, as detected for all steroid pairs of all groups studied, was explained in terms of the law of mass action, and a chemical equilibrium point was located with a high degree of reproducibility for each steroid and for each group. The theoretical and practical usefulness of urinary steroid regression analysis is emphasized in relation to the possible impact of multihormonal information on endocrinology.

[Prevalence of diabetic ocular complications and systemic factors].

The prevalence of diabetic ocular complications and the correlation between diabetic retinopathy and systemic factors were examined in 2,300 cases (4,600 eyes) with non-insulin-dependent diabetes mellitus. The prevalence of cataract was 66.7%, of retinopathy 37.0%, of refractive and accommodative change 6.2%, of glaucoma 1.9% (rubeotic glaucoma was 1.0%), of rubeosis iridis 1.5%, of iridocyclitis 0.8%, of extraocular muscle palsy 0.2%, and of ischemic optic neuropathy 0.1%. Duration of diabetes mellitus, HbA1C value, methods of diabetic control, age, diabetic nephropathy, diabetic neuropathy, hypertension, systolic blood pressure, diastolic blood pressure, and arteriosclerosis obliterans were related with diabetic retinopathy. We suggest that the management of diabetic patients needs sufficient attention in the cases with oral administration of medication, insulin therapy, and diabetic nephropathy.

The value of high-pressure hysterosalpingography with new cannula.

To achieve maximum dilatation of the Fallopian tubes so as to improve the pregnancy: non-pregnancy ratio of hysterosalpingography (HSG) treatment, a high-pressure injection technique was evaluated. For this purpose a disposable cannula and an adapted pair of tenacula were developed and a remote-control procedure using an auto-injector and an adapted pressure recorder was used to assure the safety of doctors and staff. 1780 cases who underwent 400 mmHg high-pressure HSG treatment were compared with 903 conventional HSG cases. Results indicated a higher pregnancy ratio for the high-pressure experimental group after treatment. In addition, it was found that side effects due to the use of disposable cannula and highly viscous water-soluble mediums developed for use in angiography were less common than for conventional materials.

Dissociation of chorioadenoma destruens from hydatidiform mole by urinary steroid analysis.

Dissociation between hydatidiform mole (HM) and chorioadenoma destruens (CA) was attempted by gas chromatographic analysis of urinary steroids. In the chromatogram, fraction 2 (F2) including four pregnane steroids (17-hydroxypregnanolone, pregnanolone, pregnanediol, and pregnanetriol) reflected the biologic activity of molar human chorionic gonadotropin (hCG), and the ratio of F2 to fraction 1 (F1) (17-ketosteroids) was found useful in monitoring secondary growth of trophoblastic tumor: Urinary log F2/F1 after curettage declined quickly and unidirectionally in HM, but the same parameter exhibited a temporal rise in CA at 11 to 20 days after curettage because of the molar hCG from residual tumor tissue. The resolution between HM and CA at that stage (11 to 20 curettage days) was of the order of diagnostic use and superior to that with immunoreacive hCG. The data obtained are discussed in the light of pathophysiology of CA.

The value of urinary steroid analysis in chorionic neoplasia.

The profile of urinary neutral steroids was investigated in normal pregnancy and chorionic neoplasia by gas-liquid chromatography. The whole chramatogram was divided into three metabolically distinct fractions. The excretion of fraction 2, including four menstruation-dependent steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetrial), was remarkably increased in normal pregnancy as compared with that in nonpregnant controls. But the same parameter was differentially reduced in hydatidiform mole (HM) and chorioadenoma destruens (CA) as compared with normal pregnancy, and the ratio of fraction 2 to fraction 1 (11-deoxy-17-ketosteroids) was found useful in separating normal pregnancy, HM, and CA from each other. In choriocarcinoma (CC), reduced excretion was observed in both fraction 1 and fraction 2 steroids. The linear relationship between the logarithm of fraction 2-fraction 1 ratio and that of pregnanediol excretion, as observed in the reproductive cycle of a healthy woman, was not detectable in women with CA, whose urine revealed a low value of log (fraction 2/fraction 1) in spite of an abundant HCG content. It is indicated that the above findings reflect the deficiency of ovarian steroidogenesis under the influence of abnormal HCG from tumors.