Pregnancy complicated with Buerger's disease.

Buerger's disease is an inflammatory occlusive vascular disorder involving small- and medium-sized arteries in the distal extremities and is usually complicated with thrombophlebitis. Since Buerger's disease develops most frequently in men who smoke, pregnancy complicated with this disease is extremely rare. Only three pregnancies have been reported previously. All cases indicate that Buerger's disease worsens during pregnancy. However, anti-coagulant therapy appeared to be effective in this case. Accordingly, careful observation is mandatory in pregnancies complicated with Buerger's disease.

Successful intrauterine treatment with radiofrequency ablation in a case of acardiac twin pregnancy complicated with a hydropic pump twin.

Twin reversed arterial perfusion sequence is a serious complication of monochorionic twin pregnancy, as the pump twin that perfuses blood to the acardiac twin may experience heart failure and fetal hydrops resulting in a poor perinatal outcome. A woman with an acardiac twin pregnancy complicated by a hydropic pump twin underwent intrauterine treatment with radiofrequency ablation (RFA) at 27 weeks of gestation. Obliteration of blood flow to the acardiac twin from the pump twin was successful. Fetal hydrops resolved by the time of delivery at 32 weeks of gestation, in spite of transient deterioration, and a good postnatal outcome was achieved for the pump twin. We found that RFA was an effective intrauterine treatment for acardiac twin pregnancy and suggest that it could be introduced in cases complicated by a hydropic pump twin.

Expression and activation of MAP kinases, ERK1/2, in the human villous trophoblasts.

Mitogen-activated protein kinase (MAP kinase) plays a central role in the signal transduction for diverse cellular responses, such as proliferation, differentiation, stress response and cell death, via activation after binding of growth factors to the respective receptors on the cell membrane. In the human placental tissues, however, little is known about the expression and activation of the classical MAP kinases, extracellular signal-regulated kinase1/2 (ERK1/2). We therefore examined the expression of ERK1/2 in the human chorionic and placental tissues between 5 and 41 weeks of gestation, using Western blotting, immunohistochemistry and in situ hybridization. To explore the activation of ERK1/2 protein, we used an antibody that reacts with both phosphorylated and non-phosphorylated ERK1/2 (total ERK1/2), as well as antibodies that react only with phosphorylated ERK1/2. The expression pattern of phosphorylated ERK1/2 in the trophoblasts was compared with that of various growth factor receptors, such as c-met, IGF-1R, flt-1, EGFR, PDGFR, Bek, and flg. Total ERK1/2 was immunolocalized in the villous cytotrophoblasts (CTs), but not in the syncytiotrophoblasts (STs), throughout pregnancy. In situ hybridization also showed the localization of ERK1 mRNA in the villous CTs. Interestingly, however, phosphorylated ERK1/2 was immunolocalized in the villous CTs only up to 12 weeks of gestation. Western blot also showed the stronger bands of phosphorylated ERK1/2 in the tissues of the first trimester. Among the growth factor receptors, c-met was strongly expressed in the villous CTs during the first trimester, and resembled the expression pattern of phosphorylated ERK1/2. These findings suggest that the MAP kinase pathway is activated in the villous CTs during the first trimester in the human placenta.

X-ray magnetic circular dichroism in cobalt-iron spinels and electronic states of Co ions.

Synchrotron X-ray experiments on magnetic circular dichroism (XMCD) have been performed at Co K and Fe K absorption edges for CoFe2O4, Fe(1.5)Co(1.5)O4 and FeCo2O4 with the spinel structure. The XANES studies have clarified that only Fe3+ exists in all compounds and Co2+ and Co3+ coexist in the latter two cobaltites. A systematic change in XMCD spectra has concluded that the Co2+ ions in the B sites of FeCo2O4 are in the low-spin state. Since the Co2+ ions in CoFe2O4 are in the high-spin state, the spectra of the intermediate cobaltite may be explained as a mixture of low-spin and high-spin states.

Spontaneous remission of cyclic neutropenia during pregnancy. A case report.

BACKGROUND: Cyclic neutropenia is characterized by regularly recurring episodes of neutropenia. It has been reported that pregnancy often has a mitigating effect on the symptoms. However, there have been no detailed studies on changes in the neutrophil count before, during and after pregnancy. CASE: A 24-year-old woman with cyclic neutropenia had a successful pregnancy, during which her symptoms improved spontaneously, with decreased severity. The disease recurred soon after pregnancy, and cyclic neutropenia was inherited by the child. CONCLUSION: Cyclic neutropenia may follow a favorable course during pregnancy, with decreased severity, but postpartum maternal and neonatal complications can occur.

[A patient who developed dermatomyositis during the 1st trimester of gestation and improved after abortion].

This patient was a 30-year-old woman who was in the 8th week of her first pregnancy with three embryos. She developed fever, myalgia and weakness of the proximal muscles, and erythema of the face, dorsal aspects of elbows, and knees. Routine blood examinations showed elevated serum CK. Immunologically, an anti-Jo-1 antibody was positive. Skin biopsy revealed mucinosis and edema in the superficial layer of the corium, and liquid alternation in the basal layer of the epidermis. From these findings, this patient was diagnosed as having dermatomyositis. She was placed on oral prednisolone (80 mg daily), but her clinical symptoms did not improve and all fetuses died by the 11th week of gestation. Then she underwent dilation and curettage and after this operation her disease rapidly subsided. It seemed that fetuses were causatively related to the development of dermatomyositis possibly by changing maternal immune condition. There were six reported cases with dermatomyositis/polymyositis who developed during the first trimester of gestation. Four of these 6 patients were treated with oral steroid; however, only one patient ended in normal delivery. More aggressive therapy, other than corticosteroid, may be required to improve fetal prognosis.

Loss of heterozygosity among tumor suppressor genes in invasive and in situ carcinoma of the uterine cervix.

The aim of the present study was to further clarify the histogenesis of cervical carcinoma by investigating loss of heterozygosity (LOH) among a number of tumor suppressor genes in invasive and in situ carcinoma of the cervix. Materials consisted of 16 in situ and 29 invasive carcinomas (16 squamous cell carcinomas, nine adenocarcinomas, and four adenosquamous carcinomas). DNA samples were collected by microdissection from ordinary formalin-fixed, paraffin-embedded tissues, both from the lesions and from normal tissues. LOH was analyzed using eight DNA polymorphic tumor suppressor markers. Of the 16 cases of carcinoma in situ, three cases exhibited LOH at one locus. Of the 29 cases of invasive carcinomas, six cases exhibited LOH at two loci and nine cases exhibited LOH at one locus. Overall, LOH was found more frequently in invasive carcinomas than in in situ carcinomas. LOH was most frequently detected at the PTCH (Drosophila patched gene) locus. There was no significant correlation between LOH at a specific site and either histologic subtype or clinical stage. These results suggest that LOH might already occur in a fraction of preinvasive squamous lesions and that accumulation of LOH may in part play a role in carcinogenesis of the cervix.

Embryo-dependent induction of embryo receptivity in the mouse endometrium.

The effect of intraoviductal embryos on endometrial receptivity was studied by intraendometrial and intrauterine embryo transfer. Five-week-old female ICR mice were mated after superovulation; a vaginal plug confirmed day 1 of pregnancy. On day 4 (90 h after hCG injection), blastocysts were collected and transferred to pseudopregnant female mice and to recipient mice in which the uterotubal junction had been ligated bilaterally on day 1 of pregnancy. Three embryos per uterine horn, a total of six embryos per recipient mouse at days 1-6, were transferred to the endometrium or uterine cavity and implantation and pregnancy rates were calculated. The implantation rate for intraendometrial embryo transfer to recipients of days 3, 5 and 6 was significantly higher for uterotubal junction-ligated mice (72.2, 20.8 and 9.7%, respectively) than for pseudopregnant mice (55.0, 8.3 and 0.0%, respectively). The implantation rate for intrauterine embryo transfer to recipients at days 2, 5 and 6 was significantly higher for uterotubal junction-ligated mice (11.1, 25.0 and 8.3%, respectively) than for pseudopregnant mice (0.0, 3.3 and 0.0%, respectively). Uterotubal junction-ligated mice achieved implantation and bore neonates by intrauterine embryo transfer on days 2 and 6, whereas no implantation was achieved in pseudopregnant mice. The difference in implantation rate could not be explained by a difference in progesterone concentration between the groups. The distribution of proliferating cells in the endometrium was also studied immunohistochemically by use of anti-proliferating cell nuclear antigen (PCNA) antibody in the recipient mice. PCNA-positive cells were more abundant in uterotubal junction-ligated mice and demonstrated a marked extension from the epithelium to the stroma over time, in contrast to those in pseudopregnant mice. These findings indicate that an intraoviductal embryo exerts a biological effect by sending a signal to the endometrial epithelium and stroma, thus facilitating endometrial receptivity to the embryo and improving the rate of implantation.

Structure of a plant cell wall fragment complexed to pectate lyase C.

The three-dimensional structure of a complex between the pectate lyase C (PelC) R218K mutant and a plant cell wall fragment has been determined by x-ray diffraction techniques to a resolution of 2.2 A and refined to a crystallographic R factor of 18.6%. The oligosaccharide substrate, alpha-D-GalpA-([1-->4]-alpha-D-GalpA)3-(1-->4)-D-GalpA , is composed of five galacturonopyranose units (D-GalpA) linked by alpha-(1-->4) glycosidic bonds. PelC is secreted by the plant pathogen Erwinia chrysanthemi and degrades the pectate component of plant cell walls in soft rot diseases. The substrate has been trapped in crystals by using the inactive R218K mutant. Four of the five saccharide units of the substrate are well ordered and represent an atomic view of the pectate component in plant cell walls. The conformation of the pectate fragment is a mix of 21 and 31 right-handed helices. The substrate binds in a cleft, interacting primarily with positively charged groups: either lysine or arginine amino acids on PelC or the four Ca2+ ions found in the complex. The observed protein-oligosaccharide interactions provide a functional explanation for many of the invariant and conserved amino acids in the pectate lyase family of proteins. Because the R218K PelC-galacturonopentaose complex represents an intermediate in the reaction pathway, the structure also reveals important details regarding the enzymatic mechanism. Notably, the results suggest that an arginine, which is invariant in the pectate lyase superfamily, is the amino acid that initiates proton abstraction during the beta elimination cleavage of polygalacturonic acid.

Differential effect of site-directed mutations in pelC on pectate lyase activity, plant tissue maceration, and elicitor activity.

Oligonucleotide site-directed mutations were introduced into the pelC gene of Erwinia chrysanthemi EC16 that directed single or double amino acid changes affecting disulfide linkages, calcium binding, catalysis, and protein folding. Subsequent characterization of the purified PelC mutant proteins demonstrated that pectinolytic function involves amino acids located near the calcium binding site rather than those surrounding an invariant vWiDH sequence. Wild-type PelC and the tested mutant proteins generally macerated plant tissue in proportion to their specific pectinolytic activity in vitro. However, some mutants gave higher maceration activity in plant tissue and elicited greater production of the phytoalexin, glyceollin, in soybean cotyledons than predicted by their in vitro pectinolytic activity. Most notable in this regard were three different mutations at lysine 172 with greatly reduced pectinolytic activity but as much elicitor activity as the wild-type protein. PelE macerated plant tissue 10 times more efficiently than PelC, as observed previously, but surprisingly showed equal activity in the elicitor assay. The results indicate that factors other than pectinolytic activity per se are involved in plant tissue maceration and elicitor activity.

[Ultrastructural studies of articular cartilaginous degeneration in the facet joints in spinal scoliosis].

The purpose of this study was to determine the relationship between spinal scoliosis and degeneration in the articular cartilage of the intervertebral facet joint. Histological and ultrastructural studies were performed on the articular cartilage of the apical facet joints in the area affected by spinal scoliosis. Histological examinations showed that cartilaginous degeneration in the concave side was more severe than that in the convex side. Over 70 degrees, the histological findings showed increased surface irregularities and hypocellularity in the concave facet joints. A significant correlations were found between the apical degenerative score of the articular cartilage and the pre-operative rotation index and the post-operative correction ratio of the scoliosis. Using transmission electron microscopy (TEM), the development of the organellae of the concave articular cartilage was demonstrated to be commonly disturbed, but the microstructure of the convex cartilage was intact with less than 70 degrees of spinal scoliosis, while similar findings to the concave side were demonstrated over 70 degrees. These results suggest that a biomechanical imbalance disturbed organellae of the cartilage cells in the articular cartilage of the concave apical facet joints initially and this then gradually extended to the convex side over 70 degrees with progressing scoliosis.

The influence of increased plasma protein binding on the disposition of quinidine in turpentine-treated rats.

The effect of the increased plasma protein binding of quinidine on its disposition was investigated in turpentine-treated rats, since turpentine treatment is known to increase the plasma concentration of alpha 1-acid glycoprotein which preferentially binds basic drugs. The plasma free fraction of quinidine 16 and 48 h after turpentine treatment was decreased by 30 and 76%, respectively, compared to the control value. The treatment did not cause liver injury nor alter the hepatic blood flow. The disappearance of quinidine in plasma after an intravenous injection (3.0, 7.0, 12.5 mg/kg) was analyzed by a two-compartment open model in both control and turpentine-treated rats. The blood total body clearance (CLb) of quinidine at 48 h after the treatment was decreased by 30 to 65% in a dose-dependent manner, compared to that in control rats. The distribution volume (Vdss) of quinidine (12.5 mg/kg) at 16 and 48 h after turpentine treatment was decreased by 30 and 79%, respectively. Hepatic extraction ratio (HER) of quinidine, which was determined at steady state blood concentrations from 0.5 to 2.3 micrograms/ml, was decreased from 0.8 to 0.35 with an increase in the quinidine concentration in control rats. The HER value 48 h after turpentine treatment was consistently reduced by 15 to 40% in a concentration-dependent manner compared to the corresponding control value. These findings indicate that the increased plasma binding of quinidine caused a reduction of HER of the drug, and the reduced HER resulted in the decrease in CLb in turpentine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma alpha 1-acid glycoprotein concentration in rats with chemical liver injury.

The influence of liver injury on the plasma concentrations of alpha 1-acid glycoprotein (AGP) and albumin was examined in several different models of chemically-induced liver injury. The plasma AGP concentration in carbon tetrachloride (CCl4), allyl alcohol, bromobenzene, acetaminophen or N-nitrosodimethylamine-induced liver injury was increased to 2-3.5 times the normal level at 24 h after the intoxication. The plasma AGP concentration was unchanged in ethionine-induced liver injury and was markedly decreased in galactosamine-induced injury. The plasma albumin concentration was significantly decreased by the damage due to galactosamine, allyl alcohol or N-nitrosodimethylamine-induced liver injury, while no influence was observed by other hepatotoxin-induced liver injury. The plasma protein binding of propranolol was also determined in relation to the plasma concentrations of AGP and albumin in all the experimental models. Propranolol binding, expressed as bound to free ratio, showed a good correlation with the AGP concentration (r = 0.940; p < 0.001), but not with the albumin concentration.

Summer-type hypersensitivity pneumonitis: comparison of high-resolution CT and plain radiographic findings.

Summer-type hypersensitivity pneumonitis is an immunologic disease that occurs only in Japan. It is a form of hypersensitivity pneumonitis in which the clinical symptoms appear in the summer and subside spontaneously in mid autumn. The purpose of our study was to determine the CT findings in this condition, to compare the CT findings with those on chest radiographs, and to assess the variations in the CT findings over time. Accordingly, high-resolution CT scans and chest radiographs of 15 patients with summer-type hypersensitivity pneumonitis were retrospectively studied. Seven patients had sequential CT examinations 18-37 days apart. The CT scans and chest radiographs were reviewed by two observers independently. CT findings included diffuse micronodules (n = 15), slightly elevated lung density (n = 13), and patchy air-space consolidation (n = 13). In one patient, the findings on a chest radiograph were normal, while CT showed parenchymal abnormalities. In two cases, follow-up CT showed micronodular abnormalities after findings on the chest radiograph had returned to normal. Our results show that high-resolution CT findings of summer-type hypersensitivity pneumonitis include pulmonary micronodules, increased lung density, and air-space consolidation. High-resolution CT appears to be more useful than plain chest radiographs in the evaluation of pulmonary parenchymal abnormalities in this condition.

Distribution of quinidine in rats with carbon tetrachloride-intoxicated hepatic disease.

The disposition of quinidine was investigated in rats with experimental hepatic disease caused by an intraperitoneal injection of CCl4. The plasma disappearance of quinidine after a 12.5 mg/kg i.v. bolus injection was analyzed by a two-compartment open model in both control and CCl4-intoxicated rats. In the CCl4-intoxicated rats, plasma total body clearance (CLtot), elimination rate constant of the central compartment (kel) and the volume of distribution (Vdss) of quinidine were decreased by 73, 51 and 36%, respectively, compared to those in the control rats. At a steady state of quinidine plasma concentration of 1 micrograms/ml, tissue-to-plasma partition coefficient (Kp,vivo) of the drug in the lung, spleen, heart, kidney and liver in the CCl4-intoxicated rats were decreased ranging from 32 to 42% compared to those in the control rats. The plasma free fraction of quinidine in the intoxicated rats was decreased by 34% of that in the control rats. Neither tissue binding of quinidien in vitro, nor plasma pH was altered in the intoxicated rats. Thus, the decrease in Vdss and Kp,vivo for quinidine in the intoxicated rats seems likely to be due to an increase in plasma protein binding of the drug. Metabolic activity in the liver, the hepatic extraction ratio for quinidine, and the hepatic blood flow in the CCl4-intoxicated rats were decreased by 84, 57 and 47%, respectively, compared to those in the control rats. The decrease in CLtot and kel in the intoxicated rats is considered to be attributed to both the reduction of liver functions and the increase in the plasma protein binding of the drug.

Accumulation of propranolol in cultured rat fibroblasts.

In order to clarify the involvement of phosphatidylserine (PhS) in the cellular accumulation of propranolol, we have characterized the binding of 3H-propranolol to cultured rat fibroblasts and to liposomes containing PhS. The properties of propranolol binding to the cells and liposomes were analyzed by means of a Scatchard plot. The cells contained at least two classes of propranolol binding sites, one site of high affinity/low capacity and the second site of lower affinity/higher capacity, while the liposomes contained only one class of binding site. The values of the association constant (K) and number of binding sites (n), given on a PhS basis for the propranolol binding site in the liposomes, were both very close to those of corresponding binding parameters for the high affinity/low capacity binding site in the cells. Cell death, caused by various toxic reagents, resulted in a marked decrease in propranolol accumulation in the cells. Kinetic analysis of the drug binding to dead cells showed one binding site with binding parameters comparable to those of the low affinity/high capacity binding site in the intact cells. Polar cations, methylamine and NH4Cl, completely inhibited propranolol binding to the liposomes. On the other hand, these cations partially inhibited propranolol accumulation in intact cells and failed to inhibit the drug binding to dead cells. These results suggest that PhS in cytomembranes represents the high affinity/low capacity propranolol binding site in cultured rat fibroblasts.

[Studies on the nontuberculous lung mycobacteriosis in Japan. (Report of the study in the year 1987 and 1988 of the Mycobacteriosis Research Group of the Japanese National Chest Hospitals)--pulmonary infection caused by Mycobacterium kansasii has begun to appear in all over Japan including north Japan Hokkaido].

UNLABELLED: In this study, the Mycobacteriosis Research Group of the Japanese National Chest Hospitals (MRG) presents the reports of study years 1987 and 1988. As reported previously**, pulmonary infection caused by Mycobacterium kansasii occurred principally in South-West Japan (prefectures South-West of Tokyo) and did not appear in North Japan. However, this disease appeared in 1987 and 1988 in Hokkaido (Sapporo Hospital). Accordingly, we may say the disease occurs all over Japan. This is a noteworthy finding newly recognized in the study years. The prevalence rate of nontuberculous lung mycobacteriosis was determined as 2.92 or 2.78 in 1987 and as 2.02 or 1.91 in 1988 per 100,000 population per year. The estimated rates based on the ratio of nontuberculous lung mycobacteriosis against active lung tuberculosis and based on the ratio of nontuberculous lung mycobacteriosis against culture-positive lung tuberculosis well agreed with each other. COMMENT: In this country, chest physicians customarily report their cases of nontuberculous mycobacteriosis including lung tuberculosis, because the payment of treatment for patients with tuberculosis is free. Because of this custom, tuberculosis statistics surely contain cases of nontuberculous mycobacteriosis. Caution about this has been paid in calculating the prevalence rate. From the study year 1987, the MRG chairman moved from Michio Tsukamura, The National Chubu Hospital, to Nobuhiko Kita, The National Kinki Chuo Hospital.

Increase in the plasma protein binding of weakly basic drugs in carbon tetrachloride-intoxicated rats.

Plasma protein binding of weakly basic drugs such as propranolol and quinidine was determined in rats with carbon tetrachloride (CCl4)-induced hepatic disease. Free fractions of propranolol and quinidine in the plasma of rats at 24 h after CCl4-intoxication were decreased by 41 and 30%, respectively, compared to those of control rats. An addition of Tris (butoxyethyl) phosphate (TBEP), a specific displacer for basic drugs from alpha 1-acid glycoprotein (AGP), to the plasma increased the free fractions of the basic drugs, resulting in no difference in the extent of the plasma free fraction of each drug between control and CCl4-intoxicated rats. Plasma concentration of AGP in CCl4-intoxicated rats was elevated 2.7-fold of that in control rats at 24 h after the CCl4 intoxication and reached a peak of 4.8-fold elevation at 48 h. A regression analysis revealed a high degree of positive correlation between ratios of bound to free fraction of propranolol and plasma concentrations of AGP. These results suggest that the plasma protein binding of the basic drugs was increased mainly due to the rise in the plasma AGP concentration in CCl4-intoxicated rats.