Effects of cocaine and ethanol on mouse fetuses.

In the presence of ethanol, cocaine is metabolized to its ethyl homolog, cocaethylene. To investigate the embryotoxic effects of cocaethylene, pregnant ICR mice receiving ethanol orally during pregnancy were treated with 50 mg/kg/day cocaine i.p. on days 7, 8 and 9 of gestation. Treatment with either cocaine or ethanol alone did not affect the fetal mortality rate or the mean fetal body weight. Concurrent cocaine and ethanol treatment increased the fetal mortality rate, and decreased the mean fetal body weight, although teratogenicity was not noted. These results suggest that concurrent use of cocaine and ethanol during pregnancy is more harmful to fetal body weight gain and their lives than the use of either drug alone, at least in the present experimental settings.

[Determination of bisphenol A in foods using GC/MS].

An analytical method using GC/MS was developed for bisphenol A (BPA) in foods and BPA was determined in canned foods and fresh foods such as vegetables, fruit and meat. BPA was extracted with acetone from the samples and the extract was concentrated at under 40 degrees C in vacuo to afford an aqueous solution, which was washed with hexane after alkalization and extracted with 50% diethyl ether-hexane after acidification. Extracts were cleaned up on a PSA and/or a C18 cartridge column, and BPA was derivatized with heptafluorobutyric anhydride and determined by GC/MS (SIM). This method was applicable to the detection and determination of BPA residues in food samples at the level of 1 ng/g. Among canned foods, BPA was found in 6 corned beef, 1 chicken, 9 sweet corn and 3 bean samples at the levels of 17-602 ng/g, 212 ng/g, 2.3-75 ng/g and 3.5-26 ng/g, respectively. BPA was also detected in 1 retort soup and 1 retort pack product at the levels of 11 ng/g and 86 ng/g, respectively. As for dairy products, BPA was not detected in butter and milk. Among fresh foods, BPA was detected in 2 fish and 3 liver samples at the levels of trace (tr)-6.2 ng/g and tr-2.2 ng/g, respectively. In vegetables, fruits and chocolates, a trace level of BPA was detected in only 1 chocolate. Traces of BPA were also detected in 3 samples of 6 boxed lunches.

Effects of umbilical arterial resistance on its arterial blood flow velocity waveforms.

BACKGROUND: We propose to clarify the effect of umbilical arterial resistance on umbilical arterial blood flow patterns in normal pregnant women. SUBJECTS: Pulsed Doppler examination was administered to 145 pregnant women of between 28 and 31 weeks of normal gestation without any prenatal complications. METHODS: The arterial flow velocity waveforms from two different arteries, one in the intra-abdominal portion and the other at the placental insertion, were sampled with the color flow mapping method, and the peak systolic velocity and the resistance index were calculated. RESULTS: The peak systolic velocity and resistance index on the placental side were significantly lower than those of the fetal side. CONCLUSION: A major difference exists between the umbilical arterial flow velocity waveforms on the fetal and placental sides, which might be caused by difference in the umbilical arterial resistance.

Eosinophilic apoptosis in sinus mucosa: relationship to tissue eosinophilia and its resolution in allergic sinusitis.

BACKGROUND: Apoptosis, which is regulated by both cell survival and death signals, is important for the swift clearance of unwanted cells. OBJECTIVE: We sought to elucidate whether eosinophilic apoptosis is associated with tissue eosinophilia and to determine its resolution in allergic sinusitis (AS). METHODS: Numbers of eosinophils, numbers of IL-5(+) cells, and the apoptosis index of eosinophils were calculated in the submucosa (both superficial and deep layers) of patients with AS by using histochemical methods before and after prednisolone treatment. Patients without AS were used for control groups. Anti-EG2 antibody was used to identify eosinophils. IL-5, Fas, or Bax expression of eosinophils was evaluated to elucidate the role of the factors affecting eosinophilic apoptosis. RESULTS: EG2 and IL-5(+) cells were abundant in the submucosa of patients with AS, especially in the superficial layer. About 50% to 60% of the IL-5-producing cells were eosinophils. Apoptotic eosinophils were less numerous in the superficial layer than the deep layer in these diseases. After prednisolone treatment, an induction of eosinophilic apoptosis was accompanied by a significant decrease in the number of EG2(+) and IL-5(+) cells. No remarkable difference was observed in the Fas or Bax expression of eosinophils after prednisolone treatment. CONCLUSION: Autocrine secretion of IL-5 from eosinophils may be one reason why eosinophilic disease is difficult to manage. Induction of eosinophilic apoptosis is critical for reversing tissue eosinophilia in patients with AS.

[Empyema thoracis accompanied by hyperammonemic encephalopathy].

A 50-year-old man was admitted to our hospital due to consciousness disturbance. On admission, he was comatose (200 on the Japan Coma Scale) but brain computed tomographic (CT) scans were normal. Chest radiographs and CT scans on admission revealed massive pleural effusion in the right hemithorax. A culture of purulent pleural fluid yielded three species of anaerobes, including Bacteroides fragilis. Laboratory examinations revealed markedly elevated WBC count, CRP, and serum ammonia (586 micrograms/dl). However, liver function was almost normal and no other metabolic disorders were demonstrated. After the initiation of antibiotic therapy and pleural drainage, the patient's cousciousness level gradually improved in parallel with decreasing serum levels of ammonia and CRP. Because no other potential causes of hyperammonemia were observed, we concluded that the consciousness disturbance was due to hyperammonemia presumably caused by a urease-producing anaerobe infecting the right pleural space.

Fetal peripheral bronchial fluid flow during breathing movement in normal pregnancies: a preliminary study.

OBJECTIVE: To determine the fluid flow velocity waveforms in the fetal peripheral bronchus during fetal breathing movement by means of pulsed Doppler ultrasonography. DESIGN: A preliminary cross-sectional study. SUBJECTS: Twenty-eight normal pregnant women between 32 and 38 weeks of gestation. METHODS: Velocity waveforms from fetal peripheral respiratory fluid flow were acquired from the segmental bronchus (B6 or B8) which runs along the segmental artery (A6 or A8). The maximum velocity of the intrabronchial fluid flow and duration of inspiratory and expiratory phases were quantified. RESULTS: The flow velocity signal from the fluid in the fetal segmental bronchus of 17 of the 28 fetuses was detected. We observed two types of fetal breathing movement. CONCLUSION: During fetal breathing movement, the fluid in the fetal respiratory tract moves in the fetal segmental bronchus. This movement can be detected by pulsed Doppler velocimetry aided by power Doppler ultrasonography.

Stimulation of fetal granulopoiesis by intrauterine injection of recombinant human granulocyte colony- stimulating factor into rat fetuses.

The small neutrophil reserve and exaggerated release of stored neutrophils are factors which predispose neonates to neutrophil reserve exhaustion during bacterial sepsis. Our objective is to try to improve in utero the myelopoietic function of the fetus before delivery. In the first series, recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) (rhG-CSF; 100 microg/kg) was injected subcutaneously into rat fetuses at the indicated times to assess drug absorption and fetal response. In the second series, rhG-CSF (100 microg/kg) or saline (control) was injected into the fetuses once every other day to investigate the effect of repeated injections of rhG-CSF on enhancing fetal myelopoiesis preceding birth. Delivery was performed by cesarean section on embryonic day 21. The plasma concentration of G-CSF was determined by ELISA. The effect of rhG-CSF injection on granulopoiesis was assessed by measurement of the neutrophil count in the fetal peripheral blood and by histological examination of the fetal bone marrow, spleen, and liver. Fetally administered rhG-CSF enhanced fetal myelopoiesis preceding birth.

Characteristics of blood flow in intrauterine growth-restricted fetuses with hypercoiled cord.

OBJECTIVE: To clarify the characteristics of fetoplacental blood flow of growth-restricted fetuses with hypercoiled umbilical cord. SUBJECTS: Eight growth-restricted fetuses with hypercoiled cord. METHODS: Flow velocity waveforms of the umbilical cord artery and vein, fetal abdominal aorta and fetal inferior vena cava were analyzed. RESULTS: The resistance index in the umbilical artery in the hypercoiled cases was lower than that in normal fetuses. Early-diastolic reversed flow was observed in the abdominal aorta in some cases. In all cases, umbilical venous pulsation was observed in the entire cord until delivery. In one case, fetal heart failure occurred, resulting in pre-mature delivery. An atrophic type of single umbilical artery was observed in four cases. CONCLUSION: Fetal blood flow disturbance caused by a hypercoiled umbilical cord may be a cause of growth restriction.

Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma.

BACKGROUND: Interleukin-10 (IL-10) has been implicated as an important modulator of lymphoid cells, and its sequence is homologous to an open reading frame in the Epstein-Barr virus (EBV) genome. Nasopharyngeal carcinoma (NPC) is a representative tumor related to EBV infection. METHODS: The authors investigated the expression of IL-10 in 21 primary NPCs by using an immunohistochemical approach to examine its prognostic significance. RESULTS: IL-10 staining was positive in 12 of 21 primary NPCs (57%). There was no association between IL-10 expression and gender, tumor size, the occurrence of lymph node metastases, clinical stage, or recurrence. However, there was a significant difference in overall survival between the negative expression and positive expression of IL-10 (P = 0.0348). Although 87.5% of the IL-10 negative group survived for 5 years, only 15.6% of IL-10 positive patients survived for that length of time by the Kaplan-Meier method. IL-10 expression was significant as an independent prognostic indicator of overall survival by multivariate analysis using the Cox proportional hazards model (odds ratio, 26.64; P = 0.0019). CONCLUSIONS: The results imply that expression of IL-10 is a prognostic factor in patients with NPC and may prove valuable in selecting patients with NPC who are candidates for aggressive therapy.

[Hemophagocytic syndrome associated with tuberculosis and mycoplasma infection in two patients].

Patient 1: A 48-year-old man was admitted to Osaka Red Cross Hospital because of fever and dyspnea. Laboratory examination revealed pancytopenia, liver dysfunction and hematostatic abnormality. Chest radiographs obtained on admission revealed ground-glass opacity in both lung fields, and an analysis of arterial blood showed severe hypoxemia (PaO2:46.8 Torr). Pulse therapy with methylprednisolone was started. Although the hypoxemia subsided and radiographic findings rapidly improved, pancytopenia persisted. Examination of bone marrow aspirate revealed mature histiocytes with marked hemophagocytosis. Amplified Mycobacterium tuberculosis direct tests of bronchoalveolar lavage fluid, sputum, urine, and bone marrow were all positive, and Mycobacterium tuberculosis was cultured from sputum and urine. Although the patient was taking antituberculous agents, his pancytopenia persosted. Treatment with etoposide induced remssion. Patient 2: A 19-year-old woman was admitted to Osaka Red Cross Hospital because of prolonged cough and fever. Laboratory examination revealed leukocytosis, liver dysfunction, and hematostatic abnormality. Serologic tests provided conclusive evidence of Mycoplasma infection and a CRP test was strongly positive. Chest radiographs obtained on admission revealed infiltration shadows in the middle and lower lung fields on both sides, with left pleural effusion. An analysis of arterial blood showed hypoxemia (PaO2: 54.2 Torr). Examination of bone marrow and pleural effusion samples revealed mature histiocytes with marked hemophagocytosis. Although treatment with antibiotics and pulse therapy with methylprednisolone was started, the patients respiratory functions deteriorated. Endotracheal intubation was performed. Therapy with etoposide induced remission. Hemophagocytic syndrome associated with Mycoplasma infection and tuberculosis appears to be exceedingly rare. In these 2 cases, it was difficult to achieve remission with therapy for the underlying infections, but etoposide treatment was effective.

Effects of maternal prone position on the umbilical arterial flow.

OBJECTIVE: The objective of our study was to clarify the effect of the maternal prone position on the feto-placental flow. In this position, the uterine compression of the large maternal vessels was expected to be completely eliminated. METHODS: Twenty-three normal pregnant women were cross-sectionally examined in the supine, the left lateral, the right lateral and the prone position. The systolic/diastolic ratios for the umbilical artery were calculated for each position. RESULTS: The umbilical arterial systolic/diastolic ratio in the prone position significantly decreased compared with that in the supine position. The left and right lateral position showed no significant change in the systolic/diastolic ratio. CONCLUSION: The maternal prone position can provide complete relief of uterine compression of the large maternal vessels.

Characterization of ribonucleases from culture medium of Lentinus edodes.

Lentinus edodes (shiitake) cultivated in potato dextrose medium produced five RNases in the culture filtrate. The two major RNases (RNase Le37 and RNase Le45) were highly purified and their molecular masses, base specificities, N-terminal amino acid sequences, and amino acid compositions were analyzed and compared to RNase Le2 isolated from the fruit bodies of the same mushroom. RNase Le37 and RNase Le45 are base non-specific and adenylic acid preferential RNases like RNase Le2 and their N-terminal sequences are very similar to RNase Le2, but they are glycoproteins and their amino acid compositions are significantly different from that of RNase Le2. In addition to these enzymes, a guanylic acid-specific RNase with a molecular mass 13 kDa was partially purified. Since RNase Le2, which has very similar N-terminal sequence to RNase Le37 and RNase Le45, was not excreted from the mycelia, the analysis of the structures of these two excreted RNase may shade a light on the mechanism of excretion of RNases in this organism.

[The questionnaire concerned with the start and end point of the treatment for nasal allergy].

The precise primary end point of the treatment for nasal allergy has never been indicated. In this study, we conducted a questionnaire of specialists who actually treat with nasal allergy. The questionnaire is about start and end point of the treatment for nasal allergy. Answers were obtained from 49 doctors. The results were as follows. 1. About the goal at the start of the treatment. Perennial nasal allergy was put stress on control of the symptom, keeping of remission and improvement of quality of life. Pollinosis was put stress on control of the symptom, prevention of acute exacerbation and improvement of quality of life. No significant difference was observed between adult and child. 2. About the condition at the end point of the treatment. Perennial nasal allergy was put stress on the condition that symptoms were indisposition, no obstacle to daily life and no or a little medication was necessary. Pollinosis was put stress on the condition that symptoms were indisposition, no obstacle to daily life, and a little medication was necessary or that symptoms were continually stable and acute exacerbation was very rare. No significant difference was observed between adult and child.

Cytofluorometric DNA analysis by stathmokinetic method of experimental thyroid neoplasms in rats.

Thyroid neoplasms were induced in rats by the intraperitoneal injection of N-bis(2-hydroxy-propyl)nitrosamine as a carcinogenic substance and by the oral administration of KCIO4 as a promoter. The nuclear DNA content was measured in tissue sections of the tumors by the stathmokinetic method with the use of vincristine, and was correlated with the histopathological findings in the process of tumorigenesis and progression. Histological examination showed various types of lesions were produced in 47 surviving rats. A diploid pattern was seen in 82 (92%) of 89 tumors and an aneuploid pattern in 7 (8%) of 89 tumors. Papillary carcinomas and mixed carcinomas only had a diploid pattern, while two of 17 follicular carcinomas and five of 13 anaplastic carcinomas had an aneuploid pattern. On the other hand, benign proliferative nodules only had a diploid pattern. DNA heterogeneity was noted in seven malignant tumors. In four of them it was associated with the histopathological evidence of change, but in three there was no histological difference between the aneuploid and diploid areas other than a difference in the mitotic index. Mitotic indices were significantly higher in the aneuploid than in the diploid areas. These findings suggest that changes in the DNA ploidy cause histological abnormalities and/or affect the mitotic index. It is hypothesized that a change occurs in some diploid cells in a region of a tumor, and that aneuploid cells develop from the diploid cells which then acquire high proliferative activity.

Umbilical arterial flow change during hemodialysis.

A pregnant woman was performed hemodialysis 3 times a week from early gestation. At 30 weeks of gestation, fetal growth and amniotic fluid volume were normal. We performed 3-hour hemodialysis 6 times a week. Cesarean section was performed at 38 weeks of gestation, she delivered a healthy neonate weighing 2575 g. During hemodialysis, we performed Doppler flow velocimetry on the umbilical artery. The resistance index revealed a remarkable decrease after 1.5 hour hemodialysis. But it recovered 3 hours of administration as well as after completion of treatment. We speculated this change in the resistance index of the umbilical artery was caused by transient maternal hypovolemia.

Evidence for structural differences between the two highly homologous actin-regulatory proteins, destrin and cofilin.

The amino acid sequences of destrin and cofilin are very similar (84% homology) throughout the entire range of proteins, but they have different functions. In this study, we constructed a new cofilin expression plasmid, which had high expression frequency, and the structures of destrin and cofilin were analyzed by limited proteolysis and circular dichroism (CD). When destrin was digested by trypsin, two fragments of 17.0 kDa and 9.2 kDa were obtained, whereas only one 8.4 kDa fragment was obtained from cofilin. In spite of the overall sequence homology, an N-terminal amino acid sequence analyses of the fragments revealed the cleavage sites on destrin and cofilin to be different. These results suggest that destrin and cofilin differ in their overall tertiary folds. Cofilin showed activity similar to destrin at high pH values, although no pH-dependent structural change in cofilin was confirmed by using limited proteolysis and CD.

Uterine blood flow velocity waveforms during early postpartum course following caesarean section.

OBJECTIVE: To assess the change of uterine blood flow after Caesarean section. STUDY DESIGN: Doppler flow velocity waveforms were acquired from the uterine arteries and small arteries near the myometrial wound detected by transvaginal power Doppler ultrasonography in 23 patients on the 3rd, 6th and 9th postoperative days. RESULTS: The resistance index for the uterine artery did not show any change during the study period, while that for the small arteries slightly decreased. CONCLUSION: Uterine blood flow resistance after Caesarean section did not show any change during the early postpartum period.

Favorable response to heparin in a pregnant woman with possible glomerular thrombosis as a complication of systemic lupus erythematosus and anti-phospholipid antibody syndrome.

A rare case of possible glomerular thrombosis during pregnancy is reported in a patient with active systemic lupus erythematosus and the presence of anti-phospholipid antibodies. Acute renal impairment was restored by administering infusions of heparin. Cesarean section was performed due to fetal distress, and resulted the live birth of a healthy infant.