Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy

OBJECTIVE: Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it is also secreted in the placenta and is probably a cause of pre-eclampsia. To provide a basis for elucidation of the relationship between pre-eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood. METHODS: Fifty-nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8-20 weeks' gestation (early), 11 at 28-34 weeks (middle) and 24 at 35-40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method. RESULTS: The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood. CONCLUSION: This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.     

Administration of docetaxel in cases of recurrent breast carcinoma with malignant pleural effusion controlled by intrapleural administration of OK-432

Docetaxel is an anti-tumor agent which promotes the congregation and stabilization of microtubules, there by preventing cell division. It is reported to have anti-tumor activity against breast or non-small cell lung carcinomas which have been resistant to other anti-tumor agents. On the other hand, it causes peripheral edema and effusion in the pleural or peritoneal cavities. Thus, pleural or peritoneal effusions, which require drainage have been considered to be contraindications for the administration of docetaxel. OK-432 is an agent which causes adhesion by evoking a local inflammatory reaction. We experienced two cases of recurrent breast carcinoma with malignant pleural effusion. We successfully managed their pleural effusion with the intrapleural administration of OK-432. Thereafter, we safely administered docetaxel, and obtained good outcomes. The present paper also discussed the synergistic action between these agents.     

Effect of cis-dichlorodiammineplatinum(II) on cloned ovarian adenocarcinoma cells of the rat in vitro

Cloned rat ovarian adenocarcinoma cells (ROT58/C3) treated for 1 hr with 0.5 (μg/ml or more of cis-dichlorodiammineplatinum(II) (DDP) or Adriamycin (ADM) revealed a marked decrease in survival as estimated by the colony-forming method. Compared to cloned rat uterine adenocarcinoma cells (HTP/C1), the ROT58/C3 cells were more sensitive to the cytotoxic effect of both drugs. The survival of exponentially growing ROT58/C3 cells was reduced to less than 10% by a 0.5 μg/ml dose of DDP, as compared to a 1 μg/ml dose of ADM. Extensive morphological changes such as enlargement of the nuclear and nucleolar diameters, increase in the number of nucleoli, and the appearance of coarse and opaque chromatins were observed by optical and electron microscopy at as early as 48 hr after exposure to DDP for 1 hr. In addition, accumulation of cells at the G₂ phase in the cell cycle was observed by flow microfluorometry.     

A case of endolymphatic sac tumor with long-term survival

A 72-year-old man developed left facial palsy at age 14 and left-sided hearing loss at age 20. At the age of 59, he presented with gait disturbance, and a large left cerebellopontine angle tumor was detected, which had markedly destroyed the pyramidal bone. The tumor was subtotally resected, but he required two more operations at the ages of 64 and 69 because of tumor regrowth. At the present time, recurrent tumor has destroyed the occipital bone and is invading the scalp. However, eventhough he has several cranial nerve palsies and cerebellar ataxia, he remains in stable condition and demonstrates long-term survival. The patient's surgical specimens revealed a papillary adenoma, which was recently thought to be of endolymphatic sac origin, although the origin of this kind of tumor, whether arising from the middle ear or from the endolymphatic sac, has not been established with certainty so far. In this paper, we provide further evidence that this tumor originates from the endolymphatic sac, based on anatomical, histopathological, and embryological evidence.     

Morphologic and enzyme-cytochemical changes in uterine adenocarcinoma cells of a rat by direct application of progesterone in vitro

HTP/C1/P8 culture, a subclonal cell line of HTP/C1 culture derived from a rat uterine adenocarcinoma, has been subcultivated in a culture medium containing progesterone, 8 μg/ml. HTP/C1/P8 cells revealed a more differentiated form by light and electron microscopy, compared with original HTP/C1 cells growing in a culture medium without progesterone. The effect of progesterone on these uterine adenocarcinoma cells seemed to be direct, as evidenced by the significantly higher uptake of [³H]progesterone into the cells in vitro. Enzyme-cytochemical changes of the cells by the direct application of progesterone is discussed in relation to the morphologic differentiation of these cells.     

Suspended cells from trabecular bone by collagenase digestion become virtually identical to mesenchymal stem cells obtained from marrow aspirates

Several reports describe that the explant culture of the trabecular bone after collagenase treatment produces mesenchymal stem cells (MSCs). However, the suspended cells had not been intensively examined concerning MSCs. We hypothesized that the cells would acquire the properties of MSCs during their expansion and therefore compared them with marrow aspirate-derived MSCs. Human trabecular bones were washed, digested, filtered, and expanded clonally for 14 days. Their proliferation ability (n = 9) and differentiation potentials for chondrocyte, adipocyte, and osteoblast (n = 6) were similar with those of marrow aspirate-derived MSCs. Epitope and mRNA analysis revealed some differences in both types of cells, which disappeared with expansion and subcultivation. A mixed population of collagenase-released (CR) cells had similar differentiation potentials with CR clone, CD31(+) fraction, and osteoblastic cells. For quantitative study, trabecular bone and bone marrow were harvested by single aspiration using a biopsy needle (n = 16). Although the total nucleated cell number harvested was similar, the colony-forming efficiency of CR cells was approximately 100-fold higher than that of BM cells and more than 1 million CR cells could be obtained in 14 days from all donors. Enzymatically released cells from trabecular bone became virtually identical to marrow aspirate-derived MSCs, demonstrating that a trabecular bone fragment can be an alternative source of MSCs.     

Effect of methionine-enkephalin analog (FK 33-824) on plasma motilin

In an attempt to elucidate the effect of opioid peptide on the secretion of various gastrointestinal hormones, the methionine-enkephalin analog, FK 33-824 (FK) was injected intramuscularly in healthy male adults. The plasma levels of motilin, gastrin and cholecystokinin were assessed by specific radioimmunoassay. After the injection of FK, the plasma level of motilin markedly decreased from the baseline value of 456 +/- 70.2 pg/ml to 264 +/- 44.7 pg/ml at 120 min. On the other hand, the plasma levels of cholecystokinin and gastrin remained unchanged. These data indicate that endogenous methionine-enkephalin may have an direct inhibitory effect on the secretion of motilin.     

Anti-human immunodeficiency virus type 1 activities and pharmacokinetics of novel 6-substituted acyclouridine derivatives.

The novel 6-substituted acyclouridine derivatives 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT), 1-[(2-hydroxyethoxy)methyl]-6-(3-methylphenylthio)thymine (HEPT-M), 6-cyclohexylthio-1-[(2-hydroxyethoxy) methyl]thymine (HEPT-H), and 1-[(2-hydroxyethoxy)methyl]-6-phenylthio-2- thiothymine (HEPT-S) have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell systems, including peripheral blood lymphocytes. They are not inhibitory to the replication of HIV-2. HEPT-S emerged as the most active congener, with a 50% inhibitory concentration of 1.6 microM for HIV-1 (human T-cell lymphotropic virus type IIIB) in MT-4 cells. We also examined the pharmacokinetics of the compounds following oral administration to rats. The pharmacokinetic profile varied considerably from one compound to another. The highest concentration in plasma (7.4 micrograms/ml, or 22.8 microM) was achieved by HEPT-S within 30 min after administration of an oral dose of 20 mg/kg of body weight. HEPT-S can be considered a promising candidate for the treatment of HIV-1 infections.