The anti-inflammatory mechanism of MK-447 in rat carrageenin-induced pleurisy

Intrapleural injection of 2% λ-carrageenin caused the accumulation of exudate up to 19 hr. The rate of plasma exudation, measured by the exuded dye amounts for 20 min in the pleural cavity after intravenous injection of pontamine sky blue, showed a peak at 5 hr. Aspirin (100 mg/kg, i. p.) suppressed the dye exudation up to 5 hr, but did not at 7 hr. This inhibition coincided with the decrease of the PG and TXB₂ levels, which were measured by gas chromatography-mass spectrometry, in the pleural exudate. In _vitro experiments, MK-447, a phenolic compound, stimulates PG endoperoxide biosynthesis at lower doses and inhibits it at higher doses, acting as a tryptophan-like cofactor required by PG endoperoxide synthetase. This drug (0.3, 1.0 and 3.0 mg/kg, i. p.) suppressed the dye exudation dose-dependently up to 5 hr, but did not at 7 hr even at a higher dose, in combination with the dose-dependent decrease of the pleural level of PGE₂, which was reported to be a major PG among PGs and TXB₂ in the exudate in inducing the plasma exudation (Harada ; Prostaglandins, : 881, 1982). Thus, the anti-inflammatory action of MK-447 can be explained by inhibition of PGE₂ generation, giving no consideration to the role of oxygen-derived free radicals as a prime mediator in inflammation.     

Cyclin B in fish oocytes: its cDNA and amino acid sequences, appearance during maturation, and induction of p34cdc2 activation.

Under the influence of maturation-inducing hormone (MIH) secreted from follicle cells, oocyte maturation is finally triggered by maturation-promoting factor (MPF), which consists of a homolog of the cdc2+ gene product of fission yeast (p34cdc2) and cyclin B. Two species of cyclin B clones were isolated from a cDNA library constructed from mature goldfish oocytes. Sequence comparisons revealed that these two clones are highly homologous (95%) and were found to be similar to Xenopus cyclin B1. Using monoclonal antibodies against Escherichia coli-produced goldfish cyclin B and the PSTAIR sequence of p34cdc2, we examined the levels of cyclin B and p34cdc2 proteins during goldfish oocyte maturation induced in vitro by 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17 alpha, 20 beta-DP), a natural MIH in fish. Protein p34cdc2 was found in immature oocyte extracts and did not remarkably change during oocyte maturation. Cyclin B was not detected in immature oocyte extracts and appeared when oocytes underwent germinal vesicle breakdown. Cyclin B that appeared during oocyte maturation was labelled with [35S]methionine, indicating its de novo synthesis. Introduction of E. coli-produced cyclin B into immature oocyte extracts induced p34cdc2 (MPF) activation. Although the possibility that immature goldfish oocytes contain an insoluble cyclin B is not completely excluded, these results strongly suggest that 17 alpha, 20 beta-DP induces oocytes to synthesize cyclin B, which in turn activates preexisting p34cdc2, forming active MPF.     

A case of renin producing leiomyosarcoma originating in the lung.

A 54-year-old woman was referred to our hospital for the treatment of a tumor of the right chest wall. Clinical examination revealed hypertension, hypokalemia, metabolic alkalosis, hyperaldosteronism and hyperreninemia. Computed tomography and an abdominal echogram indicated a tumor in the right phrenic area and two tumors in the retroperitoneum near the pancreas head. After the surgical resection of these tumors, the primary reninism was diminished. The pathological diagnosis of these tumors was leiomyosarcoma. Plasma active and inactive (trypsin-activated) renin activities (PRA) were 85.7 and 38.9 ng angiotensin I/ml/h, respectively. These PRA did not respond to either postural stimulation or suppression by the volume expansion. Active and inactive renin activities in a right phrenic area tumor were 208 and 32 ng angiotensin I/mg protein /h, respectively. Those of an abdominal tumor were 196 and 30 ng angiotensin I/mg protein/h, respectively. Renin mRNA identical in molecular size to that of the human kidney was identified by northern blot analysis. This is the first case report of renin producing leiomyosarcoma derived from the lung, which is characterized by relatively lower plasma prorenin concentrations.     

Maturation-promoting factor and p34cdc2 kinase during oocyte maturation of the Japanese quail

Maturation-promoting factor and a homolog of fission yeast cdc2+ gene product (p34cdc2) were investigated during the final 24 hr of maturation of quail oocytes. Kinase activity of p34cdc2 in the oocyte germinal disk (GD) increased 15 times at maturation. Two bands, at 32 and 34 kDa, were detected in immature oocytes by immunoblotting of SDS-PAGE with anti-p34cdc2 monoclonal antibody. A new band, which is close to the 32-kDa band but with a slightly faster mobility, appeared during maturation. No p34cdc2 could be detected outside the GD. Microinjection of GD extract from mature oocytes caused maturation of Xenopus oocytes.     

Herpangina surveillance in Japan, 1982-1989. A report of the national epidemiological surveillance of infectious agents in Japan.

In Japan, herpangina cases increase every summer with an incidence peak in July. During the past eight years from January, 1982 to December, 1989, a total of 3,974 viruses from herpangina cases were reported from 47 participating laboratories, and coxsackie A (CA) viruses accounted for most of them, 3,055 (76.9%). The major types associated with herpangina were, in order of frequency, CA4, 10, 5, 6, 2 and 3, representing 87.2%-80.8% of total isolations reported for each respective type in this period. Eighty-four point four percent of the total virus isolations were from children at four years of age or younger. More than 80% of total CA virus isolations were from nasopharyngeal specimens and nearly 90% of the viruses were isolated in mice.     

Functional analysis of the regulatory region of the yeast phosphatidylserine synthase gene, PSS.

The upstream region of the PSS gene contains three positive cis-acting elements, upstream activation sequences 1 and 2 (UAS1 and UAS2) and a TATA box. The 5' end of UAS1 occurs between positions -239 and -209, and that of UAS2 is between positions -172 and -164. UAS2 contains 5'-TTCACATG-3' as a core sequence at positions -161 to -154. Mutational analysis revealed that this octamer is responsible for the control of PSS expression by inositol and choline. The TATA box is located at positions -112 to -108. In addition, PSS contains a negative cis-acting sequence between UAS2 and the TATA box.     

Poliovirus surveillance: isolation of polioviruses in Japan, 1980-1991. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

This report presents an overall distribution of poliovirus isolations in Japan, where poliomyelitis has been under control over two decades as a result of legal administration of two doses of the trivalent live oral poliovirus vaccine of the Sabin strains (OPV) to children under 48 months of age. During the past 12 years from 1980 through 1991, a total of 1,126 poliovirus isolations from humans and 268 isolations from sewage/river water were reported by respectively 49 and nine of the participating laboratories. Type 2 was most frequently isolated from children after administration of one dose of OPV, followed by type 1 and type 3. On the contrary, after the second dose of OPV, the rate of isolation of type 3 exceeded those of type 2 and type 1. Seasonal and age distribution of poliovirus isolations from both humans and sewage/river water paralleled the OPV vaccination schedule in Japan. One percent of the isolations were, however, from infants younger than the vaccination-scheduled ages and 5% were from children older than those ages, including one each from 15 and 16 years olds. The data indicate that the poliovirus has silently been disseminated from vaccinated children to others and the community, thus suggesting repeated transmission of the viruses. The fact that some elder children had poliovirus colonization in their alimentary tracts indicates a potential risk of infection of such a population when exposed to a wild virus and of becoming a source of transmission to others.