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Protein S (PS) deficiency, which is caused by various factors including congenital and acquired disorders, is a risk factor for thrombophilia. We described 3 patients with different backgrounds, who all exhibited PS deficiency. The first patient was a 47-year-old woman who suffered from frequent cerebral infarctions, deep-vein thrombosis (DVT) of her lower extremities, and pulmonary thromboembolism. Her son suffered from skin necrosis due to PS deficiency and both had the same mutant allele of the PS gene. The second patient was a 50-year-old woman who experienced a cold sensation in her fingers. Her relatives had a history of cerebrovascular disease. No mutation was detected in her PS gene. The third patient was a 27-year-old man with antiphospholipid antibody. He suffered from thrombocytopenia, skin necrosis, DVT of his lower extremities, and pulmonary thromboembolism. A mutation was identified in the steroid hormone-binding globulin-like (SHBG) domain of his PS gene. Neither his parents nor siblings had a history of thrombosis. The mutations found in the first and third patients were both missense mutations in the SHBG domain that have not been reported previously. The third patient had a mutation in the site that is involved in binding to C4b-binding protein, which modifies the immune response. These three cases provide key insights into the pathophysiology of PS deficiency.

The nucleotide sequences of the 27,939-bp-long upstream and 9,448-bp-long downstream regions of the carAaAaBaBbCAc(ORF7)Ad genes of carbazole-degrading Pseudomonas sp. strain CA10 were determined. Thirty-two open reading frames (ORFs) were identified, and the car gene cluster was consequently revealed to consist of 10 genes (carAaAaBaBbCAcAdDFE) encoding the enzymes for the three-step conversion of carbazole to anthranilate and the degradation of 2-hydroxypenta-2,4-dienoate. The high identities (68 to 83%) with the enzymes involved in 3-(3-hydroxyphenyl)propionic acid degradation were observed only for CarFE. This observation, together with the fact that two ORFs are inserted between carD and carFE, makes it quite likely that the carFE genes were recruited from another locus. In the 21-kb region upstream from carAa, aromatic-ring-hydroxylating dioxygenase genes (ORF26, ORF27, and ORF28) were found. Inductive expression in carbazole-grown cells and the results of homology searching indicate that these genes encode the anthranilate 1,2-dioxygenase involved in carbazole degradation. Therefore, these ORFs were designated antABC. Four homologous insertion sequences, IS5car1 to IS5car4, were identified in the neighboring regions of car and ant genes. IS5car2 and IS5car3 constituted the putative composite transposon containing antABC. One-ended transposition of IS5car2 together with the 5' portion of antA into the region immediately upstream of carAa had resulted in the formation of IS5car1 and ORF9. In addition to the insertion sequence-dependent recombination, gene duplications and presumed gene fusion were observed. In conclusion, through the above gene rearrangement, the novel genetic structure of the car gene cluster has been constructed. In addition, it was also revealed that the car and ant gene clusters are located on the megaplasmid pCAR1.

A 29-year-old male patient with acute arterial obstruction and a medical history including thrombosis in the deep veins and pulmonary infarction presented with a reduced level of both protein S (PS) activity and free PS. Sequencing of the genomic PS gene in this patient revealed that the patient was heterozygous for the mutant PS allele, in which a nucleotide substitution occurred at the donor splice site in intron 12 (GT to GA). The patient was heterozygous for PS genes having dimorphic codons for Pro626 (CCA/CCG) and the aberrant allele in this patient was associated with the CCA form. Allelic exclusion of PS expression was demonstrated by use of Pro626 (CCA/CCG) dimorphism and only a normal mRNA sequence derived from the CCG-allele was identified in the patient. These findings suggested that the mutation at the splice site in the PS gene caused either defective production of mRNA or the gene may have produced extremely unstable RNA products, leading to reduced levels of PS activity and free PS in this patient.

Sequencing studies of the protein S gene (PROS1) in a Japanese patient suffering from recurrent thrombosis revealed the following. The proband and his first daughter, but not the second daughter, were having the type I protein S (PS) deficiency due to a novel point mutation from A to G at the intronic acceptor splice site in intron 13 of the PROS1. In the affected daughter, exclusion of the aberrant allele was assessed by the BstX1 dimorphism of PROS1 at Pro626 (CCG/CCA). The reduced PS activities in the proband and his first daughter were apparently due to defective production of mRNA from the mutant allele.

A double-blind, randomized, placebo-controlled trial was conducted to evaluate whether treatment with Antithrombin (AT) concentrates improved the clinical and perinatal outcome in patients with severe preeclampsia. Severe preeclamptic patients (24 to 35 weeks of gestation. Gestosis Index (GI) > or = 6 points) were randomized into two groups: 66 received AT and 67 received placebo. There were no statistical differences in the clinical profiles of the two groups. Study drugs were given intravenously once daily for 7 consecutive days. Maternal symptoms were evaluated from the difference of GI between before and after treatment, and fetal findings were evaluated from the changes of the biophysical profile score and the estimated fetal weight gain. Improvement was significantly greater in the AT group for both the GI (p = 0.020) and the estimated fetal weight gain (p = 0.029). The improvement of coagulation parameters was also evaluated. The D-dimer levels increased significantly in the placebo group (p = 0.026), but did not change in the AT group. Gestation was significantly prolonged (p = 0.007), and the number of low-birth weight infants was significantly smaller (p = 0.011) in the AT group. No adverse events related to AT were observed. It is revealed that AT concentrate therapy for preeclampsia is effective and safe, leading to an improved perinatal outcome.

Congenital afibrinogenemia due to a novel homozygous nonsense mutation of the fibrinogen gamma-chain gene, fibrinogen Hakata, was found in an 18-year-old Japanese girl who had received supplemental fibrinogen therapy since she was 4 months old. The plasma fibrinogen concentrations of the proband were measured as less than 10 mg/dl by a functional method and less than 17 mg/dl by an immunological method. Fibrinogen concentrations of her family were in the range of 94-164 mg/dl. The proband and her family had no other clinical symptoms. Genomic DNA of the proband and her family was isolated from leukocytes, and all exons of fibrinogen subunits and their intron/exon boundaries were analyzed. A genetic mutation, a guanine-to-thymine (G-to-T) transversion at the nucleotide position of 5860, was identified on exon 7 of the gamma-chain gene. This mutation changed the codon for the 231st residue of the gamma-chain from GAG (Glu) to TAG (stop). No other mutation was observed. Aalpha, Bbeta and gamma chains were observed in plasma of the heterozygous family members. However, only a trace amount of Aalpha chain and no gamma chain was detected in the plasma of the proband.

Reliability and validity of a rating scale for post-stroke psychiatric symptoms were examined by the videotape method. The scale comprised 10 items categorized into two symptom domains of decreased spontaneity and impaired emotion. Also, two items for global assessment of the two symptom domains were added. Each item had seven anchor points from 0, representing no impairment, to 6, corresponding to complete impairment. Face validity of the scale was confirmed through the questionnaire survey. Nine neurologists independently assessed psychiatric symptoms in 30 videotaped post-stroke patients. Weighted kappa coefficients of more than 0.5 were noted for all the items except for one item. Data from three cerebral metabolism enhancers trials were used to examine the validity. Changes in severity in the Global Change Scale (GCS) from the baseline to the final assessment was assessed by raters' impression in these trials. Factorial validity of the scale was confirmed by the factor analysis. GCS in the three trials were considerably related to the summed scores of the items in the two categories. Namely, in the box plot figures, boxes of the middle 50% of data well differentiated the adjacent categories of GCS. However, overlap from vertical bars was observed. These results suggest reliability and validity of the scale.

An adenine-to-guanine mutation at nucleotide position (np) 3243 in the mitochondrial tRNALeu(UUR) gene is closely associated with various clinical phenotypes of diabetes mellitus. Because the mutation creates a new restriction site for the restriction enzyme ApaI, the mutation is usually detected and quantified by ApaI cleavage of the PCR products including np 3243. The sensitivity of the conventional method is, however, 5-10% heteroplasmy. The percentage of heteroplasmy of the mutation is usually highest in the affected tissues and is much lower in peripheral blood cells, which are used most frequently for the analysis. The sensitivity of the conventional method, however, is not sufficient to detect the mutation from peripheral blood cells. Utilizing ligation-mediated polymerase chain reaction, we have developed a feasible and sensitive method to detect 0.01% heteroplasmy of the 3243 mutation in peripheral leukocytes.

1. The mechanism by which cicletanine (CIC) exerts its antihypertensive effects has not been fully elucidated. The present study was undertaken to examine the effects of in vivo and in vitro treatment with CIC on the pressor response and noradrenaline (NA) overflow during periarterial nerve stimulation (PNS) in perfused mesenteric arterial beds isolated from spontaneously hypertensive rats (SHR). 2. CIC at a dose of 50 mg kg(-1) day(-1) was administered orally to both SHR and normotensive Wistar-Kyoto rats (WKY) from the 6th to 10th week of age. At the 10th week, the isolated mesenteric arterial bed was perfused with Krebs-Henseleit buffer and changes in perfusion pressure and NA overflow during PNS were measured. 3. Chronic treatment with CIC suppressed the age-related elevation of systemic blood pressure in SHR but not in WKY. 4. The PNS (20 Hz)-induced mesenteric vasoconstrictor response and NA overflow were greater in SHR than in WKY. In the vasculature of SHR chronic treatment with CIC resulted in a significant attenuation of the vasoconstriction and the NA overflow during PNS, whereas it did not alter vasoconstrictor responses to bolus injections of KCl and phenylephrine. 5. Treatment with 30 microM CIC in vitro diminished the PNS-induced vasoconstriction and NA overflow but not the NA- and KCl-induced vasoconstriction in the vasculature of untreated SHR. 6. In the vasculature of SHR PNS-induced NA overflow was attenuated by prostaglandin E2 (0.05 microM), whereas it was augmented by the cyclo-oxygenase inhibitor diclofenac-Na (30 microM). In the presence of diclofenac, in vitro treatment with CIC did not attenuate the NA overflow during PNS. 7. The results suggest that the antihypertensive effect of CIC in SHR is partially due to the presynaptic inhibition of NA release during sympathetic nerve activation. Transjunctional inhibition of NA release by prostaglandins may contribute to the inhibitory action of CIC on NA release in the vasculature of SHR.

When aged BALB/c mice (approximately 6 months old) were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST)" (1 g/kg, 10 times) orally from 7 days before to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 (H1N1 subtype) by nasal site-restricted infection, replication of the virus in the broncho-alveolar cavity was efficiently inhibited at 5 days after infection in comparison with water-treated mice. The antiviral IgA antibody in the broncho-alveolar wash of the SST treated aged mice increased significantly. When mice (7 weeks old) were administered orally with SST (1 and 2 g/kg, 7 times) from 4 days before to 3 days after the infection and infected with mouse-adapted influenza virus A/Guizhou/54/89 (H3N2 subtype) or B/Ibaraki/2/85, replication of the viruses in the nasal cavity and lung were significantly inhibited at 4 days after infection in comparison with control mice. When mice infected with influenza virus A/Fukuoka/C29/85 (H3N2) before 14 days were secondary infected with A/PR/8 virus and administered orally with SST (1 g/kg, 5 times) from 2 h to 5 days after the secondary infection, replication of the virus in both nasal and broncho-alveolar cavities were significantly inhibited at 5 days after the secondary infection in comparison with water-treated control. Oral administration of SST (1 g/kg, 18 times) from 7 days before to 14 days after vaccination followed by secondary nasal inoculation of influenza HA vaccine (5 micrograms/mouse) at 14 days after the first vaccination significantly augmented nasal antiviral IgA antibody and broncho-alveolar and serum antiviral IgG antibodies. These results suggest that SST is useful for influenza virus infection on aged persons and for cross-protection of subtypes of influenza A viruses and influenza B virus. SST is also useful for the treatment of influenza virus infection on human which has a history of influenza virus infection and/or influenza vaccination.

Several 1,3-intra-strand cross-linked decadeoxynucleotide duplexes, modified with cis-diamminedichloroplatinum(II) (cis-DDP), and their base substitution analogues at the complementary site to the intervening base of the coordination sites, were synthesized and measured for UV-melting profiles to determine melting temperature (Tm) values. The results indicated the thermal stability of the oligonucleotide duplexes containing Pt-induced 1,3-intra-strand cross-linking did not depend on the kind of intervening base of the coordination site but rather on its complementary base. These results may explain the mutagenicity of cis-DDP from a chemical aspect.

The streptococcal preparation OK-432 was used by intradermal administration as an immunotherapy in 18 patients with oral cancer, and the sera from patients during OK-432 treatment were serially assayed for interferon (IFN) activity by the plaque-reduction method with vesicular stomatitis virus in FL cells derived from human amniotic membrane. The type of serum IFN was characterized by acid-treatment and neutralization test with anti-IFN-alpha and anti-IFN-beta antisera. IFN-gamma was expressed for its titer as the residual IFN activity after neutralization with both antisera. An intradermal injection of OK-432 transiently induced IFN activity and 3 patterns in the type and level of the produced IFN were observed. Although most of the patients induced IFN-gamma and acid-stable IFN or only IFN-gamma, 2 patients seemed to be unresponsive to OK-432. When we examined the relationship between natural killer (NK) activity and IFN titer, a sharply declined NK activity was found immediately post OK-432 administration, and then NK activity stayed around the pretreatment level. Most of the tested patients' induced IFN-gamma, preceding the step toward the gradual increase in NK activity, decreased with OK-432. However, even in the patients showing no IFN induction with OK-432, a significant decrease of NK activity occurred.

In order to examine the relationship between RNA polymerase I and ornithine decarboxylase (ODC), three lines of experiments were performed, with the following results. The glucocorticoid-induced increase of RNA polymerase I in rat liver nuclei was not abolished by administration of inhibitors of ODC synthesis and activity, namely 1,3-diaminopropane and 2-difluoromethylornithine respectively. Anti-ODC antibody did not cross-react with RNA polymerase I solubilized from rat liver nucleoli, indicating the absence of a common protein sequence in these enzymes. The ODC preparation which was treated with transglutaminase in the presence of putrescine could not stimulate the activity of RNA polymerase I in nuclei of liver and prostate. All these results suggest that the increases in ODC protein or activity are not a prerequisite to the increase in RNA polymerase I after hormonal or physiological stimuli, but rather that the increases in both enzymes are separate responses to the primary stimuli.

The growth inhibitory effects of 5-fluorouracil (5-Fu) and the combination of 5-Fu and human leukocyte interferon (HuIFN-alpha) on the human salivary gland adenocarcinoma cell line HSG in culture were examined by measuring colony formation in the semi-solid agar medium and cell proliferation in the monolayer culture. As a consequence, the colony-forming ability of HSG cells in the agar medium containing 5-Fu was found to be markedly inhibited as compared with the untreated control. The concentration of 5-Fu yielding 50% inhibition of colony-forming ability of HSG cells under the presence of 5-Fu was 0.08 micrograms/ml. When the growth inhibitory effects of the combination of 5-Fu and HuIFN-alpha on HSG cells were examined, the colony forming ability of HSG cells was synergistically inhibited, whereas effects of the combined treatment on HSG cells in the monolayer culture were less sensitive than those on the colony formation. These findings strongly suggest that the combination of 5-Fu and HuIFN-alpha or 5-Fu alone is selectively effective on the neoplastic cells of HSG cell population but not on the non-neoplastic cells.

Effects of Ca-free or Na-deficient Ringer solutions on the membrane currents of the bullfrog atrial muscle were studied using the double sucrose-gap method. Instantaneous outward current (Ik1) decreased in Ca-free and increased in Na-deficient conditions. The amplitude of nominal "fully activated delayed outward current" diminished under both sets of conditions. The diminution, however, was greater in Na-deficient medium (10 mM Na) and its activation curve shifted about 13.5 mV toward a more negative potential. In Ca-free Ringer, no such shift was observed, and the activation of the delayed outward current became slower and sigmoidal while the deactivation was faster than in the control. Contrarily, in Na-deficient Ringer, the activation became faster and exponential and the deactivation was slower. The current tail was composed of two exponentially declining components, and the slower, K-accumulation-related component (Ia) was suppressed in Ca-free and the faster component (Ixs) diminished in Na-deficient media. These findings may indicate that in the atrial muscle the instantaneous outward current is modified by a Na-Ca exchange mechanisms and that the delayed outward current consists of two components, Ixs and Ia, which are susceptible to Na and Ca ions, respectively.

The interferon (IFN) assay of the sera from the 26 patients with premalignant lesions such as lichen planus and leukoplakia arising in oral mucosa was performed by the plaque-reduction assay with vesicular stomatitis virus in FL cells derived from human amniotic membrane. When the serum IFN activity was characterized by acid treatment, significant increase of acid-stable IFN in the patients was found as compared with those in the normal controls. The titers of gamma-like IFN defined by anti-HuIFN-alpha and anti-HuIFN-beta in the sera of patients of 50-79 years age group (n = 17, P less than 0.002) showed a highly significant increase as compared with the relevant normal controls (n = 20). All of the 26 patients were treated with topical administration of HuIFN-beta. When the correlation between prognosis of the disease and titers of serum IFN was investigated by measuring gamma-like IFN and acid-stable IFN in the sera of patients, all of 13 patients with good prognosis after the HuIFN-beta therapy showed significantly decreased levels of gamma-like IFN (P less than 0.01), whereas the serum level of acid-stable IFN after HuIFN-beta therapy showed a significant increase compared to that before the therapy (P less than 0.05). These findings indicate that the endogenous IFN system may be associated with the pathophysiology in patients with the oral mucosal lesions.

Human fibroblast interferon (HuIFN-beta) was topically administered to 20 premalignant lesions histopathologically showing epithelial dysplasia such as leukoplakia and lichen planus which arose in the oral mucosa. HuIFN-beta was prepared in the water-soluble gel form containing 2% carboxymethylcellulose, 45% glycelin, 0.1 M citrate buffer (pH 4.5) and 0.2% SDS as stabilizing agents. This preparation was found to be effective for herpetic gingivostomatitis and zostal lesions arising along the intercostal nerve. Thus, the HuIFN-beta preparation (10(4) to 5 X 10(3) IU) was applied to the oral mucosal lesion for 1 h twice a week. The lesion with topical administration of HuIFN-beta was covered tightly with the mucosal bandage which was coated with carboxymethylcellulose, glycelin and CaCl2 on vinyl acetate matrix. The 14 oral lesions with erosion or ulcer formation accompanied by severe pain by touch, had complete remission after approximately 10 successive applications of this preparation. Although subjective symptoms such as irritation pain in the other 6 patients with severe hyperkeratotic lesion subsided, white coatings and streaks could not be completely removed by this therapy. No other side-effects excluding slight pain and reddish swelling which occurred intermittently during HuIFN-beta administration were observed.

As adenosine has a potent stabilizing action on catecholamine stimulation in the myocardium, the mode of interaction of adenosine and acetylcholine (ACh) was studied with regard to the membrane potential, current and tension components of the bullfrog atrium, using the single or double-sucrose gap method. Adenosine (10(-4)-3 x 10(-3)M) augmented the twitch contraction in the presence of ACh(10(-9)-5 x 10(-7)M) by lengthening the duration of the action potential. The dose-tension response curve for ACh was modified by adenosine, producing a rise of the inhibitory threshold of ACh, and the modification showed a non-competitive interaction of these compounds. Under the voltage clamp, ACh-induced steady current (IACh) was inhibited by adenosine non-competitively. The known inhibition of slow inward current (Is) by ACh was enhanced by adenosine, while the delayed outward current (Ix) was markedly suppressed. Is-dependent and -independent tension components were both inhibited by adenosine, thereby suggesting a decrease in intracellular concentrations of calcium. The potent suppression of IACh and Ix induced by adenosine, however, appeared to mitigate the inhibitory action of ACh on the action potential and twitch contraction.

A neoplastic epithelial duct cell line from a human submandibular salivary gland, HSG, was assayed by an in vitro semi-solid agar technique for sensitivity to human leukocyte interferon (HuIFN-alpha). The clone which showed the most stable growth and the greatest ability of colony formation in the agar medium, was isolated from the colonies of HSG cells and used in the present study. This clone was designated as HSG-1. As a consequence, cultivation of HSG-1 cells in the agar medium containing HuIFN-alpha of 1000 units/ml resulted in the inhibition of 47.6% of the colony-forming ability of HSG-1 cells, as compared with the untreated control. Addition of increasing concentrations of HuIFN-alpha (between 100 units/ml and 1000 units/ml) in the agar medium caused a linear reduction in the number of the colonies, ranging from 5.2% to 47.6%. Moreover, addition of HuIFN-alpha showed an inhibitory effect on the multiplication of HSG-1 cells in the monolayer culture. These observations strongly suggest that HuIFN-alpha has antineoplastic and antiproliferative effects on HSG-1 cells.

The interferon (IFN) assay of the sera from the 40 patients with head and neck cancer was performed by the plaque-reduction assay with vesicular stomatitis virus in FL cells derived from human amniotic membrane. The patients mainly had Stage III or IV lesion without distant metastasis, and previously had not received any cancer therapy. All of the patients were histologically diagnosed as squamous cell carcinoma. When the serum IFN activity was characterized by acid treatment, significant increases of IFN-alpha/beta/gamma (n = 24, P less than 0.05) and acid-labile IFN (n = 24, P less than 0.001), and significant decrease of acid-stable IFN (n = 24, P less than 0.001) in the cancer patients of 50-to-79-year age group were found, as compared with those in the normal controls of the same age group (n = 20). When IFN titers including various immunologic parameters of the patients and normal controls were simultaneously assayed prior to the beginning of the cancer therapy, the titers of IFN-alpha/beta/gamma, acid-stable IFN, and acid-labile IFN were significantly correlated with some immunologic parameters such as natural killer (NK) activity, the absolute number of T gamma lymphocytes, the percentages of beta- and gamma-globulin, and the amounts of IgA, IgG, IgM, and beta 2 microglobulin. To define further the nature of this IFN, both sera of the patients and normal donors of 50-to-79-year age group were characterized by a neutralization assay with an antiserum to HuIFN-alpha and HUIFN-beta. The IFN activity left when the testing sera were neutralization with these antisera was expressed as gamma-like IFN. The titers of gamma-like IFN in the sera of patients (n = 24, P less than 0.0001) showed a highly significant increase as compared with the normal controls (n = 20). When the correlation between prognosis of the disease and titers of serum IFN were investigated by measuring gamma-like IFN and acid-stable IFN in the sera of patients, all of nine patients with good prognosis after the cancer treatment showed significant decreased levels of gamma-like IFN (P less than 0.01) and acid-stable IFN (P less than 0.05) as compared with those on the time before cancer therapy. On the other hand, titers of gamma-like IFN in the sera of six patients with recurrent disease showed a significant increase as compared with those on the IFN measurement before cancer therapy (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

This study is a comparative evaluation of two commonly used screw configurations on the rigidity of the sagittal split osteotomy. A cadaver model was used to compare the immediate load strength of three screws placed horizontally above the neurovascular bundle (horizontal configuration) versus two screws placed horizontally above the bundle and one screw placed inferiorly below the bundle (triad configuration). The triad configuration was found to have a mean percentage increase in rigidity of 58% over the horizontal configuration. The paired t test was used to evaluate the data, disclosing a significant difference in load strength (p less than 0.01).

By serial transplantation of CS 1, a subline of Shionogi carcinoma SC 115, to female mice, another subline was obtained and designated CS2. The subline showed a complete loss of androgen dependency on the growth of the tumor. When male mice bearing the tumor were castrated and treated with testosterone, the activity of RNA polymerase I in isolated nuclei from the tumor hardly varied during the period of the experiments (36 h), while the activity of RNA polymerase II exhibited a transient increase (about 40%) at 6 h after the testosterone injection. The results, together with the previous ones showing 80% and 40% increases in RNA polymerase I activity at 24 h after testosterone administration in the case of SC 115 (androgen-dependent tumor) and CS 1 (less androgen-dependent tumor), respectively, indicate that the stimulation of RNA polymerase I activity by androgen in the tumor tissues is closely related to the androgen dependency on the growth of the tumors.

An immunoglobulin M mouse monoclonal antibody (MAb) to the streptococcal preparation OK-432, TS-1, was generated. The TS-1 antigen is a carbohydrate epitope. This antigen is stable upon fixation and embedding in paraffin. The tissue and cellular OK-432 localization in human salivary adenocarcinoma-bearing nude mice given OK-432 intratumorally was examined by various methods according to the immunological procedures using the purified TS-1 MAb. The presence of OK-432 antigen recognized by TS-1 MAb was clearly observed in the tumor as well as the spleen and lung 24 or 48 h after OK-432 administration, whereas transfer of OK-432 from the site of injection to the organs, such as liver and kidney, was rarely seen. The presence of OK-432 antigen in some immunocompetent cells, as defined by Mac-1 antigen or asialo GM1 antigen, was observed by the double-antibody labeling technique in the tumor and spleen from tumor-bearing nude mice. Moreover, interaction between OK-432 and macrophages or natural killer (NK) cells in relation to expression of interferon (IFN) in tumor-bearing nude mice given OK-432 was observed. Consequently, significant increases of Ia-positive or Ia-negative macrophages, NK cells as well as IFN-alpha/beta- or IFN-gamma-positive cells in the tumor and/or spleen were found when compared with those without OK-432 administration.

The activity of ornithine decarboxylase in androgen-dependent mouse mammary tumor (Shionogi Carcinoma 115) was reduced to 25% by castration of tumor-bearing mice and restored to the normal level 12 h after administration of testosterone or 5 alpha-dihydrotestosterone. Administration of estradiol-17 beta to the tumor-bearing castrated mice also stimulated the enzyme activity while progesterone and cortisol had little effect. On the other hand, the enzyme activity was affected by neither castration nor androgen injection to CS 2, which is a subline of SC 115 and completely independent of androgen for growth. The inhibition of ornithine decarboxylase activity in SC 115 by injecting alpha-difluoromethylornithine did not affect the enhancement of RNA polymerase I activity by androgen, showing independent elevation of the levels of the two enzymes by androgen.

Action of alpha- and beta-agonists on the membrane potential, current and tension components on the bullfrog atrial muscle were studied by means of the single or double sucrose-gap technique. Isoproterenol (10(-9)-10(-5) M) as well as adrenaline (10(-7)-10(-4) M) produced a dose-dependent positive inotropic effect, while methoxamine (10(-8)-10(-4) M) and phenylephrine (10(-8)-10(-3) M) with propranolol (10(-6) M) elicited a negative inotropic effect. The positive inotropic effect was accompanied by slight hyperpolarization and marked increase of over-shoot and plateau level of action potential, and the negative inotropic effect, by opposite changes. Under voltage clamp, isoproterenol and adrenaline produced enhancement of slow inward current (Is), delayed outward current (Ix) and Is-dependent phasic tension, while Is-independent tonic tension was inhibited. Contrarily, methoxamine and phenylephrine depressed these currents and elicited beta-antagonistic inotropic actions, especially when isoproterenol was present. Specific feature of alpha-agonist action in the presence of isoproterenol was an inward shift of the semi-steady I-V relationship. It is thus suggested that, in the bullfrog atrium, alpha-agonists produce a strong beta-receptor blocking action and an inward shift of the background current. A possible relationship between the latter effect and inhibition of the Na-K pump is also suggested.

A case of odontogenic myxofibroma involving the angle of the mandible is reported. This case arose in the area closely associated with the pericoronal portion of the embedded third molar. When the mandible resected was histopathologically examined, the tumor mass containing various shapes of epithelial cell nests and amorphous calcified bodies in the myxomatous fibrous tissue was found to be formed in the localized area well-demarcated by the enamel of the embedded tooth. These findings strongly suggest that this lesion is of odontogenic origin.