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The palmar metacarpal arteries in monkey hands were studied. The palmar metacarpal arteries arose from the deep palmar arch or catella palmaris proximalis and descended in the deep palm, forming the catella palmaris distalis at the distal end of the metacarpus. The palmar metacarpal arteries could be classified into four kinds in relation to the interosseous muscles and metacarpal bones: (i) the superficial palmar metacarpal (sM) arteries descending on the palmar surfaces of the interosseous muscles along the metacarpal bones, (ii) the superficial palmar intermetacarpal (sI) arteries descending on the palmar surfaces of the interosseous muscles along the intermetacarpal spaces, (iii) the deep palmar metacarpal (dM) arteries descending deep in the interosseous muscles along the metacarpal bones, and (iv) the deep palmar intermetacarpal (dI) arteries descending deep in the interosseous muscles along the intermetacarpal spaces. These findings largely coincide with those obtained from studies of the human hand by Murakami (1969).

The effects of seizure activity on the mossy fiber endings of El mice were studied by electron microscopy. During epileptic seizures of El mice, the number of clear round vesicles (50 nm) in the mossy fiber endings of the hippocampal formation decreased, while the number of large densecore vesicles (100 nm) increased. In these endings, the large dense-core vesicles were scattered during the resting state, but after seizure activity they tended to accumulate together and attach to the presynaptic membrane. Omega-shaped profiles, which seemed to be due to exocytosis of the large dense-core vesicles, were seen in the presynaptic membrane.

The analysis of bile acids in human bile was tried by high-performance liquid chromatography (HPLC). Bile acids in human bile were first prefractionated into free, glycine- and taurine-conjugated bile acids using a Seppak C18 cartridge and a piperidinohydroxypropyl Sephadex LH-20 (PHP-LH-20) column. Each fraction was then processed through a HPLC system consisting of a Zorbax ODS column and a 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) column. By these procedures the major 15 bile acids were clearly separated, and each bile acid of 10-125 ng was accurately analyzed. More than 400 times of analysis could be repeated on one 3 alpha-HSD column without loss of sensitivity. Thus the pretreatment through Seppak C18 and PHP-LH-20 made the HPLC analysis of human bile acids accurate and applicable to clinically obtained materials.

Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC), of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin) was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal), while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.

We administered serum fractions obtained from cancer patients by double-filtration plasmapheresis (DFPP) to cancer-bearing mice to examine the effects on tumor growth and metastasis. Fraction 1 (whole plasma), fraction 2 (a plasma fraction containing substances with higher particle size), fraction 3 (a plasma fraction containing substances with smaller particle size) and saline were administered intravenously to cancer-bearing mice for 10 days following the inoculation of tumor cells. The tumor growth and metastasis in mice administered fraction 2 was far more rapid than that in the control mice. On the other hand, tumor growth in mice administered fraction 3 was significantly delayed compared with that in mice injected with fraction 2. These results suggest that factors in the higher particle-size fraction of cancer patients' sera promote the growth and the metastasis of tumors in mice, and that DFPP, which remove these factors, is an effective therapy against cancer.

A clinical trial was performed to investigate the efficacy of hyperthermia in combination with chemotherapy for gynecological malignancies. Sixty-nine patients with vaginal or vulvar malignancies (9 primary vulvar, 3 recurrent vulvar, 11 primary vaginal, 4 primary cervical, 40 recurrent cervical, and 2 recurrent ovarian carcinomas) were treated by thermochemotherapy (42 cases) or chemotherapy alone (27 cases). After treatment, 7 patients underwent surgery and 46 patients irradiation. The chemotherapeutic schedule was mainly a combination therapy with bleomycin and mitomycin C (B-M). Microwaves of 2.45 GHz were applied to induce local hyperthermia. The side effects of chemotherapy were not increased by hyperthermia. The rate of partial response plus complete response increased to 84% (16/19) in primary cancers and 45% in recurrent cancers by hyperthermia, compared to the respective values of 40% (2/5) and 17% (3/17) for chemotherapy alone. However, a satisfactory prognosis cannot be expected with thermochemotherapy, unless additional treatments are performed. Subsequent surgery or radiation treatment improved the progression-free interval.

A significant amount of anticoagulant substance was released along with histamine, when human lung mast cells were stimulated with anti-IgE and Ca-ionophore A23187. Its activity was lost by heparinase, not by chondroitin-ABC lyase or chondroitin-AC lyase, and also inhibited by Polybrene, suggesting it would be heparin.

In the Japanese, Formosan and crab-eating monkeys, the dorsal metatarsal arteries and their lateral distal perforating branches were well developed and supplied, directly or via the catella plantaris distalis, the plantar digital arteries. In the black ape, the plantar digital arteries arose from the medial plantar artery. The plantar metatarsal arteries of these monkeys, including the black ape, arose from the catella plantaris proximalis or deep plantar arch and were classified into the superficial plantar metatarsal (sM), superficial plantar intermetatarsal (sI), deep plantar metatarsal (dM) and deep plantar intermetatarsal (dI) arteries in relation to the interosseous muscles and metatarsal bones. This classification largely coincides with that of the human hand and foot (Murakami, 1969, 1971) and the monkey hand (Nakai et al., 1987).

Cyclic AMP accumulation in response to norepinephrine was examined in slices of rat cerebral cortex the day after a unilateral application of anodal current of 0.3, 3.0 or 30 microA to the surface of the sensorimotor cortex. When 3.0 microA was applied, the norepinephrine-elicited accumulation of cyclic AMP was greater in the cortical area including the application point than in either the contralateral cortical area or non-polarized control cortical slices. The changes in cyclic AMP accumulation are discussed in relation to the role of the direct current in producing functional changes in the cortex.

A new acidic ninhydrin method for determining free sialic acids is described. The method is based on the reaction of sialic acids with Gaitonde's acid ninhydrin reagent 2 which yields a stable color with an absorption maximum at 470 nm. The standard curve is linear in the range of 5 to 500 nmol of N-acetylneuraminic acid per 0.9 ml of reaction mixture. The reaction was specific only for sialic acids among the various sugars and sugar derivatives examined. Some interference of this method by cysteine, cystine and tryptophan was noted, although their absorption maxima differed from that of sialic acids. The interference by these amino acids was eliminated with the use of a small column of cation-exchange resin. The acidic ninhydrin method provides a simple and rapid method for the determination of free sialic acids in biological materials.

The thalamic posterior ventral neurons with bifurcating axons to both the first and second somatosensory cortical areas (SI and SII) in the cat were examined by the fluorescent retrograde double labeling technique. After injection of Evans blue (EB) into the SI, and of 4',6-diamidino-2-phenylindol.2HCl (DAPI) into the SII of the same hemisphere, EB- and DAPI-labeled cells were observed predominantly in both the posterolateral ventral and the posteromedial ventral nuclei of the thalamus. Although EB single-labeled and DAPI single-labeled cells tended to occupy separate regions within the posterior ventral nuclei, a small number of cells double-labeled with both EB and DAPI were detected in the border zone between two single-labeled cell groups. These observations indicate that some cells in the posteromedial and posterolateral ventral nuclei project both to the SI and SII by bifurcating axons.

The role of the lumbar sympathetic nerves and supraspinal mechanism in the defecation reflex was investigated in 30 adult cats and 6 kittens. One or two propulsive contractions, whose mean pressure evoked was more than about 90 cmH2O (adult cats) and 50 cmH2O (kittens), were induced in the rectum of all animals by rectal distension. These propulsive contractions could be generated at the descending and the transverse colons. The removal of the supraspinal influence by spinal transection at T13 or removal of pelvic afferents to the supraspinal center by spinal transection at L abolished the propulsive contractions. Successive lumbar sympathectomy restored the contractions. Lumbar sympathectomy and the successive removal of the supraspinal influence did not affect the propulsive contractions. In both cases, the final exclusion of the sacral segments by pithing of the spinal cord abolished the propulsive contractions. These results suggest that the sacral excitatory reflex mediated via pelvic nerves and the lumbar inhibitory reflex mediated via lumbar sympathetic nerves can function during rectal distension in spinal cats and that the lumbar inhibitory reflex is suppressed by the supraspinal sympathetic inhibitory reflex activated by pelvic afferents in intact cats, as in guinea pigs, resulting in propulsive contractions.

Pregnant normal (N) and acatalasemic (A) mice treated with aminotriazole (AT) were exposed to metallic mercury. The mercury contents of the fetus and maternal organs were subsequently determined. The fetal and placental mercury contents were the highest in the AT-treated A mice (A-AT), and the contents decreased in the order of AT-treated N mice (N-AT), non-treated N mice (N-C) and non-treated A mice (A-C). Statistically significant differences in the fetal mercury levels were observed between N-C and A-C, A-C and N-AT, and N-AT and A-AT. The ratios of the mercury concentration in the fetus to that in the maternal blood decreased in the order of A-AT, N-AT, A-C and N-C. The differences in the ratio were significant between these groups. Similar results were obtained when the ratios of the maternal liver level to the maternal blood level or the ratios of the placental level to the maternal blood level were compared. The effect of AT on mercury uptake is remarkable in the fetus of both normal and acatalasemic mice exposed to metallic mercury.

The enzyme activities involved in the transamination of L-cysteine sulfinate (L-alanine 3-sulfinic acid), L-aspartate and L-cysteine were examined in fetal, neonatal and maternal rat liver and placenta. In fetal and neonatal rat liver, aminotransferase activity was most active with L-cysteine sulfinate as a substrate and was also active with L-aspartate, while activity with L-cysteine was very low. The activity of transamination of L-cysteine sulfinate in rat liver developed in parallel with that of L-aspartate and L-cysteine. The aminotransferase activity markedly increased after the 19th day of gestation, reaching the same value as adult liver on the 3rd day after birth. The ratios of transamination of L-cysteine sulfinate to that of L-aspartate and to that of L-cysteine were constant during development. These observations suggest that L-cysteine sulfinate, L-aspartate and L-cysteine are transaminated by the same enzyme in the rat liver during development. Since placental aminotransferase activity was extremely low compared with that of the liver, it was suggested that the placenta did not play an important role in the transamination of these amino acids during pregnancy.

The anti-ulcer action of clotiazepam (a thienodiazepine derivative) was studied in mice subjected to non-physical and physical stimuli in a communication box. There were two groups of mice: the "sender" mice that received electric shocks on the feet and responded by squealing and jumping, and the "responder" mice that were affected by the senders' responses without receiving shocks on the feet. Gastric ulcers resulted in both groups. The effect of clotiazepam was compared with that of diazepam. The incidence of gastric ulcers was suppressed by clotiazepam at a dose of 3 mg/kg, per os, in "responder" and "sender" mice, and by diazepam at a dose of 1 mg/kg, per os, in "responder" mice. These results suggest that clotiazepam has a suppressive action against gastric ulcers produced by non-physical or physical stimuli, although its potency is slightly weaker than that of diazepam.

Concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in human cerebrospinal fluid (CSF) following long-term storage at -20 degrees C for intervals of three to 60 months. No significant changes in HVA levels were detected in CSF stored for up to 60 months. On the other hand, 5-HIAA concentrations remained stable for up to 6 months, but decreased significantly in the specimens stored for longer time intervals. The results indicate that 5-HIAA should be determined within 6 months after CSF collection, while HVA determinations may be delayed.

Concanavalin A (Con A) induced cap formation in rat ascites hepatoma cells (AH7974). In these Con A-treated cells, the association of cytoplasmic proteins with cell membranes was suggested by observing their Triton shells. The transition from G-actin to F-actin occurred in these cells. The association of membrane lipid with cytoplasmic proteins extracted from AH cells was studied by the isolation of protein-bound liposomes and phase transition release. The analysis of isolated liposomes revealed that many cytoplasmic proteins which specifically associated with liposomes were cytoskeletal elements including F-actins. The association of proteins with liposomes was affected by the lipid composition of the liposomal membrane and by the Ca2+ concentration of the incubation medium. The strong interaction of liposomal membrane with cytoplasmic proteins or isolated cytoskeletal proteins was demonstrated also by phase transition release using carboxy fluorescein-containing liposomes. These experiments showed that there was a strong affinity between lipid membrane and cytoskeletal elements including F-actins and that the amount of F-actin increased due to Con A treatment. The association of the submembranous microfilaments with the cell membrane may contribute to capping of the cells caused by Con A.

The paravestibular canaliculus was studied by light microscopy in serial sections of the temporal bones from otosclerotic patients who underwent fenestration or stapes surgery. In all examined 23 specimens (13 cases), the endolymphatic duct and sac were observed to be normally developed with no pathological findings. The paravestibular canaliculus was found in 14 of the specimens (60.9%). Its course was traced from the proximal to the distal area in 12 specimens, and it appeared to merge into the distal portion of the endolymphatic sac in 7 of them. Twelve of the paravestibular canaliculi contained one vein, and 3 contained several veins. No artery was found. The paravestibular canaliculus was observed to originate from small vascular channels around the vestibule in the otic capsule, lateral to and near the internal aperture of the vestibular aqueduct.

Titers of antibody against Escherichia coli in human milk and in the sera of 11 breast-fed infants, 6 bottle-fed infants and 9 infants in the post-weaning period were measured by the passive hemagglutination method. High antibody titers were observed in human milk in the first 4 days after parturition, but the titer decreased rapidly thereafter. None of the healthy, breast-fed infants had detectable serum antibodies, while a breast-fed infant with a perianal E. coli abscess had antibodies. On the other hand, 4 of the 6 bottle-fed infants and all of the 9 infants in the post-weaning period had antibodies. The significance of these results was discussed.

The cytostatic and cytotoxic effects of highly purified natural human tumor necrosis factor (HuTNF-alpha) and natural human interferon-alpha (HuIFN-alpha) on 23 cell lines were studied in vitro. Natural HuTNF-alpha showed cytostatic and cytotoxic effects on PC-9, KHG-2, HT-1197, KG-1 and L-929 cells, and HuIFN-alpha showed both effects on KHG-2 and Daudi cells. A mixture of HuTNF-alpha and HuIFN-alpha (1:1, by unit) showed cytostatic and cytotoxic effects on HuTNF-alpha- or HuIFN-alpha-resistant cell lines such as KB, KATO-III, HEp-2, P-4788, as well as on HuTNF-alpha- or HuIFN-alpha-susceptible cells. Thus, the combined preparation of HuTNF-alpha and HuIFN-alpha expanded the spectrum of sensitive cells. The dosage of the mixed preparation required to produce 50% inhibition of cell growth was less than 20% of that of HuTNF-alpha or HuIFN-alpha alone. These results indicate that the cytostatic and cytotoxic effects of HuTNF-alpha and HuIFN-alpha are synergistically enhanced when they are administered together.