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Temporal bone histopathological findings of two patients with trisomy 18 syndrome are described. Many of the abnormalities previously described were seen in the present cases; namely, atresia of the external auditory canal, aberrant course of the tensor tympani muscle, malformed stapes, aberrant course of the facial nerve with an obtuse angulation at the first genu and displacement of geniculate ganglion cells into the internal auditory canal, shortened cochlea with decreased spiral ganglion cell population, and vestibular anomalies, such as bony and membranous blockage of the superior semicircular canal. Moreover, an extremely underdeveloped malleus and incus continuous with a persistent Meckel's cartilage were observed.

Effects of afferent stimulation of the lingual nerve (LNAS) on gastrointestinal motility and the reflex pathways which mediate the response to LNAS were investigated in rats. LNAS induced excitatory, inhibitory or biphasic responses in the stomach, duodenum and proximal colon. These responses continued after bilateral vagotomy, but were abolished after additional bilateral splanchnicotomy or transection of the spinal cord between Th4 and Th5. The inhibitory, excitatory and biphasic responses induced by LNAS were not affected by decerebration. Both after administration of atropine (0.2 mg/kg, i.v.) and guanethidine (3-5 mg/kg, i.v.), LNAS-induced excitatory and inhibitory responses were abolished in most cases, but the slight inhibitory response in the stomach and duodenum to LNAS remained in a few cases. These results suggest that the reflex centers which cause LNAS-induced excitatory and inhibitory responses are located in the dorsal nucleus of vagus and that the reflex pathways include the vagus and splanchnic nerves.

Six pregnant women with convulsions between 25 to 40 weeks of gestation were experienced. Among them, 4 patients were diagnosed as having intracranial hemorrhage and two as simple eclampsia. With the aid of brain CT scan, one case of arteriovenous malformation was detected and treated surgically with good prognosis for both the mother and the fetus. Two patients were diagnosed to have cerebral hemorrhage with subsequent penetration into the lateral ventricles and were treated conservatively. Their fetuses were delivered alive by cesarean section, but the mothers expired. The other patient with cerebral hemorrhage was treated surgically, and both the mother and the fetus survived. One of the simple eclampsia patients was noted to have a growth retarded fetus at 32 weeks of pregnancy with subsequent intra-uterine death, but the mother recovered after conservative treatment. Another patient at 40 weeks of pregnancy was also treated conservatively and both the fetus and the mother survived. Brain CT scan findings differed between these two eclampsia patients; local brain edema for the second patient and generalized brain edema for the first patient. Thus more active application of brain CT scan is recommended in managing pregnant patients with convulsions.

The extra-anatomical bypass formation and the exclusion of thoracic aortic aneurysms by the "paired clamp method" applied to the thoracic aorta of mongrel dogs, and the development of hind leg paralysis was studied experimentally in relation to the ratio between the mean excluded cavity pressure and the mean aortic pressure ratio (EA-ratio). The relationship between thrombus formation in the excluded cavity and the EA-ratio was also studied. Animals were divided into 4 groups: Group 1 underwent the cross-clamping of the descending thoracic aorta for 8 min; Group 2 underwent exclusion of the entire thoracic aorta under permanent bypass; Group 3 underwent ligation of 2/3 of the proximal intercostal arteries which branched from the excluded thoracic aorta; and Group 4 underwent division of the excluded thoracic aorta into 3 parts by ligation. No animals in group 1 developed paralysis. When EA-ratios were higher than 0.48, animals in groups 2 and 3 were not paralyzed, whereas all but 1 animals with EA-ratios lower than or equal to 0.48 were paralyzed. There was statistically significant difference between the EA-ratio of the non-paralyzed animals and that of the paralyzed animals in groups 2 and 3. Four out of 5 animals in group 4 were paralyzed. However, there was no statistically significant difference between the EA-ratio in these 4 paralyzed animals and that in the non-paralyzed animals in groups 2 and 3. When the EA-ratio was lower than or equal to 0.59, all but 1 excluded cavities of groups 2 and 3 animals were fully thrombosed 7 or 8 days after the operation. None of these animals showed the aggravation of the paralysis during the observation period and, conversely, the paralysis of almost all animals was ameliorated. These results suggested that the EA-ratio is useful in predicting the development of paralysis and thrombus formation in the excluded cavity after the operation of thoracic aortic aneurysms by the "paired clamp method".

The adductor pollicis muscle was studied in fifty hands of Japanese adult cadavers of both sexes. The radial portion of the oblique head of the adductor pollicis muscle has carpal and metacarpal origins and an insertion into the wing tendon of the extensor apparatus. This portion was located dorsal to the palmar metacarpophalangeal articular nerve and superficial palmar metacarpal artery. Thus, the radial portion of the oblique head of the adductor pollicis muscle (more strictly, the slips dorsal to the palmar-penetrating twig of the ulnar nerve) is similar to the palmar interosseous muscles, except that its slips cannot be clearly distinguished from each other.

A line of chick embryo cells (CEC) was obtained from CEC treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The cells, designated CHCC-OU2, were contact-inhibited, formed no colony in soft agar and did not produce tumors when inoculated into syngeneic chickens. The electron microscopic examination and reverse transcriptase assay showed no virus production from the cells. Subgroup A avian sarcoma virus (ASV) and Newcastle disease virus replicated well in the cells of this cell line.

Thirty-eight patients were operated on for mitral stenosis between March 1979 and September 1981. Thirty-six of them were examined as to their age, symptom duration, chest roentgenograms, electrocardiograms and echocardiograms to obtain various indices of left ventricular function. The usefulness of these indices as preoperative risk factors for predicting postoperative low cardiac output syndrome (LOS) was investigated. Cases which had values of ejection fraction, cardiac index, percent fiber shortening or mean velocity of circumferential fiber shortening less than 0.45, 2.0 l/min/m2, 25% and 0.80 circ/sec, respectively, in the preoperative echocardiographic examination were associated with a greater chance of postoperative LOS. Each of these factors was independently useful as a risk factor in cardiac surgery for mitral stenosis. Moreover, it was revealed that the combination of a preoperative percent fractional shortening (%FS) of less than 30% and a cardiac index smaller than 2.0 l/min/m2 indicated a strong predisposition toward postoperative LOS.

A rapid method was devised for the detection of virus particles in wart specimens. The upper layer of warts was cut perpendicularly to the surface, and the freshly cut surface was lightly touched to an electron microscope grid. The grid was then stained with a small drop of phosphotungstate and observed electron microscopically. On the specimen grid thus prepared, papillomavirus particles were easily discriminated from tissue debris. Papillomavirus particles were detected in 71% of verrucae plantares, 78% of verrucae palmares, 50% of verrucae vulgares and 75% of condylomata acuminata by the present method.

Protection of Escherichia coli NIHJ and C57BL mice from the effects of 60Co gamma-rays provided by S-alk(en)yl-L-cysteines and their hydantoin derivatives was examined. E. coli (10(6) cells/ml) suspended in a 20 mM aqueous solution of one of the drugs was irradiated with 60 Gy of gamma-rays. Five week-old male mice were exposed to 5.0-9.5 Gy of gamma-rays after a single intraperitoneal injection of 0.75 mmol/kg body weight of each compound. In both E. coli and mice, S-allyl compounds afforded more effective radioprotection than S-propyl compounds. The replacement of the alpha-hydrogen of S-substituted cysteines by methyl groups decreased the radioprotective effect. Hydantoin derivatives were much more radioprotective than the original sulfur-containing amino acids. Especially, DL-5-allylthiomethyl-5-methylhydantoin had a remarkable radioprotective effect in mice. The gamma-radiolysis mechanism of thiomethylhydantoin derivatives was discussed in connection with the radioprotective effect of the drugs.

Antibody-dependent macrophage-mediated cytotoxicity was studied to determine the significance of cytophilic anti-thyroglobulin antibody (ATgA) present in the sera of patients with Hashimoto's thyroiditis. Effector cells were normal human monocytes or guinea-pig peritoneal exudate cells, and target cells were human thyroglobulin(Tg)-coated chicken erythrocytes. Cytotoxicity was evaluated by morphological observation and by 51Cr-releasing assay. Normal human monocytes rapidly destroyed ATgA-bound Tg-coated chicken erythrocytes by extracellular cytolysis and by phagocytosis. On the contrary, human monocytes "armed" with cytophilic ATgA destroyed Tg-coated chicken erythrocytes slowly and to a lesser extent, and only by extracellular cytolysis. When normal monocytes or peritoneal exudate cells were incubated with Tg-coated chicken erythrocytes in the presence of the sera of patients with Hashimoto's thyroiditis, phagocytosis occurred rapidly, but extracellular cytolysis developed rather slowly. These data suggest the possibility that human monocytes participate in antibody-dependent cell-mediated cytotoxicity (ADCC) in vivo, which may be an important destructive mechanism in Hashimoto's thyroiditis. It is also possible that ATgA cytophilic for monocytes render non-immune peripheral monocytes cytotoxic against Tg-bearing cells.

To investigate factors involved in excision repair DNA synthesis, a soluble extract was prepared from permeable mouse sarcoma (SR-C3H/He) cells by homogenization and ultracentrifugation. DNA synthesis measured by using native calf thymus DNA as the template-primer and the extract as the polymerase source showed low activity. The DNA synthesis was enhanced more than ten-fold by the addition of an appropriate concentration of bleomycin, a radiomimetic DNA-damaging drug. Using selective inhibitors of DNA polymerases, it was shown that the DNA polymerase involved in the bleomycin-induced DNA synthesis was DNA polymerase beta. In addition to DNA polymerase beta, an exonuclease which converts bleomycin-damaged DNA into suitable template-primers for repair DNA synthesis appeared to be present in the permeable cell extract.

The difference in the physiological condition of drivers of manual transmission buses (MTB) and automatic transmission buses (ATB) was examined from the viewpoint of occupational health. This study was based on a self-administered questionnaire which involved items concerning subjective fatigue complaints. No differences in the mental fatigue and stress between MTB drivers and ATB drivers were observed. Although ATB drivers tended to feel less physical fatigue than MTB drivers, the difference was not statistically significant. From these results, it was suggested that there was little difference in the subjective fatigue between ATB drivers and MTB drivers.

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.