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Summary. Background: Protein S (PS) is an anticoagulant protein that functions as a cofactor for activated protein C (APC), and congenital PS deficiency is a well-known risk factor for the development of deep vein thrombosis (DVT). Recently, we and others identified the K196E missense mutation in the second epidermal growth factor-like domain of PS as a genetic risk factor for DVT in the Japanese population. The incidence of this mutation is high in the Japanese population. Objectives: In the present study, we investigated the relationship between plasma PS activity and the presence of the K196E mutation. Patients and methods: We measured PS activity as a cofactor activity for APC in 1862 Japanese individuals and determined the PS K196E genotype in this population. Results: Individuals heterozygous for the mutant E-allele had lower plasma PS activity than wildtype subjects (mean ± SD, 71.9 ± 17.6%, n = 34 vs. 87.9 ± 19.8%, n = 1828, P

OL-protocadherin (OL-pc) is a cell adhesion molecule that belongs to the cadherin superfamily. A previous study showed that expression of OL-pc mRNA was specific to certain brain nuclei including those of the olfactory and limbic systems, thus suggesting its involvement in neural circuit formation (Hirano et al., 1999). Here, we examined the distribution of OL-pc protein in the postnatal mouse brain by immunohistochemistry to confirm the possibility of such a role. The results showed that the protein could be mapped to many brain compartments including brain nuclei and higher subdivisions as previously observed for the expression pattern of the mRNA. Sharp boundaries of the distribution were often seen in areas such as the interpedunclar nucleus, cerebellar cortex, and inferior olive. In addition, the protein was detected in some fibers that could not be examined by the previous study using in situ hybridization. For example, prominent staining was noted in the stria medularis, stria terminalis, fasciculus retroflexus, optic tract, and inferior thalamic radiation, structures that seem to connect OL-pc-positive brain regions. These OL-pc-positive brain nuclei and fiber tracts coincide with some local circuits of functional systems such as the olfactory system, nigrostriatal projection, olivo-cerebellar projection, and visual system. These results support the possibility that OL-pc is involved in the formation of specific neural compartments and circuits in the developing brain.

RNA/DNA ratios and the condition factor, as determined by weight and length of glass-eels, Anguilla japonica, were evaluated for assessment of nutritional status. The negative correlation of RNA/DNA ratios and condition factor between capture months corresponded to an increase in DNA content and to a decrease in dry weight, respectively. These findings indicated that the body material decreased in the later caught glass-eels, but, in contrast, DNA content and ossification increased. These phenomena were explained by such factors as food density and metabolic energy requirements. We concluded that the development of the glass-eel with poor feeding is influenced by differences in ambient water temperature, and that expended endogenous nutrition originates in the leptocephali.

Purpose Gait rehabilitation is a fundamental requirement to avoid disuse syndrome for the long-term hospitalized person such as cerebral infarction patient or patient with dementia. In general gait rehabilitation is monotonous and dull, so some entertainment or a sense of achievement is helpful to maintain motivation during the daily exercise. This paper proposes an effective gait-rehabilitation system using a robotic dog supporting individual initiatives of the patient. Method Walking with a living dog is one way to achieve this; however as an intervention it is limited to mildly symptomatic patients because a real dog risks sudden lunging. We used a robotic dog instead of a living dog for relatively critical patients. We have studied robot-assisted activity and therapy using robotic animals in the elderly nursing home in order to improve residents’ quality of life (QOL). In the case of a man-made robot, aforementioned risks can be ignored. Moreover, it is an advantage that an in-house walking exercise with the dog is possible. The basic concept of this proposal is co-creation of steps between the elderly and dog. That is, the real-time stabilometric signal of the elderly was measured and analyzed to extract a single step and forwarded to the robotic dog to make a step. Since commercially available amusement products pass through the safety review of public administration, the proposed system was composed of those products as a hardware tool. More specifically, entertainment robot AIBO of Sony ERC was adopted as the robotic dog and Nintendo’s Wii-balance-board is used as the stabilometric human interface devices. All signals are transmitted by conventional Bluetooth and LAN systems. Results & Discussion Figure 2 shows the block diagram and enforcement scenes of gaiting exercise at standing and sitting positions, respectively. The patients both suffered from dementia and made their own steps in a positive manner shown by arrows in the figure. Such positive attitude was uncommon in the conventional daily exercise. Functions for walking back and forth walk, and turning right and left are installed. It is noteworthy that the standing patient tempts the dog to move toward another patient and the patient calls the robot to her. This means there a co-creation field is created through the robotic dog. This was followed by a chat between the patients. In the case of the sitting patient, although for her it is very hard exercise to raise her foot from the floor, she made several steps on her own initiative successively after the physical therapist guided her how to walk by patting and lifting her right and left knees alternately. The position of the center of gravity and command signal were logged every 0.1 sec in the control PC and available to be analyzed afterward. For example, the change of exhaustion during exercise was estimated from the magnitude and regularity of steps. Since all hardware tools can be packed in a suitcase the proposed gait exercise can be easily done everywhere.

2,3,5- and 2,4,5-trichlorophenyl methyl sulfides, 2,3,5- and 2,4,5-trichlorophenyl methyl sulfoxides, and 2,3,5- and 2,4,5-trichlorophenyl methyl sulfones (TCPSO2Mes) were detected in the urine of rats dosed with 1,2,4-trichlorobenzene (TCB). After the administration of 1,2,4-TCB to rats, swift decreases in concentrations of 1,2,4-TCB in blood, liver, kidneys, and adipose tissue were observed. On the other hand, 2,3,5-TCPSO2Me appeared in blood, liver, kidneys, and adipose tissue and remained detectable in the blood and the three tissues until 120 hr. The increases in the activities of aminopyrine N-demethylase and aniline hydroxylase and the contents of cytochromes P450 and b5 in hepatic microsomes produced by 1,2,4-TCB occurred after increases in the hepatic concentration of 2,3,5-TCSO2Me. 2,3,5- and 2,4,5-TCPSO2Me increased the above four parameters in rat liver microsomes. The inducing intensity of 2,3,5-TCPSO2Me was much higher than that of 2,4,5-TCPSO2Me. 2,3,5-TCPSO2Me was considered to be a potent inducer and to play a principal role in the induction by 1,2,4-TCB. When 1,2,4-TCB was injected ip into bile duct-cannulated rats, little 2,3,5-TCPSO2Me was detected in blood, liver, kidneys, and adipose tissue. In the antibiotic-pretreated rats dosed with 1,2,4-TCB, 2,3,5-TCPSO2Me concentrations in the blood and the three tissues markedly decreased. These findings suggest that the formation of methylsulfonyl metabolites from 1,2,4-TCB depends largely upon the metabolism of some precursor(s) excreted in the bile by intestinal microflora. The increasing effects of 1,2,4-TCB administration on the activities of aminopyrine- and aniline-metabolizing enzymes and the contents of cytochromes P450 and b5 in hepatic microsomes were not observed in the bile duct-cannulated rats. These findings provide evidence that the induction of drug-metabolizing enzymes by 1,2,4-TCB is not due to the action of 1,2,4-TCB itself but is due to its methylsulfonyl metabolite, 2,3,5-TCPSO2Me.

A goal of our research is to develop a colonoscopic imaging agent that enables real-time and accurate diagnosis of small-sized colorectal cancer. Colorectal cancer first develops in the mucous membrane of the large intestine. We designed an imaging agent that can recognize tumor-derived changes on the mucosal side of epithelial cells in the large intestine with high affinity and specificity. The agent is peanut agglutinin (PNA)-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) (PNVA) chains encapsulating coumarin 6. PNA is a targeting moiety that binds to β-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which is the terminal sugar of the Thomsen-Friedenreich antigen that is specifically expressed on the mucosal side of colorectal cancer cells. The tumor-derived change in the large intestinal mucosa is very small throughout the entire large intestine. To detect such a small change accurately, the imaging agent should have a strong affinity for targets with minimal nonspecific interactions with nontargets. PNVA is also immobilized on the nanosphere surface to enhance the specificity of PNA by reducing the nonspecific interactions between the imaging agent and normal tissues. Coumarin 6 is used as the fluorescent dye that provides an endoscopically detectable fluorescence intensity. It is anticipated that intracolonic (enema) administration of the imaging agent leads to the specific accumulation on the mucosal surface of tumor tissues in the large intestine with resulting fluorescence. Real-time and accurate diagnosis of small-sized early colorectal cancer can be then achieved through observations of a clear fluorescence contrast between the normal and tumor tissues using the standard fluorescence endoscopy.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and BrdU using anti-PCNA and anti-BrdU monoclonal antibodies, respectively, was performed in 16 human brain tumours, including 3 glioblastomas multiforme, 2 anaplastic astrocytomas, 1 cerebellar astrocytoma, 2 recurrent meningiomas, 4 non-recurrent meningiomas, 3 neurinomas and 1 medulloblastoma. Patients with brain tumours received an injection of bromodeoxyuridine (BrdU) intravenously during surgery, and tumour specimens were fixed in 70% ethanol and embedded in paraffin. The percentage of positive cells for PCNA was compared with a BrdU labelling index using adjacent paraffin-embedded sections. The percentage of PCNA-positive cells was correlated with the BrdU labelling index and the histological malignancy of the brain tumours. The correlation coefficient was 0.84. This suggests that the immunohistochemical staining for PCNA in paraffin sections is a good alternative to the BrdU labelling index.

Our previous studies suggest that a neutrophil-mediated inflammatory injury causes a major fraction of the pulmonary edema that occurs after smoke inhalation. Because activated neutrophils extrude cytotoxic proteases, the current study was conducted to evaluate the role of proteases in the pulmonary microvascular injury. Twelve sheep, instrumented for collection of lung lymph, were insufflated with cotton smoke. The sheep were treated 30 min after smoke inhalation with either gabexate mesilate (an inhibitor of serine proteases) or vehicle. Smoke inhalation resulted in an increased protease activity in the lung interstitium, as evidenced by decreases in both antiprotease activity and immunoreactive alpha 2-macroglobulin. Intravenous infusion of gabexate mesilate prevented the decrease in antiprotease activity. The protease inhibitor significantly attenuated the smoke-induced increase in transvascular fluid and protein flux, with untreated animals exhibiting 460% increases in flux compared with 180% in the inhibitor treated sheep. The protease inhibitor also eliminated the functional degradation in gas exchange that was observed in the untreated sheep. These studies strongly suggest that an increase in pulmonary proteolytic enzyme activity is responsible for a significant fraction of the degradation in microvascular integrity and gas exchange that is associated with smoke inhalation injury.

Hepatitis C virus (HCV) has been linked to extrahepatic manifestations such as oral lichen planus (OLP). In addition, anticardiolipin antibodies (aCL) and cryoglobulin have been demonstrated in chronic hepatitis C. The aim of this study was to investigate these prevalences in patients with HCV-associated OLP. The prospective study investigated the role of these factors in 133 subjects: 28 with OLP-HCV(+) (group 1), 22 with OLP-HCV(-) (group 2), 33 without OLP-HCV(+) (group 3), and 50 healthy volunteers matched for age and sex served as control group (group 4). Levels of immunoglobulin G (IgG) and IgM aCL antibodies, and cryoglobulin in serum were evaluated by enzyme-linked immunosorbent assay. The prevalence of aCL in groups 1, 2, 3, and 4 were 32.1, 18, 36.3, and 8%, respectively. The positive rate of aCL was significantly higher in groups 1 and 3 than that in the control group (group 1; p=0.02 vs. the control group, group 3; p

Carbon dioxide is a metabolic byproduct of mammalian cell metabolism that can accumulate in poorly ventilated cultures. A buildup of CO2 at constant pH will be accompanied by an increase in medium osmolality. We have examined the glycosylation of tissue plasminogen activator (tPA) produced under serum-free conditions by recombinant Chinese hamster ovary (CHO) cells (MT2-1-8 cell line) in response to elevated pCO2 at constant or elevated osmolality. The proportion of sialic acids comprising N-glycolylneuraminic acid decreased from 2.3-4.0% under 36 mmHg pCO2 to 1.5-2.2% under 250 mmHg pCO2. No changes were observed in the total sialic acid content, the content of other monosaccharides, the relative amounts of type I and type II tPAs, the distribution of surface charges, or the proportion of high-mannose oligosaccharides-even though these conditions have previously been shown to inhibit the specific growth rate of MT2-1-8 cells by 30-40% and the specific tPA production rate by as much as 40%. These results suggest robust glycosylation of tPA by CHO cells.

The efficacy and the side effects of a third course of indomethacin in the treatment of persistent patent ductus arteriosus (PDA) were examined by Sangem et al. [6], and the results are presented in this issue of Pediatric Cardiology. In a retrospective analysis of 259 infants of gestational age \34 weeks with a PDA, one course of indomethacin resulted in closure in 76% of the patients. A second course of indomethacin in the remaining 61 infants with PDA caused closure in 42% of the patients. Of the remaining 38 patients with PDA, 11 were referred for surgical ligation of the PDA and 26 were treated with a third course of indomethacin. A total of 43% of the patients treated with a third course of indomethacin had closure of their PDA. Comparing patients treated with two courses of indomethacin to those treated with three courses, all measures of morbidity were similar except for an increased trend (p = 0.06) in periventricular leukomalacia (PVL) in patients treated with three courses. The authors of this study conclude that a prospective study comparing the effect of multiple courses to ligation in the treatment of persistent PDA should be performed.

Polymyositis and dermatomyositis are inflammatory muscular diseases of unknown etiology which have interstitial pneumonitis as a serious complication. From 1987 to 1994, we used cyclosporine to treat 14 polymyositis/dermatomyositis patients (8 with and 6 without interstitial pneumonitis). In combination with prednisolone, cyclosporine was either added to or substituted for conventional cytotoxic drugs (azathioprine, cyclophosphamide and methotrexate). Cyclosporine was effective against both myositis and interstitial pneumonitis when used early in the course of the disease.

We implanted mineral-containing bone particles (BPs) in rats to investigate the involvement of osteoblast lineage cells in osteoclast development in vivo. BPs were implanted in subcutaneous regions on calvaria or artificial defects of calvaria, with or without adjacent parathyroid glands prepared from other rats. The structural characteristics of multinucleated giant cells (MGCs) induced by the BPs were investigated. The MGCs induced by subcutaneously implanted BPs showed membrane ruffling at the basolateral site, but not at the apical site, regardless of whether parathyroid glands were also implanted. In contrast, the MGCs induced by intraosseously implanted BPs showed the characteristics of osteoclasts i.e., ruffled borders at the apical sites, clear zone, vacuoles, many mitochondria, and scattered rough endoplasmic reticulum. When BPs and parathyroid glands were implanted in bone defects, the number of MGCs was increased compared to that induced by BPs only. These MGCs showed the typical characteristics of active osteoclasts, including developed ruffled borders and stacks of Golgi succules. The number of osteoclasts was also investigated quantitatively by counting the numbers of MGCs positive and negative for tartrate-resistant acid phosphatase. In intraosseous implantation, MGCs with the characteristics of osteoclasts were observed close to osteoblastic cells characterized by developed rough endoplasmic reticulum. These results indicate that the osteoclasts were not induced solely by the subcutaneously implant BPs, but required osteoblast lineage cells for development.

Rationale Microscopic polyangiitis (MPA) is a systemic vasculitis characterized by small vessel involvement. Studies suggest MPO-ANCA is involved in its pathogenesis, and the titer may reflect disease activity. Generally, MPA is not associated with pregnancy. Isolated case reports have only noted neonatal cutaneous vasculitis. We report a unique case of transplacental transfer of MPO-ANCA from mother to 32-week gestational age neonate resulting in neonatal pulmonary hemorrhage and renal involvement that was successfully treated. Methods We obtained MPO-ANCA titers from the cord blood and neonate on day of life (DOL) 8, 15, and 25. Corresponding neonatal and maternal labs were obtained, including: ANCA, ESR, CRP, ANA, serial UA, CBC, metabolic panels, and chest x-rays. Results The neonate was delivered by C-section secondary to maternal pre-eclampsia and dyspnea. Prior to delivery, the mother received 2 doses of betamethasone. Neonatal chest x-ray on DOL 1 showed bilateral pulmonary infiltrates, and she was intubated. Initial UA showed proteinuria and hematuria. The MPO-ANCA titer was 3.30 in the cord blood and 2.5 in the mother. Acute pulmonary hemorrhage developed DOL 3, and the neonate was infused hydrocortisone 3 mg/kg. Persistence of the MPO-ANCA and concern of cardiac septal hypertrophy secondary to prolonged steroid therapy led to neonatal exchange transfusion on DOL 5. With the therapeutic interventions and progressive reduction of the MPO-ANCA titer, neonatal pulmonary-renal symptoms resolved. Conclusions Animal studies suggest MPO-ANCA contributes to vascular damage. Our patient represents an in vivo case of MPO-ANCA transfer and pulmonary-renal pathogenicity that was successfully treated with steroids and exchange transfusion.

Eighteen sheep previously prepared for chronic study were divided into three groups of six animals each. These were given graded inhalation injury utilizing smoke obtained from burning cotton-toweling material. Smoke was insufflated into animals with a modified bee smoker at temperatures less than 40 degrees C. Group H, which received 64 breaths of smoke, showed the most pronounced changes in pulmonary function. The changes consisted mainly of a profound increase in lung lymph flow following a reduced P/F ratio (PO2 in arterial blood/inspired O2 fraction) and an elevation in both thermal and gravimetrically measured extravascular lung water. Similar changes were seen in group M (48 breaths of smoke) and group L (32 breaths of smoke). However, the injury was graded based on the changes in gravimetrically measured lung water and lung lymph flow. These were highest in group H and lowest in group L. These studies confirm our ability to accurately quantitate the injury induced by smoke inhalation. In addition, it demonstrates that lung injury associated with the inhalation of smoke can be graded depending on the duration of exposure.

Gonioscopy was performed on 110 patients with primary open-angle glaucoma over 40 years of age and an equal number of normal sugjects, matched by race and age. The frequency distribution of various angle features differed in the two groups: in the glaucoma group, there were more iris processes at all levels of insertion, a higher insertion of the iris root and more trabecular pigmentation. A congenital angle anomaly is one important factor in the pathogenesis of the elevated pressure.

The time-course of blood total radioactivity after i.v. administration of 3H-methamphetamine to rats showed a biphasic curve. The biological half-life of the alpha phase (t alpha 1/2) was 6.8 +/- 2.0 min, and that of the beta phase (t beta 1/2) was 11.3 +/- 0.8 h. The major metabolite in the blood was unconjugated p-hydroxymethamphetamine. The total radioactivity in bile peaked at 1.5 h after i.v. administration. The major metabolite in the bile was p-hydroxymethamphetamine glucuronide. The major compound excreted in urine was unchanged methamphetamine. Whole-body autoradiography was performed using 14C-methamphetamine, and tissue 3H concn. was determined after i.v. administration of 3H-methamphetamine to rats.

1. [3H]Bitolterol, an ester prodrug to colterol (N-t-butyl-arterenol), when administered orally, was excreted mostly in the urine; approx. equal amounts of 3H were found in urine and faeces after intraperitoneal or intravenous injection. 2. Half the dose was excreted in the bile following parenteral administration, while only a small amount of radioactivity was found in bile after oral dosage. The biliary-excreted material consisted mainly of glucuronides, for all routes of administration. 3. The glucuronides of colterol and 3-O-methyl-colterol were excreted in urine after oral administration of bitolterol. In addition to the glucuronides, free colterol and 3-O-methyl-colterol were excreted in urine following parenteral administration. 4. A part of bitolterol was hydrolysed to colterol in rat stomach, and bitolterol was more rapidly hydrolysed to colteral with homogenates of intestinal mucosa than with stomach homogenates in vitro.

Durch Verabreichung groser Mengen abgetoteter Bakterien per os lies sich auch beierwachsenen Mausen ein groser Teil der Tiere gegen Infektion mit kleinen, aber sicher todlichen Dosen (bis zu 100, gelegentlich auch 1000fach todlicher Dosis) schutzen. Die Versuche ermuntern zur Anwendung der Immunisierung per os beim Menschen. Insbesondere kamen jedoch Kinder fur die praktische Anwendung in Betracht, die einerseits besonders gefahrdet, andererseits per os (nachEguchi) leichter zu immunisieren sein durften.

The subcommissural organ (SCO) of the congenital hydrocephalus spontaneously occurring in CWS/Idr rats was severely reduced in size and displaced at some distance from the anterior end of the cerebral aqueduct. The cerebral aqueduct of the hydrocephalic rats was open throughout its total length during postnatal days 1-20, though it was somewhat narrower at its middle region than in the normal brain.

Die Verteilung von radioaktivem Phosphor im Gehirn virusinfizierter weisser Mause ist gepruft worden. Im Zeitpunkt maximaler Virusvermehrung nimmt die Aufnahme des radioaktiven Phosphors in den Phosphorverbindungen der infizierten Gehirne deutlich zu. Virologische und biochemische Aspekte wurden diskutiert.

The cardiopulmonary response to continuous administration of lipopolysaccharide (LPS) was studied in chronically instrumented sheep. LPS was administered in doses of 0 (sham), 6, 9, 12, and 24 ng.kg-1.h-1 for 24 h. No significant changes in the measured variables occurred in the sham group and in the 6 ng.kg-1.h-1-LPS group. With 9, 12, and 24 ng.kg-1.h-1-LPS, cardiac index rose and peripheral resistance fell to the same extent in all three groups. Lung lymph flow (QL) increased with increasing concentration of LPS. These elevations in QL occurred in the presence of only minor increases in the pulmonary artery pressure, which rose to the same extent in the 9, 12, and 24 ng.kg-1.h-1 groups. Consequently, the changes in QL were attributable to changes in fluid conductance of the pulmonary microvasculature rather than variations in hydrostatic pressure. The increase in QL correlated with a decrease in prekallikrein levels (r = 0.97), indicating that the changes in fluid conductance might have been kinin mediated.

UNLABELLED A relationship between increased peripheral resistance (TPRI) and decreased cardiac index (CI) and mortality from sepsis has been suggested. The relationship between endogenous opiates and this response was evaluated. METHODS Chronically instrumented sheep were given E. coli endotoxin (LPS, 1.5 mcg/kg x 30 minutes). In one study, survivors (n = 9) and nonsurvivors (n = 11) of LPS were compared along with survivors (n = 8) of half the dose of LPS. In a second study, two groups of animals received naloxone: one (n = 11) had a bolus of 2 mg/kg followed by a 2 mg/kg/hr continuous infusion started 30 minutes before LPS while the other had the bolus and infusion started 1 hour after LPS was begun. RESULTS Both vasoconstrictive and vasodilative phases were seen. Vasoconstriction was associated with elevated beta endorphin levels, a pattern sustained until death in the nonsurvivors. Both pre- and posttreatment with naloxone lessened the maximum increase in total peripheral resistance index compared with untreated sheep. DISCUSSION The vasoconstrictive aspects of the response to LPS correlated with elevated beta endorphin levels and with mortality. This vascular response is attenuated with naloxone blockade.

Fluorescein gonioangiography was performed in 4 eyes of 4 patients with ocular sarcoidosis and in an eye of a patient with presumptive tuberculous anterior uveitis. Small discrete whitish lesions in the ciliary body band near the iris root showed hyperfluorescent shortly after fluorescein injection. These hyperfluorescence dots seemed to be pathognomonic changes in cases with granulomatous uveitis.

• Fluid resuscitation is complicated in hypotensive septic patients by their susceptibility to pulmonary edema. This problem was evaluated in the ovine model of endotoxemia with a chronic lung lymph fistula. Escherichia coli endotoxin (lipopolysaccharide, 1.5 μg/kg) was given intravenously over 30 minutes. Group M (n=9) continued to receive baseline fluids (2 mL/kg/h), while group R (n=6) received 7 mL/kg/h of Ringer's lactate. After an initial drop in cardiac index, animals in both groups developed a hyperdynamic state. The fall in mean arterial pressure seen in group M was absent from group R. The higher fluid volume resulted in a rise in left atrial pressure and pulmonary microvascular pressure. The lung lymph flow and permeability index were elevated in both groups but were higher in group R. The calculated filtration coefficient showed a threefold increase in both groups. Augmented fluid resuscitation during endotoxemia resulted in an elevated interstitial fluid flux and permeability index secondary to an increase in pulmonary microvascular pressure and greater surface area of the injured microvascular beds being perfused. ( Arch Surg 1988;123:345-350)

The time-course of total blood radioactivity after oral administration of 3H-methamphetamine, following multiple oral administration of non-radioactive methamphetamine for 7 and 14 days to rats, was examined to elucidate the effects of multiple administration on enterohepatic circulation. Whole-body autoradiographs of rats after oral administration of 14C-methamphetamine showed high levels of radioactivity in contents of stomach and small intestine, bladder urine, liver, and various glands. Distribution of methamphetamine and the major metabolite in tissues during multiple dosing was investigated; accumulation occurred in brain, liver, testis and fat. Multiple oral administration of methamphetamine to rats slightly induced enzyme activities of N-demethylation and aromatic hydroxylation of methamphetamine in rat-liver 9000 g supernatant.

The midbrains of pups with congenital hydrocephalus spontaneously occurring in MT/HokIdr mice were histologically examined. The subcommissural organ (SCO) and the posterior commissure were completely absent in the hydrocephalic brain. The cerebral aqueduct in the hydrocephalic brain was never completely stenosed, though it was somewhat narrowed in its middle region as compared with that in the normal brain. A possible interrelationship between an absence of SCO and a cause of congenital hydrocephalus is discussed.

Early post mortem changes in the Organ of Corti are described. 15 minutes after death, when kept at room temperature, 20° C (63° F), an oedematous swelling is observed within the cytoplasm of hair cells and nerve endings, the latter being more severe affected. After 30 minutes post mortem the mitochondria of the hair cells have also become significantly swollen. Three hours post mortem the general character of the hair cells is still recognizable, but most of the nerve endings have been completely destroyed.

The instruments are the romanoscope SLA type (Machida) the laparoscope SLD type (Machida) and the fiber-broncoscope L type (Machida). As the laparoscope and the romanoscope are not flexible observation of the intrahepatic bile ducts was easy but difficult for the choledochus. Conversely the fiber-broncoscope was easily manipulated for the observation of both the intrahepatic bile ducts to the second branchies possible. But the observation of choledochus is difficult in spite of mobilization of the duodenum by the Kocher maneuver.(AUTHORS MODIFIED)