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We compared the prevalence of skin cancer and solar keratosis (SK) in patients who attended 26 Japanese university hospitals between 1976-1980 with those who attended between 1986-1990 to investigate whether the incidence of skin cancer has increased or not. Age-adjusted incidence rates of basal cell carcinomas (BCC) and SK, but not squamous cell carcinomas (SCC), from 1986-1990 were higher than those from 1976-1980. In addition, a population-based incidence study was conducted in Kasai City, Hyogo prefecture, to establish the frequency of skin cancer and SK. A total of 4736 people over 20 years of age were examined. Two BCC and 36 SK patients were identified clinically and histopathologically. SCC was not found. Age-adjusted incidence rates of BCC and SK per 100,000 were 16.5 and 486.1, respectively. The BCC incidence rate in Kasai City was significantly higher than the incidence of Japanese nonmelanoma skin cancer (NMSC) reported by Gordon in 1976. Further, subjects classified as skin type I showed statistically higher SK prevalence rates compared to skin types II and III. The present study indicates that the prevalences of NMSC and SK in Japanese have increased during the last three decades and that skin type I may be a risk factor for NMSC in Japanese.

Retinal images produced by two types of multifocal intraocular lenses (IOLs) were studied using an eye model. One of them was a refractive IOL with five zones, and the other was a diffractive lens. The IOLs were inserted into an eye model with a pupil diameter of 3 mm. The retinal plane of the eye model was observed microscopically. When the section of the IOL used for far vision was in focus, the retinal image of the refractive IOL was almost the same as that of the monofocal IOL, which was better than that of the diffractive IOL. When the near vision section of the IOL was in focus, the retinal image of the diffractive IOL had almost the same quality as the far section. The light rings produced when the multifocal IOLs were illuminated by a glare source were also examined. They showed that the diffractive IOL was stronger than the refractive IOL, but the monofocal was the smallest of the three.

We quantitatively evaluated the effects of vascular reconstruction according to the stage by 123I-BMIPP and 201TlCl using circumferential profile (CP) curve method in patients with myocardial infarction. (1) Comparison of the CP curves for the two nuclides in normal volunteers (n = 9) showed no difference in distribution. (2) In patient with myocardial infarction (n = 32) the severity score was evaluated using the CP curves obtained in the normal volunteers. Type B (marked decrease in 123I-BMIPP accumulation) accounted for 83% in the group in whom vascular reconstruction was performed in the acute stage (Group I) and 91% in the group in whom vascular reconstruction was performed in the chronic stage (Group II). On the other hand, type E (similar accumulation between the two nuclides) accounted for 79% in the group in whom vascular reconstruction was unsuccessful or was not performed (Group III). The severity score for each nuclide did not significantly differ among Group I, II and III. The 123I-BMIPP/201TlCl ratio was the highest in Group II, followed in order by Group I and Group III (p0.05). The assessment of the ratio of "severity scores" for both nuclides is considered to be useful for evaluation of the surviving myocardium, rather than the assessment of a single nuclide.

Clinical characterization of patients with allergy to Chamaecyparis obtusa (Cypress) pollen and their specific IgE antibody was investigated by using AlaSTAT assay, a new method for measurement of antigen-specific IgE antibody. Positive rate of antigen-specific antibody in patients with allergic pollinosis was 83.5% for Japanese cedar pollen and 80.0% for Chamaecyparis obtusa pollen. 76.4% of patients were sensitized both to Japanese cedar and Chamaecyparis obtusa pollen, however, 7.9% were sensitized only to the latter. As for clinical symptoms, duration of attack was short and severity was mild or moderate in the patients sensitized only to Chamaecyparis obtusa pollen. Patients who visited hospital in April, in that Chamaecyparis obtusa pollen disseminated in the air predominantly, showed significant elevation in AlaSTAT scores compared with patients who visited in February and March (p0.05).

Methamphetamine (MA) was analyzed using formalin-fixed organ tissues from experimental animals and an autopsied cadaver. The brain, lung, liver, kidney and skeletal muscles of rabbits that had been administered MA were collected, and then fixed with a non-buffered 10% formalin solution at room temperature (10-20 degrees C) for five different fixation periods (1, 3, 7, 14 and 28 days). After the Extrelut column extraction, MA was derivatized using anhydrous trifluoroacetic acid (TFA) and analyzed by GC-MS using a DB-17 column. MA-TFA in the eluates from the organ tissues after the formalin-fixation could be identified by GC-MS. Even one day after the formalin-fixation, concentrations of MA in the fixed organ tissues already significantly decreased to 1.3-3.1% when compared with those of MA in the non-fixed tissues, and to 0.04-0.4% in all of the fixed organ tissues at 28 days after the fixation. Moreover, MA in the organ eluates from the autopsied male cadaver after one-month formalin-fixation was qualitatively detected. These results obviously show the usefulness of MA detection using formalin-fixed organs in the practice of forensic medicine and police science.

As the incidence of cardiac cirrhosis at autopsy today is much lower than that from decades ago, true cardiac cirrhosis is a rare finding. With the decline in incidence of valvular disease, cardiomyopathy, in the etiology of congested liver, has increased. The pathophysiology of congestive heart failure consists of two components: forward failure with decreased hepatic blood flow and backward failure with congestive liver. Both lead to hepatocellular hypoxia. Increased serum transaminases and serum bilirubin correlate with reduction in cardiac output and elevation of venous pressure. Even when cardiac cirrhosis develops, it is difficult to diagnose clinically.

Superoxide dismutase (SOD) activity and the production site of H2O2 were studied in the developing mouse retina. The H2O2 production site moved from the inner to the outer region within the outer nuclear layer between the ages of 4 days through 12 days. This shift occurred in parallel with the development of the inner segments of the photoreceptor layer. SOD activity increased significantly at the age of 2-3 weeks. Both manganese-SOD (Mn-SOD) and copper-zinc SOD (Cu,Zn-SOD) activities (combined mean) in the retina of mice older than 2 weeks of age were 1.9 times greater in comparison with those of mice at the age of 2 weeks and younger. The mRNA of Cu,Zn-SOD did not change during these periods, suggesting that the translational efficiency of the mRNA and/or the stability of the SOD enzyme might increase, or the active form of the enzyme might increase during the development of the retina. The results of this study indicate that the localization and production of active oxygen change during the development of the mouse retina, and that SOD activity does exist in the retina from birth, increasing as its role in the protective system against active oxygen increases in the maturing mouse retina.

After the intravenous administration of lipopolysaccharide at a dose of 3.0 mg/100 g to rats, immunoreactive sites for tumour necrosis factor (TNF) and peptide leukotrienes (LTs) were examined in the heart and lung. Immunoreaction for TNF is preferentially localized on the apical endothelial cell surface of the vessels and in lysosomes of inflammatory and interstitial cells. Lysosomes of cardiac muscle cells which undergo degeneration are also reactive. Peptide LTs in inflammatory cells give almost the same reactions as those for TNF. However, the production of peptide LTs occurs uniquely in cardiac muscle cells in the media of the pulmonary vein, although lysosomes of intracardiac muscle cells which undergo degeneration do not show immunoreactivity. These results suggest that the degeneration of cardiac muscle cells may be induced not only by endogenous TNF but also by peptide LTs which are produced in muscle cells of the venous media and are transported to the myocardium via the coronary circulation.

In five patients with acute monoblastic leukemia (AMoL), the ultrastructural localization of myeloperoxidase (MPO) activity was investigated by two methods, one generally used for the detection of MPO and the other for the detection of platelet peroxidase. The MPO-positive rate achieved was lower with the former method than with the later, indicating that MPO is degraded during the fixation of AMoL cells for electron microscopy. If the ultrastructural MPO positivity of leukemic cells varies when different detection methods are used, the possibility of monocytic leukemia should be considered.

We examined the ultrastructural changes occurring in a human megakaryocytic leukemia cell line, CMK11-5, in response to stimulation with prostaglandin E1 (PGE1). The addition of PGE1 to cultured cells dose-dependently caused vacuole enlargement, the development of cell surface projections, cell surface vacuole formation, and the release of a tracer protein (horseradish peroxidase) which had been incorporated into cytoplasmic granules. These morphological changes, which occurred parallel with [Ca2+]i mobilization in the CMK11-5 cells, were similar to those observed in CMK cells in response to stimulation with ADP, thrombin, and collagen. Our present findings suggest that PGE1 has a stimulatory effect on CMK11-5 cells through the induction of [Ca2+]i mobilization, and that the PGE1-induced transmembrane signaling system in megakaryocytes is completely different from that in platelets.

Using the TOXI-LAB drug detection system, emergency toxicological screening was performed in autopsy cases and emergency cares. In 280 autopsy cases (male 182 cases 65%, female 98 cases 35%), drug positive cases were 28 cases of male (15%) and 24 cases of female (24%). The age groups which showed higher rate of drug positive cases were 10s-40s in male (approximately 20%) and 20s in female (67%). In the 238 cases of emergency care (male 129 cases 54%, female 104 cases 44%, unknown 5 cases 2%), drugs were positive in 29 cases of male (22%) and 32 cases of female (30%). The age groups which showed relatively higher rate of drug positive cases were 40s in male (64%), 20s (71%) and 30s (89%) in female. Forty-four different kinds of drugs were detected in TOXI-LAB positive cases, in which the psychotropic drugs and the sedative-hypnotic drugs amounted to approximately 70%. Methamphetamine and amphetamine, which were the main abused drugs showing a socially important problem, were detected in total 15 cases. TOXI-LAB was based on thin-layer chromatography (TLC); however, from the extraction to development, coloration and detection have been accelerated (about 50 min) and simplified. In order to perform the forensic toxicological practice in Japan, it becomes more useful that TOXI-LAB is used in autopsy cases and emergency cares, if the drugs, which have caused poisoning cares in Japan, are added to TOXI-LAB. The present study describes the advantage and problem of TOXI-LAB drug detection system through demonstrating the practical cases of autopsy cases and emergency cares.

We investigated the expression of three platelet alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fbg), in a human megakaryocytic cell line (CMK 11-5) by immunocytochemical staining, using the alkaline phosphatase anti-alkaline phosphatase (APAAP) complex method and immunoelectron microscopy of ultrathin-frozen sections. CMK 11-5, established from a Down's syndrome patient with acute megakaryoblastic leukemia, has characteristics closely resembling those of normal megakaryocytes. Under basal conditions, TSP expression was observed in the alpha-granules, whereas the other two proteins were not detected. When the cells were cultured with 12-o-tetradecanoylphorbol-13-acetate (TPA), the expression of TSP was enhanced and vWF was also detected, but not Fbg. Cells cultured in the presence of plasma for 24 h took up Fbg and stored it in their alpha-granules. These findings suggest that TSP and vWF are synthesized by CMK 11-5 cells, with the former being produced more rapidly than the latter, whereas Fbg is endocytosed from the plasma.

Two cases of personal identification based on the characteristic findings observed in the bones and teeth of unknown human remains are reported. In Case 1, a skeletonized cadaver could be identified as a 49-year-old male because the autopsy findings of the left clavicle of the cadaver, which was previously operated with metallic screw and wire after fracture, corresponded to the characteristic findings in an antemortem X-ray picture of the presumed person. In Case 2, a cadaver discovered at the seaside, could be identified as a 55-year-old male by comparison between ante- and postmortem dental X-ray findings such as root canal treatment and disease (radicular cyst) including the anatomical characteristics of the root. In forensic practice of personal identification of cadavers with advanced postmortem changes, it seems really important to find out an antemortem medical and/or dental chart and X-ray pictures as well as thorough examination for hard tissue of human remains.

A 53-year-old female in PS grade 4 was admitted to our hospital in April, 1992, with dyspnea and abdominal distention persisting for 1 month. An abdominal echogram suggested a malignant lesion of the left ovary with ascites and a chest radiogram showed massive effusion in the right pleural cavity. Cytology of the effusions confirmed adenocarcinoma. Supposing that both the ascites and the pleural effusion were due to metastases from the primary ovarian carcinoma, we soon carried out systemic cancer chemotherapy and bio-adhesio-chemo (BAC) therapy) in the right pleural space. In July, the patient underwent left oophorectomy. The tumor removed measured 23 x 18 x 11cm. Histology revealed an endometrioid adenocarcinoma of the left ovary. We placed small pieces of fibrin clots encapsulating CDDP in the abdominal cavity of the patient to prevent the recurrence of cancer. Postoperatively, the patient markedly improved to grade 0 in PS and could be discharged 2 months later. She has been receiving systemic cancer chemotherapy with periodical checkups. No evidence of either recurrence or metastasis has been observed. We obtained favorable results with our own types of therapy against advanced ovarian carcinoma.

Nitric oxide, thought to be the endothelium-derived relaxing factor (EDRF), is involved in intra- and intercellular signalling in various tissues. A system for the continuous detection of NO in the picomolar range from a perfused organ is described. The detection is based upon the chemiluminescence reaction between NO and the luminol (5-amino-2,3-dihydro-1,4-phthalazinedione)-H2O2 system. The chemiluminescence is due to the formation of peroxynitrite from NO and H2O2. The luminol-H2O2 system is specifically reactive to NO, so that other nitrogen-containing compounds, (organic nitrite, organic nitrate, and thio-nitroso compounds) or endothelium-derived compounds do not interfere. The limit of determination was approximately 100 fM. This system has been used to measure continuous NO release from isolated perfused rat kidney and the simultaneous changes of perfusion pressure. In Wistar rats basal NO release was 85 +/- 11 fmol/min-1 (g of kidney weight)-1 (39 pM in the perfusate), and acetylcholine increased NO release dose dependently with a concomitant pressure reduction. The changes in NO release were always associated with mirror image changes in the perfusion pressure. Simple pressure reduction did not interfere with the chemiluminescence. Precise titration data as well as results of some preliminary experiments using this method are presented.

To study mechanisms for attenuated endothelium-dependent vasorelaxation in hypertension, we examined the effects of acetylcholine (ACh) on renal vascular resistance (RVR) and release rates of endothelium-derived relaxing factor (EDRF) in kidneys isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA) salt-hypertensive (DOCA salt) rats, and Dahl salt-sensitive (Dahl S) rats. Decreases in RVR by ACh were smaller in hypertensive rats than in their normotensive controls. The release rate of nitric oxide into the perfusate, which was estimated using nitrite-nitrate as an index, did not differ between SHR and Wistar-Kyoto rats (WKY). However, the release rate of EDRF was markedly decreased in both DOCA salt rats and Dahl S rats compared with their normotensive controls (10(-7) M ACh: DOCA salt 45 +/- 6 vs. control 410 +/- 60 pmol.min-1.g-1 kidney wt, P < 0.001). In SHR, high-K+ perfusion or pretreatment with glibenclamide, inhibitors of endothelium-derived hyperpolarizing factor (EDHF), significantly reduced ACh-induced vasorelaxation only in WKY, resulting in no differences in the RVR reduction between SHR and WKY. Thus attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF, but to a decrease in EDRF in DOCA salt rats and Dahl S rats.

We report a case of 33-year-old man with multiple sclerosis, showing piano playing movement in both hands. His course of multiple sclerosis was remittent/progressive during 2 years and the clinical manifestation suggested the spinal cord involvement. On July 15, 1991, he was admitted with numbness of the right limbs, and then developed piano playing movement in both hands, more marked in the right side. Neurological examination revealed mild weakness in the right upper extremity, and rough touch, pain, and temperature sensation were slightly decreased. However, there was no deep sensory abnormalities, such as vibration, fine touch, and position senses. Vibration sense was lost below ilium. CSF examination showed elevation of IgG index (1.6), three oligoclonal bands and myelin basic protein content of 2.4 ng/ml. There was no HTLV-I antibody in CSF. SSEP, elicited by median nerve stimulation at the right wrist, showed no N13 and low amplitude of N20. T2-weighted images of cervical MRI revealed area of high signal intensity at the C3-C4 level. The piano playing movement gradually improved and disappeared by the initiation of steroid hormone therapy. It was considered that involuntary movement in this patient was due to the spinal cord lesion caused by multiple sclerosis. These findings suggested that the involuntary movement like pseudoathetosis could present without deep sensory abnormalities.

For the purpose of ABO-blood typing on fingerprints, the detection of blood group substances in fingerprints attached on nitrocellulose filter or paper was performed immunohistochemically using avidin-biotin-peroxidase complex (ABC) method. At first, it was fundamentally tested whether ABO-blood typing could be specifically performed for the fingerprints of known ABO blood group, being made experimentally on nitrocellulose filter or paper, and the effect of fixation and paper quality for the detection was also examined. And, ABO-typing was carried out using transferred fingerprints from a slide glass to a nitrocellulose filter. Moreover, using a fingerprint of unknown ABO-type, serially repetitive blood typing (three times) was compared to individually performed grouping (three tests) after dividing a single fingerprint into three parts. In addition, the method of serial ABO-blood typing after the morphological detection of fingerprints by ninhydrine was also considered. As results, according to primary antibodies applied, ABH activities were specifically detected in the fingerprints on nitrocellulose filter and paper. For the fixation procedure of very minute blood group substances to paper, heat fixation was the most effective and methanol fixation was also available. The intensity of immunostaining of fingerprints decreased according to the deterioration of paper quality used. And, the transferred fingerprints on nitrocellulose filter were also specifically typed. Serially repetitive blood typing (anti-B--anti-A--anti-H) was possible to fingerprints on nitrocellulose filter, but it gave poor results to those on paper. To overcome this difficulty, after being detected morphologically by ninhydrine, iodine or aluminium powder and decolored thereafter, a fingerprint on paper was divided into three parts and specific blood typing was possible. As for the double blind test to fingerprints on paper, 22 out of 35 fingerprints were specifically typed and the rate of correct typing was 62.9%. From these results, it can be considered that this method is available for ABO-typing of fingerprints of secretor type in forensic practice.

A twenty-year-old woman was suspected to ingest large amounts of 4 kinds of over-the-counter analgesic and antipyretic drugs, and was found dead. Drugs and poisons were screened by TOXI-LAB drug detection system in the serum and urine, and analyzed by GC-MS and TDx system in the blood, urine, organ tissues and contents of stomach and small intestine. The concentrations (microgram/g) of bromisovalum, apronalide, ibuprofen, ethenzamide, acetaminophen and caffeine in the heart blood were 36.5, 7.58, 43.1, 16.9, 1.22 and 177, respectively. Salicylic acid concentration in the serum was 82.1 micrograms/ml. The concentrations of bromisovalum and caffeine are high enough to be lethal levels. Neither fatal pathological findings nor traumatic wounds were seen. The overdose of both bromisovalum and caffeine and synergistic, additive or combined effects of other 5 drugs above are considered to be her cause of death.

In the present study, we investigated the cellular basis of house dust mite-driven immune responsiveness in an atopic individual with perennial rhinitis. We established 40 human T-cell clones (CD3+, 4+, 8-) reactive to Dermatophagoides pteronyssinus (Dp) antigen under the restriction of HLA-DR. By using the crude Dp antigen and its 14 molecular weight (MW) fractions, we analyzed the distribution of T-cell-recognizing sites in the whole Dp extract. We tested T-cell-mediated immunity through two parameters; the identification of Dp fractions inducing T-cell proliferation, and the ability of T-cell clones to secrete IL-2, IL-4, and IFN-gamma. According to a prominent peak among fraction-driven T-cell proliferation, we observed that T-cell clones that recognized 45,000- to 95,000-MW fractions were common, while clones reactive to 15,000- to 25,000-MW fractions were less frequent. Several clones were also reactive to antigens of Dermatophagoides farinae or other insects. Based on the responses of cloned T cells, we observed at least 9 distinct T epitopes in crude Dp antigen. These T-cell clones had a heterogenous secretory pattern of cytokines. T-cell clones showed no association between their ability to produce regulatory cytokine and their recognition of particular Dp fractions.

To further characterize the ultrastructure of the human megakaryocytic leukemia cell line, CMK, and its subclone CMK11-5, was observed. Stimulation with platelet agonists, ADP, thrombin, and collagen caused enlargement of vacuoles, projections of the cell surface, appearance of fibrous material in the enlarged vacuoles, and loss of alpha granules. We also found that horseradish peroxidase (HRP) incorporated into the granular structures of the cell could be transported out of the cell. The activation of CMK cells by platelet agonists indicates that human megakaryocytes may be activated in thrombotic states. CMK with particular megakaryocytic properties is a useful cell model for studying megakaryocytic function.

A medico-legal autopsy case of hydranencephaly in a male infant which was first suspected of maternal infanticide is reported. The infant was 48 cm in height, weighed 2.86 kg and the circumference of the head, the chest and the abdomen was 32.2 cm, 31.0 cm and 30.4 cm, respectively, with no deformities of the head or body. Autopsy examination, however, revealed a severe defect in the central nervous system. The cranial cavity was filled with a cloudy dark red fluid (ca. 310 ml) instead of the cerebral hemispheres. The residual central nervous tissues were mostly subtentorial structures from the midbrain to the spinal cord namely, corpus mamillare, corpora quadrigemina, corpus pineale, crus cerebri, pons, cerebellum, medulla oblongata and spinal cord. The basal ganglia, thalamus, hypothalamus and chiasma opticum could not be found, although atrophic hypophysis, eyeballs and optic nerves were present. The usual distribution of cerebral blood vessels, especially the branches of the anterior and middle cerebral arteries and Willis' ring, was absent despite the presence of the internal and external carotid arteries. Other organs were, in general, congestive. The marked cortical atrophy of the adrenal glands (left 0.5 g, right 0.6 g), especially the zona fasciculata, was characteristic. The hydrostatic lung test gave partially positive results, but this was considered to be due to artificial respiration by an ambulance man because amniotic fluid components were microscopically noted and fully expanded alveoli were not found. In conclusion, the cause of the infant's death was diagnosed as stillbirth due to aspiration of amniotic fluid caused by the severe defect of vegetative hypothalamic function through hydranencephaly.

Hemoglobin analysis by CO-oximeter is more easily and rapidly available method than other spectrophotometric or GC methods. In the present study, the possibility of diagnosis of asphyxia by CO-oximeter was examined experimentally using rabbits. When measured value of oxyhemoglobin (O2Hb) was lower than about 20% and that of deoxyhemoglobin (HHb) was, on the other hand, higher than about 80%, being accompanied by low measured values of both methemoglobin (MetHb) and CO-hemoglobin (COHb) (5%), asphyxia should be firstly considered as the cause of death. To the corpses found at the scene of fire, three chief factors causing death such as burns, suffocation due to oxygen deficiency and intoxication by poisonous gases may have occurred simultaneously, and through measuring the values of O2Hb, COHb, MetHb and HHb, the main lethal factor could be selected out among these three factors above and the cause of death could be examined much more closely. Because of easy and rapid analysis, it could be considered that CO-oximeter was useful for forensic practices and police activities.

Ultrastructural observations were performed to further characterize the human megakaryocytic leukemia cell line, CMK, and its subclone, CMK11-5. We found that particles derived from CMK11-5 cells had cytoplasmic projections and no nucleus, and that some particles contained alpha granules. Incubation with ADP induced fibrinogen receptors on the surface of these particles. Furthermore, the particles had glycoprotein Ib antigen on their surfaces, and attached nonreversibly to rabbit aortic subendothelium, showing associated morphological changes similar to those observed in normal platelets. CMK and CMK11-5 are the first megakaryocytic cell lines that have been found to release particles that have some of the same functions as normal platelets. In particular, CMK11-5 seems to be a useful model for studying megakaryocyte function.

Replacement of the valved extracardiac conduit with autogenous tissue was performed on a 13-year-old female. The procedure was based on that reported by Danielson in 1987. She underwent the first operation for tetralogy of Fallot with pulmonary atresia using a valved extracardiac conduit (#16 mm Björk-Shiley valve) 8 years ago. Recently, she complained exertional dyspnea and chest pain. Reoperation was scheduled because of bleeding tendency, somatic growth of the patient, and severe distal anastomotic stenosis of the conduit by right ventriculogram. At operation, the valved conduit was removed under cardiopulmonary bypass, and autogenous connective tissue around the conduit was preserved as the posterior wall of the new conduit. An onlay patch (pericardial monocusp patch) was sutured to form the roof of the new tract. Postoperative catheterization showed no residual stenosis or pressure gradient between the right ventricle and the pulmonary artery. This technique is useful as the replacement of extracardiac conduit because of its simplicity, no necessity of postoperative anti-coagulant therapy, and possibility to make a generous-sized new outflow tract.

The disposition characteristics of (-)-quinuclidinyl benzylate (QNB) were investigated in rats, and a physiologically based pharmacokinetic model was established using its linear and nonlinear tissue binding parameters. The steady-state distribution volume (Vdss) and systemic clearance (CLtot) were comparable after iv administration of 325 ng/kg and 3.2 mg/kg, suggesting that QNB pharmacokinetics based on plasma concentrations is linear. However, tissue accumulation was observed in the heart, lung, muscle, and brain. This accumulation persisted for over 12 hr after the iv administration of 325 ng/kg [3H]QNB. Tissue binding parameters were determined after continuous infusion of QNB. Irreversible and nonlinear binding parameters were obtained in various regions of the brain and other tissues. Reversible equilibrium concentration ratios between tissue and plasma were determined after high-dose infusion. QNB concentrations in the plasma, heart, lung, muscle, and brain were predicted after the administration of 325 ng/kg or 3.2 mg/kg. There was reasonable agreement between the model predictions and the observed data.

Three cases of renal cell carcinoma with tumor thrombus extending into the inferior vena cava are reported. Radical nephrectomy and thrombectomy were performed under extracorporeal circulation in all the cases. The level of tumor thrombus was preoperatively determined by computed tomography, magnetic resonance imaging or venacavography. The tumor thrombus extended into the right atrium in one, and above the hepatic vein in two cases. One patient whose thrombus reached the right atrium died of multiple metastasis of renal cell carcinoma 5 months after operation. Another patient with lung metastasis was given interferon-alpha and is alive 5 months after operation. The other patient is clinically free of disease and in good health 7 years after operation. We believe that extracorporeal circulation allows an opportunity to resect the tumor thrombus in a controlled situation, and makes the operation safer.

The O2-. production by aerobically cultured Escherichia coli in the presence of benzofurazan (1), 4,7-dimethylbenzofurazan (2), 4,7-dibromobenzofurazan (3), 4-bromo-6-cyanobenzofurazan (4), and 4,7-dicyanobenzofurazan (5) was examined by using the cytochrome c reduction method in order to elucidate the mechanism of cytotoxicity of benzofurazans. Adding compound 5 to E. coli cell suspension caused cytochrome c reduction, which was completely inhibited by superoxide dismutase. The rate of cytochrome c reduction was in the order of 1 = 2 = 3 less than 4 less than 5, which correlates well with that of the reduction potentials of these benzofurazans. Adding glucose to the E. coli cell suspension-compound 5-cytochrome c system accelerated the rate of cytochrome c reduction. The formation of 4,7-dicyanobenzofurazan anion radical in the cell suspension-compound 5-glucose system in the absence of O2 was followed by ESR spectroscopy. The ESR signal of the anion radical disappeared when O2 was added. Compound 5 was shown to have an approximately 10-fold greater increasing effect on the flux of O2-. by E. coli than paraquat (PQ) by the cytochrome c reduction method. The results were confirmed by the electrochemical method with an oxygen electrode. However, compound 5 had a bacteriostatic, but not lethal, effect, while PQ had both effects. The effect of compound 5 and PQ on lethality of E. coli showed a dramatic difference when E. coli was exposed to these two compounds and washed prior to testing the effects of that exposure. This difference probably arose because compound 5 readily leaked from the cells during dilution and plating. Also, the reduced form of compound 5 exits from the cells more readily than the reduced form of PQ and then generates O2-. in the medium by autoxidation. This suggests the importance of the intracellular production of O2-., rather than the extracellular production of O2-., for lethal effect.

Transabdominal ultrasonography was done in patients with gynecologic malignancies to detect paraaortic and pelvic lymphadenopathy. Of the 78 patients who underwent ultrasonic examination of pelvic lymph nodes, pelvic lymphadenopathy was detected in 24, of whom ultrasound-guided percutaneous fine-needle aspiration biopsies (FNAB) were done in 16. Of these 16 patients, the results of 13 biopsies were positive. Of the 41 patients who underwent ultrasonographic examination of the paraaortic lymph nodes, 27 had paraaortic lymphadenopathy. Ultrasound-guided percutaneous FNAB were done in 26 of these 27 patients, with positive findings in 21 of the 26. It was concluded that ultrasound-guided percutaneous FNAB is useful in detecting metastatic lymph nodes in gynecologic malignancies.

The 3T3-L1 preadipocytes treated with insulin, dexamethasone and 3-methyl-1-isobutylxanthine (IBMX) two days before reaching monolayer undergo differentiation into adipocytes. Cell lysates were prepared from these cells under various conditions and analyzed by SDS-PAGE and transblot. Peroxidase-conjugated avidin used to detect endogenous proteins interacted strongly with a protein with an estimated molecular weight of 120 kDa, corresponding to pyruvate carboxylase, in the differentiated 3T3-L1 cells. On the other hand, this protein was not detected in undifferentiated 3T3-L1 cells.

Lymphocytapheresis using thoracic duct drainage (TDD) is a recognized technique of extracorporeal immunomodulation for various autoimmune diseases such as rheumatoid arthritis (RA), and its clinical benefit has been reported and generally accepted. Lymphocytapheresis using TDD is very selective for removing lymphocytes (especially helper T-cells) but raises some problems such as hypoproteinemia due to the massive removal of lymph, and difficulties in repeated treatment. Along with the development of a new polyester fiber filter, we have developed a simple and effective method of lymphocytapheresis for wide adoption for these techniques. We performed lymphocytapheresis using TDD in patients with RA and previously reported its clinical efficacy indicated by the significantly lower number of peripheral lymphocytes and T4/T8 ratio. We present here our newly-developed on-line system designed to prevent hypoproteinemia. Furthermore we report on the advantages with a new subcutaneous vascular access device set up to manage the problems of repeated treatments. A small reservoir for keeping the thoracic duct open and returning lymph to the patient permitted sufficient lymph drainage and removal of lymphocytes and the clinical application of TDD is discussed.

A 83-year-old man was diagnosed with primary myelofibrosis based on the presence of leukoerythroblastosis, splenomegaly, chromosome 46 XY, a dry tap bone marrow aspiration and fibrosis on bone marrow biopsy, when he was admitted for herpes zoster in June 1987. He was admitted for a second time with multiple subcutaneous tumors over his entire body in July, 1989. He had mild splenomegaly, but no hepatomegaly nor lymphadenopathy. Laboratory tests were as follows: RBC 214 x 10(4)/microliters, Hb 5.1 g/dl, Ht 17.7%, WBC 3,200/microliters with leukoerythroblastosis, platelets 11.6 x 10(4)/microliters, s-lysozyme 251 micrograms/ml, u-lysozyme 770 micrograms/ml, NAP ratio 98%, score 278. Bone marrow aspiration resulted in a dry tap. Bone marrow biopsy showed marked fibrosis. Histologic examination of subcutaneous tumor biopsy specimens revealed a diffuse infiltration of monocytes with flexuous nuclei. These cells were positive for alpha-naphtyl butyrate esterase stain, and negative for peroxidase, alpha-naphtol ASD chloroacetate esterase stain and platelet glycoprotein IIb/IIIa stain (APAAP). Ultrastructurally, these cells were mostly monocytes and promonocytes, while phenotypically, CD11b, CD13, CD14, CD33 and HLA-DR were positive. These date indicated that the subcutaneous tumors originated from monocytes.

The authors investigate hot-carrier induced degradation of sub-micron NMOSFETs under conditions of drain and gate bias with sub-nanosecond switching times. The results are compared with estimates based on the quasi-static sum of static stresses. Hot-carrier degradation in NMOSFETs subject to sub-nanosecond transient stressing is more severe than estimates based on the quasi-static model suggest. This increased degradation is interpreted as electron traps created by hot holes during the low gate voltage phase followed by electron injecting and trapping during the high gate voltage phase. No detrapping effect was observed during subsequent transient stressing. >

Between January, 1966 and December, 1988, 66 patients with surgical-pathological stage II adenocarcinoma of the endometrium who were treated with abdominal simple or radical hysterectomy at the Osaka National Hospital were studied retrospectively. The 5-year survival rate for all patients was 75.7%. In 33 patients adenocarcinoma had invaded the cervical stroma. These patients demonstrated a significantly lower survival (60.0%) than those patients whose involvement was limited to the endocervical gland (91.7%) (p less than 0.05). For all patients, both with endocervical glandular involvement and cervical stromal invasion, radical hysterectomy improved survival rates more than did simple hysterectomy, but the difference was not statistically significant. The factor found to have a significant influence on survival was the maximal depth of invasion of the myometrium (p less than 0.05). The histologic grade, on the other hand, did not appear to influence survival. It is suggested that patients with minimal involvement of the cervix can be satisfactorily treated with simple hysterectomy, while patients with gross cervical spread should be treated with radical hysterectomy.

A novel mouse monoclonal antibody (P4-5C) has been developed which recognizes the core portion of the protein carrying ABO(H) blood group antigens in human saliva. This proved to be specific for human saliva using immunochemical investigations such as enzyme-linked immunosorbent assay, Ouchterlony method and counter-immunoelectrophoresis. By light and electron microscope studies with immunohistochemical techniques using this human saliva-specific P4-5C as primary antibody, it was shown that P4-5C reacted specifically and exclusively with mucus from the mucous gland cells of human salivary glands. P4-5C reacted neither with the mucous gland cells of other primates (hamadryas baboon, Japanese monkey and Rhesus monkey) and four mammals (dog, cat, rabbit and mouse) nor with other human tissues. The epitope on the core portion of the ABO(H)-carrying protein was defined by P4-5C and could be discriminated from the epitope of ABO(H) blood group antigens using immunoelectronmicroscopy, although these 2 epitopes were localized relatively close to each other. The P4-5C monoclonal antibody can be also used for morphological species identification of tissue specimens from submandibular glands.

The case of a 9-month-old baby girl who failed to develop normally due to nutritional neglect and secondary immunodeficiency characterized by marked thymic involution is reported. The child died of systemic Pseudomonas aeruginosa (P. aeruginosa) infection manifested in pneumonia, lung abscesses, bacterial endocarditis and ecthyma gangrenosum. At autopsy the child was 64 cm in height (normal for a 4- to 5-month-old child) and 5.1 kg in weight (normal for a 2- to 3-month-old child). Multiple gangrenous ecthymas, consisting of deep ulcers, induration and inflammation, were observed in the skin over the entire body. The lungs showed hemorrhagic pneumonia, multiple lung abscesses, and necrotizing arteritis in the abscesses and surrounding areas. The thymus weighed 2.3 g and showed marked involution. Histological examination showed so-called nutritional thymectomy characterized by severe cortical atrophy and clustering, cystic dilation and amorphous changes of the Hassall's corpuscles. In the heart, dark brown verrucae were present at the attachment sites of the tendinous cords of the papillary muscle in the anterior and posterior cusps of the mitral valve, suggesting infectious endocarditis. Bacteriological examination demonstrated P. aeruginosa in the ecthymas, lung abscesses and blood. As primary immunodeficiency was considered unlikely, immunodeficiency secondary to thymic involution following malnutrition seemed to have led to a fatal systemic infection with P. aeruginosa, whose virulence is generally weak. This suggests a close association of the development of such infection and immunodeficiency with child neglect.