Spontaneous spinal epidural hematoma: report of seven cases. From July 1984 to June 1990, seven cases of spontaneous spinal epidural hematoma (SSEH) were studied. The common clinical pictures in these cases were rather typical with an apoplectic onset of severe spinal pain followed in hours (median: four hours) by signs of progressive spinal cord compression. All cases underwent myelography and computed tomographic (CT)-myelographic studies which showed in all cases a block by a posterior extradural lesion in the spinal column; however, the correct diagnosis of SSEH was made preoperatively in only three cases. The neurologic deficits prior to surgery were complete or nearly complete paraplegia in five cases and a high grade of paraparesis in the other two. The median interval of paralysis or paresis before surgery was 28 hours. The final outcome was evaluated by the grade of functional recovery, and the following were found to be the favorable factors: 1) incomplete preoperative neurologic deficits; 2) a slow course of clinical progression, especially a long duration of pain before the onset of paralysis; 3) no delay in surgery; 4) involvement of short spinal segments; and 5) lumbosacral lesions. Particular emphasis is made on early diagnosis and prompt surgery for a favorable outcome.


Histiocytosis X with thyroid involvement: report of a case. Histiocytosis X is a disease of histiocyte proliferation in response to some unknown etiology. Thyroid involvement is extremely rare in the literature. In this paper, we present an 18-year-old female with histiocytosis X with thyroid involvement. This patient had had a goiter with normal thyroid function since 12 years of age. A thyroidectomy was done under the suspicion of thyroid cancer. Pathology revealed histiocytosis X. Hypoparathyroidism and hypothyroidism were noted after the operation and were treated with thyroid hormone, vitamin D and calcium carbonate. This patient also had lesions on the left side of mandible, in the suprasellar region and possibly in the right mastoid. A curettage biopsy of her mandibular lesion was also compatible with histiocytosis X. She was proven to have hypothalamic and pituitary dysfunction including hypogonadism and hypoadrenalism. Her thyroid lesion did not recur after the thyroidectomy. The toothache that she had also experienced subsided after the curettage biopsy of the mandibular lesion. Hypothalamic and pituitary dysfunction were controlled by hormone replacement. Because her disease had been running a benign clinical course, no chemotherapy was given.


Adult-onset, autosomal dominant, rimmed vacuolar myopathy with limb-girdle distribution--a preliminary report. Adult-onset, autosomal dominant myopathy with limb-girdle distribution in a Chinese family is reported. Nine members were affected with characteristic proximal weakness and pelvifemoral-preceded scapulohumeral involvement. The facial, extraocular and bulbar muscles were spared. Rimmed vacuoles were the most obvious characteristics in the myopathologic study of the biopsy specimens from four patients. In a review of the previous literature, we found three reported families with clinical and myopathologic features identical to ours, and these families are viewed as a distinct subgroup of myopathy.


Nosocomial outbreak of scabies.

Nosocomial outbreak of scabies. Scabies is a common infestation caused by the human itch mite Sarcoptes scabiei. Small outbreaks in communities or hospitals are not uncommon, but are rarely documented. In this paper, we report on a nosocomial outbreak of scabies originating from a patient with Norwegian scabies at the Intensive Care Unit in Taiwan Provincial Tainan Hospital. Twenty-nine individuals including four inpatients and 25 hospital personnel were involved. The diagnosis was based on history, clinical findings or a positive skin scraping. Unfamiliarity with the clinical manifestations delayed the diagnosis and the highly contagious nature of Norwegian scabies precipitated this outbreak. Early initiation of effective control measures with extensive therapeutic and prophylactic treatment of all contacts resulted in successful eradication of the outbreak.


Assessment of the association of HLA-DR 3/4 heterozygotes with diabetes mellitus and non-diabetic diseases. To evaluate the disease association with HLA-DR 3/4 heterozygotes, 1,074 subjects, who had been analyzed consecutively for HLA-DR antigens for organ transplantation or to study the disease association with HLA from June 1984 to June 1986, were enrolled in this study. Of these subjects, 278 had diabetes, 168 were healthy controls or donors, and 628 had other diseases. Of the 1,074 subjects, 35 subjects (3.2%) were DR 3/4 heterozygotes and 1,039 subjects (96.7%) were non-DR 3/4 heterozygotes. Among the 35 DR 3/4 positive subjects, 23 were diabetic (65.7%), two were healthy donors (5.7%), 10 had other diseases (28.5%) such as recurrent abortion (n = 3), hepatoma (n = 2), Graves' disease (n = 1), idiopathic hypoparathyroidism (n = 1), IgA nephropathy (n = 1), uveitis (n = 1) and gout (n = 1). Among the 23 DR 3/4 positive diabetics, 19 (82.6%) had insulin-dependent diabetes mellitus (IDDM), three (13.0%) had non-insulin-dependent diabetes mellitus (NIDDM), and one (4.3%) had maturity onset diabetes of the young (MODY). When these DR 3/4 positive diabetics were compared with the other disease and control/donor groups, significant increases in the relative risk were seen for IDDM patients (RR = 32.61, 43.80, respectively, p < 0.001). No significant association could be seen for NIDDM and MODY patients. In those non-diabetic patients positive for DR 3/4, there was no significant association with DR 3/4 heterozygotes. These findings suggest that: 1) DR 3/4 positive subjects are highly associated with IDDM; and 2) there is no significant association of DR 3/4 with NIDDM, MODY and other non-diabetic diseases.


The effect of third-trimester glycemic control on maternal and perinatal morbidities in pregestational diabetes mellitus. From May 1974 to March 1989, 48 cases of pregestational diabetes mellitus treated during the third trimester of pregnancy at the Obstetric Clinic of the National Taiwan University Hospital had complete maternal-fetal chart, and were enrolled into this retrospective review. Of these cases, 28 were class B, 13 were class C and seven were class D-R. The maternal complications and perinatal morbidities of each class were reviewed. The mean fasting, postprandial plasma glucose concentrations and the mean excursion of plasma glucose levels were calculated for statistical analysis. Among the maternal complications, urinary tract infections and preterm labor were significantly associated with mean fasting plasma glucose concentrations. Among perinatal morbidities, neonatal respiratory distress and metabolic problems (including neonatal hyperbilirubinemia, symptomatic hypoglycemia, hypocalcemia and polycythemia) were significantly associated with mean plasma fasting glucose concentrations, and perinatal asphyxia was associated with a mean excursion of plasma glucose levels. In view of the paucity of knowledge about the etiology of complications in diabetic pregnancies, it is necessary to conduct a prospective multi-center study with well-characterized morbidities to search for the role of glycemic control in obstetric and perinatal complications.


gamma-Glutamyltranspeptidase and dipeptidyl peptidase IV activity in the serum of normal and hepatoma-bearing chickens and in the plasma membranes from liver and hepatoma Mc-29. Investigations on the activity of gamma-glutamyltranspeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) in the serum of healthy chickens and those bearing hepatoma Mc-29, and in liver and hepatoma plasma membranes were carried out. There was no difference in the serum enzyme activities of control and tumor-bearing chickens but the activity of GGT was twice higher and that of DPP IV 20 times lower in hepatoma plasma membranes than in chicken liver plasma membranes. Using thin-layer analytical isoelectric focusing in agarose gels it was established that the pI range of GGT from host serum and hepatoma plasma membranes was shifted to more acidic values. This could be interpreted as a specific feature for this enzyme considered as a tumor marker.


Action of tiazofurin and 8-Cl-cAMP in human colon and pancreatic cancer cells. Tiazofurin and 8-Cl-cAMP are novel chemotherapeutic agents shown to be effective against various cancer cells in vitro and in vivo. They act through distinct mechanisms that might modulate the signal transduction pathway, which causes growth inhibition, differentiation and down-regulation of c-ras and c-myc oncogene expression. We examined the effects of tiazofurin and 8-Cl-cAMP on colony formation of HT-29 human colon cancer and BxPC-3 and PANC-1 human pancreatic cancer cell lines. The IC50 of 8-Cl-cAMP was 0.1 and 0.2 microM in the pancreatic and colon cancer cell lines, respectively, and tiazofurin yielded IC50s from 4 (PANC-1) to 18 microM (HT-29). Simultaneous incubation with 8-Cl-cAMP and tiazofurin had additive effects on the inhibition of colony formation in the three examined cell lines. These results indicate possible clinical usefulness of a combination of tiazofurin and 8-Cl-cAMP in the treatment of colon and pancreatic carcinomas.


Comparison of transcranial Doppler with DSA in vertebrobasilar ischaemia. To determine the role of transcranial doppler (TCD) in the evaluation of the vertebrobasilar circulation, we compared the results of TCD with intraarterial digital subtraction angiography (DSA) in 20 patients with vertebrobasilar ischaemia (VBI). TCD had a sensitivity of 87%, a specificity of 80%, a positive predictive value of 93% and a negative predictive value of 67%. It was also able to give functional data when combined with arteriography and correctly identified the main pathology in 92% of those with abnormal TCD and angiogram. The 2 patients with false negative TCD had vertebral artery occlusion, which may be missed because of the signal from adjacent arteries. TCD may be a useful screening method in patients with VBI for the detection of large vessel occlusive disease of the intracranial vertebrobasilar system. It is important to remember that proximal vertebral artery stenoses will be missed by TCD.


Establishment of an MT4 cell line persistently producing infective HIV-1 particles. Human T cell Lymphotropic Virus-I (HTLV-I) carrying human T cell line MT4 is highly sensitive to Human Immunodeficiency Virus-1 (HIV-1). After HIV-1 infection cell clusters characteristic of intact MT4 rapidly disintegrate, syncytia appear and the cells die. Surviving MT4 cells were subcultured following HIV-1 infection of high multiplicity. We succeeded to establish an MT4 cell line continuously producing infective HIV (MT4/HIV-1). The original and the HIV-1 infected MT4 cells were morphologically similar. The MT4/HIV-1 cells proved to be nearly 100% positive in indirect immunofluorescence assay using the serum of an HIV-1 antibody positive individual. OKT4 surface antigen could not be demonstrated on MT4/HIV-1 cells. On electron microscopic pictures typical and atypical virus particles could be seen near the surface of the cell membrane. The persistently produced virus particles were infective for H9 and MT4 cells. The antigenic structure of the virus produced by MT4 cells was similar to that produced by H9 cells.


Some neurovegetative correlates of Minnesota Multiphasic Personality Inventory (MMPI). In 57 patients with psicovegetative disorders and abnormal MMPI, abnormality in MMPI scales indicating hypochondriasis, hysteria, gender deviant, paranoia, psychastenia, schizophrenia, hypomania or introversion was accompanied by increased plasma catecholamine levels and/or responses to hypoglycemia or by an increased cardiovascular reactivity. A high depression scale was associated with lower plasma catecholamine levels. Blunted plasma growth hormone responses to hypoglycemia were found in abnormal hypomania scale, and augmented responses of plasma cortisol in abnormal hysteria or schizophrenia scales. Paranoia and hypomania traits correlated with absence of morning-evening differences in blood cortisol levels. Electrodermal responses compatible with increased sympathetic activity correlated with high hysteria, gender, paranoia, schizophrenia or hypomania MMPI scales. This study indicates that most psychopathological traits in MMPI are accompanied by humoral and/or electrophysiological signs of abnormality of the autonomic nervous system.


[The effect of a protein-free diet on insulin and somatostatin secretion in rats]. We have used a model of experimental protein-energy malnutrition induced in weaned rats by administration of a protein free diet during 2 weeks. Some malnourished rats were then refed with a control diet for 4, 9 or 30 days. Control rats were fed for the same periods with the balanced control diet. Malnourished rats showed a loss in body weight of approximately 25%. After 30 days of refeeding, the animals gained weight reaching values higher than that of control rats. Insulin secreted by perifused pancreatic slices from malnourished rats, was impaired in first and second glucose-induced secretory phases. Basal secretion was also diminished in incubation of pancreatic slices. When malnourished rats were refed for 4 days, basal insulin secretion reached control values. Stimulated insulin secretion was normalized at 9 and 30 days of refeeding. Our result on somatostatin (SRIF) secretion in malnourished rats showed basal hypersecretion and diminished first and second glucose-induced secretory phases. During refeeding basal SRIF secretion was normalized from day 4. On the contrary stimulated secretion was significantly increased at 4 and 9 days of refeeding, and on day 30 values did not differ from controls. In protein energy malnutrition, the disturbed hormonal state can represent adaptative mechanisms to the protein depletion and hormonal changes have also an essential role in refeeding.


[Current surgical aspect of primary hyperparathyroidism (100 years after F. D. Von Recklinghausen)]. The "Association Française de Chirurgie" asked to authors an update on primary hyperparathyroidism based on a retrospective multicentric study on 4883 patients operated on by 79 surgeons. Aim of this study was an update on clinical and biological aspects, localizing studies, and therapeutic aspects with their results. There were 3418 females (70%) and 1465 males (30%) mean age 53 years (9 to 91 years): 3702 solitary adenomas (75.8%), 720 multi-glandular lesions (14.7%) 92 multiple endocrine neoplasias (1.9%) and 86 carcinomas (1.8%). None lesions was found in 283 cases (5.8%). To day, diagnosis is most often made on fortuitous hypercalcemia. Localising studies showed sensibility less than 50%. Surgery was successful in 92.7%. Mortality occurred in 0.6% hypoparathyroidism in 3.8%, laryngeal palsy in 1.5% and hematomas in 0.45%. In conclusion this study shows the changes regarding the diagnosis, the uselessness of localizing studies before first cervicotomy, and the good results of surgery. Autotransplantation and cryopreservation allow reducing of hypoparathyroidism.


Quantitative immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the brains of spontaneously hypertensive rats. Immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the rat forebrain were analyzed quantitatively as a possible model for the hypertension mechanism. The brain slices of spontaneously hypertensive rats (SHR) at 12 weeks of age were stained immunohistochemically for tyrosine hydroxylase and for calmodulin, and the distributions and amounts of these proteins were measured at 40-microns intervals by a fluorescence microphotometry system in comparison with those in normotensive control, Wistar Kyoto rats (WKY, the parent strain of SHR). Tyrosine hydroxylase levels in the neostriatum, nucleus accumbens, nucleus septi lateralis and tractus diagonalis, and calmodulin levels in the medial part of the neostriatum of SHR were lower than those in WKY. We reported previously that the decrease of the serum calcium level in SHR causes a decrease of the dopamine levels in the neostriatum and nucleus accumbens regions through a calmodulin-dependent system, and subsequent low levels of dopamine in the brain which may produce an increase in blood pressure. Combining this finding and our previous reports, we also suggest that the lower dopamine levels seen in the neostriatum and nucleus accumbens regions of SHR may result from the decrease in tyrosine hydroxylase and/or calmodulin levels in these regions in addition to the abnormality of calcium metabolism, and low levels of dopamine may produce an increase in blood pressure through functions of cerebral dopaminergic neurons and peripheral sympathetic nerves.


Short-term immunosuppression enhances long-term survival of bovine chromaffin cell xenografts in rat CNS. Xenogeneic donors, a largely untapped resource, would solve many of the problems associated with the limited availability of human donor tissue for neural transplantation. Previous work in our laboratory has revealed that xenografts of isolated bovine chromaffin cells survive transplantation into the periaqueductal gray (PAG) of immunosuppressed adult rats. Electron microscopic analysis reveals that graft sites contain healthy chromaffin cells, but do not contain host immune cells typical of graft rejection. The aim of the current study was to assess the necessary conditions for long-term survival of bovine chromaffin cell xenografts in the central nervous system (CNS). In particular, the need for short-course vs. permanent immunosuppressive therapy with cyclosporine A (CsA) for the long-term survival of grafted bovine chromaffin cells was addressed. Grafts from animals receiving continuous CsA treatment for either 3, 6, or 12 wk contained large clumps of dopamine-beta-hydroxylase (DBH) positive cells in contrast to the few surviving cells observed in nonimmunosuppressed animals. In addition, grafts from animals that had CsA treatment terminated at 3 or 6 wk contained similarly large clumps of DBH-positive cells. Furthermore, short-term immunosuppression (3 wk) appeared to enhance the long-term survival of grafted cells, since clumps of DBH staining cells could still be positively identified in the host PAG at least 1 yr after transplantation. Complete rejection of graft tissue depends on several factors, such as blood-brain barrier integrity, the presence of major histocompatibility complex (MHC) antigens in either the host or graft, and the status of the host immune system.(ABSTRACT TRUNCATED AT 250 WORDS)


Neuropsychological and psychiatric correlates of intractable pseudoseizures. Psychogenic seizures can mimic convulsive epilepsy and with repetitive attacks, iatrogenic complications from aggressive treatment of status epilepticus can occur. We studied neuropsychiatric features of 20 patients in whom psychogenic seizures were intractable and at times continuous. Nineteen of 20 patients seen were female, and all but one were under 40 years of age. All had convulsive attacks resistant to various medications, normal neurological examinations, and negative imaging studies and electroencephalograms (EEGs). Sixteen had previous evidence of epilepsy and the other four had epileptic relatives. Seizures were atypically prolonged, included back arching and pelvic thrusting, and persisted despite intravenous diazepam and therapeutic phenytoin and phenobarbital levels. Seizures terminated spontaneously in five, were stopped by suggestion in four, and persisted until respiratory arrest or elective intubation in 11. Ten patients had conversion disorder, six borderline or mixed personality disorder and four mental retardation. Fifteen had had some precipitating stressor and the remainder had histories of exhibiting attention-seeking behaviour. Nine of 10 patients with conversion disorder had 'conversion V' Minnesota Multiphasic Personality Inventory (MMPI) profiles, while personality disorder patients had elevation of several psychopathological scales. Patients with conversion disorder gradually improved with anticonvulsant discontinuation, while retarded individuals were helped by behaviour modification, situational change or neuroleptics. Personality disorder patients continued to have attacks and eventually discontinued follow-up. Clinical evidence of non-epileptic seizures includes clinical atypicality and long duration, exacerbation by medications and frequent attacks despite normal examination and studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Subdural empyema--clinical experiences.

Subdural empyema--clinical experiences. The authors present the experiences from their clinic with diagnostic and treating of subdural empyema. In the years 1953-1991 altogether 5 patients were treated with this diagnosis in the Clinic of Neurosurgery in Olomouc. Nobody of the patient died. There was possible to observe in all these patients before operation symptoms of meningeal irritation, febrilities and in 4 patients the neurologic focal symptomatology. The authors arrive to the conclusion, that the most convenient operation approach is craniotomy, which must be preferred to smaller surgical approaches. One part of the intracranial operation must be sanation of the primary inflammation leading to arising of subdural empyema. The regular postoperation control of the patient by means of computed tomography renders possible the timely detection of relapse and leads to timely surgical intervention.


Lack of correlation between UV-induced enhancement of melanoma development and local suppression of contact hypersensitivity. Injection of melanoma cells into the UV-irradiated ear skin of syngeneic mice results in an increased incidence of melanomas compared with that in nonirradiated ear skin. This effect of UV is localized to the site of irradiation and appears to be immunologically mediated. In these studies we test the hypothesis that the effect of UV irradiation on melanoma development is related to its ability to alter epidermal Langerhans cells and impair the induction of contact hypersensitivity. A regimen of UV irradiation that altered epidermal immune cells and interfered with the generation of contact hypersensitivity was tested for its ability to increase the incidence of melanoma. Conversely, the ear skin of C3H mice treated with a regimen of UV radiation that enhanced melanoma development was examined for the number of appearance of ATPase+ and Thy-1+ dendritic epidermal cells and tested for the ability to initiate a contact hypersensitivity response. No correlation between these effects of UV irradiation could be detected. Furthermore, implantation of melanoma cells into UV-irradiated ear skin resulted in the generation of systemic immunity against subsequent tumor challenge. Therefore, we conclude that the ability of UV irradiation to modify melanoma development is unrelated to its effects on the afferent arm of the contact hypersensitivity response and that enhanced melanoma development is not due to an impairment in the induction of tumor immunity.


Human epidermal keratinocytes are a source of soluble ICAM-1 molecules. A soluble form of the usually membrane-bound adhesion molecule ICAM-1 was detected in supernatants derived from human epidermal keratinocytes. Specifically, supernatants harvested from long-term cultured normal human keratinocytes, or from the spontaneously immortalized keratinocyte cell line HaCaT, did not contain significant amounts of sICAM-1, but shedding of sICAM-1 was found to be markedly induced upon stimulation of keratinocytes with rh IFN gamma. In contrast, cells from the two epidermoid carcinoma cell lines, KB and A431, constitutively shed significant amounts of sICAM-1 even without cytokine stimulation, and sICAM-1 contents in supernatants harvested from these cells were further increased upon stimulation of cells with rh IFN gamma. These studies indicate, that in addition to peripheral blood mononuclear cells and human melanoma cells, human epidermal keratinocytes constitute an important cellular source of sICAM-1. By binding to leukocyte LFA-1 molecules, keratinocyte-derived sICAM-1 may influence inflammatory responses in the skin. In addition, constitutive shedding of sICAM-1 by transformed human keratinocytes may represent a possible mechanism by which neoplastic keratinocytes escape from cytotoxicity.


c-erbB-2 (HER-2/neu) oncopeptide immunoreactivity in localized, high-grade transitional cell carcinoma of the bladder. Monoclonal antibodies to the extracellular domain of the c-erbB-2 oncoprotein (p185) react with routinely processed, paraffin-embedded human tissues, and positive staining with these reagents has been shown to correlate with gene overexpression. To determine whether such antibodies would add prognostic data to the analysis of a pre-defined subset of transitional cell carcinoma (TCC) of the bladder, we studied 20 high-grade (Grade 3) TCCs from patients known to have limited disease (Jewett-Strong stages B1, B2, and C) and for whom at least 3-yr clinical follow-up was available. Data procured from this immunohistochemical analysis were compared with tumoral DNA content (determined by flow cytometry) and conventional clinicopathologic features. Overall, 13 of 20 TCC (65%) were reactive for p185-erbB-2. However, there was no apparent relationship between p185-reactivity and either DNA content, tumor stage or clinical outcome. These results suggest that c-erbB-2 expression may be augmented in localized high-grade TCC but that there is no evidence for the contention that this phenomenon has any effect on the biologic behavior of these neoplasms. The only factor that predicted a more favorable outcome was a relatively low stage at the time of diagnosis.


Biological activities of Synanceja horrida (stonefish) venom. Some biological and neurochemical properties of the venom of stonefish (Syanceja horrida) were investigated. The venom exhibited oedema-inducing, haemolytic, hyaluronidase, thrombin-like, alkaline phosphomonoesterase, 5' nucleotidase, acetylcholinesterase, phosphodiesterase, arginine esterase, and arginine amidase activities. Recalcification clotting time, prothrombin, and kaolin-cephalin clotting times were increased 1.7-2.3- and 2.4-fold respectively. The LD50 (i.v. mouse) was 300 micrograms/Kg. Its effects on uptake and stimulation of neurotransmitter synthesis and release were observed in rat brain synaptosomes. In the presence of 100 micrograms venom, uptake of [methyl-3H] choline in rat brain synaptosomes was inhibited 70%, while that of 4-amino-n-[U-14C] butyric acid was inhibited 20%. The toxin also stimulated the release of [3H]-acetylcholine from the synaptosomes.


Unusual mitochondrial DNA polymorphism in two local populations of blue tit Parus caeruleus. Mitochondrial DNA (mtDNA) from 25 blue tits Parus caeruleus sampled from two populations of the Grenoble region (France) was assayed for polymorphism with 17 restriction endonucleases. Nine genotypes were found. Several mtDNA genotypes were also analysed by amplification via the polymerase chain reaction (PCR) and direct sequencing of 903 bp of the cytochrome b gene. The mtDNA polymorphism is greater in P. caeruleus than in other comparable bird species and results from the presence of two clearly differentiated mitochondrial lineages. Using the data of restriction polymorphism, the mean sequence divergence between individuals of the two lineages is 1.23%. Therefore, P. caeruleus should fall into the category II of phylogeographic pattern sensu Avise et al. (1987): discontinuous mtDNA genotypes which co-occur in the same region. P. caeruleus, like humans and other mobile species with high gene flow, seems to have lost its geographic structure in terms of mtDNA phylogeny. This unusual mitochondrial polymorphism can be explained by the recent admixture of two long-term isolated populations. This could be accounted for by two different scenarios. One assumes a simultaneous post-glacial colonization of the Grenoble region by two isolated European populations of P. caeruleus. Alternatively, hybridization between P. caeruleus and P. cyanus could have caused the observed pattern of mtDNA variation.


[Peripheral facial paralysis and HIV infection. 2 case reports]. Two cases of peripheral facial paralysis in subjects with HIV infection are reported. On the basis of these two cases and data from the literature, the clinical and paraclinical features of this facial nerve lesion are described. The various aetiological hypotheses put forward are discussed, but it is probable that the paralysis results from a direct effect of the virus on the nerve. HIV-associated peripheral facial paralysis may occur irrespective of the number of CD4 lymphocytes and does not seem to have a prognostic significance. However, it appears by preference in stages I, II and III and may then reveal the HIV infection.


Conservation genetics of whales and dolphins. Whales and dolphins (cetaceans) are found in all the world's oceans and in some of the major rivers, yet little is known about the distribution and behaviour of many species. At the same time, cetaceans are under threat from a variety of pressures including direct and indirect takes, pollution, and competition for habitat and prey. To ensure their long-term survival it will be necessary to preserve genetic diversity through the identification and protection of differentiated populations, the assessment of variation within local populations, and through a better understanding of reproductive and dispersal behaviour. The application of molecular genetic techniques is helping to provide answers to some of these previously intractable questions. Early results suggest few consistent patterns. Obvious geographic boundaries correlate to genetic distance in some species, and not in others. Furthermore, morphological variation within species can be fairly extensive without correlating to genetic distance, or relatively minor between morphotypes that are as genetically distinct as some species. These examples emphasize the need for further study.


Evolutionary history of the honey bee Apis mellifera inferred from mitochondrial DNA analysis. Variability of mitochondrial DNA (mtDNA) of the honey bee Apis mellifera L. has been investigated by restriction and sequence analyses on a sample of 68 colonies from ten different subspecies. The 19 mtDNA types detected are clustered in three major phylogenetic lineages. These clades correspond well to three groups of populations with distinct geographical distributions: branch A for African subspecies (intermissa, monticola, scutellata, andansonii and capensis), branch C for North Mediterranean subspecies (caucasica, carnica and ligustica) and branch M for the West European populations (mellifera subspecies). These results partially confirm previous hypotheses based on morphometrical and allozymic studies, the main difference concerning North African populations, now assigned to branch A instead of branch M. The pattern of spatial structuring suggests the Middle East as the centre of dispersion of the species, in accordance with the geographic areas of the other species of the same genus. Based on a conservative 2% divergence rate per Myr, the separation of the three branches has been dated at about 1 Myr BP.


Prospective study with Tinset tablet.

Prospective study with Tinset tablet. Fifty-seven patients suffering from seasonal rhinitis have been treated with oxatomide (Tinset) tablets. In the well-responding cases the drug was prescribed for prophylactic purpose to prevent the expectable rhinitis attacks in later seasons. In the first season the preventive action of the drug was registered in a relatively high rate of the patients, but this action was significantly less marked in the second period. According to the opinion of the author oxatomide is a drug of high value both for therapeutic and preventive purposes. Nevertheless, the sedative action of the drug has to be taken into consideration in the course of therapy.


[Beta-blockers in the prevention of the rupture of esophageal varices. A meta-analysis]. The meta-analysis of 5 trials for primary prevention and of 18 trials of secondary prevention emphasizes the effect of beta-blockers in the decrease of variceal bleedings in cirrhosis. Beta-blockers are reducing the bleeding events with 32% in the primary prevention and with 28% in the secondary prevention. The mortality is reduced by 15%, respectively by 23%. This is the first meta-analysis reported in the Romanian gastroenterological literature.


The metabolic and circulatory response to beta-blockade in hypertensive men is correlated to muscle capillary density. Both haemodynamic and metabolic variables have been shown to be related to the fibre composition and capillary density of skeletal muscle in man. In the present study, the change of several metabolic variables during beta-blockade was investigated and related to muscle fibre composition and capillary density in 28 men with essential hypertension. They had been given atenolol (50 mg/day) or metoprolol (200 mg/day) or propranolol (160 mg/day) for 4-12 months. Serum triglycerides increased during treatment and individual changes were significantly inversely correlated with capillary density. Insulin concentrations in the fasting state and at the end of an i.v. glucose tolerance test were significantly higher during beta-blockade, and individual changes were inversely correlated with capillary density. Furthermore, body weight increased and heart rate decreased, changes that were also correlated with capillary density. It is concluded that many of the previously but poorly understood large interindividual differences in response to beta-blocker treatment may be explained by the degree of development of the capillary net in muscle tissue. Obesity, physical training as well as genetic factors are known determinants of capillary density.


Resistance to medical ulcer therapy--possible reasons and management. In 112 patients with duodenal ulcer (males, mean age 29, range 18-35) with a history of at least 3 years, and never being treated with H2-antagonists, maintenance therapy with Tagamet was started. All of them had ulcer recurrence when entering the study. The first two months a full dose was applied, after this bedtime doses up to 24 months. Endoscopy was performed at the beginning, after the first and second months and then every two-month period. Gastric secretion was measured every 2-3 months. A resistant ulcer was defined as one 1/not healing within the two initial months, 2/recurring on maintenance treatment. in 78% the ulcer was healed within one month, in 96% within two months, in the rest within the following 3-4 weeks. Relapses occurred in 21 patients, altogether 27 times. Factors likely to contribute to recurrence included a large ulcer size, longer duration, an inflamed mucosa and--most frequently--heavy smoking. Patients with relapses had higher initial secretory values and smaller decrease during maintenance treatment. Helicobacter pylori (examined in a subgroup) was not clearly associated with ulcer recurrence.


The oxygen-centered radicals scavenging activity of sulfasalazine and its metabolites. A direct protection of the bowel. Oxygen-centered radicals, such as superoxide (O2-) and hydroxyl radicals (.OH) generated by phagocytes have been suggested to be involved in the pathogenesis of chronic inflammations of the bowel, such as Crohn's disease and colitis ulcerosa. Recently, sulfasalazine (SASP) and its metabolites have been reported to exert their effects as a direct scavenger of oxygen-centered radicals in the bowel. To scavenge oxygen-centered radicals in vivo, however, SASP and its metabolites have to react with O2- and/or .OH in vitro very rapidly, furthermore they have to reach an appropriate (possible millimolar) concentration range at the site of inflammation. To test this possibility, we investigated the direct O2- and .OH scavenging activity of SASP and its metabolites using the specific electron paramagnetic resonance/spin trapping method, and we compared the 50% inhibition rates of SASP and its metabolites with their known concentrations in the bowel and in the human plasma. It was found that SASP and its metabolites, such as 5-amino-salicylic acid (5-ASA), and acetyl-5-amino-salicylic acid (AC-5-ASA), but not sulfapyridine (SP) and acetyl-sulfapyridine (Ac-SP) have a direct O2- and .OH scavenging activity in vitro systems. Among the compounds, SASP and 5-ASA can reach a concentration which is appropriate to scavenge oxygen-centered radicals in the bowel but not in the human plasma. It was concluded that the in vivo antiinflammatory effects of SASP and its metabolites are, at least partly, due to the direct oxygen-centered scavenging activity of these drugs.


Adequate enzymatic substitution in treating exocrine pancreatic insufficiency. The chymotrypsin in the stool test was used to monitor adequate enzymatic substitution in treating exocrine pancreatic insufficiency with 18 patients (16 suffering from chronic pancreatitis and 2 having passed duodenopancreatectomy due to pancreatic cancer). This test helps to identify pancreatic insufficiency and can be successfully used in monitoring the adequate amount of pancreatic substitute, which, we have found, differs from patient to patient. The dosage can be higher in cases of chronic pancreatitis than in those required after duodenopancreatectomy.


[A new therapeutic approach tp drug-resistant schizophrenia: clozapine. Long-term prospective study in 16 patients]. Clozapine, a dibenzodiazepine derivative, has potent antipsychotic activity; but bone marrow suppression resulting in agranulocytosis has been associated with clozapine treatment and has restricted the administration of this drug to treatment-resistant schizophrenic patients. This report describes preliminary results of an open prospective study of the effects of clozapine on symptomatology and social function in 16 treatment-resistant schizophrenic patients. Authors prospectively followed up for 18 months 16 DSM III-R schizophrenic patients who had failed to respond to various neuroleptics (n: 7.2 +/- 2.8); when clozapine treatment was initiated, the mean duration of the illness was 14.2 (+/- 6.7) years. Total BPRS, BPRS "positive" and "negative" symptoms scores were used for evaluation. Social integration and side effects were also studied. 14 of 16 patients are still receiving clozapine; 1 out of 14 patients has a more than 60% decrease in total BPRS, 11 out of 14 have 30 to 60% decrease in total BPRS and 2 out of 14 have less than 30% decrease in total BPRS. Improvements in both total and positive symptoms BPRS scores were observed within the first month of treatment (p < 0.001); improvement in negative symptoms was noted within the third month (p < 0.02). At the end of the follow up period, 43% of patients showed marked improvement in family life and 21% found a job during the study. Beyond noteworthy improvement of clinical symptoms in these patients who presented with severe schizophrenia, clozapine also significantly reduced the use of concomitant medication. Side effects are studied but none required treatment disruption; neurological side effects were less reported than with usual neuroleptics. It is concluded that clozapine offers particular benefits for some treatment-resistant schizophrenic patients; however the increased comparative risk requires a restricted use of clozapine to selected patients.


[The effect of neuroleptics in a attempt at understanding the vulnerability to schizophrenia]. Animal and human data suggest that neuroleptic drugs act by decreasing the special significance of some stimulations, especially those of importance for the subject. The two following hypotheses are therefore considered as a basis for the work presented in this paper: 1) the target of neuroleptic drugs is a neuro-psychological mechanism whose function is to focalize the subject on important stimulations and to involve the subject in responding; 2) schizophrenia vulnerability could imply an excessive and abnormal propensity to be over-involved, especially in existentially loaded problems. A careful clinical study of the mode of decrease, and sometimes of disappearance, of schizophrenic delusions under the influence of neuroleptic treatment confirms the hypotheses. Results are of interest for clinical treatment and for research.


GAP-43 as a modulator of G protein transduction in the growth cone. Much circumstantial evidence that GAP-43 is involved in neuronal growth cone function has accumulated over the last ten years. The expression of the protein is closely correlated both temporally and spatially with periods of axonal outgrowth, and the protein is highly concentrated in the growth cone membrane. There is direct evidence that overexpression of the protein can alter cell shape. This review focuses on the molecular mechanisms whereby GAP-43 could exert these actions. One important requirement for GAP-43 function is its localization to appropriate regions of the cell. The ability of this hydrophilic protein to associate with membrane fractions is determined by a short 10 amino acid stretch of the amino terminus of the protein, which contains two cysteine residues subject to palmitoylation. Whether this region can direct growth cone targeting in neurons is not yet clear. Once appropriately localized, GAP-43 may modulate complex cellular properties such as growth cone motility, synaptic plasticity and neurotransmitter release. One possible molecular mechanism for these cellular changes in GAP-43 regulation of the GTP-binding protein, G(o). The observation that the growth cone membrane contains extremely high concentrations of G(o) led us to investigate the interaction of G(o) and GAP-43. There is evidence that G protein-mediated transduction systems can control the same cellular functions thought to be altered by GAP-43: growth cone motility, neurotransmitter release and synaptic plasticity. Purified GAP-43 does stimulate guanine nucleotide binding to G(o). Its action in stimulating GDP release is quite similar to that of G protein-coupled transmembrane receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cystic dystrophy of aberrant pancreatic tissue in the duodenal wall. Diagnostic and therapeutic problems]. The authors report the case of a 28-year-old man with a cystic dystrophy of aberrant pancreatic tissue (C.D.A.P.T.) presenting with a history of major abdominal pain. First diagnosis was chronic pancreatitis because of clinical presentation, alcoholic intoxication, and the results of medical imaging techniques. A vagotomy associated with a gastroenterostomy was performed. Several years later the abdominal pain relapsed and failed to be cure by means of medical treatment. A duodenopancreatectomy was performed. Histology demonstrated the diagnosis of C.D.A.P.T. C.D.A.P.T. is a benign disease of the pancreas, limited to its cephalic portion, without demonstrated pathogenesis. C.D.A.P.T. can be either isolated or associated with a chronic pancreatitis. Clinical diagnosis can be particularly difficult as indicated by a literature review. Abdominal pain is the main symptom. Clinical presentation is rarely related to a complication (stenosis). Endoscopy, sonogram, and CAT scan are three techniques of diagnosis value, but intraluminal-sonography is more efficient. Tumor excision is not recommendable. Treatment of C.D.A.P.T. by duodeno-pancreatectomy (D.P.) is often indicated because of concurrent chronic pancreatitis or suspected pancreatic carcinoma. In case of clinical diagnosis of C.D.A.P.T., fenestration of the cysts under endoscopic control is the only local treatment that can avoid D.P.


The effect of TSH and TSI on the thyroglobulin expression of cultured human thyroid cells. Human thyroid cells in culture stimulated by TSH and TSI were used in order to detect thyroglobulin expression. After three days stimulation the cells were incubated with monoclonal thyroglobulin antibody and FITC-conjugated antiglobulin. Fluorescent index (the intensity of fluorescence related to hundred analysed cells) was estimated for each experimental group. The most effective stimulation of the thyroglobulin expression was detected after TSH stimulation at the concentration of 0.1 mU/ml. TSI from active Graves' patients provoked the highest expression of thyroglobulin at concentration of 1.0 mg/ml, but the fluorescence index was lower than after TSH stimulation. The thyroglobulin expression was intracellular, large, partly confluent granules were detectable mainly in the perinuclear area. Antigen expression on the surface of cultured thyroid cells could not be detected. The morphology of thyroglobulin expression as detected by immunofluorescence, was the same after TSH and TSI stimulation. It is concluded, that both stimulating factors, i.e. TSH and TSI, are involved in the thyroglobulin expression of human thyroid cells.


T-cell subpopulations in pediatric healthy children: age-normal values. Assessment of the percentage and absolute number of T cells as well as of their main subpopulations is presently a routine procedure for the diagnosis and follow-up of a wide array of pediatric immunologic disorders. For several clinical applications (severe immunodeficiencies or leukaemias) the diagnostic usefulness of their enumeration does not require close comparison with age normal values, while in other circumstances such as follow-up of immunomodulating or immunosuppressive treatments or detection of minor immune defects, the expected changes of T cell subsets are more subtile and they are likely to be detected only by comparison with well-defined age normal values. In the present study CD3, CD4 and CD8 positive cells were enumerated in a group of 410 healthy children of age ranging from 30 days to 9 years. No significant changes in percentage or absolute number were observed during infancy and childhood. Furthermore the sum of CD4 and CD8 positive cells was close to the percentage of CD3 positive cells, suggesting a phenotype maturity of T cells from infancy.


[Magnetic resonance tomography of the sellar region in patients with endocrine diseases]. The authors discuss the present-day problems of radiotherapy. They show the major prospective trends in this field and describe the OS3Dplan system, made in this country, that represents a working place of a radiologist and serves for the development, analysis and storage of the schemes of long-distance gamma-beam therapy of oncologic patients. The OS3Dplan system is realized via the IBM PC/AT-286/287 computer but can operate with any of the IBM PC/XT/AT/PS-2--8086/80486 computers, made before 1986 with the videoadapter EGA/VGA, and functioning under MS-DOS, Microsoft (version 3.3 or older). The mathematical provision of the videodigitizer (distance control and videocamera) permit the introduction of videoinformation into the personal computer in the 256 x 256 format, 512 x 512 pixels. The mathematical provision of the OS3Dplan proper permits a volume planning of long-distance gamma-beam therapy. This module type system will be of interest for various specialists (radiologists, roentgenologists, oncologists, students, etc.), for it permits a collection and maintenance of a data bank on patients with imaging of roentgenograms, CT, NM tomography, ultrasonic data on the computer display and printing these data, perform metric analyses and reconstruct the volume.


Corneal endothelial structure and function under normal and toxic conditions. Our understanding of the function of the corneal endothelium in corneal thickness regulation, and the role of ion transport mechanisms in endothelial physiology, has expanded greatly over the past 25 years. The basic events occurring across the apical and basolateral membranes of the cells are far better understood today, although gaps still exist in the area of the relationship of the cellular and paracellular pathways and their relative contribution to the overall behavior of the endothelium. Little is known about the movement of ions or fluid between the cells or in what proportion this may occur compared to the cellular events. Furthermore, although our knowledge of the ionic movement processes has been enhanced, the link between fluid transfer across the endothelium and ion movements remains an enigma. Important questions also remain concerning the link between electrical characteristics and either ion movement or fluid transport. Improved storage solutions are needed that will preserve endothelial function after transplantation through the provision of a significant improvement in long-term cell survival. The limit to preservation time at present is about 14 days, and the use of other variables in the storage solution may extend this time. In reality, however, extension of preservation time is now of secondary importance relative to the need to enhance cell survival and reduce cell loss following surgery. Whether such improvement can be made with manipulation of the solution alone, or whether refinements are needed in the surgical technique awaits further study. Our comprehension of the biochemical linkage between energy supply and ion movement also remains uncertain in view of the particular intracellular localization of the anionic ATPases to mitochondrial loci. Despite numerous attempts there have been only a few chemicals identified that stimulate the fluid pump, but the level of stimulation has been relatively small and short-lived. No sustained effects have been found that would be of clinical benefit in reducing corneal thickness. A considerable variety of chemicals has been tested on the endothelium and it is unlikely that any new compounds will be identified that will cause enhancement of the fluid pump that would be of clinical benefit in dystrophic, or otherwise swollen, corneas. Of all the toxic responses of the endothelium the majority have been identified because of a malfunction of corneal thickness regulation, with the resultant corneal swelling, or by morphological examination. Only in a few instances has the permeability to non-electrolytes (carboxyfluorescein, inulin/dextran) been measured, and even more rarely have ion fluxes, or pump activity (3H-ouabain binding), been measured.(ABSTRACT TRUNCATED AT 400 WORDS)


Retinoids and their nuclear receptors.

Retinoids and their nuclear receptors. Retinoids (retinoic acid and its biofunctional analogs) are widely involved in the control of cell proliferation, cell differentiation, and embryogenic development. A series of novel synthetic retinoids (called retinobenzoic acids), which include retinoid antagonists, have been developed and have been shown to be useful tools to investigate retinoidal action molecular mechanisms. Retinoids elicit their biological effects by binding to specific nuclear receptors (RARs) belonging to a steroid/thyroid nuclear receptor superfamily. RARs act as retinoid-dependent transcription factors which bind to a specific gene site and control the gene's expression. The diversity of retinoidal actions can possibly be interpreted by considering the following characteristics, all of which are quite diversified: the structure and spatial/temporal distribution of RARs, the base sequences which interact with RARs, the cell type specifically determined hierarchy of gene expression, and the nuclear coregulators which interact with RARs. Abnormality of an RAR gene which might cause acute promyelocytic leukemia is also discussed.


The effects of ovomacroglobulin on gingival wound healing in rats. The effects of ovomacroglobulin (OMG), an alpha 2-macroglobulin-like protease inhibitor, were tested on periodontal surgical would healing in 60 Wistar rats. The animals were divided into two groups, one receiving topical application of 0.1% wt/wt OMG ointment and the other receiving ointment base (base). Rats were killed at one, three and seven days after surgery for histological and immunohistochemical observation. Compared with base group samples, OMG samples displayed enhanced capillary formation on anti-laminin-stained sections from day-3 specimens and a greater quantity of collagen fibers on Azan-Mallory-stained sections from day-7 specimens. Results were quantified using an automatic computerized pixel image analyzer. Hematoxylin-eosin-stained sections revealed that the length of regenerated junctional epithelium was shorter in the OMG group than in the base group. The data indicate that the application of OMG to surgical wounds accelerated fibroblast growth, collagen deposition, and capillary formation in granulation tissue. Thus, OMG could be a useful healing promoter for flap surgery.


Familial gingival hyperplasia: a case of pseudo-Laband syndrome. Three siblings with familial gingival hyperplasia and abnormal feet are reported. Despite the resemblance to the Laband syndrome, where there are anomalies of the terminal phalanges, the abnormalities of the feet in these children were caused by the persistent wearing of "flip-flop" sandals. Care is required in the conduct of history and examination.


Alteration of root surface morphology by topical application of doxycycline hydrochloride on periodontally diseased human teeth. The objective of this study was to describe the surface morphology of periodontally involved root cementum and its alteration following topically applied doxycycline hydrochloride to root-planed and non-planed samples. Root surfaces were treated with 100 mg/mL doxycycline hydrochloride solution for three minutes. A control group was treated with sterile saline. Observations made by scanning electron microscopy showed that treating the periodontally diseased cementum surfaces altered the surface topography significantly. Root planed, doxycycline-treated surfaces showed characteristics similar to those reported for citric acid conditioning. An important finding of the study was that the topical application of doxycycline hydrochloride also removed and/or altered the surface integument on non-planed root surfaces.


[Carcinogenic risk assessment of chemicals]. Assessment of human cancer risk associated with any particular specified chemical exposure required a complicated scientific procedure, starting with careful review of all pertinent information on the chemical, derived from experimental, epidemiological and clinical studies. It is generally agreed within the scientific community that there are four steps or components which are typically involved in carcinogenic risk assessment. The first step, which is referred to as hazard identification, entails a qualitative evaluation of data concerning the potential of the chemical to produce a carcinogenic effect in man. The second step, exposure assessment, is the process of measuring or estimating real or hypothetical human exposure to the chemical of interest. The third step, dose-response assessment, is the evaluation of both hazard and exposure information to estimate the mathematical probability that the carcinogenic potential associated with the agent in the human population under defined conditions of exposure. In the final step, referred to as risk characterization, all relevant information from the first three steps is integrated to characterize the carcinogenic risk associated with expected human exposure to the chemical of interest. The process of carcinogenic risk assessment, therefore, relies strongly upon the availability and quality of information on the chemical of interest. In conclusion, risk assessment is defined as a scientific procedure or logical frame-work to assess or infer the risk level of risk profile of the agent of interest in man on the basis of existing information. The execution of any given risk assessment, however, may be hampered by involvement of various uncertainties resulting from deficiencies or critical gaps in the necessary information on the chemical. On such occasions, it is necessary to make assumptions on the basis of the prevailing scientific thought concerning carcinogenic process, to take account of these uncertainties, so that risk assessment can still be completed. Therefore, risk assessment is regarded as a complex mixture of currently available data on the chemical of interest (Specific Information) and assumptions or inference rules based on the prevailing scientific thought on chemical carcinogenesis (General Information). From these points of view, the common ground for risk assessment can be divided into two categories. The first one is the issue of the specific information necessary for assessment, which includes the methodology of data production and the system of data distribution.(ABSTRACT TRUNCATED AT 400 WORDS)


[Studies on a modified plasma spray LC/MS device]. A probe device for LC/MS interface for a sector type mass spectrometer by VG Analytical Ltd. is described. The probe capillary for introduction of LC eluent to the ion source has a coaxial structure, ie. outer and inner capillary. The outer capillary is made of stainless steel to heat the probe, while the inner fused silica capillary has the role of insulating the eluent from the high voltage of the ion source. This prevents the eluent from excess electric charge which causes discharge of ions and disturbs MS experiments. The device also contributes to easy management and quick diagnosis as the structure of the probe is simple compared to the original and the duplicate structure of the capillaries make it possible to examine the probe facilities without taking off the interface from the ion source. The cleaning of the probe is also easily accomplished by the use of another fused silica capillary.


[Studies on chemical analysis of mycotoxin (XXI). A rapid analytical method for aflatoxins by immunoaffinity column chromatography and high performance liquid chromatography]. An analytical method for aflatoxins using solvent extraction, affinity column (containing monoclonal antibodies against aflatoxins bound onto agarose) clean-up and high performance liquid chromatographic determination was applied to the analysis of aflatoxins in peanuts, pistachio nuts, white and black peppers and corn. Recoveries of aflatoxins B1, B2, G1 and G2 spiked to peanuts, pistachio nuts and corn at the level of 20 ppb were 77.4-81.4, 70.1-77.9 and 72.3-94.8%, respectively. In the case of white and black peppers, because the spiked aflatoxin recovery rate was low, further purification steps should be studied. The stability of the affinity column was good. This procedure is recommended as a rapid and reliable method for the analysis of aflatoxins in the three kinds of foods, peanuts, pistachio nuts and corn.


[Determination of butylated hydroxy-anisole in oily foods by high-performance liquid chromatography with fluorescence detection]. Simple and rapid determination method for butylated hydroxyanisole [2(3)-tert-butyl-4-hydroxyanisole)] (BHA) (CAS no. 25013-16-5) is developed. BHA was extracted from oily foods with hexane and from hexane layer to acetonitrile. The acetonitrile layer was either directly or after concentration injected to high-performance liquid chromatograph (HPLC) equipped with a fluorescence detector. As the internal standard for determination, tert-butyl-p-cresol was used. The conditions for HPLC were as follows. Column; Shim-pack CLC-ODS (6 mm i.d. x 15 cm): Mobile phase; 75% methanol: Excitation wave length for the fluorescence detector 298 nm; Emission wave length 332 nm. The recoveries of BHA from salad oil, margarine, and butter added 10 micrograms/g or 200 ng/g of BHA were satisfactory.


[Measurement of prostaglandin E2 content in lung tissue of mouse]. A radioimmunoassay (RIA) was applied for the determination of PGE2 levels in the lung from 4 groups of male ICR mice 1) fed a standard diet, 2) fed a 20% corn oil-supplemented diet (HFD) for 2 weeks, 3) given a single s.c. injection of 15 mg/kg of 4NQO, a potent lung carcinogen and 4) given a s.c. injection of 4NQO and subsequently fed HFD for 2 weeks. Animals were sacrificed at week 3, and the lung was carefully excised and frozen in liquid nitrogen to prevent the postmortem synthesis of PGE2. PGE2, extracted from the lung tissue, was purified and then measured with or without adding a known amount of PGE2. The lung levels of PGE2 were shown to be significantly higher in the groups treated with HFD and/or 4NQO than the group fed a standard diet. These results show that the modified RIA method can be used for the measurement of PGE2 contents in the tissue of animals.


[Studies on activated charcoal concerning the determination of sulfate in food coal-tar dyes]. It is very difficult to determine the content of sulfate in food coal-tar dye by the method designated in the "Japanese Standards of Food Additives(V)", because the endpoint on titration is difficult to gauge. We determined the concentration of sulfate in food dye nephelometrically after decolorization with charcoal but obtain different values depending on the kind of charcoal used. Because the adsorbed or eluted sulfate in the various charcoals were dispersed widely, so we tested the sulfate contents in five kinds of charcoals. It was found that all kinds of charcoals eluted or adsorbed sulfate in varying degrees. Therefore no charcoal was found to be satisfactory for use in the sulfate test.


[Studies on the identification of psychotropic substances (VII). Preparation and various analytical data of standard references of some hallucinogens, 3,4-methylenedioxyamphetamine (MDA), 3,4- methylenedioxymethamphetamine (MDMA) and 5-methoxy-3,4- methylenedioxyamphetamine (MMDA)]. The Reference Standards of 3, 4-methylenedioxyamphetamine (MDA), 3, 4-methylenedioxymethamphetamine (MDMA) and 5-methoxy-3,4-methylenedioxyamphetamine (MMDA) were prepared. Their purities determined by HPLC were 99.8% for DMA hydrochloride, 99.8% for MDMA hydrochloride and 99.5% for MMDA hydrochloride. For the identification and determination, various analytical data of the three drugs were measured and studied by TLC, UV, IR, HPLC, GC/MS and NMR.


[DNA damage test in forestomach squamous epithelium of F344 rat following oral administration of ethyl acrylate]. The alkaline elution assay were applied for testing DNA damage of forestomach squamous epithelium in male F344 rat after oral administration of ethyl acrylate (EA), a forestomach carcinogen. The animals were starved for 18 hr and then given a single oral dose of EA. No DNA damage were observed by EA at the concentration of 0.1-4.0%. The weights of the forestomach increased with EA dose, reflecting edema and inflammation, but that of glandular stomach did not change with its dose.


[Preliminary screening for antiviral AIDS drugs. I. Report on fiscal year 1988]. Preliminary screening for antiviral AIDS drugs has been carried out, using three different in vitro assay systems. Among 105 samples tested, 13 were found to inhibit the growth of HIV in vitro. Eleven of 13 were well-known anti-HIV chemicals, while the remaining two of plant origin were new chemicals whose anti-HIV activities have not been reported elsewhere.


[Study on essential metal concentration in the organs of rats (report 1)]. Concentration of 5 elements (Ca, Cu, Fe, Mg, Zn) in 10 organs (brain, heart, lung, liver, kidney, spleen, testis, thymus, salivary gland and bone) and serum of rats were determined by inductively-coupled argon plasma atomic emission spectrometry (ICP). Samples were digested with nitric acid and perchloric acid in a sealed double Teflon vessel with polypropylene jacket by heating with a microwave oven. The concentration of 5 elements in the organs can be grouped into 5 categories as follows. (1) heart, liver and spleen (Mg > Fe > Ca > Zn > Cu) (2) lung and kidney (Mg > Ca > Fe > Zn > Cu) (3) brain, thymus and testis (Mg > Ca > Fe = Zn > Cu) (4) serum and bone (Ca > Mg > Fe = Zn > Cu) (5) salivary gland (Ca = Mg > Fe > Zn > Cu).


[Thiamine Hydrochloride Reference Standard (Control 891) of National Institute of Hygienic Sciences]. The raw material of thiamine hydrochloride was examined for preparation of the "Thiamine Hydrochloride Reference Standard". Analytical results were as follows: melting point 242.7 degrees; pH 3.2 (1 g, water, 100 ml); IR spectrum the same as that of JP Reference Standard (Control: 841); one and two impurities detected by TLC and by HPLC analyses, respectively; assay by thiochrome method 100.3% and by HPLC 100.1% against the JP Reference Standard. Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Mestranol Reference Standard (Control 881) of National Institute of Hygienic Sciences]. The raw material of mestranol was examined for preparation of the "Mestranol Reference Standard". Analytical results for the sample were as follows: UV spectrum indicated absorption maxima at 279 and 287 nm and absorptivity at 279 nm E1%1cm 66; IR spectrum indicated specific absorption at 1612, 1578, 1505, 1253, and 1060 cm-1; optical rotation +3.9 degrees; melting point 153.1 degrees; loss on drying 0.03%; TLC and HPLC analyses indicated one impurity, respectively; the purity was assumed to be 99.3% by HPLC analysis. Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Betamethasone Sodium Phosphate Reference Standard (Control 881) of National Institute of Hygienic Sciences]. The raw material of betamethasone sodium phosphate was examined for preparation of the "Betamethasone Sodium Phosphate Reference Standard". Analytical results for the sample were as follows: pH 7.90; optical rotation + 100.5 degrees; IR spectrum the same as USP Reference Standard of Betamethasone Sodium Phosphate; TLC indicated no impurities, but 5 kinds of impurities were detected in small amounts by HPLC; water content 14.7%; assay 100.2% by HPLC. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Dexamethasone Sodium Phosphate Reference Standard (Control 891) of National Institute of Hygienic Sciences]. The raw material of dexamethasone sodium phosphate was examined for preparation of the "Dexamethasone Sodium Phosphate Reference Standard". Analytical results were as follows: UV spectrum indicates absorption maxima at 242 nm and absorptivity at 242 nm is E1%1cm 304; optical rotation +79.0%; pH 7.7; ethanol 5.2%; water 6.0%; HPLC analysis indicates small amounts of three impurities and the purity was assumed to be 99.8%; assay by HPLC indicated 100.9% against the USP Reference Standard of "Dexamethasone Phosphate". Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Hydrocortisone Acetate Reference Standard (Control 891) of National Institute of Hygienic Sciences]. The raw material of hydrocortisone acetate was examined for preparation of the "Hydrocortisone Acetate Reference Standard". Analytical results were as follows: E1%1cm (242 nm) 403; IR spectrum indicates specific absorption at 3424, 1745, 1721, 1630, and 1374 cm-1; optical rotation +164.4 degrees (in dioxane); melting point 219.5 degrees (decomposition); loss on drying 0.16%; TLC and HPLC analyses indicated one and three impurities, respectively; assay by HPLC was 99.7% against the previous Reference Standard. Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Hydrocortisone Sodium Phosphate Reference Standard (Control 891) of National Institute of Hygienic Sciences]. The raw material of hydrocortisone sodium phosphate was examined for the preparation of the "Hydrocortisone Sodium Phosphate Reference Standard". Analytical data obtained were as follows: pH, 8.2; optical rotation [alpha]D20, +124.1 degrees; Infrared spectrum, same as that of BP Reference Standard of Hydrocortisone Sodium Phosphate; thin-layer chromatography, no impurities were detected; high-performance liquid chromatography (HPLC), 2 kinds of small amount of impurities were detected; assay, 99.2% by the enzyme method and 99.9% by the HPLC method in terms of the BP Reference Standard. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Prednisolone Sodium Phosphate Reference Standard (Control 891) of National Institute of Hygienic Sciences]. The raw material of prednisolone sodium phosphate was examined for preparation of the "Prednizolone Sodium Phosphate Reference Standard". Analytical data obtained were as follows: pH 7.6; optical rotation [alpha]D25, +99.0 degrees; Infrared spectrum, same as that of BP Reference Standard; Thin-layer chromatography, 4 impurities were detected; high-performance liquid chromatography (HPLC), 7 kinds of impurities were detected; residual solvent, 0.76% (ethnol) and 0.23% (hexane); assay, 100.2% by the enzyme method and 99.7% by the HPLC method in terms of the BP Reference Standard. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Tocopherol Succinate Reference Standard (Control 881) of National Institute of Hygienic Sciences]. Tocopherol succinate was tested for the preparation of "Tocopherol Succinate Reference Standard (Control 881)". Analytical data obtained were as follows: infrared spectrum, same as Tocopherol Succinate Reference Standard (Control 851); absorbance, E1cm1% (286 nm) = 40.5; thin-layer chromatography, contaminants were not detected until 50 micrograms; high-performance liquid chromatography, three contaminants were detected; loss on drying, 0.09%; assay, 100.0%. On the basis of the above results, this material was authorized as the Japanese Pharmacopoeia Standard (Control 881).


[Methyldigoxin Reference Standard (Control 881) of National Institute of Hygienic Sciences]. Methyldigoxin was tested for preparation of the "Methyldigoxin Reference Standard (Control 881)". Analytical data obtained were as follows: infrared spectrum 3456, 1738, 1086 cm-1; ultraviolet spectrum lambda max = 219 nm; absorbance E1cm1% (219 nm) = 193.1; water 0.99%; optical rotation [alpha]546.1(20) = +22.5 degrees; thin-layer chromatography and high-performance liquid chromatography indicates two impurities, respectively; quantitative analysis of acetone 3.87%; assay by spectrophotometry 100.3% against Digoxin Reference Standard (Control 802). On the basis of the above results, this material was authorized as the National Institute of the Hygienic Sciences Reference Standard (Control 881).


[Cyanocobalamin Reference Standard (Control 891) of National Institute of Hygienic Sciences]. Cyanocobalamin was tested for preparation on the "Cyanocobalamin Reference Standard (Control 891)". Analytical data obtained were as follows: loss on drying, 9.77%; infrared spectrum, same as that of the Cyanocobalamin Reference Standard (Control 871); thin-layer chromatography, five contaminants were detected; high-performance liquid chromatography, nine contaminants were detected; assay, 100.00% by JP XI method and 99.79% by HPLC method in terms of the JP Reference Standard (Control 871), respectively. On the basis of the above results, this material was authorized as the Japanese Pharmacopoeia Standard (Control 891).


[National Institute of Hygienic Sciences Standard (the Japanese Pharmacopoeia Standard) "Endotoxin Reference Standard" (Control 891)]. The second "Endotoxin Reference Standard" (Control 891) of the National Hygienic Sciences (Japanese Pharmacopoeia Standard) was prepared. As a result of the test of its potency against the preceding lot of the Reference Standard (Control 881), the second "Endotoxin Reference Standard" (Control 891) containing 16000 endotoxin units per vial was authorized.


[On a minor component found in the lysozyme reference standard]. A minor component separated by HPLC from egg-white lysozyme was found to have a different substrate specificity from the main component, lysozyme. However, it did not show any difference in molecular weight and immuno-cross reactivity from lysozyme. There was no evidence based on our study that this minor component is an artificially-produced substance.


[Studies on the quality of enzyme preparations (XI)--Kallidinogenase preparations]. Qualitative tests of 22 kinds of commercially available kallidinogenase preparations were carried out by the enzymological method. These preparations consisted of 16 kinds of tablets, 5 kinds of capsules and 1 kind of ampoule. One sample of tablet showed kallidinogenase activity less than 80% of the labeled amount by spectrophotometry, pH stat and kinin-liberating methods. All other preparations were found to have 90-120% 120% of the labeled amount by spectrophotometry using S-2266 as the substrate. Other enzymes, i.e. kininase, trypsin and chymotrypsin were found as impurities, but the cntants were very low.


[Gas chromatographic determination of azinphos-methyl in imported crops]. A gas chromatographic method for the quantitative analysis of azinphos-methyl in agricultural products was studied. Azinphos-methyl was extracted with acetone. The extract was cleaned up by charcoal column chromatography for the treatment of wheat and soybean and by using coagulating reagent for the treatment of lemon and orange, then determined by a gas chromatograph equipped with a flame photometric detector (FPD). The mean recovery of azinphos-methyl added to wheat, soybean and lemon at the level of 0.1 or 0.2 microgram/g was 96.6-101.0%. The detection limit of azinphos-methyl was 0.04 microgram/g in the case of wheat and soybean extracted from 10 g of each sample and 0.02 microgram/g in the case of lemon and orange extracted from 20 g of each sample. Azinphos-methyl was not detected in any of the imported, 6 wheat, 6 soybean, 5 lemon and 4 orange tested using the above mentioned method.


Production and characterization of monoclonal and polyclonal antibodies against digoxin. Three hybridoma cell lines (DIG 64. 2B. 5, DIG 104. H10.1 and DIG 222. 4D. 5) producing monoclonal antibodies against digoxin were established, and the properties of these monoclonal antibodies were characterized and compared with three polyclonal rabbit anti-digoxin antisera. Both polyclonal and monoclonal antibodies gave association constants ranging from 10(9) to 10(10) (M-1). The monoclonal antibodies were of the IgG1(kappa) or IgG2b(kappa) subclass. Cross-reactivities of these monoclonal antibodies and polyclonal antisera with various related cardenolides and their aglycones were determined by competitive radioimmunoassay. The monoclonal antibodies were specific for digoxigenin-containing glycosides such as lanatoside C and deslanoside, but not for digitoxigenin-containing glycosides. On the other hand, the specificities of the polyclonal antisera were less strict than the monoclonal antibodies and relatively cross-reactive with digitoxin. It was shown that the RIA for digoxin using DIG 64. 2B. 5 is sensitive enough to detect 0.2-0.3 nM (30-60 pg/tube) of digoxigenin-containing cardenolides.


[Future development of the Japanese chemicals regulation data search system and the effective use of the IRPTC legal file]. After ten years of international cooperation in developing the IRPTC Legal File, its usefulness in searching for chemicals regulation data from abroad and in Japan was studied. The superiority of the database in offering summaries of the legal texts from 50 countries and 7 international organizations was obvious, but the need for improvements in the coverage and the accuracy of the data was found. The development of a Japanese database of legal information on chemicals based on international information exchange is desirable.


[Evaluation of immunotoxicity testings using azathioprine-treated rats: the International Collaborative Immunotoxicity Study (Azathioprine)]. The immunotoxicological effects of azathioprine (AZP) were examined by enhanced histopathological and function tests in the rat which is routinely used in toxicological tests. Male F344 rats were orally administered AZP in doses of 0, 2.5, 12.5 and 25.0 mg/kg/day for 28 days. Reductions in the organ weights of the thymus, spleen, liver, kidney, and testis in a dose-dependent manner were confirmed. Hematological examination revealed a marked decrease in the number of WBCs, which was associated with a decrease in the number of lymphocytes. In the femoral bone marrow, a significant reduction in the total cell number attributed to the decrease in the number of lymphocytes and granulocytes was observed. Histopathologically, atrophy and obfuscation of the corticomedullary junction in the thymus, the decrease of lymphocytes in the thymus and spleen, and the disappearance of germinal centers in the lymph nodes were observed. As for the functional testings, azathioprine treatment did not affect remarkably the PFC number and the NK cell activity per unit spleen cell number. However, the total spleen cell number per spleen was decreased in a dose-dependent manner. Therefore, the total functional activities (PFC and NK) per spleen were decreased. Thus, in the AZP-treated F344 rats, it was shown that the enhanced histopathological tests were useful to evaluate potential risks to the immune system.


[Twenty-eight-day repeated dose toxicity test for tetrachlorvinphos in Wistar rat]. A 28-day oral toxicity test of tetrachlorvinphos (TCV) was conducted in male and female Slc: Wistar rats by gavage at dose levels of 0, 10, 100 or 1000 mg/kg/day. The male and female rats showed dose-related inhibition of serum cholinesterase activity and erythrocyte acetylcholinesterase activity. At a dose of 1000 mg/kg, body weight gain was decreased in males, and there were 6 deaths in females. Adrenal gland, liver, kidney and thyroid gland weights were increased. The adrenal lesions were characterized by vacuolization and swelling of the cortex cells. The hepatic lesions consisted of vacuolization and necrosis of the hepatocytes. The renal lesions consisted of regeneration and necrosis of the tubular epithelial cells. These lesions were mostly observed at a dose of 1000 mg/kg. After a 14-day recovery period in the 1000 mg/kg group, the changes of cholinesterase, total cholesterol, gamma-glutamyltransferase, alkaline phosphatase, aspartate aminotransferase and blood urea nitrogen in serum were restored or showed a tendency toward recovery. However, the lesions in the kidney and adrenal remained. More than 14 days are therefore considered to be needed for recovery. At doses of more than 10 mg/kg, significant inhibition of the serum cholinesterase activity in both sexes, erythrocyte acetylcholinesterase activity in males, and lesions of the adrenal gland in females were observed. Target organs for TCV-treated rats were the adrenal, liver and kidney. It was concluded that the NOEL under this experimental condition is less than 10 mg/kg/day.


[Studies on the teratogenic potential of 2,2'-methylenebis (4-methyl-6-tert-butylphenol) in rats]. 2,2'-Methylenebis (4-methyl-6-tert-butylphenol), an antioxidant, was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 93.5, 187 or 375 mg/kg body weight during days 7 to 17 of pregnancy, and the effects of the compound on dams and fetal developments were examined. In the dams at the two higher doses of 187 and 375 mg/kg, toxic signs such as hair fluffing and diarrhoea were observed, and their body weight gain and food consumption were suppressed. Two dams, which showed marked diarrhoea in the highest dose group, died. However, there was no evidence of fetal malformation attributable to treatment with the compound in any of the dose groups treated, although a slight increase in fetal death was found in the highest dose group. It is concluded that 2,2'-methylenebis (4-methyl-6-tert-butylphenol) has a weak lethal effect on fetal development but not a teratogenic effect in the rat.


[Effects of crude soybean trypsin inhibitor on pancreatic atrophy induced by BOP treatment in hamsters]. Experiment I: Female Syrian golden hamsters were given 5 weekly sc injections of N-nitrosobis (2-oxopropyl)amine (BOP) while simultaneously being treated with SBTI diet for 5 weeks (BOP+ SBTI). Other two groups were treated with BOP or SBTI alone. Sacrificed at week 30, the numbers of both adenocarcinomas and dysplastic lesions were decreased in the BOP+SBTI group relative to the BOP alone group. Experiment II: Female hamsters were given 3 weekly sc injections of BOP and then fed a SBTI diet for 40 weeks. The numbers of dysplastic lesions was decreased in the BOP and SBTI group relative to the BOP alone group. An inhibitory effect was observed for the pancreas in hamsters fed SBTI after BOP treatment. In experiments I and II, atrophic changes of pancreatic exocrine tissues and fatty tissue infiltration were observed in hamsters treated with BOP. The ratios of exocrine atrophy in pancreas sections were measured with the aid of an image processor. Areas (2.4 mm2) of splenic and gastric lobes were selected randomly, and the included exocrine tissue measured to allow calculation of percentage area of exocrine tissue atrophy. In hamsters simultaneously treated with BOP and SBTI, the percent areas of intact exocrine tissues in both splenic and gastric lobes were significantly higher (87% and 83%) as compared to the BOP group values (61% and 61%), at the level of p < 0.01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


[Early histopathological changes in trachea, bronchus and lung, and changes in lipid peroxidation in hamsters, due to inhaled cigarette smoke]. The main objective of this work was to determine the influence of cigarette smoke exposure on the mechanisms which promote respiratory tumors. And another aim was the accumulation of basic data regarding the effect of cigarette smoke exposure in hamsters in the Hamburg II smoking machine. Male Syrian golden hamsters were caused to inhale cigarette smoke in the Hamburg II smoking machine. The hamsters inhaled cigarette smoke twice a day, for 9 minutes, 5 times a week. The administration period were 1,2,4,8 and 12 weeks. For each inhalation, the rotating disk was fitted with 30 cigarettes. Each puff, 35 ml in volume, was diluted seven times with room air. At the completion of administration, subjects were examined histopathologically, and lung and serum lipid peroxidation levels were also measured. Histopathological examination of the respiratory tract and alveolar epithelium disclosed no cigarette smoke-related hyperplastic lesion in any animal. And in the hamsters which inhaled cigarette smoke, "smoke cells" accumulation were observed in the alveolar space after 8 and 12 weeks exposure. Significant increase in the number of BrdU positive cells were not observed following cigarette smoke exposure, but a tendency for lung malondialdehyde (MDA) levels to increase was evident. On the other hand, serum lipid peroxide (LPO) levels showed a marked decrease in the animals exposed to cigarette smoke for 2,4 and 8 weeks in comparison with the identically handled control animals. But serum LPO levels showed a tendency to increase with cigarette smoking during all experimental periods. The above results suggested that cigarette smoking may cause a change in lipid peroxidation levels such as lung MDA and serum LPO levels.


[Ultrastructural localization of myelin bodies and acid phosphatase activities in the liver and kidney induced by quinacrine in rats]. Electron microscopic studies were conducted to reveal the ultrastructural aspects of the myelin body and acid phosphatase activity in rats induced by quinacrine, an antimalarial drug. Each of 22 rats in three groups were examined. The first group of control rats was initially given a single i.p. dose (200 mg/kg) of diethylnitrosamine (DEN) only and then fed a CRF-1 basal diet for 8 weeks. The second and third group were treated with DEN or saline, and starting 2 weeks later, were fed a CRF-1 basal diet supplemented with 500 ppm quinacrine for 6 weeks. All animals were subjected to a partial hepatectomy at week 3, and then sacrificed at week 8. Liver and kidney tissues specimens from 2 rats per group were collected for routine electron microscopic study. Furthermore, the activity of acid phosphatase, a key enzyme for lysosomal activity, was also investigated. In this study, tissues were fixed with a solution of 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer. After fixation, tissues were frozen and their 8 microns sections were treated with Gomori's lead nitrate buffer solution, and post-fixed with a 1% osmium solution. After being embedded in Epon 812, ultrathin sections were made. Intracellular myelin bodies were observed in the hepatocytes, interlobular bile duct cells, renal glomerular podocytes and renal tubular cells in the quinacrine treated groups, but not were observed in rats treated with DEN alone.(ABSTRACT TRUNCATED AT 250 WORDS)


[Twenty-eight day repeated dose toxicity test of dicyclopentadiene in F344 rat]. A twenty-eight day repeated dose toxicity test of dicyclopentadiene (DCPD) was carried out in male and female F344 rats at the dose levels of 200, 40, 8 or 0 mg/kg/day. Thirty six animals of both sexes were divided into 6 groups of equal number. All groups were treated i.g. administration for 28 days daily, and two groups of them, at the dose levels of 200 and 0 mg/kg, were used for investigation of recovery. Inhibition of body weight gain was observed in the 200 mg/kg groups in both sexes and the 40 mg/kg group in male, but in female this inhibition was recovered at day 17 of the treatment. Increases in liver and adrenal gland weights, and decrease in thymus weight were noted in the 200 mg/kg groups in both sexes, and increase in kidney weight was also observed in the 200 and 40 mg/kg groups in male. On histopathological examination, hypertrophy of the adrenal cortex, and foamy cytoplasm in hepatocytes were observed in the 200 mg/kg groups of both sexes. Repair of histopathological lesions occurred within 14 days resting period. Based on these findings, it was concluded that the No Observed Effect Level of DCPD would be 8 mg/kg/day.


[Subchronic oral toxicity study of tannic acid in F344 rats]. A 13-week subchronic oral toxicity study of tannic acid (TA) was carried out in F344 rats at dose levels of 0, 0.025, 0.05, 0.1, 0.2 and 0.4% in the drinking water, to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 6 groups, each consisting of 12 males and 12 females. No animals died during the administration period. There were no significant difference in body weight gain, food consumption and organ weights between the treated and control groups, although a slight decrease in water intake was seen in the 0.4% TA treated group. No specific changes were observed in any parameters in the hematological and biochemical investigations. Histopathological examination, revealed toxic changes in the TA treated male groups, in the form of necrosis in the liver, but toxicologically it was of minor importance. From these results, it was concluded that the provable maximum tolerable dose of TA in the drinking water would be more than 0.4%. In consideration of the avoidance of drinking water, the maximum tolerable dose of tannic acid was determined to be 0.5%, when given in the drinking water.


[Toxicity and carcinogenicity studies of musk xylol in B6C3F1 mouse]. Toxicity and carcinogenicity studies of musk xylol were examined in B6C3F1 mice. The LD50 of the chemical was considered to be more than 4000 mg/kg. In the acute toxicity and 14-day repeated-dose oral toxicity studies, tremor was observed in some animals given high doses of the chemical. In the 17-week repeated-dose oral toxicity study, musk xylol was given at dietary dose levels of 0.0375, 0.6%. During the experimental period, almost all mice given 0.3% or more died. There was no difference in the body-weight gain between the treated groups given 0.15% or less and the control group. Histologically, enlargement and irregularity of hepatocyte were found in both sexes given 0.15% or more. Based on the results, the chemical was given at dietary levels of 0 (control), 0.075 or 0.15% for 80 weeks in the carcinogenicity study. Overall tumor incidences in all treated groups of both sexes were significantly higher than those in the respective controls. Combined malignant and benign liver cell tumors increased clearly in both sexes and a significant positive trend for the occurrence of hepatocellular carcinomas was noted in males. Incidences of lung and Harderian gland tumors and lymphomas in treated groups were also slightly higher than those in controls. In addition, incidences and total numbers of malignant tumors increased significantly in treated groups of both sexes, although no dose-relation was evident. The results demonstrated that musk xylol is carcinogenic in B6C3F1 mice of both sexes when given at dose-levels of 0.075 or 0.15% in the diet for 80 weeks.


[Usage of chitosan as a pharmaceutical material effectiveness as an additional additives of sodium alginate]. Application of chitosan, a deacetylated compound of chitin obtained from shells of shrimps, was investigated with reference to the pharmaceutical excipient for directly compressed tablets. Several drugs were chosen as model compounds and their in vitro dissolution tests were carried out according to the JP XI dissolution test. When chitosan was used alone as an excipient, immediate-release tablets were obtained, as already reported. But when more than 5% of sodium alginate, 1000 cps, was added as excipient, tablets showed an extended-release property under the present experimental conditions.


[Identification of nutmeg by thin-layer chromatography and its introduction to Japanese standards for non-pharmacopoeial crude drugs]. When nutmeg was extracted with hot methanol and cooled, much precipitate was produced. The colorless crystals, obtained on recrystallization, were identified as trimyristin by spectroscopic means and by direct comparison with the standard. Then, the identification of nutmeg was established by using the same extraction as above and subjecting the precipitate to thin-layer chromatography. This method was newly introduced to the Standards for Non-pharmacopoeial Crude Drugs.


[Recent world-wide advances in irradiation of food and its identification]. Irradiation (ionizing radiation) of various foods is growing in popularity internationally. For example, it is used as a substitute for the use of post-harvest pesticides. This trend has served to intensity research on the identification of irradiated foods. The first Research Co-ordinated Meeting on Analytical Detection Method for Irradiated Foods was held in Poland under the sponsorship of FAO/IAEA in 1990 in order to solve problems related to the international trade of irradiated foods and to ensure their correct labelling in the market. In this review, the world-wide advances in the irradiation of food and its identification are introduced and discussed.


[Determination of thiabendazole (TBZ) in grapefruit]. The officially recognized gas chromatographic method (detector: nitrogen-phosphorus detector) for determination of thiabendazole (TBZ) in grapefruits, tends to give results that are higher than the actual values. This may be due to the fact that more of the TBZ in authentic TBZ solution is adsorbed on the column than TBZ in the sample solutions that contain a lot of impurities. Because of this difficulty, two liquid chromatographic methods were compared. If a fluorescence detector is available, the method of Nakazato et al. (ethyl acetate extraction and ion pair HPLC) is the best for preparation of test solution. When an ultraviolet detector is used, clean-up of the ethyl acetate extract is necessary. By the method of Kitada et al., the retention time of TBZ becomes shorter after injection of many samples. In view of these results, the method of Nakazato et al. is the methods-of-choice for TBZ in grapefruit.


Migration and material tests of some food-contact plastic wares made in Thailand. Migration and material tests of food-contact plastic wares were carried out in compliance with the Thai Food Act. Sample materials studied were melamine resin, polyethylene, polypropylene, polystyrene, and polyvinyl chloride. Migration levels of phenol, formaldehyde, colors and heavy metals were determined. A test for vinyl chloride monomer in polyvinyl chloride was carried out. Migrant and residual levels in all samples were in compliance with the Act.


[Preliminary screening for antiviral AIDS drugs. II. Report on fiscal year 1989]. Preliminary screening for antiviral AIDS drugs was carried out using three different in vitro assay systems. Among 104 samples tested, six were found to inhibit the growth of HIV in vitro. Four of six were acidic polysaccharides of sea weed origin and one was a well-known anti HIV chemical whose anti-HIV activity has not been reported.


[A study on toxicological information search--an example from a study on food additives]. The information search method for toxicological evaluation of food additives was examined. Both a survey of the existence of critical reviews or specific databases for toxicological evaluation and the performance of preliminary online-search are important for a comprehensive and effective search. Examples of file selection and search scheme examination are reported. The results are considered to be generally applicable to toxicological information search for other groups of chemicals.


[Summaries on the first draft of the EHC monographs in 1990]. The first drafts of the EHC monographs in 1990 were summarized into Japanese. The chemicals consist of hexachlorocyclopentadiene, trichlorfon, fenitrothion, methylparathion, trichloroethane, platinum and selected platinum salts, di(2-ethylhexyl)phthalate, partially halogenated chlorofluorocarbons, methyl ethyl ketone, and propachlor.


[Enhancing effect of L-histidine on the formation of 8-hydroxy-deoxyguanosine induced by hydrogen peroxide in vitro]. Treatment of deoxyguanosine with H2O2 (56 mM) at 37 degrees C for 2 hrs resulted in the formation of 8-hydroxydeoxyguanosine (8-OH-dG). The formation of 8-OH-dG by H2O2 was increased about 3-folds in the presence of 78 microM L-histidine (L-His). The result suggests that oxidative DNA damage induced by H2O2 in vitro might be enhanced by L-His.


[Study on essential metal concentration in the organs of rats (report 2)--lung.liver.kidney.spleen]. The objective of this study was to obtain the normal ranges of essential metals in male and female Slc: Wister rats aged 9 or 11 weeks. Concentration of 10 elements (Ca, Cu, Fe, K, Mg, Mn, Na, P, S and Zn) in the lung, liver, kidney and spleen of rats was determined by inductively coupled argon plasma atomic emission spectrometry (ICP). Each sample was digested with nitric acid and perchloric acid in a sealed double Teflon vessel with polypropylene jacket by heating with a microwave oven. The concentrations of Fe and Mn in the liver were different between males and females. The Fe level in the female was higher than that in the male, and Mn level in male was higher than that in female. The concentration of Fe in the spleen was different by sex and ago. The Fe level in female was 2.3 times higher than that in male, and that in rats of 11 weeks was 1.8 times higher than that of 9 weeks.


[A study on the usefulness of the OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)]. We studied the usefulness of the OECD combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox) using cyclophosphamide (CP), which is well known for its toxicological properties. CP was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague-Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body weight and food consumption were observed in males given 6.7 mg/kg and in all treated females. One, 3 and 12 females died during pregnancy in the groups given 3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group. Leukopenia and anemia were evident in treated males. The thymus and spleen weights were significantly decreased in treated rats. Histopathologically, atrophy of the thymus, spleen and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss and postnatal death of pups were found in treated dams. The body weight of pups from treated dams was significantly lowered. Thus, most of the known toxicological properties of CP regarding systemic toxicity and reproductive/developmental toxicity were clearly demonstrated in this study. Therefore ReproTox can be considered a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume, although teratogenic potential and adverse effects on spermatogenesis and fertility were not detected under the present experimental conditions.


[Cholecalciferol Reference Standard (Control 901) of the National Institute of Hygienic Sciences]. Cholecalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 85.8 degrees C; UV and IR spectra were in agreement with both of the previous JP RS and USP RS of Cholecalciferol; absorptivity at 265 nm E1%lcm = 476; optical rotation [alpha]20D = + 110.1 degrees; no impurities were detected by TLC and HPLC analyses; assay 100.1% by HPLC against the USP RS. Based on the above results, the raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.


[Ergocalciferol Reference Standard (Control 901) of the National Institute of Hygienic Sciences]. Ergocalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 118.4 degrees C; UV and IR spectra were in agreement with both of the previous JP RS and USP RS of ergocalciferol; absorptivity at 265nm E1%lcm = 467; optical rotation [alpha]20D = 103 degrees; no impurities were detected by TLC and HPLC analyses; assay 100.1% by HPLC against the USP RS. Based on the above results, the raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.