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Biomedical subjects

M Nagai

Publications and source records attributed to M Nagai.

At least 19 recordsLinked to original sources

Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia.

Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients.

Aged

Bordetella heat-labile toxin causes release of radioactivity from smooth muscle cells labeled with [14C]arachidonic acid.

The effect of Bordetella heat-labile toxin (HLT) on cultured vascular or tracheal smooth cells labeled with [14C]arachidonic acid for 3 h was examined. At 37 degrees C, in the presence of Ca2+, HLT induced the release of radioactive substances from the cells in a dose-dependent manner but HLT had no effect on release of radioactivity from cells at 0 degrees C or in the absence of Ca2+. After cells were exposed to HLT, a 2-h lag period occurred before release of radioactivity was detected. The substances released from cells by HLT were identified as arachidonic acid and phosphatidylcholine.

Animals

Proliferation-linked regulation of type II IMP dehydrogenase gene in human normal lymphocytes and HL-60 leukemic cells.

Human IMP dehydrogenase (IMPDH; EC 1.1.1.205) was recently found to consist of two molecular species (types I and II) with high expression of type II isozyme in leukemic cells. Here we report that the low level of type II mRNA in normal lymphocytes was up-regulated by phytohemagglutinin stimulation (3.2-fold) and Epstein-Barr viral transformation (5.7-fold). The type II mRNA expression in quiescent HL-60 cells was also elevated 2.8-fold by serum stimulation. Conversely the enhanced level of type II IMPDH mRNA in HL-60 cells was down-regulated to less than 5% along with differentiation induced by retinoic acid (1 microM), phorbol-12-myristate-13-acetate (33 nM), or dimethyl sulfoxide (1.25%) independent of end-stage phenotype. By contrast, type I IMPDH mRNA was expressed constitutively in the various states of proliferation and differentiation. The type II IMPDH stringently linked with cell proliferation should be a crucial target for antileukemic and immunosuppressive chemotherapy.

Blotting, Northern

Successful surgical obliteration of a huge intradural arteriovenous fistula of the spinal cord in a child.

We report the case of an 8-year-old boy with a huge intradural spinal arteriovenous fistula (AVF), which was successfully obliterated by surgery. The symptoms were episodic headaches and progressive motor and sensory deficits. He had suffered a subarachnoid hemorrhage twice before but no ensuing neurological deficits. Neuroradiological examinations revealed an intradural AVF with a huge venous aneurysm ventral to the spinal cord of C7 to T2, which was fed by the left 5th intercostal artery and the right thyrocervical artery. These two feeding arteries were occluded intradurally just at the venous aneurysm emerging point. MR images taken sequentially after surgery demonstrated complete thrombosis and subsequent disappearance of the thrombosed malformation. Neurological symptoms improved gradually. Treatment of such malformations is discussed.

Angiography

Regulation of GTP biosynthesis.

In the regulation of GTP biosynthesis, complex interactions are observed. A major factor is the behavior of the activity of IMPDH, the rate-limiting enzyme of de novo GTP biosynthesis, and the activity of GPRT, the salvage enzyme of guanylate production. The activities of GMP synthase, GMP kinase and nucleoside-diphosphate kinase are also relevant. In neoplastic transformation, the activities and amounts of all these biosynthetic enzymes are elevated as shown by kinetic assays and by immunotitration for IMPDH. In cancer cells, the up-regulation of guanylate biosynthesis is amplified by the concurrent decrease in activities of the catabolic enzymes, nucleotidase, nucleoside phosphorylase, and the rate-limiting purine catabolic enzyme, xanthine oxidase. The up-regulation of the capacity for GTP biosynthesis is also manifested in the stepped-up capacity of the overall pathways of de novo and salvage guanylate production. The linking with neoplasia is also seen in the elevation of the activities of IMPDH and GMP synthase and de novo and salvage pathways as the proliferative program is expressed as cancer cells enter log phase in tissue culture. The activity of GMP reductase showed no linkage with neoplastic or normal cell proliferation; however, in induced differentiation in HL-60 cells the activity increased concurrently with the decline in the activity of IMPDH. This reciprocal regulation of the two enzymes is observed in differentiation induced by retinoic acid, DMSO or TPA in HL-60 cells. In support of enzyme-pattern-targeted chemotherapy, evidence was provided for synergistic chemotherapy with tiazofurin (inhibitor of IMPDH) and hypoxanthine (competitive inhibitor of GPRT and guanine salvage activity) in patients and in tissue culture cell lines. These investigations should contribute to the clarification of the controlling factors of GMP biosynthesis, the role of the various enzymes, the behavior of GMP reductase in mammalian cells and the application of the approaches of enzyme-pattern-targeted chemotherapy in patients.

Animals

Acute myelocytic leukemia associated with thrombocytosis and inv 3(q21.3; q26.2) in a case of Grönbland-Strandberg syndrome.

Grönbland-Strandberg syndrome is an inherited connective tissue disorder with cutaneous, ophthalmologic, and systemic manifestations. Here we report a case of AML with thrombocytosis arising in a patient with this syndrome. Karyotypic analysis of bone marrow cells revealed the inversion 3 (q21.3;q26.2). To our knowledge, this is the first report of the association of AML with thrombocytosis and Grönbland-Strandberg syndrome. This might be a coincidental association, but it suggests some interesting speculations regarding the pathogenesis of these diseases.

Chromosome Inversion

Stimulative effects of cadmium on bone resorption in neonatal parietal bone resorption.

Effects of cadmium on bone resorption were investigated using neonatal mouse parietal bone culture system. Cadmium at 0.5 microM and above stimulated hydroxyproline release as well as 45Ca release. As cadmium-stimulated bone resorption was inhibited by calcitonin, bone resorption induced by cadmium is osteoclast-mediated bone resorption. CI-1, collagenase inhibitor, depressed cadmium-stimulated bone resorption in a dose-dependent manner. Osteoblasts are also involved in cadmium-induced bone resorption. Indomethacin-inhibited cadmium-stimulated bone resorption and cadmium-treated bones released prostaglandin E2 to a greater extent than untreated bones. Cadmium-stimulated bone resorption was shown to be dependent on the production of prostaglandin E2. 3-Isobutyl-1-methylxanthine potentiated cadmium-stimulated bone resorption and verapamil depressed it. It is possible that an increase in levels of cAMP and calcium ion in bone cells is involved in cadmium-induced bone resorption. From these results, cadmium was found to stimulate osteoclast-mediated bone resorption which is dependent on prostaglandin E2. Second messengers in cadmium-induced bone resorption may be cAMP and calcium ion.

Animals

Direct assay method for guanosine 5'-monophosphate reductase activity.

A sensitive and simple micromethod for the accurate measurement of GMP reductase (EC 1.6.6.8) activity in crude extracts is described. The reaction product of [8-14C]IMP was separated from the substrate [8-14C]GMP by descending chromatography on Whatman DE81 ion-exchange paper. This separation method provides an analysis of the possible interfering reactions, such as the metabolic conversion of the substrate GMP to GDP, GTP, and/or guanosine, and guanine and the loss of the product IMP to inosine, hypoxanthine, and other metabolites. Low blank values (70-90 cpm) were obtained consistently with this assay because the IMP spot moves faster than the GMP spot. The major advantages of this method are direct measurement of GMP reductase activity in crude extracts, high sensitivity (with a limit of detection of < 10 pmol of IMP production), high reproducibility (< +/- 5%), and capability to measure activity in small samples (9 micrograms protein).

Animals

Eruptive lichen planus.

We herein report a case of a rare variety of the acute eruptive form of lichen planus. The patient was a 51-year-old male who developed an intensely pruritic eruption on the lower legs which spread rapidly to all four extremities and trunk within a few months. The papulosquamous lesions were more than ten thousand in number. Topical steroid, cyclosporine, and systemic griseofulvin treatments were ineffective. However, there was a dramatic response to oral etretinate.

Etretinate

Heat-labile toxin from Bordetella parapertussis induces contraction of smooth muscle cells in culture.

The ability of Bordetella heat-labile toxin (HLT) to contract various types of cells in culture was examined. HLT from B. parapertussis induced contraction of cultured smooth muscle cells from trachea, intestine, uterus and vas deferens as well as from aorta. The time required for contraction decreased as the dose of B. parapertussis HLT increased from 3 to 100 MID/ml. Upon exposure of cells to concentrations of toxin greater than 100 MID/ml, at least 2 hr was required for contraction. HLT from B. parapertussis did not affect cultured cardiac or skeletal muscle cells within 8 hr after the exposure to HLT (100 MID/ml). No effect on other types of primary culture cells or established cells such as Chinese hamster ovary (CHO) cells has been described. These data indicate that the primary target cells for HLT might be smooth muscle cells.

Animals

Dose-dependent enzyme suppression in spleen induced by GM1 (monosialoganglioside 1) administration to mice.

Our previous studies suggested that the administration of exogenous gangliosides to the body modulates enzymatic networks in the brain. In the present study, we tested whether that is the case with another organ, spleen. By testing the dose response relationship, we found that there is a optimum dose for the effect of enzymatic modulation of GM1 (monosialoganglioside 1) administration. Although the optimum level varied depending on each of the examined hydrolytic enzymes, it usually fell in the range around 50 micrograms/kg body weight. The findings led us to conclude that the enzyme-modulating actions of gangliosides come not merely from the bizarre actions in vivo of high molecular exogenous substances.

Animals

[Study of yearly changes in intractable disease patients receiving financial aid for treatment].

Yearly changes of intractable disease patients receiving financial aid for treatment were observed for 24 intractable disease patients from 1983 to 1987. The results obtained were as follows. 1. The number of intractable disease patients receiving financial aid for treatment increased from 1983 to 1987 for 23 of the diseases. Only the number of SMON patients did not increase. 2. Medical care expenditures for these patients also increased since 1983. Greater increases for in-patients than for out-patients were seen for Huntington's chorea and Behcet's disease, while larger increases were seen for out-patients with Parkinson's disease, Scleroderma.dermatomyositis.primary multiple myositis, Buerger's disease, and others. 3. The proportion of national health insurance holders among intractable disease patients was 42.1% as compared with 34.7% among total national patients. The proportion was especially higher for Huntington's chorea (64.6%), Parkinson's disease (64.1%) and SMON (59.4%) patients.

Behcet Syndrome

[Characteristics of medical institutions visited by 30 intractable disease patients receiving financial aid for treatment].

In order to determine the characteristics of medical institutions which patients with 30 intractable diseases visited, we analyzed data of a nationwide survey conducted by the Epidemiology of Intractable Diseases Research Committee in 1989. Each of 47 prefectural governments in Japan reported information of all patients with 30 intractable diseases who received financial aid for the diseases between April 1988 and March 1989. Information collected about each patient consisted of identification numbers, which included the disease code, sex, age, the code of the municipality where the patient lived, the medical institution which treated the patient, etc. Out of 173,637 patients whose information was reported by prefectural governments, we used data of 159,910 patients whose medical institutions were reported completely. The results can be summarized as follow: 1) Of the 159,910 patients, 8.6 percent visited medical institutions outside of the prefectures where the patients lived. Many patients living in prefectures located close to large cities, such as Tokyo, visited medical institutions in large cities. 2) The proportion of patients who visited hospitals of medical schools was 27.9 percent. 3) Patients who were affected by diseases causing physical disabilities such as SMON and malignant rheumatoid arthritis tended to visit medical institutions located in their neighborhoods and were treated in small hospitals or clinics. Old patients had the same tendency as patients with such diseases. 4) Although the number of patients receiving aid in 1988, whose data we analyzed in the current study, was larger than that in 1984, the proportion of patients visiting medical institutions outside of the prefecture where the patients lived, and the proportion of patients visiting hospitals of medical schools were nearly equal to those in 1984.

Adolescent

[Reproductive and developmental toxicity study of prednisolone farnesylate (PNF)--study of subcutaneous administration of PNF during the perinatal and lactation periods in rats].

The effects of Prednisolone farnesylate (PNF), a newly synthesized corticosteroid, administrated during the perinatal and postnatal periods were studied in Sprague-Dawley rats. This compound was injected subcutaneously to female rats at dose levels of 0(control), 0.05, 0.5 and 5 mg/kg/day, once a day, for the period from day 17 of pregnancy to day 21 after parturition. Twenty-two to 25 dams in each dose group were allowed to litter naturally, and observations were made on the postnatal growth and development of their offspring. 1. In the dams treated at doses of 0.5 and 5 mg/kg, decreased body weight gains, atrophy of the thymus and retention of the substance at the injected site were noted. However, general signs, food consumption, parturition, lactation and nursing behaviors were not affected by the administration of PNF. 2. In the F1 newborns, the postnatal growth, development, responses, behaviors, learning ability and reproductive ability were not influenced. Additionally, no embryonic or fetal abnormalities of their fetuses (F2) were detected. From these results, the no-effect dose levels of PNF on the parental general states, the parental reproductive ability and those of the F1 offspring are thought to be 0.05 mg/kg/day, 5 mg/kg/day or more and 5 mg/kg/day or more, respectively, under the experimental conditions of this study. Moreover, the F2 fetuses are not affected by doses up to 5 mg/kg/day of PNF.

Animals

Post-splenectomy meningitis in patients with lymphoid malignancy.

This report describes pneumococcal meningitis in two splenectomized patients with lymphoid malignancy. Early diagnosis and emergency treatment of pneumococcal infection in splenectomized patients is proven to be of significant value. Prophylactic antibiotics targeted against pneumococcus should be considered for the clinical management of such conditions in splenectomized patients, particularly during cytotoxic chemotherapy.

Adult

Lobar intracerebral hemorrhage. A clinical, radiographic, and pathological study of 29 consecutive operated cases with negative angiography.

The authors operated consecutively on 50 patients with lobar intracerebral hemorrhage during a prospectively designed study period from January, 1986, to March, 1990. They investigated the correlations between the underlying causes and the clinicoradiographic features in 29 patients who showed no angiographic vascular abnormalities, in order to elucidate the operative indication for such cases. Patients with ruptured saccular aneurysm or trauma were not included in this study. There were 15 males and 14 females, ranging in age from 7 to 76 years (mean 52.4 years). Histological diagnoses of the surgical specimens were as follows: vascular malformation in nine cases (arteriovenous malformation (AVM) in six and cavernous malformation in three), microaneurysm in 11, cerebral amyloid angiopathy in six, and brain tumor in two; in the remaining case the cause was not verified histologically. The underlying cause was determined in 96.5% of cases. The mean patient age was lowest in the cavernous malformation group (27.0 years), followed by the AVM (45.8 years), microaneurysm (59.8 years), and cerebral amyloid angiopathy (70.0 years) groups. Four patients with vascular malformation (three AVM's and one cavernous malformation) had previous episodes of bleeding at the same site, whereas none of those with microaneurysms or cerebral amyloid angiopathy had such episodes. On computerized tomography (CT) scans, the round to oval hematoma was related to the presence of an AVM or cavernous malformation in contrast to microaneurysms and cerebral amyloid angiopathy. Upon infusion of contrast material, variable enhancement was seen in five (two AVM's and three cavernous malformations) of the nine vascular malformations while no enhancement was noted in any patient with microaneurysm or cerebral amyloid angiopathy at the acute stage. Subarachnoid extension of the hematoma was associated with cerebral amyloid angiopathy significantly more frequently than with AVM's (p less than 0.05) and microaneurysms (p less than 0.01). The results suggest that clinicoradiographic pictures in cases with negative angiography are quite different among the three major pathological categories; namely, vascular malformation (AVM and cavernous malformation), microaneurysm, and cerebral amyloid angiopathy. It is suggested that the underlying etiology of a given lobar intracerebral hemorrhage with negative angiography may be predicted by a combination of patient age, history of previous bleeding at the same site, hematoma shape, and subarachnoid extension of the hematoma on CT scans. Based upon these findings, the authors discuss operative indications for such cases.

Adolescent