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Biomedical subjects

Y Fujisawa

Publications and source records attributed to Y Fujisawa.

At least 145 records · Page 8Linked to original sources

[A 17-year experience with ileal conduit urinary diversion--early and late complications].

A series of 185 patients, 133 males and 52 females, were treated by ileal conduit urinary diversion in the past 17 years. The patients ranged in age from 7 months to 81 years with an average of 59 years. Diversions were performed for malignant diseases in 174 patients, 85% of whom underwent a simultaneous radical surgery. The follow-up covered the postoperative period from 4 months to 16 years 8 months with an average of 4 years 8 months. Six patients (3%) died within 1 month of operation, and 43 of a total of 58 mortal cases died of cancer thereafter. The survival rates of 143 patients with bladder cancer were 84% for 1 year, 72% for 3 years, 67% for 5 years, 62% for 10 years and 54% for 15 years. Early complications were noticed in 38% of the patients. Delayed wound healing due to local infection (20%) and intestinal obstruction (10%) were the two major complications in this period. Late complications were encountered in 51% of the patients. Mild peristomal dermatitis (22%) and gradually developing renal complications (22%) are two major problems in the standard ileal conduit urinary diversion. The latter was significantly more frequent in patients who underwent the operation between 1973 and 1981 than in those who had the surgery between 1982 and 1989. Postoperative hydronephrosis was observed in 15 (13%) of 117 patients who showed normal urograms preoperatively. Ileoureteral reflux was observed in 50% of the cases with nonobstructing conduits, while it increased up to 70% along with obstruction of the conduit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Motor neuron disease with Parkinson's disease--case report].

The patient was a 64-year-old woman who showed muscle weakness and tremor of upper extremities and gait disturbance at the age of 62 years. The symptoms progressed and she was admitted to our hospital. Neurological examination revealed muscle weakness, muscle atrophy and fasciculation bilaterally in the upper extremities. The deep tendon reflexes were reduced in the upper extremities and increased in the lower extremities, but Babinski's sign was not present. There was mild hand tremor at rest (right greater than left). Muscle rigidity was also evident. Her gait was small-stepped and her trunk was bent forward. She showed hypomimia, but no dementia was detected. She died of respiratory failure 7 months after admission. The duration of the illness was about 2 years. At autopsy, macroscopic examination showed depigmentation of the substantia nigra and locus ceruleus, and atrophy of the anterior roots of the spinal cord. Microscopic examination revealed a few senile plaques in the temporal cortex. In the substantia nigra, the number of melanin-containing cells was decreased in its central parts. A few Lewy bodies were found in some of the remaining neurons, and melanin pigment migrated into the parenchyma. In the locus ceruleus and dorsal motor nucleus of vagus, abundant Lewy bodies and mild astrocytosis were seen. A few Lewy bodies were also seen in the nucleus raphe, nucleus basalis of Meynert and hypothalamic nuclei. Severe neuronal loss of the anterior horn cells was observed in the cervical segment, and to a lesser degree, in the lumbo-sacral segments. segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

[Subacute subdural hematoma--report of 4 cases and a review of the literature].

Subdural hematoma is divided roughly into two types acute and chronic. The two show an entirely different mode of illness. The authors have encountered 4 cases of subacute subdural hematoma in which characteristics of both types coexisted. These cases are characterized by the following. 1) The disease develops in the elderly persons with a history of trauma unknown or after minor head injury. 2) There is a relatively long period of clear consciousness and they visit a hospital when they are in the subacute stage, 3) They have a history of drinking alcohol heavily as a habit and there is a high risk of hypertension and diabetes. 4) Brain CT findings sometimes reveals mixed density hematoma. 5) Hemorrhage from the cortical artery is occasionally noted as the operative findings. Hematoma membrane is absent. 6) The outcome is generally poor because of systemic complications. As described above subacute subdural hematoma was similar to chronic subdural hematoma in the clinical course and CT findings. But operative findings of this disease indicated acute subdural hematoma. Repeated minor hemorrhage, related to coagulation disorder and brain atrophy would be important as the mechanism of subacute subdural hematoma. The effectiveness of perforation craniotomy as radical operation was low and removal of hematoma by major craniotomy was needed. The concept of subacute subdural hematoma is considered important in deciding on a therapeutic policy.

Acute Disease↗

Efficient expression of genetically engineered hepatitis B virus surface antigen P31 proteins in yeast.

We have constructed plasmids that express modified hepatitis B virus surface antigen (HBsAg) P31-coding genes (M-P31c, d, e, f, and i) having various genetically engineered pre-S2 regions. The plasmids contain the GAPDH (gene coding for glyceraldehyde-3-phosphate dehydrogenase) promoter and the PGK (gene coding for 3-phosphoglycerate kinase) terminator, both isolated from sake brewing yeast, Saccharomyces cerevisiae Kyokai III. Expression levels of the modified HBsAg P31 proteins in yeast are greatly increased from 0.4% to 11.7% of total cell protein. However, the specific mRNAs are expressed at equal levels and the degradation rates of the modified P31 proteins do not vary significantly. Therefore, we considered that different expression levels of the modified P31 proteins are attributed to the changes of the post-translational efficiency. And it was suggested that the conformational stability of the N-terminal peptide (Met-1-Phe-46) in the endoplasmic reticulum membrane determines the expression level of modified P31 proteins.

Amino Acid Sequence↗

Immunogenicity of a new type of yeast-derived hepatitis B vaccine consisting of M (pre-S2 + S) protein particles.

Genetically modified M (pre-S2+S; P31) protein (M-P31c) particles were formulated into a vaccine (TGP-943) through adsorption on to an alum adjuvant. The immunogenicity of this vaccine was investigated using guinea-pigs and various kinds of mice. In terms of anti-HBs(S) response, TGP-943 was found to be as immunogenic as the control plasma-derived vaccine (PDV) and yeast-derived S vaccine (YDSV) in Balb/c mice. TGP-943 induced anti-S antibodies even in S low-responder mice. In addition to the anti-S antibodies, TGP-943 was shown to elicit anti-pre-S2 antibodies dose-dependently, and the anti-pre-S2 antibodies were maintained at a high level after immunization with a high dose of TGP-943. The antibody response to pre-S2 had a tendency to appear earlier than that to S. M-P31c particles induced in vitro proliferation of TGP-943-primed lymph node cells, indicating that TGP-943 is more immunogenic than conventional vaccines in terms of T-cell levels. These results suggest that TGP-943 would be a promising candidate for a third generation hepatitis B vaccine.

Animals↗

Procoagulant activity of human neuroblastoma cell lines, in relation to cell growth, differentiation and cytogenetic abnormalities.

Procoagulant activity (PCA) was investigated in relation to cell growth, differentiation, and cytogenetics in seven human neuroblastoma cell lines. Before 5-bromodeoxyuridine (BrdUrd) treatment, PCA was notably heterogeneous, with the highest activity in NCG (S-type in morphology) 40- to 100-fold greater than the lowest activity in SK-N-DZ (N-type). PCA was not related to 1p abnormalities. After BrdUrd treatment at 5 micrograms/ml for 6 days, PCA increased 6.8-fold in GOTO and 2.7-fold in SK-N-DZ with associated growth inhibition and morphological changes (I-type morphology converted to S-type in GOTO and N-type converted to an advanced N-type in SK-N-DZ). In contrast, only growth suppression was observed in 2 other cell lines, and no changes in PCA, growth or morphology were induced in the remaining 3 cell lines.

Blood Coagulation Factors↗

Biological activities of ganglion extracts from a prosobranch mollusc, Fusinus ferrugineus.

Acetone extract of the ganglia of Fusinus ferrugineus was applied to C-18 cartridges, and the flowthrough and retained materials were bioassayed on the radula retractor muscle of the animal. The flowthrough was found to have a potent contractile action and the retained material a potent contraction-inhibiting action in addition to a weak contractile action. The retained material was then applied to a column (2.6 x 40 cm) of Sephadex G-15. Fractions of 4 ml each were collected, and their activities were assayed on twitch contractions of the radula retractor. Three peaks (E1, E2 and E3) of contraction-potentiating activity and one peak (I) of contraction-inhibiting activity were obtained. The maximum activities of peaks E1, E2 and E3 were found at fractions 22, 44 and 50, respectively. The maximum activity of peak I was found at fractions 28-30. All of the activities of these peaks were destroyed by incubating the fractions with the peptidase subtilisin, suggesting that the active substances in the peaks are peptides. Using some kinds of molluscan muscles, the actions of the substances were examined in greater detail. The results suggest that peak E1 may contain a novel excitatory peptide whose molecular weight is more than 1,000, and that peaks E2 and E3 may contain FMRFamide-related peptides. It is also suggested that peak I may contain two or more myomodulin-CARP-related inhibitory peptides.

Animals↗

Calcitonin gene-related peptide(CGRP) stimulates the release of atrial natriuretic peptide(ANP) from isolated rat atria.

The effect of calcitonin gene-related peptide(CGRP) on the release of atrial natriuretic peptide(ANP) was studied in spontaneously beating, isolated rat atria. CGRP stimulated the ANP release in a dose-dependent manner. When the atria were incubated with a combination of phentolamine, propranolol, and atropine, these antagonists blocked neither the rise in ANP release nor the positive chronotropic and inotropic effects of CGRP. Therefore, we conclude that CGRP stimulates ANP release as well as cardiac contractility independently of adrenergic and cholinergic receptors.

Animals↗

A supersensitive dot-hybridization method: rapid and quantitative detection of host-derived DNA in recombinant products at the one picogram level.

We have developed a highly sensitive method of DNA dot-blotting hybridization to detect host-derived DNA (nuclear DNA and plasmid DNA) in a recombinant product. This method has two distinctive features compared to the conventional hybridization method: firstly, a highly specific radioactive probe is prepared by using ultrasonicated DNA, instead of untreated DNA, as a template for the oligo-labeling reaction; secondly, the signal to noise ratio is increased by the use of lambda phage DNA as non-homologous DNA. This method enabled us to detect host-derived DNA at the one picogram level without using a radioisotope of high specific activity and long exposure times.

Cell Nucleus↗

Molecular structure of the chicken vitamin D-induced calbindin-D28K gene reveals eleven exons, six Ca2+-binding domains, and numerous promoter regulatory elements.

The seco-steroid hormone 1,25-dihydroxyvitamin D3 is known to induce the expression of a calcium binding protein termed calbindin-D28K in a variety of target tissues. In order to comprehend the mechanism of induction we have cloned and sequenced the chicken calbindin-D28K gene. The gene spans some 18.5 kilobases (kb) of chromosomal DNA from the putative Cap site to the polyadenylation site of the 2.8 kb mRNA. It is split into 11 coding exons by 10 intervening sequences. The promoter region of this gene is markedly G + C-rich (60-80%) extending from -225 to +400. Within this region we find 70 CpG dinucleotides, four G-C boxes, and numerous known promoter regulatory signals. These putative regulatory signals include a TATA box (ATAAATA) at -30 and a CAT box (CCAAT) at -326. Ten additional variant CAT boxes are found in the upstream promoter region (-218 to -770) of this gene. Furthermore we have identified a glucocorticoid-like responsive element at -410 (TCTACACACTGTTCC) and this element overlaps a metal responsive element (TGCACTC) and a variant CAT box (CCAAAT) and juxtaposes an enhancer-like core element (AAATGGT) on its 3'-side. In addition, the calbindin-D28K promoter is composed of a variety of simple repeated sequences, some of which are components of putative regulatory signals. All splice junctions were found to conform to the GT-AG rule. A consensus sequence of the 5'-splice junction reads AG/GTAAG-TTATA. A consensus sequence of the 3'-splice site consists of two elements: a pyrimidine track (mainly T) followed by ACAG/G-T. A two-dimensional model of calbindin-D28K was constructed which projects the existence of 6 alpha-helix-loop-alpha-helix regions characteristic of calcium binding domains. The 3'-end of the gene consists of a single large (2039 base pair) uninterrupted exon, an organizational feature common to other members of the calcium binding protein gene family which include calmodulin, parvalbumin, Spec I, myosin light chains, etc. Another feature common to the gene family is the presence of the repeated sequence ATTT or TTTA located in the 3'-untranslated exons. These simple repeat sequences could be involved in regulating mRNA degradation by serving as a ribonuclease recognition signal.

Amino Acid Sequence↗

Effects of a synthetic atrial natriuretic polypeptide on intrarenal hemodynamics in dogs.

The effects of a synthetic human atrial natriuretic polypeptide (alpha-hANP) on the intrarenal distribution of blood flow were examined in anesthetized dogs. Intrarenal infusion of alpha-hANP at a rate of 0.05 microgram/kg per min resulted in a significant increase in renal blood flow, urine flow and urinary excretion of sodium with no change in renal perfusion pressure. Measurement of the intrarenal blood flow by the microsphere method indicated a greater increase in flow rate in the juxtamedullary than in the superficial area. A significant correlation was observed during alpha-hANP infusion between changes in both urine flow and sodium excretion and inner cortical blood flow; changes in inner cortical blood flow may reflect changes in medullary blood flow. However, a smaller dose of alpha-hANP (0.01 microgram/kg per min) increased urine flow and electrolyte excretion but had no effect on the distribution of renal blood flow. Thus, neither the increased inner cortical blood flow nor the redistribution of blood flow is the sole cause of the natriuresis during infusion of alpha-hANP. Changes in intrarenal hemodynamics could contribute to the natriuresis induced by alpha-hANP, via washout of medullary solutes.

Animals↗

Salidiuretic action of the calcium antagonist nitrendipine in dogs.

In an attempt to define the effects of a calcium antagonist, nitrendipine, on renal function, intrarenal hemodynamics, and renin release, we infused the drug into the renal artery of anesthetized dogs. Infusion of nitrendipine at a rate of 5 micrograms/min in both hydropenic and hydrated dogs resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow and renin release, with no change in systemic blood pressure, indicating a significant renal vasodilation. The urinary excretion rate of sodium increased by the same proportion as that of calcium. The intrarenal blood flow as measured by hydrogen washout rate showed that the outer cortical flow increased by the same proportion as the inner cortical flow. During nitrendipine infusion, free water reabsorption rate (TcH2O) in hydropenic dogs or free water clearance (CH2O) in hydrated dogs increased in proportion to the urine flow. Neither the ratio of TcH2O nor that of CH2O to osmolar clearance changed throughout the experiment. These data suggest that nitrendipine may not inhibit sodium transport in the medullary portion of the ascending limb of Henle and may induce an enhancement of the delivery of sodium to the Henle loop. Thus, nitrendipine exerts its diuretic and natriuretic actions via the alteration of renal hemodynamic and the inhibitory effect on proximal sodium reabsorption.

Animals↗

A case of acute diffuse lymphocytic meningoencephalitis.

"Acute diffuse lymphocytic meningoencephalitis" is characterized neuropathologically by swelling of the brain and an unproportionally slight degree of inflammatory findings. Although many cases of this encephalitis have been reported in Japan, it was scarcely reported in other countries. The present case is a girl who had been well until fifteen years of age. She became psychotic on the 7th day after she seemed to have caught a cold. She fell into coma on the 15th day, then neurologic symptoms, such as nuchal rigidity and athetoid movement became prominent. She developed the status epilepticus with a high temperature of 41 degrees C, and died on the 23rd day. Although there was an increase of mononuclear cells in the cerebrospinal fluid (32/microliters), various antiviral titers were normal both in serum and cerebrospinal fluid. Neuropathologic changes were edema, perivascular lymphocytic infiltration in leptomeninges and parenchyma, and proliferation of rod-shaped microglia particularly prominent in the cerebral cortex and hippocampus. It is peculiar that thickening of leptomeninges formed by collagen fibers and inflammatory cells was observed. On the systemic study, centrolobular fatty change of the liver was found. This case had to be differentiated from several other neuro-psychiatric illnesses. The problems were discussed clinically and neuropathologically.

Acute Disease↗

Synthesis in yeast of hepatitis B virus surface antigen modified P31 particles by gene modification.

The pre-S2 portion of hepatitis B virus surface antigen P31 gene was modified to make gene products resistant to trypsin-like proteases in Saccharomyces cerevisiae. The coding sequence for 6 amino acids (Ser44 - Thr49) including Arg48 was removed, and the altered gene was inserted into an expression vector. The modified HBsAg P31 (M-P31c) gene products, consisting of GP37 and GP34, formed particles having both HBsAg antigenicity and polymerized-albumin receptor activity. Since the M-P31c particles can elicite two kinds of protective antibodies against hepatitis B virus, anti-S and anti-pre-S2 antibodies, the M-P31c particles are expected to be potentially effective to S-nonresponders.

Animals↗