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Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 919 records · Page 51Linked to original sources

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in the pediatric field].

Cefozopran (CZOP, SCE-2787), a newly developed parenteral cephem antibiotic, was administered to children with bacterial infections. We determined its antibacterial activity, pharmacokinetics, efficacy and safety in these patients. 1. Antibacterial activity MICs of cefmetazole, ceftazidime, cefuzonam, flomoxef and CZOP were determined against a total of 19 strains. For Gram-positive cocci, MICs of CZOP ranged from 0.39 to 0.78 microgram/ml against Staphylococcus aureus (3 strains), from 0.05 to 6.25 micrograms/ml against Streptococcus pneumoniae (5 strains), and 12.5 micrograms/ml against Enterococcus faecalis (1 strain). These MICs were generally similar to those of other cephems, but the MIC of CZOP against E. faecalis was lower than those of the other cephems examined. For Gram-negative bacilli, MICs of CZOP were 25 micrograms/ml against Citrobacter freundii (1 strain), and 6.25 micrograms/ml against Pseudomonas aeruginosa (1 strain). These values were similar to or lower than those of other cephems, MICs of CZOP against Haemophilus influenzae (7 strains) ranged from 0.1 to 0.39 microgram/ml. However, the MIC of CZOP against Serratia marcescens (1 strain) was higher than 100 micrograms/ml, and CZOP was as ineffective as the other cephems against this organism. 2. Pharmacokinetics CZOP was administered to children at 20 or 40 mg/kg via intravenous injection, and determinations were made for its serum concentrations, urinary concentrations and concentrations in cerebrospinal fluid (CSF) using the bioassay. Serum concentrations at 30 minutes after administration were 60.4 micrograms/ml with a dose of 20 mg/kg to one patient and 93.9 and 99.0 micrograms/ml with 40 mg/kg to two patients. The corresponding half-lives were 1.55 hours for 20 mg/kg administration, and 1.10 and 3.41 hours for 40 mg/kg, while the AUCs were 136.5 micrograms.hr/ml for 20 mg/kg, and 194.4 and 264.5 micrograms.hr/ml for 40 mg/kg. The rates of urinary recovery in the first 8 hours after administration were 45.0% in the patient receiving 20 mg/kg, and 84.6 and 97.6% in the two patients receiving 40 mg/kg. The concentrations in the CSF determined in 3 patients with purulent meningitis ranged from 2.6 to 16.0 micrograms/ml 1 hour after administration, and the CSF/serum concentration ratio ranged from 6.5 to 39.0%. These values for pharmacokinetic parameters obtained in the bioassay were similar to those obtained using HPLC. 3. Clinical evaluation Forty-eight patients were clinically evaluated. Of these patients, 75% were less than 3 years of age and there were slightly more male children than female children.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

[Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field].

Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children. The following results were obtained: 1. MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S. aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM. MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC). Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM. 2. Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment. Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response. Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg. Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay. 3. Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC. 4. Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis. In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml. Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

Medical consultation rate of allergic rhinitis and pollinosis surveillance in Aichi, Japan.

The medical consultation rate of allergic rhinitis (AR) was analysed using Japan National Health Insurance records of Aichi Prefecture for May 1989. Data collected from 88 cities, towns and villages were tabulated and divided into five-year age groups. The standardized medical consultation rate (SMCR) of AR in each municipality was then calculated. It was found that SMCR of AR did not correlate well with the pollen count for Japanese cedars, Japanese cypresses or gramineae, respectively, but a weak correlation with the mean yearly levels of nitrogen dioxide was suggested by the data. There was a significant positive correlation between SMCR of AR and the mean yearly levels of suspended particulate matter, the major element of which is diesel exhaust particulate.

Adolescent↗

[Pathological and molecular analyses of mammary tumors induced in HTLV-I pX transgenic rats].

The pX gene of human T-cell leukemia virus type I (HTLV-I) is known to be a potent transactivator of the viral gene and the host genes which are important for cell proliferation in vitro. It has been reported that various diseases occur in transgenic mice harboring either tax, pX, or env-pX gene, such as mesenchymal tumor, neurofibroma, thymic atrophy, muscle degeneration, exocrinopathy and arthropathy. We previously demonstrated that rat but not mouse CD4 positive T cells could be easily infected and immortalized by HTLV-I and infectious transmission of HTLV-I induced HAM/TSP-like myelopathy in WKAH rats after long incubation periods of 16 months. These observations prompted us to produce a series of transgenic rats that expressed the pX gene products under the control of mouse H-2Kd promotor in order to evaluate further the biological and pathological function of the pX gene in vivo. In various tissues of pX transgenic rats (pX rats), pX mRNA was constitutively expressed irrespective of age. PX rats developed mammary tumors with massive infiltration by neutrophils as early as 9 months of age. Pathological and immunohistochemical examination revealed that the tumors were undifferentiated carcinomas of the mammary gland origin. They were transplantable into pX rats, but not into normal syngenic rats. High levels of mRNA expression of not only the pX transgene but also the host genes such as Gro (melanoma growth-stimulatory activity/KC), MIP-2 (macrophage inflammatory protein-2) and IL-1 alpha were demonstrated in the tumor tissues. Gro and MIP-2 which were known as IL-8 families were likely to be produced by tumor cells and appeared to be responsible for neutrophil infiltration in the tumor tissues. Lastly, pX rats described here appear to be suitable animal models for elucidating mechanisms involved in the tumorigenesis and the transactivation of the cellular genes by HTLV-I, especially by the pX gene products in vivo.

Animals↗

Stereotactic pallidotomy results for Parkinson's exceed those of fetal graft.

Fetal graft research and renewed interest in Leksell's postero-ventral pallidotomy (PVP) stimulated reconsideration of surgical therapy for Parkinson's disease (PD), particularly with regard to improving akinetic symptoms previously thought resistant to surgical lesions. Review of our series and other published results of PVP and fetal graft show that PVP has beneficial effects on both akinetic and hyperkinetic symptoms that better the results reported for fetal graft implantation and other conventional stereotactics. Presented are the results of 60 consecutive patients, 55 of whom underwent PVP, and 5 who underwent fetal graft implantation. Using the Unified Parkinson's Disease Rating Scale (UPDRS), we found that PVP gave significant (P < 0.05) reductions in akinetic symptomatology including freezing, arising from a chair, posture, gait, postural instability, and bradykinesia. Fetal graft patients had significant reductions in two akinetic symptoms: bradykinesia and postural instability. PVP's dramatic therapeutic effects on akinesia may be explained by interruption of amplified collateral inhibitory output from the pallidum to brain stem locomotor centers such as the pedunculopontine nucleus, whereas interruption of collaterals to ventral lateral thalamus by PVP may account for the elimination of hyperkinesia. The excellent results of PVP represent a significant advance in the surgical treatment of PD.

Activities of Daily Living↗

Distribution of WGA-binding sites on the surface of clinical isolates of Staphylococcus aureus.

Distribution of wheat germ agglutinin (WGA)-binding sites on the surface of clinical isolates of Staphylococcus aureus was examined by WGA-gold. Labelings on three methicillin-sensitive S. aureus (MSSA) isolates were heavier than those on three methicillin-resistant (MRSA) isolates and the 209P (MSSA) strain. These results were confirmed by an alkaline phosphatase-WGA assay. The WGA-binding on the MRSA was consistently poor, whereas wide ranging diversity was observed in WGA-binding among the MSSA. These results strongly suggest diversities in not only distribution, but also the quantity of WGA-binding carbohydrates exposed on the surface of the organisms.

Methicillin Resistance↗

[Effects of mianserin hydrochloride on delirium: comparison with the effects of oxypertine and haloperidol].

Mianserin (10-60 mg), haloperidol (2-6 mg) and oxypertine (20-60 mg) were administered once before bedtime in patients with delirium in Kurume University Hospital. The therapeutic effects of these drugs were investigated in the pre- and post-treatment using Delirium Rating Scale (DRS: Trzepacz et al., 1988). Mianserin was observed to be effective on 67% of the cases, and haloperidol and oxypertine in about 60%. Based on the clinical results and on the measurement of plasma concentration of mianserin, mianserin was considered to be an effective drug particularly against delirium in elderly patients because the effect and plasma concentration of mianserin were observed in the early stage of treatment without any side effects. The reduction of plasma free-MHPG was accompanied with improvement in the delirious state. The reason for the changes in plasma free-HVA was unclear.

Adult↗

[Clinical significance of serum and urinary neopterins after transcatheter arterial embolization for hepatocellular carcinoma].

To elucidate the immunological effects of transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC), serum and urinary neopterins were measured using the radioimmunoassay in patients with HCC before and after TAE (n = 11), and compared with one shot arterial injection (AI)(n = 8). At the third day after TAE, serum and urinary neopterin levels were maximally elevated up to 164% and 158% from their respective baselines (p < 0.01). By contrast, these levels were unaffected after AI. In considering the changes of natural killer cell activity, C-reactive protein, transaminase and alpha-fetoprotein, these results suggest that the determination of neopterin levels after TAE may be not only valuable to assess the necrotic effect of TAE, but also be useful for evaluating cellular immunity after TAE.

Adult↗

Intracytoplasmic granulofilamentous inclusion bodies in a meningioma. Immunohistochemical and ultrastructural studies.

A case of cerebellar tentorial meningioma, with abundant, large, eosinophilic intracytoplasmic inclusions, was studied immunohistochemically and ultrastructurally. These intracellular inclusions were periodic acid-Schiff negative and ultrastructurally appeared as a condensation or aggregation of numerous intracytoplasmic intermediate filaments. These inclusions were not related to microvillus-lined ductules, indicating that these inclusions were distinct from pseudopsammoma bodies. In addition, these inclusions were intensely immunopositive for vimentin, whereas staining for glial fibrillary acidic protein, epithelial membrane antigen, cytokeratin, neurofilament, desmin, actin, or type IV collagen was negative. To our knowledge, this is the second reported case of meningioma with such unusual inclusions, but the first one to demonstrate that the intracytoplasmic intermediate filaments and their related inclusions were mainly composed of vimentin.

Cytoplasm↗

Angiotensin II receptor subtypes in bovine and human ventricular myocardium.

Angiotensin II (AII) binding sites in bovine and human ventricular myocardium were characterized by a radioreceptor assay. The specific binding of [125I]AII to myocardial membranes appeared to be saturable, and it was of high affinity with apparent dissociation constants of 1.60 nM (bovine) and 1.09 nM (human). The Bmax values were 39.7 fmol/mg protein (bovine) and 6.07 fmol/mg protein (human). Both losartan (angiotensin type 1 receptor subtype selective antagonist) and PD123177 (the angiotensin type 2 receptor subtype selective antagonist) inhibited specific [125I]AII binding to bovine myocardium, and their Hill coefficients were less than unity. Nonlinear least-squares regression analysis has suggested the existence of two populations of [125I]AII binding sites that have high and low affinity for losartan or PD123177. The relative proportions of high- and low-affinity sites for losartan in bovine myocardium were 68% and 32%, and those for PD123177 were 33% and 67%, respectively. On the other hand, specific [125I]AII binding in human myocardium was inhibited by losartan with much lower affinity and also by PD123177 with higher affinity, compared with bovine myocardium. The Hill coefficients for both drugs were close to one. Dithiothreitol enhanced specific [125I]AII binding to bovine myocardium in the presence of losartan, but it reduced [125I]AII binding in the presence of PD123177. This agent markedly enhanced specific [125I]AII binding to human myocardium. Thus, it is possible that bovine myocardium has both angiotensin type 1 receptor and the angiotensin type 2 receptor subtypes of AII receptors whereas human myocardium has predominantly the angiotensin type 2 receptor subtype.

Aged↗

Synthesis and bioactivity of monobiotinylated DALDA: a mu-specific opioid peptide designed for targeted brain delivery.

Delivery through the blood-brain barrier of opioid peptide-based therapeutic agents may be achieved with the use of conjugation of avidin and blood-brain barrier transport vectors. However, this drug delivery strategy requires that 1) the peptide is monobiotinylated and 2) the peptide is biologically active after cleavage of a disulfide linker and peptide release from the avidin-vector conjugate. Whether these criteria may be successfully fulfilled was examined in the present studies. The highly mu receptor-specific dermorphin analog, Tyr-D-Arg-Phe-Lys-NH2 (DALDA), was selectively monobiotinylated at the epsilon-NH2 group of Lys4 with the cleavable biotin linker, sulfosuccinimidyl-2-(biotinamidoethyl) 1,3'-dithioproprionate to obtain biotinylated DALDA (bio-DALDA). The N-terminal alpha-NH2 group of the peptide was protected during biotinylation with the N-9-fluorenylmethoxycarbonyl group. Cleavage of the disulfide bridge yielded the desbiotinylated derivative, desbio-DALDA. The identity of these peptides was verified by secondary ion mass spectrometry. In receptor binding assays with 3H-Tyr-D-Ala-Gly-Phe-(N-Me)-Gly-ol, the Kis of DALDA, bio-DALDA and desbio-DALDA for mu opioid receptors were determined to be 2.3 +/- 0.4, 6.5 +/- 1.1 and 4.0 +/- 0.9 nM, respectively. Binding of bio-DALDA to avidin resulted in a Ki of 14.5 +/- 2.4 nM. The i.c.v. administration of DALDA and desbio-DALDA induced potent and long-lasting analgesia in the rat tail-flick assay. It was found that 1 microgram of DALDA was equipotent to 3 micrograms of desbio-DALDA and 20 micrograms of morphine. The analgesic effect could be blocked by naloxone pretreatment. In conclusion, these studies 1) described methods for the preparation of a biologically active monobiotinylated mu opioid receptor-specific ligand and 2) demonstrated the advantages of using cleavable biotinylation of opioid peptides because the affinity of desbio-DALDA for the receptor approximated the affinity of DALDA and had a 3- to 4-fold higher affinity than did the bio-DALDA-avidin complex.

Amino Acid Sequence↗

[Toxic cirrhosis].

Carbon tetrachloride induces diffuse fatty degeneration and centrilobular necrosis in the liver and the severity of liver injury is roughly proportional to the dosage administered. Nonetheless, the incidence of cirrhosis by this agent is rare. Several drugs, including methyldopa, methotrexate, isoniazid and vitamin A, have occasionally been reported to cause chronic active hepatitis, fibrosis and cirrhosis. There is no question that continued administration of the drug in the presence of clinically apparent hepatitis can lead to chronic active hepatitis, fibrosis and cirrhosis. Early recognition that a therapeutic drug is the probable cause of liver injury, followed by prompt withdrawal of such a drug, generally suffices in the management of drug-induced chronic liver disease.

Carbon Tetrachloride Poisoning↗

[Intractable bacterial infections in the nervous system].

It is not exaggeration to say that infectious meningitis is most often seen among infections of the nervous system caused by various microorganisms, in which viruses are main causative pathogens. Infectious meningitis due to bacteria includes purulent one with acute progress, tuberculous and fungal ones which are representative for subacute meningitis. They can not be easily treated. As brain abscess is similar to them, diagnosis and chemotherapy on these four diseases are briefly summarized here. It is needless to say that the prognosis is influenced by early diagnosis and how fast appropriate chemotherapy is started in all four diseases. Dexamethasone therapy should be tried in purulent meningitis in order to decrease hearing disturbance which is unable to be prevented by chemotherapy.

Anti-Bacterial Agents↗