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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 649 records · Page 36Linked to original sources
PubMed1994

Synthesis of 2''-amino-2''-deoxyarbekacin and its analogs having potent activity against methicillin-resistant Staphylococcus aureus.

Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2''-hydroxyl group by an amino group in arbekacin was designed to synthesize derivatives that would be active against MRSA. 2''-Amino-2''-deoxyarbekacin and five analogs were synthesized starting from dibekacin. Among them, 2''-amino-2''-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin.

Carbohydrate Sequence↗
PubMed1994

Characterization of epidermal cytokine profiles in sensitization and elicitation phases of allergic contact dermatitis as well as irritant contact dermatitis in mouse skin.

Epidermal cytokines are known to participate in the initiation of immune and inflammatory processes in the skin. In the present study, we examined epidermal cytokine mRNA levels to elucidate the initial molecular events in the sensitization and elicitation phases of allergic contact dermatitis (ACD) as well as in irritant contact dermatitis (ICD). BALB/c mice were sensitized on the dorsal skin with 0.5% dinitrofluorobenzene (DNFB) and challenged with 0.2% DNFB on the ears 6 days later to elicit allergic contact hypersensitivity (ACDe), the elicitation phase. To examine cytokine profiles during the sensitization phase from the same anatomic area, other animals were sensitized on ear instead of dorsal skin. The sensitization phase of ACD (ACDs) was induced by painting the ears of naive mice with 0.5% DNFB. Sodium lauryl sulfate (SLS), utilized as an irritant control, was also applied to the ears of another group of mice to induce ICD. Total RNA was extracted from the epidermis of the treated ears at various time points after each treatment, reverse transcribed to cDNA, and amplified by PCR using radiolabeled cytokine-specific primers. Amplified products were sized by electrophoresis and autoradiography and semiquantitated by densitometry. Autoradiographs were normalized relative to beta-actin signals. ACDs and ACDe showed similar patterns of cytokine mRNA levels; that is, at 6 h after hapten application, interleukin (IL)-1 beta, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA levels were upregulated, and this upregulation was observed until 24 h after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. First communication: plasma concentration, distribution, metabolism and excretion of the new monoclonal antibody, regavirumab after intravenous administration in rats and rabbits.

TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The pharmacokinetics of MCA C23 was investigated in rats and rabbits. Plasma concentrations of radioactivity were shown to increase dose-dependently after 2, 10 or 50 mg/kg of 125I-labeled TI-23 was administered intravenously to rats. Their elimination of half-lives from plasma were 11-13 days. The radioactivity in plasma corresponded with the idiotype activity (antigenicity against idiotype antibody) of the monoclonal antibody. No significant difference was detected in plasma concentration and half-lives between male and female rats. Quantitative and qualitative distribution studies demonstrated that high radioactivity was distributed predominantly to the blood and blood-rich organs. The idiotype activity which remained in those tissues was attributable to the blood in the tissues. The radioactivity was mainly excreted in the urine as free iodine, and about 40% of the dose remained in the body. After the rabbits received 2 mg/kg of 125I-TI-23, the initial radioactivity in plasma was higher than in rats, and a larger distribution volume and shorter elimination half-lives of radioactivity in plasma were observed.

Animals↗
PubMed1994

Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. Second communication: distribution and elimination of the new monoclonal antibody, regavirumab after repeated administration in rats, and placental transfer and milk-passage study after single administration to pregnant and lactating rats.

TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The tissue distribution or pharmacokinetics of MCA C23 was investigated after repeated administration in male rats and single administration in pregnant and lactating rats. Radioactivity and MCA C23 idiotype activity (antigenicity against idiotype antibody) in plasma increased with weekly injections during repeated administration of 125I-labeled TI-23 (2 mg/kg/week). After the fourth injection, the plasma radioactivity concentration reached a steady state and the elimination half-life was determined to be 11.2 days. No significant difference was observed between the radioactivity and the idiotype activity in plasma, indicating that MCA C23 was stable in vivo. The plasma concentration curve after repeated administration corresponded with that simulated by the pharmacokinetic parameters obtained previously and the minimum steady state concentration (Css-min) at 168 h after repeated administration was about 33 micrograms eq. of MCA C23/ml. Trans-placental tissue distribution of radioactivity was investigated after single administration of 125I-TI-23 to 19-day pregnant rats. About 12% of the dose was transferred to the fetus and the idiotype activity remained in fetal tissues at 24 h after injection. In lactating rats, some radioactivity was secreted into the milk and the ratio of milk to plasma radioactivity reached 0.28 after a single administration of 125I-TI-23. Some MCA C23 idiotype activity was observed in the milk.

Animals↗
PubMed1994

Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. Third communication: correspondence of the idiotype activity and virus neutralization activity of the new monoclonal antibody, regavirumab in rat serum and its pharmacokinetics in rats and monkeys.

TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The pharmacokinetics of MCA C23 was studied in rats and monkeys, and virus neutralization activity was investigated after intravenous administration of TI-23 in rats. MCA C23 idiotype activity (antigenicity against idiotype antibody) was not affected by heat treatment. The rat serum obtained after injection of TI-23 showed a potent inhibition activity of plaque formation. A good correlation (r = 0.873) was observed between idiotype activity and the inhibition activity of plaque formation in the diluted serum samples. After single or repeated injection of TI-23 to cynomolgus monkeys, the MCA C23 concentration in plasma was determined by an immunological method. 1 h after single injection, 60.8 +/- 5.1 micrograms/ml of MCA C23 was detected in plasma, then the plasma level decreased with an elimination half-life of 20.5 +/- 6.2 days and the AUC value was 18.3 +/- 3.4 mg.h/ml. In the repeated administration experiment (2 mg/kg/week, 5 times), the MCA C23 plasma concentration reached a steady state (74.4 +/- 11.8 micrograms/ml) at 24 h after the fourth injection. The elimination half-life after the final injection was similar to that after the single injection.

Animals↗
PubMed1994

Allogeneic skin grafting for extensive skin chronic graft-versus-host disease.

A 35-year-old female with chronic myelogenous leukemia in chronic phase underwent allogeneic bone marrow transplantation from her genotypically-matched brother in 1990. The extensive chronic graft-versus-host skin disease supervened with skin ulcers on both lower legs in 1992. Conservative therapy was unsuccessful for these lesions. Therefore, not only autologous skin grafting but also allogeneic skin grafting from the marrow donor was successfully performed. She has been maintaining her daily activities (Karnofsky performance status 90%) with little limitation for 17 months after the final skin grafting.

Adult↗
PubMed1994

Hemolytic uremic syndrome without hemolytic anemia: a case report.

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Most cases of HUS are caused by E. coli O157:H7 verotoxin. In the case reported here, diarrhea continued for twenty days after an E. coli 0157:H7 infection and was followed by acute renal failure and thrombocytopenia. Examination of percutaneous renal biopsy tissue showed typical HUS findings, e.g., mesangiolysis in glomeruli and thickening of capillary walls with prominent double outlines, but there was no indication of hemolytic anemia. LDH and haptoglobin, indications of hemolytic anemia, were in the normal range throughout the patient's clinical course. The patient's red blood cells had P1 antigen, which reportedly provides protection by adsorption of toxin into the red blood cells thereby preventing or limiting toxic damage to other organs. Therefore, we assumed that because of the expression of P1 antigen in this patient, the kidneys were not severely damaged and microangiopathic hemolytic anemia was thereby avoided.

Acute Kidney Injury↗
PubMed1994

[Cerebral blood flow and oxygen metabolism in patients with pure akinesia and progressive supranuclear palsy].

We studied cerebral blood flow and oxygen metabolism in 6 patients with pure akinesia (PA), 8 patients with progressive supranuclear palsy (PSP), 16 patients with Parkinson's disease (PD), and 10 normal control subjects using positron emission tomography (PET). Regions of interest were studied in the cerebral cortex (the frontal, temporal, parietal, and occipital lobe), thalamus, cerebellar hemispheres, cerebellar vermis, and brainstem. In patients with PA, regional cerebral blood flow (CBF) was significantly decreased in the frontal cortex, thalamus, and brainstem compared with normal control subjects. PSP patients showed significantly decreased CBF in the entire cerebral cortex, thalamus, cerebellar hemispheres, and brainstem and regional cerebral oxygen metabolic rate (CMRO2) in the frontal cortex, thalamus, and brainstem, whereas patients with PD were revealed to be normal in both CBF and CMRO2 values. In conclusion, a part of patients with PA may be in the early stage of PSP or may be atypical presentations of PSP whose symptom is only akinesia judging from the followings. 1) PET findings demonstrated a close similarity between PA and PSP; a pattern of CBF and CMRO2 decrement especially in the frontal cortex, thalamus and brainstem. 2) Patients with PA were shown to have similar pathological changes to PSP in recent studies. 3) Several authors reported that some PSP cases could show only akinesia initially, later developing dementia, supranuclear ophthalmoplegia, pseundobulbar palsy, and nuchal rigidity during their illnesses.

Aged↗
PubMed1994

[A case report of light and heavy chain deposition disease (IgG2 lambda)].

A 73-year-old male was admitted to the renal division of our hospital because of hypertension, proteinuria and bilateral pretibial edema. Eight years previously, he was diagnosed as being afflicted with interstitial pneumonia on the basis of a chest X-ray examination. Laboratory tests conducted during the current admission showed normocytic normochromic anemia, renal dysfunction and mild proteinuria. Total IgG was normal, but a high proportion of IgG2 was observed. M-protein in the serum was positive for both IgG lambda and Bence Jones protein (lambda type). A bone marrow biopsy showed the proportion of plasma cells to be 10.6%, but atypical cells were not found. We diagnosed the patient's condition as plasma cell dyscrasia. Light microscopy examination of a renal biopsy specimen showed moderate mesangial proliferation with a deposition of PAS-positive and Congo red negative materials in the mesangial area: nodular gomerulonephritis was seen in some glomeruli. Immunofluorescence revealed IgG and lambda light chains, strong linear staining along the glomerular basement membrane and tubular basement membrane and positivity in the mesangial area. Results of staining for IgA, IgM, fibrinogen and C3 were weakly positive in the mesangium area, while those for C4, Clq and free kappa were negative. Positive staining of IgG2 was seen by immunoperoxidase study, but the tissue was negative for IgG1, IgG3, IgG4. Electron microscopy demonstrated a dense granular deposition in the mesangial, subendothelial and peritubular area and a microfibrillar structure in the mesangial area. The diameter of the microfibrillar structure was 14 nm on the average.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Effects of a novel topical immunomodulator, imiquimod, on keratinocyte cytokine gene expression.

A novel immunomodulator, imiquimod, has been shown to be an effective topical antiviral and antitumor agent in animal models. Imiquimod has been reported to induce interferon-alpha and other cytokines in animals and humans, but its precise role as an immunomodulator at skin sites has not been determined. We investigated its effect on cytokine gene expression in the human epidermal carcinoma cell line COLO-16 and human keratinocytes. COLO-16 cells were incubated with imiquimod (1 and 10 micrograms/ml) and human keratinocytes with 5 micrograms/ml for 6 or 24 h. Cytokine gene expression was analyzed by reverse-transcriptase PCR. In COLO-16 cells, imiquimod stimulated IL-6 mRNA levels 2.3- and 4.4-fold at 1 and 10 micrograms/ml after 6 h. IL-8 mRNA increased 4-fold at both 1 and 10 micrograms/ml. At 24 h, though IL-6 mRNA level at 1 micrograms/ml was further stimulated, enhanced expressions of IL-8 at 1 micrograms/ml and both IL-6 and IL-8 at 10 micrograms/ml were down-regulated. In human keratinocytes, 5 micrograms/ml of imiquimod stimulated IL-6 mRNA levels 1.4-fold at 6 h and 2.1-fold at 24 h, and IL-8 mRNA levels 1.7- and 2.0-fold at 6 and 24 h. IL-1 alpha mRNA levels in COLO-16 or keratinocytes were unchanged by either dose or incubation time. These results suggest that stimulation of IL-6 and IL-8 expression may be involved in the immunomodulating action of imiquimod.

Adjuvants, Immunologic↗
PubMed1994

[Development of arbekacin and synthesis of new derivatives stable to enzymatic modifications by methicillin-resistant Staphylococcus aureus].

Our studies on the resistance mechanisms and chemical modifications of aminoglycoside antibiotics led to the synthesis of arbekacin (ABK), which was refractory to most aminoglycoside-modifying enzymes in resistant bacteria. In 1990, ABK was launched into clinical uses in Japan as a chemotherapeutic agent for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). By 1993 only a few MRSA strains moderately resistant to ABK (MIC, 6.25-12.5 micrograms/ml) had clinically been isolated. ABK was modified by the reaction with an excess of an enzyme preparation extracted from an ABK-resistant strain (12.5 micrograms/ml) and three inactivated products were produced, consisting mainly of ABK 2''-phosphate along with small amounts of 6'-N-acetyl-ABK and the doubly modified ABK. Based on these results, replacement of the 2''-hydroxyl by amino group in dibekacin (DKB) or in ABK was designed to obtain potent active derivatives against MRSA. Conversion of the 2''-hydroxyl group by DMSO-DCC oxidation followed by reductive amination with NH4OAc-NaBH3CN gave 2''-amino-2''-deoxy-DKB (D1) and -ABK (A1). Their 5-deoxy (D2 and A2), 5-epifluoro (D3 and A3) and 5-epiamino (D4 and A4) derivatives were also synthesized. All 2''-amino-2''-deoxy-ABK derivatives (A1, A2, A3 and A4) showed excellent activities against MRSA and Gram-negative bacteria, as expected. Among them, A4 having low acute toxicity and nephrotoxicity was selected as a new candidate for anti-MRSA agent.

Aminoglycosides↗
PubMed1993

The effects of nitric oxide on chondrocytes and lymphocytes.

ConcanavalinA (ConA)-activated lymphocytes markedly induced the production of nitric oxide from chondrocytes. The nitric oxide significantly inhibited the proliferation of both the chondrocytes themselves and the lymphocytes. When culture supernatant from ConA-activated lymphocytes was added to culture of chondrocytes, a large amount of nitric oxide was produced. NG-monomethyl-L-arginine (MMA) significantly eliminated both the production of nitric oxide and the inhibition of chondrocyte and lymphocyte proliferation. Furthermore, when MMA was added to the mixed culture of chondrocytes and lymphocytes with ConA, their proliferation was markedly enhanced compared with individual summation. These results indicate that chondrocytes produce not only nitric oxide but also a lymphocyte stimulating factor, the effects of which are, however, usually masked by the nitric oxide.

Animals↗