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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 469 records · Page 26Linked to original sources
PubMed1993

Propagation of hepatitis A virus in a renal cell line JTC-12.P3 of cynomolgus monkey origin.

Human hepatitis A virus (HAV) derived from 10% HAV infected marmoset liver homogenate and faeces from acute hepatitis A was successfully propagated in vitro in a new cell line, JTC-12.P3. The cell line originated from the renal cortex of cynomolgus monkey which was adapted to growth in a serum free, protein free, chemically defined synthetic medium. Replication of the virus was followed by solid phase RIA, immunofluorescent staining, and immunoelectron microscopy. The propagation of HAV occurred over several passages, with the 1st and 2nd passages requiring at least 8 weeks each. However, with the increasing serial passage of virus, the period needed to detect it was shortened, suggesting the adaptation of HAV to the cells. The identity of the newly synthetized virus particles with HAV was established by immunoelectron microscopy and immunofluorescent blocking effect with human convalescent serum. The HAV propagated in JTC-12.P3 cells banded predominantly at a density of 1.32 g/cm3 in CsC1 gradient. The infected cells showed no specific signs of CPE. Ultrastructurally, clusters of virus particles 27 nm in diameter were observed mainly in the lysosomal vesicles and freely in crystalline array in the cytoplasm, too. Addition of 0.1% of various anti-HAV negative sera or of prostaglandin E1 to the culture medium caused accelerated propagation of HAV.

Animals↗
PubMed1993

Cytolytic activity of natural killer cells and lymphokine activated killer cells against hepatitis A virus infected fibroblasts.

The role of Natural Killer (NK) cells, Lymphokine Activated Killer (LAK) cells and the induction of cytokines in the hepatocellular injury of hepatitis A were studied in vitro using a 51Cr release assay in hepatitis A virus (HAV) infected MRC-5 cells (MRC-HAV). When fresh peripheral mononuclear cells (PBMC) from healthy, anti-HAV antibody (-) and (+) human donors, or patients with acute hepatitis A were used as effector cells, MRC-HAV were lysed more extensively than uninfected cells. Similarly, in models using recombinant interleukin-2 (rIL-2) pretreated PBMC from HAV antibody (-) and (+) donors or patients with hepatitis A as effector cells, MRC-HAV were lysed more extensively than uninfected MRC. Both fresh PBMC and rIL-2 pretreated PBMC from anti-HAV antibody (+) donor lysed MRC-HAV cells more effectively than PBMC collected from anti-HAV antibody (-) patients. PBMC from patients with hepatitis A during the acute phase demonstrated more severe lysis of both uninfected MRC and MRC-HAV target cells. However, MRC-HAV lysis was enhanced to a greater degree. In an attempt to identify which cells were involved in cell lysis, cytotoxicity assays were performed by separating PBMC by cell sorter using monoclonal antibodies against all T cells, NK and B-cell fractions and culturing each with supplemental rIL-2. The NK cell fraction selectively destroyed MRC-HAV, but the lytic activity of both the pan T-cell and B-cell fractions was too weak to demonstrate any significant difference. Therefore, NK-LAK cells appeared to play a more significant role in cytolysis than did T-LAK cells. Morphologic observations of cellular damage were accomplished with PBMC obtained from healthy anti-HAV antibody (+) donors. PBMC were suspended in media containing rIL-2 and incubated for 4 days on monolayers of uninfected MRC and MRC-HAV. IFN-alpha and IFN-gamma in the supernatant of the cultured media were simultaneously assayed. Severe damage to HAV-infected cells was observed. Moreover, strong induction of IFN-alpha and IFN-gamma was found with high levels measured in the supernatant. Therefore, it is likely that non-specific immune mechanisms involving NK and LAK cells play a central role in hepatocellular damage prior to the initiation of damage due to Cytotoxic T Lymphocytes (CTL).

B-Lymphocytes↗
PubMed1993

[Pharmacokinetics and pharmacodynamics of hydrocortisone in asthmatic children].

Corticosteroids are very efficacious in the treatment of asthma. In the present study, the conversion rate of hydrocortisone succinate (HCS) to hydrocortisone in plasma was examined and pharmacokinetic study was carried out for the two compounds after a single intravenous injection of hydrocortisone sodium succinate (HCSS). Moreover, it was examined whether hydrocortisone improved acute asthmatic attacks. In a randomised cross-over trial at 5 to 7 days intervals, 10 asthmatic children aged 9-14 years were treated with a single intravenous injection of HCSS in a dose of 5 mg hydrocortisone/kg body weight or without HCSS. After 4-hour pulmonary function studies, they were received a subcutaneous injection of epinephrine (0.004 mg/kg). The plasma concentrations of HCS and hydrocortisone were measured by the HPLC and/or radioimmunoassay. The mean of maximum concentration of HCS was 26.38 mg/L. The concentration of HCS decreased rapidly with a half-life of 0.09 hr (5.38 min). The concentration of hydrocortisone reached to a peak value of 4.96 mg/L after 10 min, and then decreased with a half-life of 1.24 hour. It is predicted that an intravenous injection of HCSS every 6 hours in a dose of 5 mg hydrocortisone/kg would maintain hydrocortisone level at 100 to 150 micrograms/dl. HCSS did not show a rapid improvement of the pulmonary functions, but showed a tendency to improve the functions over 4 hours. Subcutaneous injection of epinephrine after HCSS resulted in a significant improvement of pulmonary functions compared to those by epinephrine alone. We concluded that hydrocortisone showed a slowly evolving improvement of pulmonary function and increased the responsiveness to beta-agonists.

Adolescent↗
PubMed1993

[Assessment of the amount of drug deposited in the lungs of asthmatic children using disodium cromoglycate as the marker].

Disodium cromoglycate (DSCG) is easily absorbed from the airways and lungs, and is excreted unchanged in the urine and bile. Therefore it is possible to estimate the dose of DSCG deposited in the airways and lungs based upon urinary excretion. The urinary concentration of DSCG was measured by the HPLC method in 78 asthmatic children aged 0 to 16 years after they had inhaled 20 mg nebulizer solutions with facemasks. Jet-type nebulizers were used. The mean urinary excretion of DSCG in the patients aged 0, 1, 2 and 3 years from 4-hour urinary collection represented 0.204%, 0.231%, 0.593%, 0.790%, respectively, of the dose administered. In the patients aged 3, 4, 5-6, 7-9 and 10-16 years, from 24-hour urinary collection, the figures were 0.625%, 0.895, 0.855, 1.176%, 1.070%, respectively. The mean dose deposited in the airways and lungs of the age groups 0-1, 2, 3, 4-6, 7-9, and 10-16 years represented approximately 0.5%, 1.4%, 1.4-1.8%, 2.0%, 2.7%, 2.4%, respectively, of the dose administered. Although there was a wide range in the total amount of DSCG deposited in the airways and lungs of asthmatic children, these data seem to provide a useful guide to standardizing the dosing in inhalation therapy.

Administration, Inhalation↗
PubMed1993

Preparation of a human monoclonal antibody derived from cervical lymph nodes of a patient with anaplastic carcinoma of the thyroid.

An anaplastic carcinoma cell line, KOA-2, was established from a 59-year-old patient with anaplastic carcinoma of the thyroid who died only one month after diagnosis in association with rapid progress of her disease. A human monoclonal antibody, 3C5 (IgM), was generated by a fusion of human B lymphoblastoid cell line, HO-323, with lymphocytes from cervical lymph nodes of the patient, who had been treated with local immunotherapy. Immunocytostaining demonstrated that 3C5 reacted with KOA-2, and membrane immunofluorescence demonstrated that 3C5 reacted with cell membranes. Immunohistochemical staining studies demonstrated selective reaction of 3C5 with three malignant tumors, anaplastic carcinoma of the thyroid (2/4 sampled tested), papillary carcinoma of the thyroid (8/12), and breast cancer (2/6), but no reaction with specimens of benign thyroid disease or normal thyroid gland was demonstrated. The monoclonal antibody and the cell line established from one patient have potential use in the analysis of carcinogenesis and applications to therapy of anaplastic carcinoma of the thyroid.

Antibodies, Monoclonal↗
PubMed1993

[Phenylketonuria with adult-onset neurological manifestation].

We report a male patient with phenylketonuria (PKU) who developed multisystem neurological manifestation in his fourth decade. He was born in 1957 when a neonatal mass screening had not been available. His neuropsychological development was entirely normal and he was a good athlete during his high school days. He was in good health until the age of 32, when his vision was blurred. In four months his gait progressively deteriorated to bind him to a wheel chair. On physical examination he had red hair and gray eyes. IQ was 68. Visual field showed concentric narrowing and his visual acuity was 0.2/0.3 (2.0/2.0). The limbs were spastic and weakened. He complained of pain in the extremities. He suffered from pollakisuria. Routine blood tests and CSF findings were normal. He was also found to be normal in peripheral nerve conduction studies and central conduction studies of SEP and VEP. EEG showed diffuse slowing in background activities. T2-weighted MRI of the head revealed widespread high-intensity areas in the deep white matter especially in bilateral occipital lobes. Serum aminogram disclosed the remarkably elevated phenylalanine (Phe) level to 1663 nmol/ml (normal range 50-90) and reduced tyrosine. Urinary secretion of endogenous tetrahydroxy-biopterin (BH4; coenzyme of Phe hydroxylase) remained in a normal range, and oral administration of 100 mg/kg of BH4 failed to normalize the serum Phe level. Despite a strict dietary control (oral intake of Phe less than 0.5 g/day), the serum Phe level remained high around 500 nmol/ml and his neurological deficits still deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Rapid recovery of chronic inflammatory demyelinating polyneuropathy induced by steroid pulse therapy--changes in nerve conduction].

A 47-year-old female patient with chronic inflammatory demyelinating polyneuropathy started to recover from her numbness and weakness within a few hours following the commencement of intravenous methylprednisolone 1,000 mg. In parallel with the recovery of muscle strength, a prolonged latency time of the M-wave was normalized within a day by a revival of the new motor units with a normal latency. In many cases with CIDP, it has been recognized that the gradual decrease in latency time over weeks is a later phenomenon following early increase in amplitude of the M-wave during recovery of weakness, which is explained by remyelinating process. On the other hand, the revival of motor units with a normal latency time from demyelinating conduction block is difficult to explain by remyelinating process, because remyelinating fibers usually have a very slow conduction velocity. Some minor morphological changes of paranodes or humoral factors may be partly responsible for development conduction block in CIDP.

Chronic Disease↗
PubMed1993

[Chronic inflammatory demyelinating polyneuropathy in childhood].

Clinical, electrophysiological and histopathological findings in 6 children with steroid-responsive acquired demyelinating neuropathy are presented. The clinical features and nerve conduction findings are basically similar to those of chronic inflammatory demyelinating neuropathy (CIDP) in adults, although early-onset cases had prominent pes cavus deformity and thickened nerves, which are rare findings in acquired neuropathies in adults. The diagnostic criteria of adult CIDP can be adopted for most of the cases, however, repeated electrophysiological tests may be required to identify multifocality of the nerve lesion, especially when conduction block is not apparent before treatment. The biopsied sural nerves showed many thinly-myelinated fibers, subperineurial and endoneurial edema, and cellular infiltrations. Varied fascicular involvements were common. Two cases with almost complete or considerable loss of myelinated fibers in the biopsied sural nerve revealed good clinical response to steroid therapy. The degree of nerve degeneration in the sural nerve thus, may not be helpful to estimate the prognosis and the responsiveness to treatment. Therapeutic trials should be employed when the main conduction findings are those of demyelinating neuropathies, even if genetically-determined neuropathy is suggested from the clinical pictures.

Adolescent↗
PubMed1993

[Report of two cases presenting with myelodysplastic syndrome during treatment of recurrent breast cancer].

Two women with recurrent breast cancer presenting with myelodysplastic syndrome (refractory anemia) during chemotherapy were reported. At diagnosis of myelodysplastic syndrome, white blood cell count, hemoglobin and platelet count were 3,300/mm3, 4600/mm3, 5.5 g/dl, 6.3 g/dl, 1.1 x 10(4)/mm3 and 6.8 x 10(4)/mm3, respectively, in case 1 and 2. Bone marrow taps showed hypercellular marrows with dysplastic changes of erythrocytes, granulocytes and megakaryocytes in both cases. Before the occurrence of the myelodysplastic syndrome, both patients received various cytotoxic agents (mitomycin C: 77 mg, 108 mg; cyclophosphamide: 34,400 mg, 40,000 mg; doxorubicin: 340 mg, 460 mg; methotrexate: 410 mg, 700 mg; and vincristine: 9.5 mg, 14 mg, in case 1 and 2, respectively). One patient died 2 months after the onset of the myelodysplastic syndrome, and the other died 3 months after due to progression of metastatic breast cancer. Risk-benefits analysis of chemotherapy, especially adjuvant chemotherapy, should be performed in cases of breast cancer.

Adult↗
PubMed1993

[Chronic inflammatory demyelinating polyneuropathy in childhood--a case with markedly hypertrophic nerves and pes cavus].

We describe a 9-year-old boy with chronic inflammatory demyelinating polyneuropathy (CIDP), whose distal dominant, slowly progressive motor sensory involvement developed since infancy. Thickened peripheral nerves were visible in his neck and palpable in the extremities. The hand muscles were atrophic and both feet showed pes cavus deformity. He was unable to walk. Nerve conduction study revealed no sensory potentials. Compound muscle potential (CMP) was absent in the legs. In the arms, CMP showed markedly low amplitude and temporal dispersion. Motor conduction velocities were 1.7 to 2.7 m/sec, showing extremely high threshold to electrical stimuli. Conduction block was not convincing, nevertheless the asymmetric conduction abnormalities strongly suggested multifocality of the lesion. In the biopsied sural nerve no myelinated fibers were found. Considerable improvements in muscle power and electrophysiological findings were brought about by corticosteroid therapy. CIDP in childhood may masquerade hereditary neuropathies presenting hypertrophic peripheral nerves and pes cavus deformity. A careful nerve conduction study is thus desirable to find out electrophysiological multifocality.

Child↗
PubMed1993

[Surgical treatment of double-outlet right ventricle with left ventricular outflow tract obstruction].

Three patients with double-outlet right ventricle (DORV) and left ventricular outflow tract obstruction (LVOTO) were described. In each patient, LVOTO was produced by restrictive VSD which resulted from malalignment of the conal musculature and a discrete subaortic membrane. All patients underwent surgical repair with enlargement of the ventricular septal defect and rerouting of the outflow tract from the left ventricle to the aorta. One patient died of congestive heart failure three months postoperatively. Causes of LVOTO and surgical management of DORV with LVOTO were discussed.

Cardiac Surgical Procedures↗
PubMed1993

[Skin reaction(s) to culture supernatant(s) from Dermatophagoides farinae (Df)-stimulated lymphocytes, and their correlation with Df-induced interleukin 2 responsiveness by lymphocytes from patients with bronchial asthma].

To investigate the inflammatory function of Dermatophagoides farinae (Df)-activated lymphocytes, supernatants from cultures of the lymphocytes were intracutaneously injected into donors' forearms. Injection of the supernatants of Df-stimulated lymphocytes from mite-sensitized atopic individuals with such diseases as bronchial asthma induced a profound inflammatory reaction in the autologous skin, characterized by erythema extending more than 15 mm in mean diameter and edema. The inflammation was at its peak after approximately 20 min, which was followed by gradually re-growing erythema lasting for as long as 24 hours after injection. Supernatants of unstimulated lymphocytes were also capable of inducing the same reaction, indicating the presence of in vivo activated lymphocytes, although the extent of the response was always smaller. The induced response in normal individuals was erythema of less than 15 mm in mean diameter. The supernatants obtained from cultures at 4 degrees C failed to induce such inflammation. The culture supernatants of ovalbumin-restimulated lymphocytes were also incapable of augmenting the response. The combined data show that the production of inflammatory response-inducing factor(s) from Df-stimulated lymphocytes was antigen specific. Significant skin reactions was correlated with the IL2 responsiveness of Df-stimulated lymphocytes. The skin reaction induced by factor(s) derived from Df-stimulated lymphocytes, which might be similar to the bronchial hyperreactivity of patients with bronchial asthma. The in vitro assay for Df-induced IL2 responsiveness by lymphocytes might reflect the in vitro immediate, late and/or delayed type hypersensitivity.

Animals↗
PubMed1993

[MR findings in traumatic cerebrospinal fluid leakage with special reference to indications of the need for dural repair].

Eleven cases of traumatic cerebrospinal fluid (CSF) leakage (8 cases of rhinorrhea and 3 cases of otorrhea) were reviewed to discuss magnetic resonance (MR) findings and surgical indications of the need for dural repair. Five patients had delayed onset of CSF rhinorrhea, 12 to 66 days (mean 28 days) after the trauma, and in the remaining 6 patients (3 rhinorrhea and 3 otorrhea) CSF leakage was noted on admission. MR study was carried out within 7 days after the onset of CSF leakage using a 0.5 tesla imager. In 7 cases of rhinorrhea, MR images demonstrated brain herniation into the ethmoid or frontal sinuses and the dural defects were repaired with the vascularized periosteum flap taken from the frontal bone or the fascia lata. In the operations, brain parenchyma was found to be plugged into the fracture line as MR images showed, and also to adhere to the margin of dural fistula. In the remaining 4 patients (without the MR findings of brain herniation into the paranasal sinuses) spontaneous cessation of CSF leakage occurred and their clinical course was good. Spontaneous cessation of CSF leakage in these cases may suggest the complete healing of the lacerated dura. However, in cases with the brain herniated into the paranasal sinuses CSF leakage may not be observed, and natural healing of the dural defect cannot be expected. Therefore, such brain herniation indicates the absolute need for dural repair even if CSF leakage is not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Potential anti-AIDS naphthalenesulfonic acid derivatives. Synthesis and inhibition of HIV-1 induced cytopathogenesis and HIV-1 and HIV-2 reverse transcriptase activities.

Several naphthalenedi- and trisulfonic acids have been synthesized and evaluated for inhibitory potential against cytopathogenesis and purified recombinant human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptase (RT). The most potent derivative that emerged from the anti-RT study was a small molecule 6 (MW = 840), a dipalmitoylated derivative of 2,7-naphthalenedisulfonic acid. Analog 6 demonstrated 50% inhibitory concentration (IC50) values of 2.42 and 0.86 microM for HIV-1 and HIV-2 RT, respectively. The second most active compound was also a derivative of the same naphthalenedisulfonic acid but contained only one palmitoyl moiety. This compound 9 displayed IC50 values of 4.8 and 3.7 microM for HIV-1 and HIV-2 RT, respectively. Both analogs 6 and 9 are active at noncytotoxic doses, exhibit slightly higher potencies for the RT of HIV-2 over HIV-1, and demonstrate activities superior to the hexasulfonic acid derivative suramin (IC50 values of 9.4 and 15.5 microM for HIV-1 and HIV-2 RT, respectively). In the cytopathogenesis assay, the most active compound is a bis naphthalenedisulfonic acid derivative 17, containing a flexible octamethylene spacer and exhibiting an in vitro therapeutic index of 29.7. Most striking, however, is the influence of the palmitoyl functionality in the naphthalenedisulfonic acid series to confer activity against both HIV-1 and HIV-2 RT.

Enzyme Inhibitors↗
PubMed1992

Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

The effect of substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out based on alkylation of HEPT with primary alkyl halides. Preparation of the 1-[(alkyloxy)methyl]-6-(phenylthio)thymine (26-31) and 1-[(alkyloxy)methyl]-6-(arylthio)-2-thiouracil (32-45) derivatives was carried out on the basis of LDA lithiation of 1-[(alkyloxy)-methyl]thymine (9-14) and 1-[(alkyloxy)methyl]-2-thiouracil (15-25) followed by reaction with diaryl disulfides. The oxidative hydrolysis of the 2-thiouracil derivatives gave 1-[(alkyloxy)methyl]-6-(arylthio)uracil derivatives (46-57). 1-Alkyl-6-(phenylthio)thymine (59-61) derivatives were prepared on the basis of alkylation of 6-(phenylthio)thymine (58). Methylation of the hydroxyl group of HEPT did not affect the anti-HIV-1 activity of HEPT. Substitution of the 1-(2-hydroxyethoxy)methyl group by ethyl, butyl, methoxymethyl, (propyloxy)methyl, and (butyloxy)-methyl groups somewhat improved the original anti-HIV-1 activity of HEPT. Substitution with ethoxymethyl and (benzyloxy)methyl groups further potentiated the activity [EC50: 1-(ethoxy-methyl)-6-(phenylthio)thymine (27), 0.33 microM; 1-[(benzyloxy)methyl]-6-(phenylthio)thymine (31), 0.088 microM]. When the 5-methyl group of 27 and 31 was replaced by an ethyl or an isopropyl group, the anti-HIV-1 activity was improved remarkably [EC50: 5-ethyl-1-(ethoxymethyl)-6-(phenylthio)-uracil (46), 0.019 microM; 5-ethyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (52), 0.0059 microM; 5-isopropyl-1-(ethoxymethyl)-6-(phenylthio)uracil (55), 0.012 microM; 5-isopropyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (56), 0.0027 microM]. Introduction of two m-methyl groups into the phenylthio ring also potentiated the activity.

Antiviral Agents↗