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Biomedical subjects

T Haruta

Publications and source records attributed to T Haruta.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Clinical studies on cefozopran in pediatrics].

Cefozopran (CZOP) was administered via intravenous injection to 9 patients (ages ranging from 1 month to 13 years) with pediatric bacterial infections, at daily dose levels between 56.7 and 200 mg/kg, divided into 3 or 4 doses. The following results were obtained. 1. Eight patients, including 1 with purulent meningitis, 1 with sepsis, 3 with acute pneumonia and 3 with lymphadenitis, were treated and subjected to clinical evaluation. Clinical effects were excellent in 6 cases and good in 2, with an overall efficacy rate of 100%. One case with pyoderma was not evaluated because of a combined use of an external antibiotic. 2. Organisms suspected as pathogens included 5 strains: 3 strains of Haemophilus influenzae, 1 strain of Staphylococcus aureus and 1 of Escherichia coli. Bacteriologically, all the strains were eradicated. 3. Side effects or abnormal laboratory test results were observed in 4 cases; wheal in 1 case, elevated GOT and GPT in 2 cases and eosinophilia in 1 case. 4. From the results described above, we considered that CZOP would be an effective drug for use in pediatric bacterial infections.

Adolescent↗
PubMed1994

[Studies on the efficacy and safety of biapenem (L-627) against infections in pediatrics].

The efficacy and the safety of biapenem (L-627), a new carbapenem antibiotic, against infections in pediatrics were studied. The obtained results are summarized as follows. 1. L-627 at dose levels of 5.4 mg/kg to 12.4 mg/kg (daily doses of 16.2 mg/kg to 37.2 mg/kg) was administered by intravenous drip infusion 3 times daily for 5 to 7 days to 2 cases of pneumonia, 3 cases of skin and soft-tissue infections and 1 case of urinary tract infection for a total of 6 cases. As results, all the cases showed good or better responses including 4 excellent and 2 good results. Bacteriological efficacies in all of the 3 eligible cases were assessed as "eradicated". 2. As for the safety, a decrease in the WBC count and slight elevation of GOT and GPT were observed in 1 case as abnormal changes in the laboratory tests results, only incidence of side effect observed was the eruption in 1 case. 3. The results above indicate that L-627 is useful for the treatment of general infections in pediatrics.

Bacterial Infections↗
PubMed1994

[Transferability of biapenem (L-627) to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus].

The transferability of biapenem (L-627) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean plasma concentration was 192 +/- 12.8 micrograms/ml at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 45 minutes after administration at 11.4 +/- 2.19 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows, Cmax (CSF/plasma): 5.96%; AUC (CSF/plasma): 8.15% between 15 and 60 minutes, 12.1% between 15 and 120 minutes and 15.0% between 15 and 180 minutes; T1/2 for L-627 in CSF: 152 minutes; T1/2 (CSF/plasma): 3.34. In comparison with those of other beta-lactam antibiotics that were obtained in the same way, the transferability of L-627 was intermediate, and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for this drug.

Animals↗
PubMed1993

Importance of Asp1191 for tyrosine kinase activity of the insulin receptor: functional difference of universally conserved Asp between tyrosine kinase and c-AMP dependent serine/threonine protein kinase.

Asp1191 of the tyrosine kinase domain in the insulin receptor is located in the almost perfectly conserved Ser-Asp-X-Trp motif of all tyrosine kinases, and the function of the motif has not been clarified. In this motif, Asp1191 is universally conserved in all protein kinases and corresponds to Asp220 in catalytic subunit of c-AMP dependent protein kinase. However, while other universally conserved amino acid residues are involved in catalysis, only Asp220 is not. To determine whether this motif was not also involved in catalysis, Asp1191 was replaced either by alanine, asparagine, or glutamic acid and Met1192 was replaced by valine. Asp1191-->Ala, Asn or Glu receptor lacked tyrosine kinase activity, while Met1192-->Val receptor showed normal kinase activity. These mutant receptors had no effect on insulin binding. These results suggested that the universally conserved Asp1191 in all protein kinases, which was not required for catalytic action of c-AMP dependent protein kinase, was essential for the tyrosine kinase activity of the insulin receptor.

Amino Acid Sequence↗
PubMed1993

Co-expression of mutant and normal human insulin receptors in COS 7 cells.

In order to assess the interference of the mutant insulin proreceptor on normal receptor function and formation of proreceptor-receptor heterotrimers (alpha beta-proreceptor), COS 7 cells were transfected with the same amount of expression plasmid (pGEM3SV) containing wild-type, a mutant proreceptor cDNA and both, using the DEAE-dextran method. Scatchard analysis of insulin binding data revealed that there was an approx. 50-fold higher receptor concentration in the transfected cells than in untransfected cells. After 0.025% trypsin treatment, insulin binding to the cells expressed with wild-type, proreceptor and both increased by 1-fold, 2.9-fold and 1.5-fold of the untreated cells, respectively. In the presence of 167 nM insulin, the amounts of phosphate incorporated into the 95 kDa protein beta-subunits and 210 kDa proreceptors from co-transfected cells, were identical to those of an in vitro mixture of the wild-type and the mutant receptors. At 10 nM insulin, the proreceptors from co-transfected cells normally autophosphorylated by insulin stimulation, whereas those mixed in vitro did not (73.3 +/- 9.3 vs. 29.6 +/- 2.6% of the maximal effect, n = 4, P < 0.01). However, at a similar concentration of insulin, the phosphate incorporation into Glu-80/Tyr-20 polymers by receptors from co-transfected cells was decreased when compared with a in vitro mixture (9.0 +/- 2.6 vs. 22.5 +/- 6.7% of the maximal effect at 4 nM, n = 6, P < 0.01), although the basal and maximally stimulated phosphate incorporation were comparable among these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

[A case of familial insulin resistance due to type A insulin receptor disorder].

We report a case of familial insulin resistance due to Type A insulin receptor disorder. The patient, a product of consanguineous marriage, was a 34-year-old man who had had diabetes mellitus since the age of 14 years. He was treated by insulin therapy but became blind due to diabetic retinopathy at the age of 25 years. He was 154 cm tall and weighed 41kg. He had hirsutism and acanthosis nigricans. Laboratory data revealed hyperinsulinemia (140-350 microU/ml), and glucose clamp study showed insulin resistance, i.e. decreased glucose metabolic clearance rate, 20% of normal. Insulin binding was decreased to 10.7-16.6% of normal in erythrocytes, cultured fibroblasts and transformed lymphocytes. Glucagon stimulated C-peptide levels decreased gradually during a 3 year follow-up period. Homologous missense mutation from Proline193 to Leucine193 was found in this patient. Heterologous mutation was found in his mother who showed mild diabetes but did not show hirsutism or acanthosis nigricans. These findings suggested that the patient's father had this mutation in his insulin receptor gene and that the homologous mutation gene provoked more severe diabetes mellitus than heterologous mutation in this case. The efficacy of sulfonylurea agents was seen in this patient. Furthermore, sulfonyl urea agents may be indicated for treating these patients, probably by increasing insulin sensitivity.

Acanthosis Nigricans↗
PubMed1993

Campylobacter jejuni strains from patients with Guillain-Barré syndrome belong mostly to Penner serogroup 19 and contain beta-N-acetylglucosamine residues.

Campylobacter jejuni was isolated from stool cultures from 14 (30%) of 46 patients with Guillain-Barré syndrome and from 6 (1.2%) of 503 healthy persons, and the difference was highly significant (p < 0.0001). In addition, serological evidence of recent C. jejuni infection was found in 5 of 29 patients with negative stool cultures. Therefore, 41% of patients were associated with C. jejuni infection. Ten of 12 (83%) isolates from patients with Guillain-Barré syndrome belonged to Penner serogroup 19, which is a rare serogroup in sporadic patients with C. jejuni enteritis. In the lectin typing study, all serogroup 19 strains from patients with Guillain-Barré syndrome were shown to contain terminal beta-N-acetylglucosamine residues on their cell surface, but serogroup 19 strains from patients with enteritis were not.

Acetylglucosamine↗
PubMed1993

A mutation (Trp1193-->Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance.

We evaluated a 35-year-old diabetic male patient with type A insulin resistance, showing acanthosis nigricans. Insulin binding to the patient's Epstein-Barr-virus transformed lymphocytes was mildly reduced. The maximal insulin-stimulated autophosphorylation of the insulin receptor from the patient's transformed lymphocytes was decreased to 45% of that from the control subjects. On examination, the biological activities of insulin and insulin-like growth factor I in the patient's cultured fibroblasts, insulin sensitivity of amino isobutyric acid uptake and thymidine incorporation was decreased, but insulin-like growth factor I action was normal. The sequence analysis of amplified genomic DNA revealed that the patient was heterozygous for a mutation substituting Leu for Trp at codon 1193 in exon 20 of the insulin receptor gene. The patient's mother and sister were also heterozygous for a mutation in the insulin receptor gene that substituted Leu for Trp1193 in the beta subunit of the receptor. Therefore, the mutation causes insulin resistance in a dominant fashion. They were less hyperglycaemic and more hyperinsulinaemic than the proband after glucose loading. The mother had diabetes mellitus but did not show acanthosis nigricans, while the sister did not have diabetes and showed acanthosis nigricans. These results suggest that this mutation causes defective tyrosine kinase activity of the insulin receptor, which results in insulin resistance. Insulin action and phenotypic appearance may be mediated by different factors.

Adult↗
PubMed1993

Ala1048-->Asp mutation in the kinase domain of insulin receptor causes defective kinase activity and insulin resistance.

We identified a heterozygous missense mutation that substituted aspartic acid (GAC) for alanine (GCC) at codon 1048 of the insulin receptor gene in a patient who displayed typical symptoms of Type A syndrome of insulin resistance. The proband's mother and younger brother were also found to be heterozygous for the mutation. We constructed the identified mutant insulin receptor cDNA by site-directed mutagenesis, transfected the mutant cDNA into COS 7 cells, and found that kinase activity of the mutant insulin receptors was markedly impaired. Ala1048 is located in the kinase domain of the insulin receptor beta-subunit and is conserved in most of protein-tyrosine kinases. Besides, neighboring Glu1047 is invariant in all protein kinases and is thought to be involved in interaction with ATP. Photoaffinity labeling of the mutant insulin receptor with ATP analogue, 8-azido (alpha-32P)ATP was not influenced by the mutation, suggesting that the mutation did not inhibit ATP binding but possibly interfered with subsequent phosphoryl transfer. Insulin-stimulated phosphorylation of exogenous substrate by partially purified insulin receptors prepared from COS 7 cells that were cotransfected with wild-type and mutant insulin receptor cDNAs was markedly impaired, whereas autophosphorylation was decreased by approximately 50% of wild-type receptors. These results indicated that the identified heterozygous substitution of Asp for Ala1048 in insulin receptor was responsible for insulin resistance of this patient.

Adolescent↗
PubMed1993

[Clinical studies of S-1108 granules in the pediatric field].

We studied the clinical use of S-1108 granules in the pediatric field. The results are summarized as follows. 1. S-1108 was administered orally at doses ranging 6.85 and 17.6 mg/kg/day t.i.d. to 9 patients, including 5 cases of pharyngitis and 1 case each of lacunar tonsillitis, bronchitis, pneumonia and urinary tract infection. Clinical efficacies were excellent in 4 cases and good in 5 cases, hence an efficacy rate of 100% was obtained. 2. Haemophilus influenzae, Haemophilus parainfluenzae (2 strains each) and Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli and Enterococcus faecalis (1 strain each) were identified in these cases. Seven of the 8 strains were eliminated upon treatment and the other strain was decreased, hence an eradication rate of 87.5% was obtained. 3. Side effects observed were 1 case each of soft stools and diarrhea. As an abnormal laboratory test result, an increase in GPT level was observed. 4. No refusal of the drug occurred. 5. From the above results, we consider that this drug would be a useful new oral antibiotic for the pediatric field.

Administration, Oral↗
PubMed1993

[Transferability of vancomycin to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus].

The transferability of vancomycin (VCM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. VCM was administered intravenously for 30 minutes at a dose level of 30 mg/kg. Serum concentration reached a maximum of 75 +/- 3.80 micrograms/ml (mean +/- S.E.) at the completion of administration (i.e., 30 minutes) and CSF concentration reached a maximum of 2.4 +/- 0.39 micrograms/ml at 60 minutes. Pharmacokinetic parameters calculated from this concentration-time curve were as follows: Cmax (CSF/Serum) 3.21%, AUC (CSF/Serum) 2.39% between 15 and 60 minutes, 3.99% between 15 and 120 minutes, and 4.40% between 15 and 150 minutes. T 1/2 for VCM in CSF: 143 minutes, T1/2 (CSF/Serum):2.09. Based on this investigation, VCM appears to be effective in the treatment of meningitis caused by MRSA (Methicillin-resistant S. aureus).

Animals↗
PubMed1992

Short stature with normal growth hormone and elevated IGF-I.

We report on a Japanese girl with short stature, malar hypoplasia, up-slanting palpebral fissures, blue sclerae and thin, stiff and slightly brownish hair. Short stature started in utero and her psychomotor development was normal. Menarche appeared at 13 years 8 months. Height at 14 years 5 months was 132 cm (-4.6 SD). Her growth hormone (GH) sleep pattern and responses to insulin, L-dopa, arginine, propranolol-glucagon and growth hormone-releasing hormone were normal. Plasma insulin-like growth factor I (IGF-I) was high (2170-4860 units/l) and increased from 4860 to 7080 units/l 20 h after biosynthetic GH injection. Gel infiltration patterns of the free and protein-bound IGF-I in plasma from the patient were not different from the controls; IGF-I fraction of the high and low molecular weight binding protein and the non-protein bound fraction were 75.5%, 15.8% and 8.7%, respectively. IGF-I from the patient showed normal bioactivities when determined by [35S]sulphate and [3H]thymidine uptake into cultured rat chondrocytes, and by [3H]thymidine and [3H]alpha-aminoisobutyric acid uptake into the patient's skin fibroblasts. IGF-I binding to cultured skin fibroblasts from the patient was comparable to that of controls. These results suggest that tissue specific defects of IGF-I receptors may be the cause of increased IGF-I levels in the patient.

Animals↗
PubMed1992

[Clinical studies on cefprozil granules].

Cefprozil granule preparation was administered orally to 16 patients (ages ranging 8 months to 9 years and 6 months) with pediatric bacterial infections at daily dose levels between 29.4 and 35.7 mg/kg divided into 3 or 4 doses. The following results were obtained. 1. Sixteen patients including 5 with pharyngitis, 3 with tonsillitis, 3 with lacunar tonsillitis, 2 with pneumonia, 2 with contagious impetigo and 1 with scarlet fever were treated. Clinical effects were excellent in 9 cases and moderate in 7, with an overall efficacy rate of 100%. 2. Organisms suspected as pathogens included 17 strains (10 strains of haemophilus influenzae, 2 of Haemophilus parainfluenzae, 3 of Streptococcus pyogenes and 2 of Staphylococcus aureus). Bacteriologically, eradication of pathogens were observed for 11 strains, but no changes were obtained for 5 (all Haemophilus), and unknown results were obtained for 1, thus the eradication rate was 68.8%. 3. No side effects were observed. Abnormal laboratory test results included 2 cases of increase in platelets, and 2 of increase in eosinophils, but those were not significant. 4. No refusal of the drug occurred due to its taste or odor.

Administration, Oral↗
PubMed1992

[Studies on efficacy and safety of panipenem/betamipron against infections in pediatrics and on its movement to cerebrospinal fluid including cases of penicillin-resistant Streptococcus pneumoniae meningitis].

The efficacy and the safety of panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic against infections in pediatrics were studied. The obtain results are summarized as follows. 1. The transfer of PAPM/BP to cerebrospinal fluid (CSF) was studied in 2 cases of purulent meningitis. The PAPM/BP levels in CSF in a dose 26.1 mg/kg peaked at 3.21 micrograms/ml on sampling 30 minutes after administration, followed by decreasing gradually with the improvement in clinical symptoms and came to 0.86 micrograms/ml on the 12th day (30 minutes after administration). 2. PAPM/BP at dose levels of 50 mg/kg to 69 mg/kg a day (daily doses of 104 mg/kg, 175 mg/kg 4 times a day for 2 cases of purulent meningitis) was administered by intravenous drip infusion 3 times daily for 4 to 15 days to 2 cases of purulent meningitis (including 1 case of penicillin-resistant Streptococcus penumoniae meningitis), 3 cases of pneumonia, 2 cases of phlegmon, 2 cases of periproctal abscess and 2 cases of urinary tract infections for a total of 11 cases. As results, all the cases showed good responses including 5 excellent and 6 good responses. Bacteriological efficacies in all of the 9 eligible cases were assessed as "eradicated". 3. As for the safety, an increase in the platelet count and slight evaluation of GOT and GPT were seen in 1 case as abnormal changes in the laboratory findings, although no side-effect was observed. 4. The results above show that PAPM/BP is useful for the treatment of general infections in pediatrics and that a daily dose of about 60 mg/kg given in 3 divided doses in effective enough.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

[Transferability of meropenem to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus].

The transferability of meropenem (MEPM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 93.1 +/- 13.5 micrograms/ml at 15 minutes after intravenous administration of MEPM at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 15 minutes after administration at 4.42 +/- 2.24 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows: Cmax (CSF/serum) 4.75%, AUC (CSF/serum) 10.4% between 15 and 60 minutes, 13.9% between 15 and 120 minutes and 15.7% between 15 and 180 minutes, T 1/2 for MEPM in CSF: 50.9 minutes, T 1/2 (CSF/serum): 2.19. In comparison to those of imipenem which were obtained in the same way, the transferability of MEPM was similar and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worth-while of running clinical trials for this drug.

Animals↗
PubMed1992

[Studies on meropenem in the field of pediatrics].

The pharmacokinetics and the clinical effectiveness of meropenem (MEPM) were examined in the field of pediatrics. The results are summarized as follows. 1. A 4-year-6-month-old girl with suppurative meningitis (Haemophilus influenzae) was treated by intravenous drip infusion of MEPM in a daily dose of 29 mg/kg which was divided into 4 dosages, each dosage being infused over 30 minutes, and the drug concentration in cerebrospinal fluid was determined. Upon completion of infusion on the 2nd day of treatment, the drug concentration was 2.52 micrograms/ml, which corresponded to 3.6% of the drug concentration in the blood. 2. MEPM was used in 10 patients, including 3 with suppurative lymphnoditis, 2 with staphylococcal scalded skin syndrome (SSSS) and 1 each with pneumonia, suppurative meningitis, suppurative knee arthritis, facial phlegmon and pyelonephritis. The daily doses ranged from 30 to 117.6 mg/kg, divided into 3 to 4 dosages and administered via intravenous drip infusion over 30 minutes. Clinical responses were evaluated as very good in 7 patients, good in 2 patients and fair in 1 patient, with an efficacy rate of 90%. 3. Isolated pathogens were 2 strains of Staphylococcus aureus, 1 strain of Klebsiella pneumoniae and 3 strains of Haemopilus influenzae. All of the 6 strains were eradicated, with an eradication rate of 100%. 4. In the safety evaluation, none of the patients was observed to have any side effects. Furthermore, no abnormal variations were found in laboratory test data possibly attributable to administration of MEPM.

Bacterial Infections↗