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Biomedical subjects

Hiroyuki Kobayashi

Publications and source records attributed to Hiroyuki Kobayashi.

At least 163 records · Page 9Linked to original sources
PubMed2003

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2001)].

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.

Adult↗
PubMed2002

Distribution of adenosine A(2A) receptor antagonist KW-6002 and its effect on gene expression in the rat brain.

A novel adenosine A(2A) receptor selective antagonist, KW-6002 [(E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], possesses antiparkinsonian activities in rodent and primate models. In the present study, we investigated the distribution of [14C]KW-6002 in forebrain after oral administration at pharmacologically effective doses. Also, we monitored the effects of the compound on preproenkephalin (PPE) and preprotachykinin (PPT) gene expression in rat striatum. The highest level of radioactivity was observed in the striatum after oral administration of [14C]KW-6002; 30 min after 0.1 and 0.3 mg/kg, the density values in the striatum were 2.45 and 2.43 times higher than those in a reference region (frontal cortex), respectively. At the dose of 3 mg/kg, p.o., the ratio was only 1.58 and the compound was distributed more extensively in the brain. The distribution pattern and intensity of radioactivity were maintained even 90 min after the administration of [14C]KW-6002. Oral administration of KW-6002 (0.3 and 3 mg/kg/day) to rats for 14 days reversed the increased gene expression of PPE in striatum that had been depleted of dopamine by prior treatment with 6-hydroxydopamine (6-OHDA). On the other hand, KW-6002 did not alter the decreased gene expression of PPT in 6-OHDA-treated rats. These results are the first to show directly that orally administered KW-6002 is distributed selectively to the striatum and that it modulates the activity of striatopallidal enkephalin-containing neurons but not striatonigral substance P-containing neurons.

Administration, Oral↗
PubMed2002

[Met5]enkephalin-Arg-Gly-Leu-induced antinociception is greatly increased by peptidase inhibitors.

Previous in vitro studies showed that the degradation of [Met(5)]enkephalin-Arg-Gly-Leu by cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors: amastatin, captopril and phosphoramidon. The present investigations showed that the inhibitory effect of [Met(5)]enkephalin-Arg-Gly-Leu administered intra-third-ventricularly on the tail-flick response was increased more than 1000-fold by the intra-third-ventricular pretreatment of rats with three peptidase inhibitors. The inhibition produced by the enkephalin octapeptide in rats pretreated with any combination of two peptidase inhibitors was significantly smaller than that in rats pretreated with three peptidase inhibitors, indicating that any residual single peptidase could inactivate significant amounts of the octapeptide. The present data, together with those obtained from previous studies, clearly show that three types of enzymes, amastatin-, captopril- and phosphoramidon-sensitive enzymes, play important roles in the inactivation of endogenous opioid penta- and octa-peptides administered intra-third-ventricularly to rats.

Analgesics↗
PubMed2002

Rectal biopsy: what is the optimal procedure?

Rectal suction biopsy (RSB) is a well-known diagnostic procedure for disorders of bowel motility such as Hirschsprung's disease (HD). However, there are few reports about the optimal method of obtaining rectal tissue. We introduce a new technique using Gruenwald's nasal cutting forceps (NCF). From 1986 to 1999, we performed 130 sets of rectal biopsies in patients suspected of having HD. In group I (1986 to 1994), 68 sets of three-site biopsies (2, 3, and 5 cm above the dentate line) were performed using a conventional blind RSB technique. In group II (1995 to 1999), 62 sets of one-site biopsies (2 cm above the dentate line) were performed using Gruenwald's NCF after anal dilatation during general anesthesia. Hematoxylin-eosin staining and acetylcholinesterase histochemistry were used to examine all specimens. Biopsy specimens in group II (4.39 +/- 1.07 mm(2)) were larger than in group I (1.59 +/- 0.39 mm(2)) ( P < 0.01). In 18 cases (26 %) in group I, normal and HD bowel could not be differentiated because the specimens were too small to detect ganglion cells (i.e., only lamina propria [9 cases] or a small area of submucosa [9 cases] was present). These cases required repeat biopsy. All cases of HD diagnosed in group I (n = 20) were based on the findings of biopsies taken at 2 cm; biopsies from 3 and 5 cm did not provide additional information. There were 2 cases of post-biopsy hemorrhage in group I. In group II, 18 subjects were diagnosed with HD and 39 were confirmed to have normal bowel. There were no complications and repeating the biopsy was unnecessary. Three cases of hypoganglionosis (1 in group I and 2 in group II) were missed because the myenteric plexus abnormalities could not be detected by RSB. Intestinal neuronal dysplasia (IND) was diagnosed in 5 cases (2 in group I by repeat full-thickness biopsy and 3 in group II by rectal biopsy). We conclude that our new technique is advantageous and safe to differentiate between normal bowel, HD, and even IND on the basis of a single biopsy taken 2 cm above the dentate line. The biopsy can be taken under direct vision and is histopathologically accurate.

Adolescent↗
PubMed2002

Complete discontinuity of the distal fistula tract from the developing gut: direct histologic evidence for the mechanism of tracheoesophageal fistula formation.

The embryogenesis of tracheoesophageal anomalies remains controversial. The purpose of this study was to better define the embryogenesis of developing esophageal atresia with tracheoesophageal fistula (EA/TEF), with specific attention to the controversial issue of whether a discontinuity exists in the foregut during its development of EA/TEF. Pregnant outbred rats were injected with adriamycin (2 mg/kg i.p.) on days 6-9 of gestation (E6-E9). At E12.5 and 13.5, microdissection of the entire foregut was performed. Foreguts were examined by phase microscopy, and serial, precisely transverse sections were created for hematoxylin and eosin (H&E) staining. Gross microdissection of the developing foregut at E12.5 (n = 9) revealed a blind-ending, bulbous fistula tract arising from the middle branch of the tracheal trifurcation (as seen by direct and phase microscopy). No connection with the gut could be appreciated at E12.5, but by E13.5 (n = 10) there was an obvious connection between the fistula and the stomach. Serial H&E transverse sections also demonstrated a blind-ending fistula tract arising from the trachea at E12.5. This fistula tract was clearly discontinuous from the developing stomach, which appeared much further caudal to the end of the fistula tract. These results strongly support a model of experimental TEF wherein the fistula tract arises from a trifurcation of the trachea, and (only during a specific gestational window between days 12.5 and 13.5) there is discontinuity between the fistula tract and the stomach. By day 13.5, the fistula joins with the stomach anlage. These observations in the developing EA/TEF should help to resolve the controversy about the mechanism of EA/TEF formation.

Animals↗
PubMed2002

Acetylcholinesterase distribution and refractory constipation - a new criterion for diagnosis and management.

To describe manifestations of acetylcholinesterase (AchE) activity in the bowel of patients presenting with refractory constipation and correlate them with outcome, rectal biopsy specimens (RBS) from 165 patients who presented with refractory constipation between 1988 and 1999 were examined. Age at biopsy ranged from 4 days to 17 years; 45 subjects were excluded because they satisfied diagnostic criteria for Hirschsprung's disease, intestinal neuronal dysplasia, or hypoganglionosis. Thirty-five autopsy subjects were used as controls. All RBS were compared and AchE activity was assessed in the lamina propria (LP), muscularis mucosae (MM), and around the submucosal vessels (V). Variations in AchE distribution were classified as grade I (no AchE-positive nerve fibers in the LP or MM), grade II (some positive fibers in the LP or MM), grade III (moderate positive fibers in the LP or MM), grade IV (many positive fibers in the LP, MM, or V), or grade V (fibrillar, foamy, or amorphous staining for AchE). All grade I (11/120) and V (12/120) subjects achieved normal bowel control with laxatives alone and all grade II subjects (58/120) did with laxatives and enemas. Grade III subjects (34/120) required addition of cisapride. All grade IV subjects (5/120) were unresponsive to conservative management and 4/5 were found to have a megarectum, which was treated surgically. AchE distribution correlated well with eventual outcome and requirement for surgery. AchE distribution could also be used to classify bowel motility disorders, and we suggest the term AchE-positive disease be used to describe them.

Acetylcholinesterase↗
PubMed2002

Lectin as a marker for staining and purification of embryonic pancreatic epithelium.

The embryonic pancreatic epithelium, and later the ductal epithelium, is known to give rise to the endocrine and exocrine cells of the developing pancreas, but no specific surface marker for these cells has been identified. Here, we utilized Dolichos Biflorus Agglutinin (DBA) as a specific marker of these epithelial cells in developing mouse pancreas. From the results of an immunofluorescence study using fluorescein-DBA and pancreatic specific cell markers, we found that DBA detects specifically epithelial, but neither differentiating endocrine cells nor acinar cells. We further applied this marker in an immunomagnetic separation system (Dynabead system) to purify these putative multi-potential cells from a mixed developing pancreatic cell population. This procedure could be applied to study differentiation and cell lineage selections in the developing pancreas, and also may be applicable to selecting pancreatic precursor cells for potential cellular engineering.

Animals↗
PubMed2002

Retinoid signaling controls mouse pancreatic exocrine lineage selection through epithelial-mesenchymal interactions.

BACKGROUND & AIMS: The early embryonic pancreas gives rise to exocrine (ducts and acini) and endocrine lineages. Control of exocrine differentiation is poorly understood, but may be a critical avenue through which to manipulate pancreatic ductal carcinoma. Retinoids have been shown to change the character of pancreatic ductal cancer cells to a less malignant phenotype. We have shown that 9-cis retinoic acid (9cRA) inhibits acinar differentiation in the developing pancreas, in favor of ducts, and we wanted to determine the role of retinoids in duct versus acinar differentiation. METHODS: We used multiple culture systems for the 11-day embryonic mouse pancreas. RESULTS: Retinoic acid receptor (RAR)-selective agonists mimicked the acinar suppressive effect of 9cRA, suggesting that RAR-RXR heterodimers were critical to ductal differentiation. RARalpha was only expressed in mesenchyme, whereas RXRalpha was expressed in epithelium and mesenchyme. Retinaldehyde dehydrogenase 2, a critical enzyme in retinoid synthesis, was expressed only in pancreatic epithelium. 9cRA did not induce ductal differentiation in the absence of mesenchyme, implicating a requirement for mesenchyme in 9cRA effects. Mesenchymal laminin is necessary for duct differentiation, and retinoids are known to enhance laminin expression. In 9cRA-treated pancreas, immunohistochemistry for laminin showed a strong band of staining around ducts, and blockage of laminin signaling blocked all 9cRA effects. Western blot and RT-PCR of pancreatic mesenchyme showed laminin-beta1 protein and mRNA induction by 9cRA. CONCLUSIONS: Retinoids regulate exocrine lineage selection through epithelial-mesenchymal interactions, mediated through up-regulation of mesenchymal laminin-1.

Alitretinoin↗