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Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 199 records · Page 11Linked to original sources

Changes in bone mineral density of lumbar vertebrae after parturition in African green monkeys (Cercopithecus aethiops).

We examined the effect of lactation on the maternal bone components in laboratory-bred African green monkeys. Bone mineral density (BMD) with bone mineral content (BMC), bone area and mean width of lumbar vertebrae (L3-L5) were measured by dual-energy X-ray absorptiometry (DXA). Measurements were conducted at two-week intervals from parturition up to 40 weeks after parturition. The BMC and BMD values gradually decreased during the lactation period and then gradually increased after weaning, but the BMC and BMD of the maternal lumbar vertebrae did not recover completely to the values at parturition even at 40 weeks after parturition.

Absorptiometry, Photon↗

Effect of food intake on the delivery of fluorescein as a model drug in colon delivery capsule after oral administration to beagle dogs.

The effect of food on the release time of a model drug, fluorescein (FL), has been studied after oral administration to beagle dogs in colon delivery capsule in comparison to conventional gelatin capsule and enteric capsules. The dose of FL was 30 mg for each animal. After oral administration of each test preparation in fasted or postprandial condition (100 grams of commercial solid food was given at 30 min before drug administration), blood samples were collected and plasma FL concentrations were measured spectrofluorometrically. Pharmacokinetic analysis was performed with plasma FL concentration vs. time data and the following parameters were determined; Tmax (the time when plasma FL concentration reaches to its maximum concentration), Cmax (peak plasma FL concentration), Tlag (the time when FL appeared at first into the systemic circulation), AUC (area under the plasma FL concentration vs. Time curve) and MRT (mean residence time). For gelatin capsule, mean Tmax appeared at 0.83 +/- 0.33 (S.E.) h after administration and MRT was 2.67 +/- 0.21 h in fasted condition. By feeding, Tmax and MRT increased to 1.50 +/- 0.76 h and 3.09 +/- 0.49 h. For two enteric HPMCP and Eudragit S capsules, MRT were 2.90 +/- 0.48 h and 5.24 +/- 0.32 h in fasted condition, and 11.30 +/- 1.10 h and 12.83 +/- 0.34 h in postprandial condition, respectively. Tlag also increased by postprandial administration. As colon delivery capsule, time-controlled release capsule (TCC) and two types of intestinal inner pressure-controlled release capsules (PCC) (#1 is a separate type and #2 is a seamless one) were tested. MRT of TCC was 4.76 +/- 0.29 h and 6.43 +/- 0.66 h in fasted and postprandial conditions, respectively. This capsule did not receive the effect of food intake. For #1 PCC, MRTs were 5.32 +/- 0.22 h and 12.28 +/- 0.26 h in fasted and postprandial conditions, respectively. For #2 PCC, MRTs were 5.51 +/- 0.26 h and 13.36 +/- 0.84 h in fasted and postprandial conditions, respectively. In addition, the effect of two times feedings was studied with two PCCs and longer MRTs, 28.44 +/- 1.39 h and 26.32 +/- 1.64 h, were obtained. The release time of FL from PCCs increased by postprandial administration. As compared to the results on two enteric capsules, these PCCs are thought to disintegrate in the colon. However, TCC is thought to disintegrate in the stomach after postprandial administration.

Administration, Oral↗

[Diagnostic values and limitations of conventional urodynamic studies (uroflowmetry.residual urine measurement.cystometry) in benign prostatic hypertrophy].

PURPOSE AND METHODS: Diagnostic values and limitation of conventional urodynamic study (UDS) were assessed in 380 patients with benign prostatic hypertrophy (BPH), in terms of uroflowmetry, measurement of postvoid residual urine and cystometry. RESULTS: Maximum and average flow rate on uroflowmetry improved with increasing voided volume. Neither maximum nor average flow rate correlated with size of the prostate, subjective symptom (International Prostate Symptom Score) and bothersomeness for prostatism. Pre-TUR maximum flow rate did not predict outcomes on postoperative flow rate and surgical treatment failures. Uroflowmetry did not differentiate between obstruction and weakness of detrusor contraction. The intraindividual variation of postvoid residual urine was great and the volume of residual urine correlated poorly with subjective symptom, size of the prostate, maximum and average flow rate. On filling cystometry, although uninhibited detrusor contraction was much more frequently observed in patients with urge incontinence as compared with continent patients, there was no significant difference in other parameters between the two groups. Every parameter on cystometry did not correlate with nocturnal frequency. Postoperative persistence of urge incontinence did not correlate with the bladder volume at the first desire to void or at the maximum desire to void, an amplitude of uninhibited detrusor contractions, or bladder compliance. In some cases, evaluation of the intravesical pressure on voiding phase and uroflowmetry was diagnostic of apparent obstruction. CONCLUSIONS: In diagnosis of BPH, conventional UDS has limitation for certain and some caution showed be taken in interpretation of the data. However, since conventional UDS provides important and objective information on obstruction and detrusor function, which are independent of subjective symptom and prostate size, these should be necessary in diagnosis, determination of treatment options and evaluation of treatment outcomes in BPH.

Humans↗

Precursor directed biosynthesis of aureobasidins.

The antifungal antibiotic aureobasidin A (AbA) is a cyclic depsipeptide composed of eight amino acids and a hydroxy acid. New Ab analogs were produced by feeding various amino acids to Aureobasidium pullulans R 106 c-712 in a chemically-defined medium containing glucose and ammonium sulfate. The constituent amino acids of AbA at positions 3 (L-phenylalanine), 4 (N-methyl-L-phenylalanine), 5 (L-proline), 6 (L-allo-isoleucine) and 8 (L-leucine) were replaced by respective analogous amino acids such as o-fluoro-L-phenylalanine, 4-hydroxy-L-proline, L-norleucine and L-norvaline, resulting in the production of eight new Ab analogs. This is the first paper to describe amino acid replacements at positions 3, 5 and 8. L-[1-13C]-Valine exogenously added was incorporated into the three valine-related moieties of AbA at positions 2, 7 (both N-methyl-L-valine) and 9 (beta-hydroxy-N-methyl-L-valine), but these moieties were never replaced by exogenous amino acid analogs. The comparative antifungal activities of AbA and the eight new Ab analogs were determined.

Amino Acid Sequence↗

Survey for Pneumocystis carinii infection of wild-born and laboratory-bred monkeys by indirect immunofluorescence and cyst-staining methods.

A serosurvey for Pneumocystis carinii infection of laboratory-bred and wild-born monkeys was made by the indirect immunofluorescence method. The antibody titers of wild cynomolgus (Macaca fascicularis) and Japanese monkeys (Macaca fuscata fuscata) to P. carinii (Pc) were higher than those of laboratory-bred cynomolgus monkeys; 54.9% of the wild cynomolgus and 40% of Japanese monkeys had antibody titers higher than 1:40, although only 9.4% of the laboratory-bred cynomolgus monkeys did so. Pc cysts in the lungs were examined in the laboratory-bred cynomolgus monkeys by using toluidine blue O stain, and the number of cysts in the lung was small, when compared with those in the lungs of SIV-infected monkeys showing severe pneumosystosis. The results obtained from the studies suggested the possibility that P. carinii infection was more widely epidemic in the wild-born monkeys than in laboratory-bred monkeys.

Animals↗

[Synthetic vectors for gene transfection].

Although viruses can be efficient gene transfer vehicles developed by natural evolution, progress also has been made toward developing nonviral gene delivery systems. Various methods for nonviral gene transfer have been proposed and shown to be generally safe. Basically, synthetic vectors have to be capable of binding to DNAs and carrying them inside into target cells. Synthetic vectors are classified into three groups with respect to the chemical structure: cationic lipids, ligand-polycation conjugates and polycationic polymers. In this review, we summarize their ability to mediate gene transfer in relation to their structural characteristics. Although the molecular mechanisms including internalization via cell membrane and nuclear transport are still poorly understood, in the future systematic studies on the structure-activity relationship will be helpful for the design of more efficient artificial vectors.

Cations↗

Injury to a duplicated cystic duct during laparoscopic cholecystectomy.

Duplication of the cystic duct is a rare variation of the biliary system. It is important to pay attention to this variation to avoid intraoperative biliary system injury, especially during laparoscopic cholecystectomy. In a 66-year-old woman with gallstones, endoscopic retrograde cholangiopancreatography (ERCP) revealed no anomaly of the biliary system. At laparoscopic cholecystectomy, although intraoperative cholangiography demonstrated the second cystic duct, we misdiagnosed the duplication of cystic duct because preoperative ERCP had demonstrated normal anatomy. It was thought that the second cystic duct was dissected during the operation and the patient suffered from postoperative bile leakage. After reoperation, the patient recovered well. The diagnostic and therapeutic problems of such an anomaly are discussed below with the review of the literature.

Aged↗

Systemic lupus erythematosus with ischemic peripheral neuropathy and lupus anticoagulant: response to intravenous prostaglandin E1.

We report a case of systemic lupus erythematosus with cutaneous vasculitis and peripheral neuropathy. Results of laboratory examinations revealed lupus anticoagulant in the patient's serum. His lower limbs showed asymmetry. A sural nerve biopsy specimen showed modest degeneration of nerve fibers and incomplete obstruction of nutrient vessels. His cutaneous vasculitis responded to treatment with high-dose corticosteroid, but the lower limb neuropathy responded incompletely. Daily intravenous prostaglandin E1 treatment improved his neurologic and cutaneous symptoms markedly. Our case implied that nutritional vascular ischemia caused by lupus anticoagulant is involved in the pathogenesis of lupus neuropathy in addition to well-known peripheral nerve vasculitis. It also documented the effectiveness of intravenous prostaglandin E1 in the treatment of systemic lupus erythematosus.

Adult↗

Carboxyl end-specific monoclonal antibodies to amyloid beta protein (A beta) subtypes (A beta 40 and A beta 42(43)) differentiate A beta in senile plaques and amyloid angiopathy in brains of aged cynomolgus monkeys.

Senile plaques (SPs) and cerebral amyloid angiopathy (CAA) in the brains of five aged (20-26 years old) cynomolgus monkeys were investigated immunohistochemically using two monoclonal antibodies (anti-A beta 40 (BA27) and anti-A beta 42(43) (BC05)) that can differentiate the carboxyl termini of amyloid beta protein (A beta) subtypes. In four of five animals, all types of SPs (i.e. diffuse, primitive, and classical plaques; DPs, PPs, and CPs, respectively) were identified by BC05. However, BA27 did not label DPs and stained only about one third of PPs and CPs, mainly labeling granular structures and cored portions, respectively. In CAA, lesions of cortical capillaries reacted to BC05 in four of five cases, but rarely and weakly to BA27 in two of five cases. On the other hand, lesions of parenchymal and meningeal arterioles were stained by both BA27 and BC05. These staining profiles of SPs in cynomolgus monkeys correspond well to those in humans, although there are two remarkable features in cynomolgus monkeys. First, BA27 stained PPs associated with granular structures. Secondly, capillary A beta reacted intensely to BC05 but only slightly to BA27. Despite these unique features, the results suggest that aged cynomolgus monkeys can be used to investigate the pathogenesis of A beta deposition in SPs and CAA.

Amyloid beta-Peptides↗

Diaminoalkanes with an odd number of carbon atoms induce compaction of a single double-stranded DNA chain.

We have performed direct observations on the conformational change of a single double-stranded T4 DNA molecule induced by diaminoalkanes, NH3+(CH2)nNH3+(n = 1-6), by use of fluorescence microscopy. It was found that diamines with three and five methylene groups show a significant effect on the compaction of individual single DNA molecules. On the other hand, diamines with two, four and six methylene groups are not effective in the compaction of DNA. Such a drastic difference in the action of diamines suggests that not only the number of charge but also the length between the amino groups in the diamines plays an essential role in their interactions with DNA.

Alkanes↗

Effect of chemical sympathectomy on the neural spread of pseudorabies virus in mice.

To investigate the routes of neural spread of pseudorabies (Aujeszky's disease) virus (PRV), the effects of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) on clinical signs and viral spread in mice inoculated intraocularly with PRV were examined. Similar to non-treated mice, the treated mice developed pruritus as a major clinical sign, followed by peracute death, but the time of death tended to be slightly delayed in about half of the treated mice. On immunohistological examination, viral antigens in treated mice were found to be markedly reduced in all the ipsilateral retinae; they were detected diffusely in the forebrain area with a localization in the mammillary area. In the treated mice, viral antigens were also reduced in the ipsilateral trigeminal nerve ganglia as well as in its central nuclei. These findings indicate that both the sympathetic nervous system and the trigeminal nervous system play an important role in the neural spread of PRV. Possible involvement of the dopaminergic nervous system, particularly in the eye, as the main site of viral growth was discussed.

Animals↗

Immunohistochemical analysis of pseudorabies virus spread through neurons innervating the eyeball.

Pseudorabies virus (PRV) was inoculated intraocularly into BALB/c mice, and the distribution pattern of cells positive for several neurotransmitters and viral antigens in the eyeball, trigeminal nerve ganglia, and superior cervical ganglia was examined immunohistochemically to clarify the neural route of the virus spread. In the eyeball, substance P (SP)- and calcitonin gene-related peptide (CGRP)-positive cells were detected in the ipsilateral iris and ciliary body, neuropeptide tyrosine (NPY)-positive cells were detected in the choloid membrane, and tyrosine hydroxylase (TH)-positive cells were detected in the ipsilateral inner nuclear layer of the retina; all these cells contained viral antigens. In the superior cervical ganglia, viral antigen-positive cells containing TH or NPY were found at bilateral sites. In the trigeminal nerve ganglia, viral antigen-positive cells containing SP or CGRP were found at bilateral sites. These findings indicated that the SP- and CGRP-positive ganglion cells of the trigeminal nerve ganglia innervating the iris or ciliary body, and the NPY-positive ganglion cells of the superior cervical ganglia innervating the iris, ciliary body, and choroid membrane served as the route for the virus spread. These findings also suggested that dopaminergic neurons, such as the TH-positive retinal cells and TH-positive ganglion cells of the superior cervical ganglia, served as the route for virus spread.

Animals↗

Construction and evaluation of a virG thyA double mutant of Shigella flexneri 2a as a candidate live-attenuated oral vaccine.

A virG thyA double mutant of Shigella flexneri 2a was constructed as a candidate live-attenuated oral vaccine. In the keratoconjunctivitis model it did not provoke any adverse reaction by itself on guinea pigs' eyes and completely protected them from provoking keratoconjunctivitis. When (2.7-4.8) x 10(10) of the vaccine was inoculated intragastrically after 1 day fasting in cynomolgus monkeys three times at weekly intervals, a watery stool was observed at 40% as a side-effect. Upon intragastric challenge after 1 day fasting with 7.5 x 10(9) of the virulent strain four weeks after the last vaccination, a statistically significant difference was obtained in the mortality rate but not in the morbidity rate between the vaccine and the control group, although the clinical findings were less severe in the vaccine group than in the control group. These results together with the histopathological and immunological findings indicate that the vaccine deserve further detailed studies.

Animals↗

A computer program for the analysis of chromatograms used in pharmacokinetic studies.

An analog/digital (A/D) converter and software written in BASIC language have been developed for the analysis of chromatographic data which are needed for pharmacokinetic (PK) studies in humans and in experimental animals such as dogs and rats. Using an A/D converter, widely sold personal computers produced by NEC or EPSON are applicable to both high-performance liquid-chromatography (HPLC) data analysis and PK analysis. When chromatographic data is taken up by the computer and treated as a variable, a maximum of 12,000 data points are saved by the computer. As 10 digital data points are taken up by the computer per second through the A/D converter, the maximum run time of a chromatogram is 20 min. For the purpose of HPLC analysis, however, five digital data points per second are usually enough for routine analysis. In this software, the program is written to take and save five digital data points/s. Therefore, the maximum run time of this software increased to 40 min per chromatogram. All the digital data through the A/D converter are saved into the data file on a floppy disk or hard disk. For the chromatogram analysis, both automatic peak identification and manual peak identification, which must be selected with the use of the mouse driver, are available. All the data, peak area, peak height, etc. are also saved into the data file. After a calibration curve is produced, following the input of peak analysis data of known spiked samples, the drug concentration for each sample is estimated. These concentration-time data are also saved into the data file.(ABSTRACT TRUNCATED AT 250 WORDS)

Analog-Digital Conversion↗

Surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia.

The various surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia (SEA) are discussed by presenting three such cases. As gastric adenoma with SEA had been considered to be a precancerous condition but not normally an indication for gastrectomy, we devised an operative strategy of laparotomy and thoracotomy. For Case 1, with early oesophageal cancer and gastric adenoma with SEA in the body of stomach, a laparotomy and local resection of the gastric lesion were carried out prior to thoracotomy in order to determine the safest reconstructive method after measuring the length of the well-nourished gastric tube. In Case 2, with advanced oesophageal cancer, a thoracotomy was first performed to assess the curability of surgery for the oesophageal cancer and a gastric adenoma was removed. In contrast, for Case 3 with advanced oesophageal cancer, and in whom post-operative survival was deemed to be short, a gastric adenoma was not resected. The most appropriate operative methods should thus be decided after careful consideration of the stage of the oesophageal cancer and characteristics of the gastric adenoma.

Adenoma↗

The role of p53 inactivation in human cervical cell carcinoma development.

We investigated the association between human papillomavirus (HPV) infection and p53 gene mutation in 47 primary uterine cervical cancers. HPV DNA sequences were present in 43 cancers (91.5%), and one of these cancers contained a p53 gene mutation. In addition, one of the remaining four HPV-negative cancers also contained a p53 gene mutation. As a result, p53 inactivation corresponded to the development of 44 of the primary uterine cervical cancers studied (93.6%). We obtained both primary and recurrent tumours from four cases. In two of these cases, the HPV genomes that were present in an episomal state in the primary tumours were observed to have disappeared in the recurrent tumours. One of these recurrent tumours also contained a p53 gene mutation, which suggested the possibility that p53 inactivation was required in order to maintain the aggressive behaviour in this cancer either by an HPV infection or by a p53 gene mutation. No MDM2 gene amplification was observed in the tumours that carried neither HPV DNAs nor p53 gene mutations.

Adenocarcinoma↗

Activation of complement in quails bearing Rous sarcoma virus-induced tumors.

The concentration of serum C3 in quails bearing tumors induced by Rous sarcoma virus (RSV) was elevated in parallel with tumor growth, whereas serum C3 levels in quails inoculated with avian leukosis virus, which lacks transforming activity, showed a pattern similar to that in mock-infected quails. C3 deposition was also observed in almost all tumor cells at the tumor developing stage. These findings obtained in vivo suggest that the cells transformed by RSV activated the C3 on their surfaces.

Animals↗

Activation of homologous complement via the alternative complement pathway by quail cells transformed by Rous sarcoma virus.

After incubation of the cells with fresh quail serum, deposition of the third component of complement (C3) was demonstrated on the cell surface of various quail cell lines transformed by Rous sarcoma virus (RSV) as well as on that of primary quail embryo (QE) cells transformed by RSV. The C3 deposition occurred irrespective of virus production. On the other hand, the C-3 deposition was not observed on two quail cell lines transformed by a chemical carcinogen, QE cells infected with avian leukosis virus or normal QE cells. Moreover, QE cells infected with a temperature-sensitive mutant of RSV activated the complement at 37 degrees C but not at 41 degrees C. Since the progeny virus was generated even at 41 degrees C, viral molecules on the cell surface may not play an essential role for the activation. The activation of complement was blocked by EDTA but not by EGTA-Mg++. Therefore, the complement activation on the transformed cells appears to be mediated via the alternative complement pathway (ACP). Similar results were obtained with the complement consumption test; the residual cytolytic activity of fresh quail serum via ACP was markedly reduced by pre-incubation of the serum with transformed cells.

Animals↗