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Biomedical subjects

H Machida

Publications and source records attributed to H Machida.

At least 91 records · Page 5Linked to original sources
PubMed1992

In vitro drug combination of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil with anti-human immunodeficiency virus or anticancer nucleosides.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and E-5-(2-bromovinyl)uracil, a metabolite of BV-araU, did not affect either the anti-human immunodeficiency virus activity or the cytotoxicity of azidothymidine in MT-4 and MOLT-4 cells. Similarly, the bromovinyl compounds did not affect the in vitro antitumor activities of arabinosylcytosine, 5-fluorouracil, and 5-fluoro-2'-deoxyuridine. The anti-varicella-zoster virus activity of BV-araU was not influenced by azidothymidine, 2',3'-didehydro-2',3'-dideoxythymidine, or arabinosylcytosine, whereas relatively high concentrations of fluorinated antitumor agents enhanced the anti-varicella-zoster virus activity.

Antiviral Agents↗
PubMed1992

Effects of inline filtration on delivery of gentamicin at various flow rates.

The effects of inline filtration on delivery of gentamicin (GM) in the pediatric field were studied. The filter sets (Pall 0.20 micron. JMS 0.20 micron, and IVEX 2.022 micron) were studied using a simulated system. 10 mg of GM was injected into the system containing 5% dextrose in water (flow rate: 50 ml/hr, 10 ml/hr and 2 ml/hr) with horizontal and vertical settings of the inline filters. In case of 50 ml/hr, delivery of GM of Pall showed nearly the same delivery pattern as compared with no filter setting. However, JMS and IVEX 2 showed little differences. In case of 10 ml/hr and 2 ml/hr those differences became more significant. Delivery of GM was influenced by the priming volume of the filters, increasingly so at slow flow rates. Filter settings also influenced the delivery of GM. Furthermore, with regards to the results of the Vitamin K2 delivery and the technetium radiotracer method, JMS and IVEX 2 filters were observed to have some stagnation of drugs in the filter. Not only priming volumes of the filters affect delivery of drugs, filter designs also have an influence. The use of the inline filters is important in the pediatric field, but their charactaristics for drug delivery pattern should be considered.

Drug Contamination↗
PubMed1992

[Bezafibrate myopathy in two patients with chronic renal failure].

Case 1, a 60-year-old man and case 2, a 70-year-old man had several year history of chronic renal failure with hypertension and hyperlipidemia due to diabetes mellitus. Treatment of hyperlipidemia was started by oral bezafibrate intake 1,200 mg per day in case 1 and 400 mg per day in case 2 respectively. Three to fourteen days later, both patients noticed symmetrical muscle pain and weakness. Then the symptoms worsened and they were hospitalized. At the time of admission, both patients revealed weakness in the proximal muscles of their upper and lower limbs and the serum creatine kinase and myoglobin levels were remarkably elevated. Myoglobinuria was also noted. Routine light microscopic examination of biopsied quadriceps femoris muscles of two patients showed scattered necrotic muscle fibers, some of which were under phagocytosis. The symptoms of the patients were immediately resolved after the drug was discontinued. Serum concentration of bezafibrate was remarkably elevated during treatment. Thus the diagnosis was established as having bezafibrate induced myopathy and, as far as we know, this is the first report of bezafibrate induced myopathy in Japan. On the basis of the above description, bezafibrate may induce muscle damage if dose is excess over the renal capacity. Extreme caution is warranted when the patient is placed on bezafibrate and has renal dysfunction. Strict dose adjustment is necessary in taking account of renal function to avoid muscle damage including rhabdomyolysis.

Aged↗
PubMed1992

[A case of invasion of the hyaloid artery into the lens].

A 6-year-old boy with hyaloid artery invasion into the crystalline lens is reported. Both lenses had localized opacities and some brown membranous tissue attached to the posterior lens capsule. He had bilateral persistent hyaloid arteries, and in the right eye this vessel penetrated the lens capsule and invaded the lens. The lens opacity had not increased for 6 years. In persistent hyperplastic primary vitreous we can often see the invasion of fibrovascular tissue into the lens, and this process usually leads to destruction and absorption of the lens. This is an unusual case because the lens showed no significant changes for long period of time in spite of vascular invasion into the lens.

Arteries↗
PubMed1991

The role of gastroesophageal reflux in pediatric dysphagia.

The history, physical examination, and the results of the upper gastrointestinal series, esophageal manometry, 24-h pH recording, endoscopy, and biopsy are reviewed in 16 children (mean age of 10.6 years, range of 3 years 5 months to 15 years 3 months) who presented to the Alberta Children's Hospital with dysphagia ("food-sticking") without previously identified provocative disorders since January 1985. Of the 16 patients, 11 had had intermittent obstruction, and 7 had had intervention to relieve obstruction (2 Heimlich maneuvers, 1 intravenous glucagon, and 4 endoscopy after failure of intravenous glucagon). Although only five children had a recent history suggestive of gastroesophageal reflux, 12 had histologic evidence of reflux esophagitis (including 1 with a peptic stricture, 1 with "nutcracker" esophagus, and 1 with esophageal dysmotility characteristic of Down's syndrome) and all responded clinically to antireflux therapy. Of the remaining four patients, one had extrinsic esophageal compression from a vascular ring (right aortic arch with left ligamentum arteriosum), one had a single and another had recurrent episodes of food-sticking without any identified abnormality, and one declined investigation. In childhood, dysphagia may be the presenting symptom of reflux esophagitis in the absence of a history suggestive of gastroesophageal reflux and without evidence of a peptic stricture.

Adolescent↗
PubMed1991

Inhibition of DNA synthesis in varicella-zoster virus-infected cells by BV-araU.

The inhibitory effect of BV-araU on DNA synthesis in human embryonic lung cells infected with varicella-zoster virus (VZV) or herpes simplex virus type 1 (HSV-1) was compared with that of acyclovir. Cellular uptake of [3H]thymidine and its incorporation into DNA was markedly stimulated by the infection with VZV or HSV-1, suggesting that the incorporation was mainly due to viral DNA synthesis. DNA synthesis in VZV-infected cells was dose-dependently suppressed by BV-araU and acyclovir, although cellular uptake of [3H]thymidine decreased in cells treated with a high concentration of drugs for an extended time. DNA synthesis in HSV-1-infected cells was also markedly inhibited by both drugs in a dose-dependent manner, without affecting cellular uptake of [3H]thymidine. The concentration of drugs inhibiting DNA synthesis was well correlated to their in vitro anti-VZV and anti-HSV-1 activities. The inhibitory concentration of BV-araU for DNA synthesis in VZV-infected cells was one-thousandth of that of acyclovir. Our results suggest that the antiviral action of BV-araU against VZV and HSV-1 is based on the inhibition of DNA synthesis in herpesvirus-infected cells.

Acyclovir↗
PubMed1991

Different antiviral potencies of BV-araU and related nucleoside analogues against herpes simplex virus type 1 in human cell lines and Vero cells.

Antiviral potencies against herpes simplex virus type 1 (HSV-1) of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and ten other nucleoside analogues in human embryonic lung fibroblast (HEL) cells were compared with those in Vero cells. 5-Halogenovinylarabinosyluracils, highly active in HEL cells, were inactive against all three laboratory-stocked strains of HSV-1 but exerted moderate antiviral effects on three clinical isolates in Vero cells. The reduction in anti-HSV-1 potencies of other representative nucleoside analogues in Vero cells was much less than those of 5-halogenovinylarabinosyluracils. However, significant antiviral potencies of BV-araU against laboratory strains were observed in other human and monkey fibroblast cells including an immortalized cell line. Significant enhancement of antiviral activity of BV-araU against a laboratory strain and a clinical isolate was demonstrated in Vero cells by the addition of 0.1 microM aminopterin or FUdR, an inhibitor of thymidylate synthesis. The potentiated anti-HSV-1 activity in Vero cells was comparable to the potency in HEL cells without the inhibitor. These results suggested that high activity of thymidylate synthesis and a large thymidylate pool size in Vero cells seem to be related to loss of anti-HSV-1 potency of BV-araU. Original tissue type, species, and the immortality may not be responsible for the reduced antiviral activity of BV-araU in Vero cells.

Aminopterin↗
PubMed1991

Myasthenia gravis, muscle twitch, hyperhidrosis and limb pain associated with thymoma: proposal of possible new myasthenic syndrome.

We describe a 54-year-old man with myasthenia gravis, thymoma, systemic muscle twitch particularly of both lower limbs, hyperhidrosis and lower limb pain. The muscle twitch resembled to fasciculation rather than to myokymia and was persistent after discontinuation of anti-acetylcholinesterase drug. No attenuation nor disappearance of the muscle twitch was educed by spinal anesthesia. However, it disappeared when a nondepolarizing type muscle relaxant (pancuronium bromide) was used. The muscle twitch was thus considered to originate from peripheral axons. Thymoma was considered to be involved in the pathogenesis of these unusual clinical manifestations which may constitute a new myasthenic syndrome.

Biopsy↗
PubMed1991

[A case of acinar-islet cell tumor of the pancreas body].

Combined carcinoma of the pancreas is very rare. The case of pancreatic tumor featuring both acinar cell and islet cell tumors presented, may be only the fifth case of acinar-islet cell tumor in the world. A 34-year-old-woman visited our hospital complaining of weight loss (8 kg/6 months). A clearly demarcated pancreatic tumor was visualized by ultrasonography, body CT and MRI. Class 3 cells were extracted via ultrasonography guided fine-needle biopsy. Tumor was enucleated on October 5, 1988. Histologic appearance of the tumor by light microscopy was consistent with that of both acinar cell and islet cell tumors. Electron microscopy revealed two distinct populations of zymogen and neuroendocrine granules. The patient is doing well 1 year and 7 months postoperatively with no evidence of liver metastasis or recurrence. This case is significant in terms of the close histogenic relationship between pancreatic exocrine and endocrine components.

Adenoma, Islet Cell↗
PubMed1991

Postprandial hyperglycemia and pancreatic function in cystic fibrosis patients.

Pancreatic endocrine function was studied in 50 patients with cystic fibrosis (CF) and 15 healthy controls by measuring glucose, insulin, C-peptide, glucagon and gastro-inhibitory polypeptide responses to an oral glucose tolerance test (OGTT). Biochemical and clinical parameters were also measured, including glycosylated hemoglobin A1, serum immunoreactive trypsin, fasting urinalysis, pulmonary function, percentage body fat and 3-day dietary records. According to National Diabetes Data Group (NDDG) criteria, 6 CF patients had impaired glucose tolerance (ICF), with elevated serum glucose concentrations and reduced and delayed insulin secretion compared with control (CON) subjects, although none were overtly diabetic. Although the remaining 44 CF patients (NCF) did not meet NDDG criteria for impaired glucose tolerance, mean area under the concentration curve (AUC) for glucose was greater than control values and AUC for insulin diminished. HbA1 levels in the 2 CF groups were greater than that of controls subjects, but there was little difference between ICF and NCF groups. C-peptide levels paralleled those of insulin for the 3 groups throughout OGTT. There was little difference in GIP secretion between groups, and the enteroinsular axis was intact in the control and NCF groups and slightly increased in the ICF group. Basal glucagon concentrations and AUC for glucagon during OGTT were similar for the 3 groups, but glucose-induced glucagon suppressibility i.e., basal to nadir change in each subject, was reduced in the ICF group. Serum IRT concentration was significantly lower in the ICF and NCF groups compared to control subjects, and was lowest in the ICF group. A strong correlation was observed in the ICF group between FEF25-75 and AUC for insulin, as well as HbA1 level and AUC for glucose. The prevalence of impaired glucose tolerance in 50 CF patients was 12%. Despite extensive comparisons of biochemical and clinical parameters with endocrine function in this population, we were unable to define reliable criteria for predicting glucose intolerance.

Adolescent↗
PubMed1991

[Roentgenological manifestation of ossification of the posterior longitudinal ligament in the cervical spine causing severe spinal canal stenosis--a group comparison with and without marked spinal cord dysfunction].

Relationship between the degree of clinical symptoms and the lateral roentgenograms of the cervical OPLL causing severe spinal canal stenosis was studied among patients whose roentgenological minimum antero-posterior diameters of the available spinal canals were under 9mm. Lateral roentgenograms of 28 clinically mild patients were compared with those of 20 clinically severe patients. The type of ossification, the extent of OPLL, the narrowest level of the available spinal canal, and the minimum a-p diameter were not statistically significant parameters. The degree of canal stenosis at the 1cm cranial and 1cm caudal levels from the narrowest level, and the axial extent of canal stenosis around the narrowest level were less significantly in the group with mild symptoms than in the group with severe symptoms.

Adult↗
PubMed1990

Importance of retinal pigmentation as a subclinical marker in familial adenomatous polyposis.

Surgery was performed in 35 patients with familial adenomatous polyposis (FAP) from 22 family trees. To clarify retinal pigmentation as an important subclinical marker in patients with FAP, precise retinal examinations were performed in 41 cases (82 eyes), including 23 patients and 18 family members including 12 second-generation and third-generation possible carriers. In 27 patients, precise studies were done on accompanying lesions, and the number of polyps was counted at the time of surgery in each patient in every family tree. The overall incidence of retinal pigmentation in patients was 82.6 percent. The incidence of retinal pigmentation in possible carriers was found to be 50 percent, which is comparable with the calculated expressibility of the polyps. The shape and distribution of pigmentations were classified into two categories--large and small. A total of 1984 control retinal examinations were performed, which revealed only six retinal pigmentations (0.3 percent). In the control group, all pigmentation was solitary and unilateral. No large pigmentations in bilateral eyes were found in the control group. In large pigmentation, the sensitivity and specificity were calculated as 0.652 and 0.999, respectively, and in small pigmentation, the sensitivity and specificity were calculated as 0.783 and 0.997, respectively. Small pigmentation appears to increase in number around the age of the appearance of the polyp. Earliest recognition of the pigmentation in this series was one year of age.

Adenomatous Polyposis Coli↗
PubMed1990

Comparison of antiviral efficacies of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) and acyclovir against herpes simplex virus type 1 infections in mice.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) and acyclovir were compared for their antiviral effects against herpes simplex virus type 1 (HSV-1) model infections in mice. Both drugs were not toxic to mice when they were administered orally by the same schedule used for therapeutic experiments. Brovavir was less toxic than acyclovir when injected by the intraperitoneal (i.p.) route. Marked efficacies of brovavir by either oral or i.p. administration were demonstrated in both experimental encephalitis and i.p. infection with HSV-1 WT-51 strain. Treatment with brovavir at a dose of 15 or 25 mg/kg twice daily resulted in increasing both survival rate and mean survival time of the infected mice. On the contrary, acyclovir showed only marginal effect against the experimental encephalitis. Survival rates of mice treated with brovavir were higher than those treated with acyclovir at corresponding doses with statistical significance. The superiority of brovavir was also found in the intracerebral infection with strain VR-3, a highly virulent strain for mice. Brovavir, but not acyclovir, at a dose of 200 mg/kg reduced the mortality. Acyclovir, however, were significantly effective in reducing mortality of systemically infected mice by both oral and i.p. administrations. The effective dose of acyclovir was lower than that of brovavir against i.p. infection with strain WT-51. Differences in mortality of strain VR-3-infected mice were statistically significant between acyclovir- and brovavir-treated groups.

Acyclovir↗
PubMed1990

Drug susceptibilities of isolates of varicella-zoster virus in a clinical study of oral brovavir.

Susceptibilities to brovavir [1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)-uracil] and acyclovir of clinical isolates of varicella-zoster virus obtained from 58 patients with herpes zoster, included in a clinical trial of oral brovavir, were tested by a plaque reduction method. All 101 isolates were significantly susceptible to brovavir; 50% effective dose of brovavir for these isolates ranged between 0.6-4.0 ng/ml (average: 1.29 ng/ml). Brovavir was about 3,000 times more potent than acyclovir against these isolates. No marked change in the susceptibility of isolates from these patients during treatment with brovavir was observed.

Acyclovir↗
PubMed1990

Antiviral potencies of BV-araU and related nucleoside analogues against varicella-zoster virus in different cell lines.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and nine other antiherpesviral nucleoside analogues were compared for their potencies against four strains of varicella-zoster virus (VZV) on three different cell lines: HEL cells, Vero cells, and MS cells established from a human malignant schwannoma. In contrast to the activity against herpes simplex virus type 1 previously reported, BV-araU showed extremely marked antiviral activity against VZV even on Vero cells. ED50, 50% plaque reduction dose, of BV-araU for VZV was 0.20-3.1 and 0.14-0.63 ng/ml on Vero cells and on HEL cells, respectively. Potency of BV-araU on MS cells was similar to that on these cell lines. There was not significant variation in anti-VZV activities of other nucleoside analogues on these three different cell lines except a few combinations of VZV strain and test compound.

Animals↗
PubMed1990

Effect of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil against herpes simplex virus type 1 infection in immunosuppressed mice.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) reduced the mortality rates of (i) 7-week-old, cyclophosphamide-treated, immunosuppressed mice (CYP mice) intraperitoneally infected with a moderately virulent strain of herpes simplex virus type 1 and (ii) 4-week-old CYP mice infected with a less virulent strain at doses of 20 and 50 mg/kg of body weight twice daily and 5 mg/kg, respectively. The degree of efficacy of BV-araU was equivalent to that of acyclovir in 4-week-old CYP mice infected with the less virulent strain. BV-araU (20 mg/kg) suppressed viral growth in various organs of CYP mice.

Acyclovir↗
PubMed1990

Effect of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) on experimental infections in mice with herpes simplex virus type 1 strains of different degrees of virulence.

In vivo antiherpesvirus effects of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) were tested in two mouse model infections with herpes simplex virus type 1 (HSV-1) strains which showed different degrees of virulence in mice. Successful efficacies of oral and intraperitoneal (i.p.) treatments with brovavir were demonstrated in both intracerebral and i.p. infections with the HSV-1 WT-51 strain of moderate virulence. However, only weak or modest effects of brovavir were observed against the two model infections with a highly virulent strain, HSV-1 VR-3. Brovavir was not effective in reducing mortality of mice infected i.p. with HSV-1 KOS, which exhibited the highest virulence in mice among HSV-1 strains used when inoculated i.p. However, the drug had a significant effect on intracerebral infection with the KOS strain. Efficacies of oral treatment with brovavir were almost equal to those of i.p. administration in the model infections. After intracerebral inoculation, the VR-3 strain grew in brains of mice at a higher rate than the WT-51 strain. By oral treatment with 50 mg of brovavir per kg twice daily, replication of the WT-51 strain in the brains was markedly suppressed and was eliminated after transient elevation of the titer. Growth of the VR-3 strain in the brains was simply delayed by the drug treatment. Thus, the antiviral efficacy of brovavir in mice was affected by the degree of virulence of the challenge virus strain used for infection.

Animals↗