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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 307 records · Page 17Linked to original sources

Epidemiology of diseases of unknown etiology, specified as "intractable diseases".

In Japan, epidemiological studies on intractable diseases have been undertaken and greatly promoted for more than 20 years by the Research Committee on Epidemiology of Intractable Diseases, with the financial supports from the Ministry of Health and Welfare of Japan. In this paper, chronological history of development of the Research Committee and some scientific accomplishments by the recent Research Committee (1993-1995) were summarized, mainly focusing on descriptive, analytical and other epidemiological studies. Hoped is that the readers are to be acquainted with the recent research activities by the Research Committee and seek for possible international collaborations in epidemiological studies on intractable diseases.

Epidemiologic Methods↗

Sodium balance and hypertension in obese and fatty rats.

To investigate the role of sodium in obesity induced hypertension, Wistar fatty rats (WFR) were employed. This rat has the following characteristics: (1) hyperglycemia, (2) hyperinsulinemia, and (3) hypertriglycemia. Four percent sodium chloride with constant amount of food intake was administered to these rats from 8 to 16 weeks. During this period, body wt, food intake, water consumption, urine volume, systolic blood pressure, urinary excretion of sodium and potassium, urinary albumin excretion, plasma sodium and potassium, and plasma glucose and immunoreactive insulin (IRI) were measured before, and twice more during eight weeks. No remarkable changes were observed in plasma glucose level during these periods between the two groups. On the other hand, in group 1 IRI significantly increased compared with group 2. Mean blood pressure was increased from 110 +/- 5 to 130 +/- 8 mm Hg (P < 0.01). To ascertain whether this salt sensitivity relates to the abnormalities in pressure-natriuresis responses, the pressure-natriuresis (P-N) was characterized. The P-N curve in WFR was shifted to the right and its slope was flattened compared to its control Wistar lean rats. In conclusion, an excess of dietary sodium intake may contribute to an elevation of blood pressure in Wistar fatty rat with hyperglycemia and hyperinsulinemia. This salt sensitivity may change the abnormal pressure-natriuresis responses.

Animals↗

[Combination chemotherapy with 5-FU and CDDP or CDDP analog for head and neck cancer].

Combination chemotherapy with CDDP and 5-FU is one of the effective regimens for head and neck cancer. We studied the difference in the effects and adverse effects between two kinds of schedules of CDDP administration for CDDP-5-FU combination chemotherapy. For 13 patients, CDDP was administered on 5 consecutive days from day 1 to day 5 at a daily dose of 16 mg/m2 (Regimen A). For 14 patients CDDP was administered 80 mg on day 1 (Regimen B). 5-FU was administered 700 mg/m2/ day as a continuous drip infusion for 120 hours from day 1 to day 5. For regimen A, the response rate was 77%; for regimen B, it was 64%. The pattern of adverse effects showed a difference. Regimen B was more toxic for renal function than regimen A. But regimen A showed toxicity for bone marrow function. Acute phase nausea and vomit appeared more frequently in regimen B. The difference in the adverse effect pattern, which depends on the schedule of CDDP administration, seems important in order to apply this regimen for head and neck cancer patients safely. The schedule of CDDP administration should be changes depending on the renal and bone marrow function of patients. In order to evaluate the efficacy of UFT as adjuvant chemotherapy, UFT was administered p.o. to patients with maxillary sinus carcinoma for more than one year after definitive treatment with surgery or radiotherapy. Fifteen patients with UFT adjuvant chemotherapy showed significantly better survival rates than patients without adjuvant chemotherapy. We also studied adjuvant chemotherapy with CBDCA and FT for patients with advanced head and neck cancer. Administration with UFT (600 mg/day) from day 1 to day 14 with CBDCA 350 mg/m2 at day 7 was repeated more than twice. This regimen showed low toxicity and better survival for nasopharyngeal cancer patients. More clinical trials with this regimen for adjuvant chemotherapy are needed.

Adolescent↗

Successful foscarnet therapy for mucocutaneous infection with herpes simplex virus in a recipient after unrelated bone marrow transplantation.

A 36-year-old Japanese man who received an unrelated bone marrow transplant (BMT) developed severe mucocutaneous infection with herpes simplex virus (HSV) type 1 during oral acyclovir prophylaxis. The lesions progressed despite treatment with intravenous acyclovir and vidarabine. The HSV isolates were sensitive acyclovir, vidarabine and foscarnet in vitro, but peripheral CD3- or CD19-positive cells were barely detectable even 4 months after transplant. A 12-day course of treatment with foscarnet led to a rapid improvement. Foscarnet therapy should be considered for all severe HSV infections following BMT, regardless of whether or not the HSV isolates are sensitive to acyclovir.

Acyclovir↗

[Commencement and discontinuance of receiving financial aid for intractable disease treatment].

Data concerning all patients receiving financial aid for 26 types of intractable diseases in 1984, 1988 and 1992 were individually linked. Proportions of patients who discontinued financial aid in 1988 or 1992 among patients who were receiving aid in 1984 (ratio of discontinuance per patients); and ratios of the numbers of patients newly commencing aid in 1988 or 1992 to the numbers of patients who were receiving aid in 1984 (ratio of commencement per patients) were calculated. The results were as follows; 1. Among patients receiving financial aid in 1984, ratios of discontinuance per 100 patients were 28 in 1985-88 and 43 in 1985-92. Ratios of commencement per 100 patients were 96 in 1985-88 and 203 in 1985-92. 2. Ratios of discontinuance and of commencement per 100 patients in 1985-92 among 26 intractable diseases were 27-96 and 31-1,068, respectively. 3. Ratios of discontinuance per patients were higher an age groups 0-19 year and 60 year and over than in other age groups. Ratios of commencement per patients were higher in age groups 20-29 year and 70 year and over than in other age groups. Both ratios were higher among males than among females. 4. Ranges of ratios of discontinuance per patients and of ratios of commencement per patients were smaller among 47 prefectures than among diseases and age groups. The number of patients receiving financial aid in 1984 per population among prefectures was inversely correlated to ratios of commencement per patients, and were not correlated with ratios of discontinuance per patients.

Adolescent↗

[Teratogenicity study of magnesium chloride hexahydrate in rats].

Teratogenicity of magnesium chloride hexahydrate (MgCl2.6H2O) was examined in rats. Magnesium chloride hexahydrate dissolved in distilled water was given to pregnant Wistar rats by gavage once a day from day 6 through 15 of pregnancy at doses of 0, 200, 400 and 800 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Magnesium chloride hexahydrate caused no increased incidences of fetal malformation, and no toxic signs in the pregnant rats and the fetuses. It was concluded that magnesium chloride hexahydrate has no teratogenicity in rats when given by gavage. The no observed adverse effect level was estimated to be over 800 mg/kg/day for both pregnant rats and rat fetuses.

Abnormalities, Drug-Induced↗

A newly established megakaryoblastic/erythroid cell line that differentiates to red cells in the presence of erythropoietin and produces platelet-like particles.

In August, 1992, we established a leukemic cell line (NS-Meg) from a patient in megakaryoblastic transformation of Philadelphia chromosome-positive chronic myeloid leukemia. The NS-Meg cells were positive for alpha-naphthyl acetate esterase and periodic acid-Schiff (PAS) staining and for surface CD4, CD7, CD13, CD34, CD41a, and glycophorin A antigens. Ultrastructurally, the cells had alpha-granules, demarcation membranes, and platelet peroxidase activity. The NS-Meg cells spontaneously produced platelet-like particles which contained alpha-granules, mitochondria and dense bodies, strongly suggesting platelet production. Erythropoietin (Epo), granulocyte/macrophage colony stimulating factor(GM-CSF), and interleukin 3 (IL-3) promoted the growth of NS-Meg cells. Phorbol-12-myristate-13-acetate increased the expression of both CD41a and CD61 antigens. Ten-day exposure to Epo induced mature erythroblasts and red cells. These benzidine-positive cells were positive for hemoglobin F staining. Untreated NS-Meg cells expressed mRNA for the Epo receptor (EpoR), for GATA-1, and for alpha 1, alpha 2 and gamma globin genes. These results indicate that NS-Meg cells undergo terminal differentiation of both megakaryocytic and erythroid lineages. This cell line should be a very useful tool for the investigation of both megakaryocytic and erythroid maturation.

Adult↗

Subsite-specific risk factors for colorectal cancer: a hospital-based case-control study in Japan.

To investigate the subsite-specific risk factors for colorectal cancer, we conducted a case-control study, using a common questionnaire which inquired about general lifestyles over the past five years (1988-92), at the Aichi Cancer Center Hospital, Nagoya, Japan. This study compared 432 patients with histopathologically diagnosed colorectal cancer (94 proximal colon [cecum, ascending colon, transverse colon]; 137 distal colon [descending colon, sigmoid colon]; 201 rectum [rectosigmoid, rectum]); and 31,782 first-visit outpatient controls who were free from cancer. In both genders, habitual smoking selectively increased the risk for rectum cancer. Soft or loose feces increased the risk for all subsites of colorectal cancer, particularly in female rectum cancer (odds ratio [OR] = 4.5). Among female dietary habits, Japanese-style foods decreased the risk for distal colon cancer, but increased the risk for proximal colon cancer. These results suggested that the risk factors for colorectal cancer differ by subsite among such a low-risk population as the Japanese. It is suggested also that 'irritable bowel' (soft or loose feces) might be associated with distal subsites of colorectal cancer, independently or combined with habitual smoking.

Adult↗

Effects of human middle ear effusions on the mucociliary system of the tubotympanum in the guinea pig.

Effusion fluid resulting from otitis media contains a variety of inflammatory substances. This middle ear effusion (MEE) may be itself affect the mucosa of the tubotympanum and contribute to chronicity of the condition. The present study was designed to elucidate in vitro and in vivo effects of MEEs on the mucosa of the guinea pig tubotympanum. The results obtained demonstrated that the ciliary activity of the eustachian tube was reduced in the presence of human MEEs. This activity decreased to approximately 80% in the presence of serous MEE at 48 h and was 60% after exposure to mucoid MEE. Intratympanic inoculation of human MEEs resulted in accumulation of a serous effusion in the tympanic cavity. Histologic study of the tubotympanum in inoculated animals demonstrated mucociliary dysfunction as well as a general inflammatory process and increased vascular permeability. This damage was more prominent following inoculation with the mucoid MEEs. The ciliary depression and inflammation found in the tubotympanum suggest that the pathologic nature of MEEs may be, at least partially, responsible for the chronicity of otitis media.

Animals↗

Alcohol dehydrogenase (ADH) isozymes in the AdhN/AdhN strain of Peromyscus maniculatus (ADH-deermouse) and a possible role of class III ADH in alcohol metabolism.

Although the AdhN/AdhN strain of Peromyscus maniculatus (so-called ADH- deermouse) has been previously considered to be deficient in ADH, we found ADH isozymes of Classes II and III but not Class I in the liver of this strain. On the other hand, the AdhF/AdhF strain (so-called ADH+ deermouse), which has liver ADH activity, had Class I and III but not Class II ADH in the liver. In the stomach, Class III and IV ADHs were detected in both deermouse strains, as well as in the ddY mouse, which has the normal mammalian ADH system with four classes of ADH. These ADH isozymes were identified as electrophoretic phenotypes on the basis of their substrate specificity, pyrazole sensitivity, and immunoreactivity. Liver ADH activity of the ADH- strain was barely detectable in a conventional ADH assay using 15 mM ethanol as substrate; however, it increased markedly with high concentrations of ethanol (up to 3 M) or hexenol (7 mM). Furthermore, in a hydrophobic reaction medium containing 1.0 M t-butanol, liver ADH activity of this strain at low concentrations of ethanol (< 100 mM) greatly increased (about sevenfold), to more than 50% that of ADH+ deermouse. These results were attributable to the presence of Class III ADH and the absence of Class I ADH in the liver of ADH- deermouse. It was also found that even the ADH+ strain has low liver ADH activity (< 40% that of the ddY mouse) with 15 mM ethanol as substrate, probably due to low activity in Class I ADH. Consequently, liver ADH activity of this strain was lower than its stomach ADH activity, in contrast with the ddY mouse, whose ADH activity was much higher in the liver than in the stomach, as well as other mammals. Thus, the ADH systems in both ADH- and ADH+ deermouse were different not only from each other but also from that in the ddY mouse; the ADH- strain was deficient in only Class I ADH, and the ADH+ strain was deficient in Class II ADH and down-regulated in Class I ADH activity. Therefore, Class III ADH, which was found in both strains and activated allosterically, may participate in alcohol metabolism in deermouse, especially in the ADH- strain.

Alcohol Dehydrogenase↗

Evaluation of a low-dose intravesical bacillus Calmette-Guérin (Tokyo strain) therapy for superficial bladder cancer.

To examine whether intravesical instillation of low-dose bacillus Calmette-Guérin (BCG) therapy is effective with low toxicity, we reviewed data for 111 patients with superficial bladder cancer (stages Ta and T1). Among them, 74 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection, and the remaining 37 therapeutically for Ta or T1 tumours. The patients were divided into two groups by instillation dose of BCG (Tokyo 172 strain): 40 mg (n = 55) and 80 mg (n = 56), and statistically compared for recurrence, antitumour effect and toxicity. The mean instillations were done 8.4 times in the 40 mg dose group and 8.6 times in the 80 mg dose group. Among the 74 patients with BCG therapy for prophylaxis those with a previous episode of bladder cancer treatment (n = 47) experienced a significantly (p = 0.006) shorter recurrence-free interval than those with no episode (n = 27). Among 47 patients with a previous treatment episode, those receiving the 80 mg dose demonstrated a significantly longer recurrence-free interval than those given the 40 mg dose (p = 0.03). Among the 27 patients without previous treatment no significant difference in recurrence-free intervals was found between the two dose groups. Univariate and multivariate analyses using Cox's proportional hazards model confirmed the above findings. The recurrence index was also significantly reduced after BCG therapy in the 80 mg and 40 mg groups and similar antitumour effects for Ta or T1 tumours were observed in the two dose groups. The degree of toxicity due to BCG therapy was significantly (p = 0.02) lower with the 40 mg dose. The present study suggests that (1) a 40 mg BCG low-dose (Tokyo 172 strain) regimen is useful for preventing recurrence, with sufficient therapeutic efficacy and low frequency of toxicity, among patients without a previous treatment, and (2) prophylactic effects with the 80 mg dose regimen are much superior for previous treatment cases.

Aged↗

Complete disruption of the main pancreatic duct: a case successfully managed by percutaneous drainage.

The authors report on a 7-year-old boy who sustained blunt abdominal trauma on a bicycle handlebar. A large traumatic pancreatic pseudocyst developed, for which percutaneous external drainage under ultrasound guidance was performed. Both the catheter fistulogram and endoscopic retrograde cholangiopancreatogram showed complete disruption of the main pancreatic duct. During continuous external drainage, the pseudocyst disappeared. The drainage flow decreased gradually and ceased. The patient is well, with normal endocrine and exocrine pancreatic functions, 2 years after discharge.

Abdominal Injuries↗