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Biomedical subjects

K Furumi

Publications and source records attributed to K Furumi.

At least 19 recordsLinked to original sources

Defect in pancreatic exocrine and endocrine response to CCK in genetically diabetic OLETF rats.

Clinical as well as experimental studies in insulinopenic diabetes mellitus have demonstrated abnormal pancreatic exocrine responses to cholecystokinin (CCK). In the present study, we examined pancreatic exocrine and endocrine function in the recently developed genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and compared them with those in the control Long-Evans Tokushima Otsuka (LETO) rats of the same age. Stepwise increasing doses of CCK octapeptide (CCK-8; 0.027-7.0 nmol.kg-1.h-1) evoked a characteristic biphasic dose-response curve for pancreatic juice and protein output in the LETO rats, whereas the OLETF rats were totally insensitive to CCK-8 stimulation. However, the responsiveness and the sensitivity to both carbamylcholine and secretin were similar in the two groups. Intraduodenal infusion of casein (500 mg/h) failed to stimulate pancreatic exocrine secretion in the OLETF rats despite a greater CCK response than in the LETO rats (peak response: 8.43 +/- 0.97 vs 5.12 +/- 0.30 pmol/l in LETO, P < 0.01). Intravenous infusion of CCK-8 (4.4 nmol.kg-1.20 min-1) caused a significant increase in serum insulin concentrations and a concomitant decrease in glucose levels in the LETO rats but not in the OLETF rats. On the other hand, an intravenous bolus injection of 1.1 mmol/kg glucose caused a greater insulin release in the OLETF rats than in the LETO rats. In contrast, gastric acid secretion in the OLETF rats was significantly high in basal and in response to intravenous infusion of CCK-8 compared with that in the LETO rats. Four subcutaneous injections of 20 micrograms/kg caerulein at hourly intervals over 3 h induced acute pancreatitis in the LETO rats but did not elicit any significant increase in serum amylase or lipase activities and pancreatic wet weight or histological evidence of acute pancreatitis in the OLETF rats. These results indicate that the exocrine and endocrine pancreas of the recently developed genetically diabetic OLETF rats are totally and specifically insensitive to exogenous and endogenous CCK stimulation, whereas parietal cells in these rats are sensitive to CCK stimulation.

Acute Disease

Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats.

Pancreatic exocrine function of a new inbred strain Otsuka Long-Evans Tokushima Fatty (OLETF) rat that develops spontaneous persistent hyperglycemia was evaluated in in vitro isolated pancreatic acini and compared with that in the control Long-Evans Tokushima Otsuka (LETO) rat. Serum glucose and insulin concentrations in the OLETF rats were significantly high (glucose: 270 +/- 12 vs. 208 +/- 10 mg/100 ml, P < 0.01; insulin: 12.4 +/- 1.7 vs. 4.9 +/- 0.6 ng/ml, P) < 0.01), whereas pancreatic wet weight was significantly low (803 +/- 20 vs. 1,138 +/- 17 mg, P < 0.01) compared with those in the LETO rat. Pancreatic acini isolated from the OLETF rat were totally insensitive to cholecystokinin (CCK)-8 stimulation at concentrations of up to 100 nM. However, neither the responsiveness nor the sensitivity to carbamylcholine, bombesin, and secretin of the acini from the OLETF rat was altered or even increased, probably due to the larger amylase content in the OLETF rat acini compared with those of the LETO rat acini (31.5 +/- 2.0 vs. 13.0 +/- 1.1 Somogyi units/micrograms DNA, P < 0.01). The responsiveness to fluoride, a direct activator of guanine nucleotide-binding protein, in the OLETF rat acini was similar to that in the LETO rat, suggesting that the transmembrane signaling and effectors and subsequent intracellular signal transduction molecules in the OLETF rat acini are normal. Moreover, 125I-CCK binding to the acini prepared from the OLETF rat was totally absent. These present results indicate that the OLETF rat has a selective defect in the binding of CCK to its receptors on the acinar cell surface.

Amylases

[A 10-year field surveillance in Hinohara Village of Tokyo Prefecture from 1981 to 1990].

We conducted a surveillance to clarify the relationship between risk factors for diseases of adulthood and lifestyle in a Japanese rural community, Hinohara Village, a small village outside of Tokyo. The survey, carried out from 1981 to 1990 among residents aged 40 and over, comprised physical examination and blood chemistry with a questionnaire about dietary intake. Mean systolic blood pressure significantly decreased (p < 0.0001) from 140.9 mmHg in 1981 to 132.3 mmHg in 1990, whereas mean serum total cholesterol, mainly of male examinees, increased (p < 0.0001) from 181.4 mg/dl in 1981 to 191.7 mg/dl in 1990. Dietary salt intake significantly decreased (p < 0.0001) from 14.3 g/day in 1981 to 12.1 g/day in 1990. Adjusted mortality rate per 1,000 residents from cerebrovascular disease in this village decreased from 1.80 in 1981 to 0.50 in 1990. In contrast to its decline, the mortality rates from heart disease, bronchitis/pneumonia and neoplasms were 0.40, 0.35 and 0.55 in 1981 and increased to 1.25, 1.10 and 0.64 in 1990. The prevailing practice of maintaining a low-salt diet might cause the decrease of systolic blood pressure, which in turn was thought to decrease the mortality rate from cerebrovascular diseases. Although our previous study before 1981 suggested that total cholesterol was one of the preventive factors against cerebrovascular disease, in the present study a preventive effect of cholesterol was not substantiated. In contrast, cholesterol is a possible risk factor for ischemic heart disease. Thus, a changing pattern of risk factors of diseases of adulthood was observed in this village.

Adult

Solid-phase immunofluorometric assay for quantification of CSF immunoglobulins. Determination of normal reference values.

Because a highly sensitive method is required to quantify low concentrations of immunoglobulin (Ig) classes in cerebrospinal fluid (CSF), there have been a few papers reporting normal values of CSF IgG, IgA and IgM determined in the same samples. Enzyme immunoassay (EIA) is most frequently used, but has such drawbacks as susceptibility of enzyme to inhibition and denaturation and the requirement for additional incubation with a substrate. Therefore, solid-phase immunofluorometric assay was evaluated for quantification of CSF IgG, IgA and IgM in the nanogram range. We found this to be rapid and reproducible. The mean (SD) values of normal CSF samples obtained from 22 subjects with tension headache were 23.9 (7.6) micrograms/ml for IgG, 2.00 (0.90) microgram/ml for IgA and 197 (87) ng/ml for IgM. The normal mean (SD) values of indexes were 0.51 (0.10) for IgG, 0.25 (0.05) for IgA and 0.044 (0.017) for IgM. These values agreed quite well with those determined by EIA. The values of CSF albumin correlated significantly with those of CSF IgG or IgA, but did not with those of CSF IgM. Levels of each of the three Ig classes in CSF and serum were significantly correlated. When CSF/serum ratio was introduced, a significant correlation between the albumin ratio and each Ig ratio was found. These results suggest that the Ig content of normal CSF may depend upon that of serum and upon the characteristics of the Ig molecule.

Adolescent

[Total gastrectomy after VEPA therapy in a case of primary gastric lymphoma (stage III of Naqvi's clinical staging)].

A 51-year-old male was referred to our hospital with complaints of chest and back pain. He was diagnosed as primary gastric lymphoma after medical examination. Because of a spreading of the lesion and his poor condition, we concluded that a curative operation would be impossible, and used VEPA therapy as combination chemotherapy. After three cycles of VEPA therapy, the man underwent total gastrectomy, which resulted in better prognosis and no malignant cells in the resected stomach. According to Naqvi's clinical staging, stage III gastric lymphoma is inoperable. We report here a case of stage III gastric lymphoma which could undergo curative operation after chemotherapy and continue to be in good condition.

Antineoplastic Combined Chemotherapy Protocols

[In vitro culture of mouse embryos for toxicological evaluation. (3): Effect of carcinogens on development of the embryos].

Mouse embryos were collected at the 2 cell or 8 cell stage. The embryos of each stage were exposed to 1 pM-10 nM 4-nitroquinoline-1-oxide (4-NQO) or 1 nM-10 microM N-methyl-nitro-nitrosoguanidine (MNNG) for 24 hr, and cultured to develop to blastocysts within clean medium. Since after exposure to 4-NQO, the appearance of early blastocysts and blastocysts were increased in exposure groups compared with controls, the growth to the 8 cell stage embryo (8-E) appeared to be late in development. Frequency of sister chromatid exchange (SCE) and mitotic index were increased with doses in the blastocysts (2-B) which derived from 2-E. There was little change in the SCE and mitotic index for blastocysts (8-B) which derived from the 8 cell stage embryo (8-E). Cessation of development in the 2 cell stage embryo (2-E) appeared in the 10 microM group during the period of exposure to MNNG. Development to the 8-E stage appeared to be slightly late in the other exposed groups. Thereafter at 48 hr after the initiation of culture, the exposed groups appeared to be more advanced in development than the controls. After this period, developmental rates to blastocysts were increased in the 10-100 nM groups. It appeared that the development of these groups was more advanced. In 2-B after exposure to MNNG, cell counts were dose-responsively increased in the 1 and 10 nM groups. The mitotic index in the 1 to 100 nM groups was higher than the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Nitroquinoline-1-oxide

Impairment of blood-cerebrospinal fluid barrier in multiple sclerosis.

The blood-CSF barrier (BCB) function in active multiple sclerosis (MS) was studied by means of CSF proteins analysis using disc electrophoresis and immunofixation. Forty-five CSF samples were obtained by repeat lumbar punctures at various intervals, from four autopsy-proven cases and three male and nine female patients with clinically definite MS. When total protein content was increased, the percentages of prealbumin and tau fraction were decreased significantly in association with the presence of haptoglobin (Hp) polymers in nearly all the samples, as a result of increased permeability of the BCB. Even when the total protein content was normal, Hp polymers were detected in 56% of the samples, and the tau fraction tended to be decreased. Monoclonal immunoglobulin and Hp polymers were both recognized in some cases. The results suggested a more frequent occurrence of BCB impairment in MS than had formerly been revealed by CSF albumin analysis, and accorded with the recent reports of contrast-enhancing lesions of MS brain in computerized tomography.

Adolescent

Characteristic protein fractions of cerebrospinal fluid disc electrophoretic analysis.

The present work was undertaken to determine characteristic proteins of normal cerebrospinal fluid (CSF) by disc electrophoresis in polyacrylamide gel, and to evaluate their usefulness as indicators of blood-brain-CSF barrier disturbance. The technique has been applied to 1280 samples of unconcentrated CSF obtained from 27 reference subjects and 847 neurological patients, with a simultaneous analysis of 361 sera. The pre-albumin content (mean +/- S.D. as a percentage of total protein, 11.0 +/- 2.3%) was higher than formerly reported. One reason for this is that preliminary concentration was not necessary, and the second is related to the principle of protein resolution. The no. 5 protein band of the post-albumin group (3.9 +/- 1.1%) was characteristic, though it has not yet been identified. The no. 3 protein band of the post-transferrin group (5.2 +/- 1.7%) was highly specific to CSF; it was found to be closely related to transferrin, and may correspond to tau fraction obtained by other methods. Barrier dysfunction was easily recognizable by the appearance of polymers of haptoglobin 2-1 or 2-2, because only haptoglobin 1-1 was detected in normal CSF. The percentage of the main region of the G-zone (13.7 +/- 2.6%) was postulated as normal content of CSF immunoglobulins.

Albumins

Polyacrylamide-gel disc electrophoresis of unconcentrated urine samples with special reference to Bence Jones proteins.

The polyacrylamide-gel disc electrophoresis has been applied to the fractionation of 27 samples of unconcentrated urine obtained from the patients with monoclonal gammopathy. It was shown that 44% of the whole Bence Jones protein bands examined were detected in the area between 0.70 and 0.90 expressed in terms of relative migration based on transferrin. The method provided a satisfactory separation of native urine proteins with good reproducibility and few technical difficulties. It may become an efficient tool in clinical chemistry.

Bence Jones Protein