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Biomedical subjects

S Fukuchi

Publications and source records attributed to S Fukuchi.

At least 19 recordsLinked to original sources

[A case of insulinoma with frequent hypoglycemic attacks not showing evident hyperinsulinemia].

Confirmation of inappropriate hyperinsulinemia is an indispensable requisite for the diagnosis of insulinoma. We report here a case of insulinoma without evident hyperinsulinemia at an early stage. The patient, a 49-year-old woman, had been admitted to our hospital for the evaluation of frequent hypoglycemic attacks. At that time, plasma immunoreactive insulin (IRI) after an overnight fast ranged from 7 to 16 microU/ml. The ratio of IRI/fasting blood sugar (FBS) (Fajans index; normal range, below 0.3) was always between 0.13 and 0.28 even at hypoglycemic states. In addition, because computed tomography and arteriography of the abdomen failed to settle the diagnosis of insulinoma, the patient was discharged and followed up at our outpatient clinic for 2 years. She was admitted to our hospital at 51 years of age for the re-evaluation of hypoglycemic attacks. Laboratory examinations revealed high fasting plasma levels of IRI ranging from 20 to 29 microU/ml. Fajans index also increased to 0.47-0.89. Celiac arteriography was able to confirm the existence of insulinoma. We suggest that insulinoma should be considered in the presence of unexplained hypoglycemic attacks even when there is no evident hyperinsulinemia.

Blood Glucose

Evolution of metabolic pathways by chance assembly of enzyme proteins generated from sense and antisense strands of pre-existing genes.

In order to get an insight into the evolutionary aspect of metabolic pathways, especially of the ubiquitous glycolytic pathway, we have carried out an extensive search of sense-sense and sense-antisense similarities for enzyme proteins in the glycolytic pathway, the pentose phosphate cycle, alcohol and lactate fermentation pathways and the TCA cycle. This investigation of amino acid sequences reveals a curious pattern of similarity relations; no similarity can be found between the enzyme proteins in a section of the glycolytic pathway where the glyceraldehyde-3-phosphate or even glycerol-3-phosphate is converted into the pyruvate while many examples of sense-sense and sense-antisense similarities are found even between enzyme proteins in distant blocks, e.g. between the proteins in the TCA cycle and those in the pentose phosphate cycle, as well as between the functionally associated proteins in each of these blocks. Complementary to this characteristic pattern of amino acid sequence similarity, the search for similarities of nucleotide sequences also finds that the similarities of glycolytic enzyme genes, some sense-sense and others sense-antisense similarities, are concentrated on the nucleotide sequences of prokaryotic 16S or eukaryotic 18S ribosomal RNA gene with its flanks, although some of the copy sequences are also found in transfer RNA genes as well as in 23S or 26S ribosomal RNA gene. These results strongly suggest that the metabolic pathways have been developed by the chance assembly of enzyme proteins generated from the sense and antisense strands of pre-existing genes, e.g. the fermentation pathways and pentose phosphate cycle by the proteins from the genes of enzymes in the glycolytic pathway and the TCA cycle from all these successively increased genes, ascribing the origin of metabolic enzyme genes to the close relation between the glycolytic enzyme protein genes and the RNA gene cluster.

Animals

Antihypertensive and hormonal activity of MK 954 in spontaneously hypertensive rats.

MK 954 (DuP 753), a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally for 2 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Whereas the basal levels of plasma Ang II were lower in SHR than in WKY, treatment with MK 954 markedly reduced blood pressure in SHR but not in WKY. Plasma renin activity, Ang I and Ang II were increased, while plasma aldosterone was decreased in both strains. These results no only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but also support the idea that the renin-angiotensin system plays an important role in the control of blood pressure in SHR.

Angiotensin I

Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats.

Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor antagonist, was administered orally to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per day) lowered blood pressure markedly. Losartan reduced significantly the left ventricular weight by 11% compared with control rats. The left ventricular Ang II content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue, control, p less than 0.05), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and Losartan-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.563, p less than 0.05). These results provide evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension.

Analysis of Variance

Hypotensive activity of TCV-116, a newly developed angiotensin II receptor antagonist, in spontaneously hypertensive rats.

TCV-116, a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally (1 mg/kg per day) to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Blood pressure and plasma components of the renin-angiotensin-aldosterone system were determined in these rats. TCV-116 produced a marked reduction in blood pressure without altering heart rate. Whereas plasma renin concentration (PRC), angiotensin I (Ang I) and angiotensin II (Ang II) all were significantly increased, plasma aldosterone was decreased by approximately 70% compared with control animals. These results not only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but support also the concept that the renin-angiotensin system plays an important role in the control of blood pressure in this animal model of human essential hypertension.

Angiotensin Receptor Antagonists

Clinical evaluation of the efficacy and safety of manidipine in hypertensive patients with renal disorders.

Hypertension is an important factor that accelerates deterioration in renal function. This study evaluated the antihypertensive effectiveness, tolerability, and safety of manidipine hydrochloride, a new dihydropyridine calcium channel antagonist. Sixteen patients (10 men and 6 women) with hypertension and renal disorders received 10 or 20 mg of manidipine once daily for 12 weeks. After 4 weeks of therapy, manidipine treatment produced significant reductions in both systolic and diastolic blood pressures to 146.9 +/- 3.2/87.1 +/- 2.1 mmHg from a baseline value of 174.4 +/- 3.0/98.4 +/- 3.0 mmHg. The antihypertensive effect was well tolerated and sustained during drug administration. Biochemical variables including serum creatinine were essentially unchanged during therapy despite the marked reduction in blood pressure. In addition, renal function did not deteriorate during manidipine therapy as assessed by urinary excretion of phenolsulfonphthalein (22.6 +/- 4.0% vs. 27.9 +/- 6.0%, control). No severe adverse effects were encountered during therapy. We conclude that manidipine is a safe and useful antihypertensive agent for the management of hypertensive patients with renal disorders.

Adult