Biomedical subjects

T Tsuchihashi

Publications and source records attributed to T Tsuchihashi.

At least 73 records · Page 4Linked to original sources

PubMed1992

Comparison of effects of enalapril and captopril on serum potassium concentration in the treatment of malignant hypertension.

To compare the effects of enalapril and captopril on blood pressure, serum creatinine (S-Cr), and potassium (S-K) levels, patients with malignant hypertension treated with either 5-10 mg of enalapril (eight cases) or 75-400 mg of captopril (eight cases) were investigated retrospectively. After 2 weeks of treatment, the average blood pressure fell from 214/138 to 132/89 mmHg on enalapril and from 240/145 to 147/95 mmHg on captopril. The percent change in mean blood pressure during the 2 weeks of treatment with enalapril (-35.6 +/- 4.0 SE%) was similar to that with captopril (-35.8 +/- 2.8%). S-Cr did not change in both groups, while S-K increased significantly from 3.9 +/- 0.2 to 5.2 +/- 0.2 mEq/l on enalapril and from 3.6 +/- 0.2 to 4.2 +/- 0.1 mEq/l on captopril. S-K at the second week was significantly higher in the enalapril than in the captopril group. The maximum S-Cr concentration during the treatment was correlated with the corresponding S-K concentration similarly in both groups. These results indicate that both enalapril and captopril increase S-K without deterioration of renal function in patients with malignant hypertension and that the way these drugs are used in clinical practice may be more likely to result in elevated S-K with enalapril.

Adult↗

PubMed1992

Differential modulation by mu- and delta-opioids on baroreceptor reflex in conscious rabbits.

We examined the role of central mu- and delta-opioids on both neurohormonal responses and baroreceptor reflex in conscious rabbits. Both intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a mu-selective agonist, and [D-Ala2,D-Leu5]-enkephalin, a delta-selective agonist, caused dose-related increases in arterial pressure and renal sympathetic nerve activity, whereas intravenous injection of the same maximum dose of these peptides as that used in the intracerebroventricular experiment did not cause any cardiovascular and neuronal responses. On the other hand, increases in plasma epinephrine, norepinephrine, and glucose levels induced by intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin were significantly greater than those by [D-Ala2,D-Leu5]-enkephalin. Both enkephalins did not cause any responses in plasma renin activity, plasma vasopressin, and serum sodium and potassium concentrations. The sensitivity of the baroreceptor reflex control of renal sympathetic nerve activity using a logistic model was enhanced by a subpressor dose of intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10 pmol/kg) but not by [D-Ala2,D-Leu5]-enkephalin. Conversely, a mu-selective dose of intravenous naloxone (0.1 mg/kg) attenuated baroreceptor reflex sensitivity. Intravenous naloxone methobromide, which has been shown not to cross the blood-brain barrier, did not change baroreceptor reflex sensitivity, suggesting that naloxone acts at the central nervous system. In conclusion, in conscious rabbits, 1) intracerebroventricular mu- and delta-receptor agonists caused pressor responses and 2) mu-opioid agonist altered baroreceptor reflex control of renal sympathetic nerve activity and produced changes in sympathoadrenal responses.

Animals↗

PubMed1992

Hashimoto's thyroiditis in HTLV-I carriers.

We describe two HTLV-I virus carriers who have biopsy-proven Hashimoto's thyroiditis. The first patient, a 64-year-old female, has had goiter and hypothyroidism since the age of 56. The second patient, a 66-year-old male, developed hyperthyroidism and goiter at the age of 44, but at present he is hypothyroid. Both patients are positive for anti-thyroid antibodies and anti-HTLV-I virus antibody. Findings of the thyroid biopsy specimens were consistent with Hashimoto's thyroiditis. These data suggest that Hashimoto's thyroiditis develops in HTLV-I carriers who have no clinical evidence of HAM/TSP.

Aged↗

PubMed1992

Chronic cardiovascular effects of central vasopressin in conscious rats.

To clarify the cardiovascular effects of central vasopressin (AVP), a chronic intracerebroventricular (ICV) infusion of AVP was performed in conscious Wistar normotensive rats. Animals were divided into 3 groups: 1) AVP 1 ng/hr (Low), 2) AVP 100 ng/hr (High), and 3) saline (control) ICV infusion. After a 6 day control period, AVP or saline was continuously infused into the lateral cerebroventricle at a rate of 1 microliter/hr using osmotic minipump for 7 days. As a result, a dose-related elevation of AVP concentration in CSF was achieved. Systolic blood pressure in both Low and High AVP infusion was slightly (7-12 mmHg) but significantly higher than that in control. ICV infusion of AVP did not alter urine volume, electrolytes excretion or osmolality, and AVP vascular antagonist injected intravenously failed to affect mean arterial pressure. Furthermore, plasma catecholamines and renin activity did not differ significantly among the groups. Thus, chronic ICV infusion of AVP induced the elevation of blood pressure, which is due to centrally mediated effect of AVP.

Animals↗

PubMed1992

Cerebrospinal fluid sodium and enhanced hypertension in salt-loaded spontaneously hypertensive rats.

OBJECTIVE AND DESIGN: The present study was designed to determine whether increases in sodium concentration in the cerebrospinal fluid (CSF) play a role in the augmented hypertension induced by long-term salt loading in spontaneously hypertensive rats (SHR), and whether the enhanced arginine vasopressin (AVP) activity and/or the sympathetic nervous system contribute to the increased hypertension. METHODS: Measurement of CSF sodium concentration and systolic blood pressure of SHR during salt loading, with or without uninephrectomy, for 7 weeks. Assessment of the hypotensive response to AVP antagonist and hexamethonium, and the plasma levels of AVP and catecholamines. RESULTS: Salt-loading for 7 weeks led to gradual increase in hypertension in SHR. CSF sodium in the SHR was increased by a combination of uninephrectomy and saline-drinking after 7 weeks, but not 3 weeks. The difference in mean arterial pressure (MAP) among the three groups of SHR disappeared after the combined blockade of AVP and sympathetic nervous function. CSF sodium correlated with both resting MAP and the fall in MAP induced by the combined administration of AVP antagonist and hexamethonium. Plasma levels of AVP were significantly elevated in the salt-loaded uninephrectomized SHR. Plasma catecholamines did not change significantly as a result of treatment. CONCLUSIONS: We tentatively conclude that chronic salt loading may lead to an increase in CSF sodium, in association with an enhancement of sympathetic nerve activity and, to some extent, of AVP release. These events may explain the augmented development of hypertension in SHR.

Animals↗

PubMed1992

Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors.

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.

Adenoma, Islet Cell↗

PubMed1991

Retroperitoneal neurilemoma presenting with humoral hypercalcemia associated with markedly elevated plasma prostaglandin levels.

A 72-year-old woman complaining of somnolence and thirst was diagnosed to have a hypercalcemic crisis (corrected serum calcium level, 17.4 mg/dl) associated with encephalopathy and nephropathy. Imaging diagnostic techniques demonstrated a retroperitoneal tumor at the median site of right renal pelvis. Hormonal studies revealed that plasma levels of thromboxane B2, prostaglandin (PG) E2, 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin F2 alpha (PGF2 alpha) were markedly elevated. The tumor was successfully removed by operation; her serum calcium level and PG levels normalized without any treatment indicating that this case belongs to the category of humoral hypercalcemia of malignancy (HHM). Pathologically, this tumor was diagnosed to be a benign neurilemoma. Parathyroid hormone-related protein (PTHrP) radioimmunoassay and Northern blot hybridization for PTHrP mRNA were negative. The current case demonstrates that hypercalcemic crisis could be induced by a curable benign neurilemoma, and suggests that this HHM-like morbidity was associated with markedly elevated plasma PG levels.

Aged↗

PubMed1991

Ambulatory blood pressure monitoring in elderly hypertensives treated with the new calcium antagonist, nilvadipine.

A newly developed calcium antagonist, nilvadipine, was administered to 7 hypertensive patients aged 75.6 y. Nilvadipine 4 mg b.d. decreased the average 24-h blood pressure significantly from 169/89 mmHg to 152/81 mmHg after 7 to 14 days without any change in the pulse rate. The circadian patterns of blood pressure and pulse rate were not affected by nilvadipine. Although the present study was a preliminary one done over a short period in a small number of patients, the results suggest that nilvadipine exerts an antihypertensive effect without altering the circadian pattern or the variability of blood pressure in elderly hypertensive patients.

Aged↗

PubMed1991

Production of parathyroid hormone-related protein in tumour xenografts in nude mice presenting with hypercalcaemia.

This study examined the pathophysiological role of parathyroid hormone-related protein (PTHrP) in humoral hypercalcaemia of malignancy (HHM). Seven human tumour xenografts were analysed in nude mice; five tumours (KEsC-2, oesophageal carcinoma; FA-6, pancreatic carcinoma; SEKI, melanoma; Lu-65A and Lu-61, lung carcinomas) were associated with hypercalcaemia and two tumours (MIA PaCa-2, pancreatic carcinoma; PLC/PRF/5, hepatocellular carcinoma) with normocalcaemia. Northern blot analyses, radioimmunoassay and bioassay confirmed the synthesis of PTHrP-like peptides by all five tumours associated with hypercalcaemia, but not by the two associated with normocalcaemia. These observations indicated a very close relationship between the production of PTHrP and the development of HHM. Gel filtration studies of three tumour tissue extracts revealed at least two different molecules with both PTHrP-like immunological and biological activities. One peak eluted at a position between PTHrP (1-141) and cytochrome C and the other at a position identical to cytochrome C. These results suggest that PTHrP molecules with a molecular size equal to or greater than cytochrome C participate as causative agents of HHM. All five tumour xenografts caused hypercalcaemia when grown to a size of 1.5 g in nude mice. Under cell culture conditions, four original cell lines, KEsC-2, FA-6, SEKI and Lu-65A secreted 450.0, 45.0, 3.6 and 3.0 pmol of immunoreactive PTHrP/1.5 x 10(9) cells (approximately equivalent to 1.5 g wet weight) 24 h-1 into their respective culture media. Since a subcutaneous infusion of 100 pmol 24 h-1 of PTHrP (1-34) into nude mice was sufficient to induce significant hypercalcaemia, we speculate that PTHrP alone released from tumour cells could induce hypercalcaemia at least in the case of KEsC-2, and possibly in FA-6. With regard to other tumours associated with hypercalcaemia, further examination of PTHrP and other compounds with bone-resorbing activity in these transplantable tumours is required to obtain a better understanding of this morbidity.

Animals↗

PubMed1991

Central effect of endothelin on neurohormonal responses in conscious rabbits.

It has been shown that endothelin-1 (ET-1) binding sites exist in the central nervous system and that the injection of intracerebroventricular ET-1 induces a pressor response. Therefore, we determined the neurohormonal and cardiovascular responses to intracerebroventricular ET-1 (25 pmol/kg) in conscious rabbits with chronically instrumented electrodes on the renal sympathetic nerve. Intracerebroventricular ET-1 provoked a prompt increase in arterial pressure and in renal sympathetic nerve activity within 5 minutes, and peak values were obtained at 20 and 40 minutes, respectively. Plasma epinephrine and norepinephrine reached peak values at 5-20 minutes. Plasma vasopressin and plasma glucose levels also increased significantly, but plasma osmolality, hematocrit, and serum sodium and potassium concentrations did not show any changes. Arterial blood gas analysis showed respiratory alkalosis. However, pretreatment with intravenous pentolinium (5 mg/kg), a ganglion blocking agent, abolished these neurohormonal and cardiovascular responses. Conversely, the same dose of intravenous ET-1 (25 pmol/kg) as that used in the intracerebroventricular experiment failed to cause any cardiovascular or renal sympathetic nerve responses. These results suggest that intracerebroventricular ET-1 acts in the central nervous system and causes a pressor response mainly through the enhancement of sympathoadrenal outflow.

Animals↗

PubMed1991

Effects of continuous vindesine administration of advanced breast cancer resistant to chemotherapy including adriamycin.

Vindesine (VDS) at a dose of 1.2 mg/m2/day was administered by intravenous drip infusion for five days to advanced breast cancer patients with multiple organ metastases who had developed a clinical resistance to various chemotherapeutic agents. The blood concentration of VDS was determined serially by radioimmunoassay, and the anticancer effect and side effects were evaluated. Of the 31 patients selected for this study, 29 were eligible, and the treatment was effective (complete or partial remission) in 11 (38%). There was, however, no correlation between clinical effects and VDS blood concentration. Continuous VDS administration induced various side effects, but all were controllable. Blood concentration was correlated with side effects. Continuous intravenous administration of VDS is considered to have a therapeutic effect on advanced breast cancer which has developed resistance to multiple-drug therapy including adriamycin.

Adult↗

PubMed1990

Parathyroid hormone-related protein in tumor tissues obtained from patients with humoral hypercalcemia of malignancy.

We assessed the relationship between the parathyroid hormone-related protein (PTHrP) and the development of humoral hypercalcemia of malignancy (i.e., hypercalcemia due to the production by solid tumors of hypercalcemic factors) by assaying tumor extracts from hypercalcemic and normocalcemic patients with cancer for immunoreactive PTHrP contents. Immunoreactive PTHrP was demonstrated in extracts of 21 of 22 tumor tissues obtained from 22 patients with humoral hypercalcemia of malignancy. Immunoreactive PTHrP was rarely seen in tumor tissue extracts obtained from 34 normocalcemic patients with cancer and two hypercalcemic patients with cancer with severe bone metastases. Gel filtration studies of tumor extracts revealed a molecular-size heterogeneity of immunoreactive PTHrP. These radioimmunoassay data indicate a close relationship between detection of PTHrP in tumor tissues and the development of humoral hypercalcemia of malignancy.

Adult↗

PubMed1990

Effects of meals and physical activity on blood pressure variability in elderly patients. A preliminary study.

Twenty-four-hour blood pressure (BP) was determined noninvasively in 11 ambulatory (active group, 78 +/- 2 years old) and 11 bedridden (passive group, 79 +/- 2 years old) elderly patients. Postprandial reduction in BP was evident in both groups. BP variability during the daytime was significantly greater in the active group than in the passive group. Consequently, only patients of the passive group showed a significant day-night difference in BP and a significant circadian rhythm of BP as well. We conclude the following: 1) postprandial reduction in BP contributes to BP variability during daytime in elderly patients, 2) the greater BP variability seen in ambulatory patients obscures the day-night rhythm of BP, and 3) the day-night rhythm of BP exists in bedridden patients.

Aged↗

PubMed1990

Chloride ion plays an important role in sodium induced volume expansion in normal humans.

Eight normal women took part in a randomized crossover study to investigate the effect of dietary supplementation with 105 mEq sodium chloride (NaCl) for 3 days or equimolar sodium citrate (NaCit) after salt depletion. NaCit supplement induced greater urinary sodium and potassium excretions than did the NaCl supplement (197 +/- 10 v 107 +/- 19 mEq/3 days for sodium, P less than .01, 130 +/- 7 v 96 +/- 6 mEq/3 days for potassium, P less than .01, respectively) and less body weight gain (+0.6 +/- 0.1 v +1.6 +/- 0.1 kg, P less than .01). Suppressions of plasma norepinephrine, renin activity and aldosterone concentration were significantly smaller with NaCit than with NaCl supplement. We conclude that the anionic component of sodium salts may have some effects on renal sodium handling and modulates volume expansion and humoral factors.

Adolescent↗

PubMed1990

Suppression of the renin-angiotensin system induced by streptozotocin treatment in neonatal spontaneously hypertensive rats.

We studied whether or not neonatal streptozotocin (STZ) treatment would alter mean arterial pressure (MAP) and blood pressure regulating factors in conscious and unrestrained spontaneously hypertensive rats (SHR). Neonatal STZ administration to SHR resulted in type 2 diabetes mellitus with reduced MAP and heart rate. Plasma glucose was markedly increased in these diabetic animals and was inversely correlated with MAP. In the diabetic SHR, the hypotensive responses to captopril (SQ) or enalapril, administered intravenously, were diminished, regardless of preceding administrations of vasopressin V1-antagonist (AVPA) or hexamethonium (C6), when compared to findings in control rats. In contrast, the C6-induced hypotension was similar in rats with diabetes and control animals. AVPA led to no decrease in MAP in either group. Hypotensive responses to SQ following AVPA and C6 inversely correlated with the plasma levels of glucose in the diabetic group. The combined blockade of the renin-angiotensin system (RAS), sympathetic nervous system and vasoconstrictive action of vasopressin (AVP) abolished the differences in MAP between the groups. Pressor and bradycardic responses to intravenous noradrenaline, angiotensin II and AVP were practically identical in the diabetic and control SHR. Urinary aldosterone excretion rate was not altered by neonatal STZ treatment. In conclusion, a decrease in MAP in SHR with neonatal STZ treatment may be attributed to the suppressed pressor activity of RAS.

Angiotensin II↗

PubMed1989

A case of leiomyosarcoma associated with humoral hypercalcemia of malignancy: demonstration of biological and immunological activities of parathyroid hormone-related protein in the tumor extract.

Hypercalcemia occurred in a patient with leiomyosarcoma when multiple lung metastases developed. Despite normal plasma parathyroid hormone (PTH) levels and low 1,25-dihydroxyvitamin D, this hypercalcemic patient had a marked hypercalciuria and phosphaturia associated with an increased excretion of nephrogenous cyclic AMP (NcAMP). Administration of cisplatin ameliorated both the hypercalcemia and hypercalciuria without any reduction in tumor size of NcAMP excretion. Terminally, acute pancreatitis occurred producing a profound hypocalcemia. In the extract of tumor tissue obtained post mortem, bioactivity stimulating the generation of cyclic AMP in osteogenic cells was demonstrated along with the immunoreactive PTH-related protein (PTH-rP). the first report of a solid non-epithelial malignancy producing PTH-rP and associated with humoral hypercalcemia of malignancy. The hypercalcemia in this case caused acute pancreatitis, which led to a profound hypocalcemia.

Calcium↗

PubMed1989

Effect of single-administration captopril on plasma and urinary vasopressin in normotensive subjects and patients with essential hypertension and primary aldosteronism.

Effects of a single administration of captopril on plasma and urinary vasopressin (AVP) were examined in 8 normotensive (NT) female volunteers, 17 patients with essential hypertension (EHT) and 2 patients with primary aldosteronism (PA). Orally-administered captopril (25 mg) had no effect on plasma AVP levels in the three groups. However, urinary excretion of AVP decreased significantly after use of captopril in both NT and EHT subjects (-57% and -67%, respectively), and also in PA subjects. The magnitude of reduction in urinary AVP was significantly correlated with the pretreatment levels of plasma renin activity (r = 0.85) and plasma aldosterone concentration (r = 0.88) in NT subjects. Such correlation was not found in EHT subjects. These results suggest that captopril decreases AVP secretion in both normotensive and hypertensive subjects, but the relation of the magnitude in AVP reduction by captopril to the peripheral renin-angiotensin system might be different.

Adult↗

PubMed1989

Effects of sodium depletion and orthostasis on plasma and urinary vasopressin in normal subjects.

We investigated the effects of sodium depletion and orthostasis on the plasma concentration and urinary excretion of vasopressin (AVP) in eight normal female subjects. After 4 days on a sodium controlled diet (130 mEq/day), the subjects were placed on a low sodium diet (30 mEq/day) for 3 days and 120 mg of furosemide was administered orally on the first day of the low sodium regimen. Sodium depletion in the present study reduced body weight by 1.6 kg and increased hematocrit by 3.5%. A significant (p less than 0.05) increase in plasma AVP and a significant (p less than 0.05) decrease in 24-h urinary excretion of AVP were observed during sodium depletion. One-hour ambulation significantly increased plasma AVP in both control and sodium depleted phases (p less than 0.01). The percent change in plasma AVP tended to correlate with that in mean blood pressure in the control phase (r = 0.69, 0.05 less than p less than 0.1), and significantly correlated in the sodium depleted phase (r = 0.86, p less than 0.01). The present results suggest that AVP may play an important role in the maintenance of blood pressure during orthostasis in the sodium depleted state.

Adult↗