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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 379 records · Page 21Linked to original sources

Effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with urogenital cancer.

The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 micrograms/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period.

Adolescent↗

Aluminum decreases the zinc concentration of soft tissues and bones of rats fed a low calcium-magnesium diet.

The relationship between magnesium (Mg) and zinc (Zn) in soft tissues and bone of rats was studied after administration of unbalanced mineral diets. Minerals and metals in soft tissues and bone were determined using inductively coupled plasma emission spectrometry (ICP). There were significant positive correlations between serum Zn and Mg levels, between serum Zn and Zn content of soft tissues and bone, and between serum Mg levels and Zn content of bone and soft tissues in rats fed unbalanced mineral diets. A significant positive correlation was also found between Zn and Mg content in the lumbar spine and femoral bone of rats. It appears that altered bone mineralization induced by unbalanced mineral diets leads to mobilization of Mg and Zn from rat bones in similar ways.

Aluminum↗

Distribution of calcium in central nervous system tissues and bones of rats maintained on calcium-deficient diets.

Current changing epidemiological pattern in the Western Pacific area suggests a contribution of the environmental factors to the pathogenetic process of amyotrophic lateral sclerosis (ALS). The condition of unbalanced mineral levels found in the soil and drinking water samples from the ALS foci showing low content of calcium (Ca) and magnesium (Mg) plus high content of aluminum (Al) was experimentally mimicked in this study using rats. In the groups fed low Ca, low Ca-Mg, and low Ca-Mg plus high Al diets, serum Ca levels were lower than that in the group fed the standard diet. Ca content of CNS tissues showed higher values in the unbalanced diet groups, especially in the spinal cord of low Ca-Mg plus high Al diet group, than those in the standard diet group, determined by inductively-coupled plasma emission spectrometry (ICP). Ca content in heart, liver, kidney, and abdominal aorta in groups fed low Ca-Mg, and low Ca-Mg plus high Al diets was higher than that in low Ca, and standard group. Ca content in muscle in the three unbalanced diet groups was significantly higher than in the standard diet group. Ca and Mg contents in lumbar spine and cortical bone showed lower values in the unbalanced diet groups than those values in the standard diet group. These findings suggest that under the condition of derangement of bone mineralization induced by unbalanced mineral diets fed to the experimental rats, Ca and Mg may be mobilized from bone, keeping their content in soft tissues, including CNS tissue, for utilization of vital activities, thereby resulting in a deposition of Ca while maintaining an almost normal value of magnesium in the CNS tissues.

Animals↗

Review of ubenimex (Bestatin): clinical research.

An immunomodulating agent, ubenimex (Bestatin) has low toxicity even after long-term oral administration and brings about significant modifications in immunological response. In a cooperative randomized controlled study of Bestatin immunotherapy for adult acute nonlymphocytic leukemia, prolongation of remission duration and survival was achieved with Bestatin immunotherapy combined with remission maintenance chemotherapy. The significant prolongation of remission duration and survival was seen in the Bestatin group, especially in the elderly patients. Randomized controlled studies of Bestatin immunotherapy were performed in solid tumors including malignant melanoma, carcinoma of the lung, stomach, bladder, head and neck and esophagus, and therapeutic benefits regarding disease free-interval or survival were observed in certain types of the above-mentioned cancers; however, Bestatin immunotherapy for these cancers should be further investigated in large-scale controlled studies to confirm its activity.

Adolescent↗

Effects of ubenimex, a biological response modifier, on myelodysplastic syndrome and chronic leukemia.

Twenty cases of myelodysplastic syndrome (MDS) were treated with ubenimex. Seventeen cases were treated with the drug over 90 d. Among these, 10 showed improvement of anemia, 12 an increase in platelet count which had decreased before treatment and 10 an increase in neutrophil count; however, 14 showed an increase in blast percentage in bone marrow aspirate. CD4/CD8 ratio was increased in 4 cases and shifted to a normal from an abnormal range in 6 cases. When the MDS cases were observed in refractory anemia (RA) and refractory anemia with excess blasts (RAEB), great improvement was seen, but in RAEB increase in blast percentage was also observed. CD4 increased mostly in RA and CD8 increased in RAEB. Ten cases of chronic myelocytic leukemia (CML) were first treated with ubenimex and cytostatics, then with ubenimex only. Six cases attained partial remission within 3 months, but one case showed a marked increase in white cell count and blast count and in another case a progression of splenomegaly associated with increase in white cell count. From these findings we conclude that ubenimex could be utilized in MDS or CML if the patient was at risk for strong chemotherapy.

Adult↗

Central effects of endothelin-1 on vasopressin and atrial natriuretic peptide release and cardiovascular and renal function in conscious rats.

In order to investigate the central effect of endothelin-1 (ET-1) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular and renal function, either a high dose of ET-1 (3.5 ng/kg/min, HET-1) or a low dose (0.35 ng/kg/min, LET-1) was administered into the cerebral third ventricle in conscious rats. ET-1 increased the mean arterial blood pressure, but not heart rate, in a dose-related manner. LET-1 slightly stimulated AVP release, but not ANP release. HET-1 increased plasma AVP and ANP. Pretreatment with a V1-antagonist (TMeAVP) attenuated the blood pressure response to ET-1 and completely abolished increases in plasma ANP. Moreover, prazosin given i.v. completely prevented the residual pressure response. ET-1 did not significantly affect renal electrolytes and water handling. These results suggest that centrally administered ET-1 may increase the activity of the sympathetic nervous system and vasopressinergic neurons, resulting in an increase in blood pressure.

Animals↗

Cyclical edema in a patient with hypothalamic disorders and chronic glomerulonephritis: arginine vasopressin-dependent atrial natriuretic hormone release.

A 28-year-old woman had hypothalamic disorders (amenorrhea, obesity, psychiatric abnormalities, polydipsia and fever) and chronic glomerulonephritis. She also suffered from general edema associated with cyclical oliguria and polyuria. Her body weight and plasma osmolality increased during the oliguria phase lasting 2 to 8 days and decreased after paroxysmal polyuria accompanied by the natriuresis. These episodes occurred repeatedly, regardless of the treatment with or without diuretics. The release of arginine vasopressin in response to increased plasma osmolality was exaggerated, but changes in plasma volume did not affect arginine vasopressin release. Plasma atrial natriuretic hormone increased in response to a rise in plasma arginine vasopressin and plasma volume during the oliguria phase, thereby resulting in the diuresis and natriuresis. The renin-angiotensin-aldosterone system was secondarily activated by body fluid depletion and diuretics, and this might play an additive role in general swelling. Plasma gonadal hormones did not change to explain the edema. The mechanism of this cyclical edema remains unknown, but it is likely that hypothalamic dysfunction related to psychiatric abnormalities may exaggerate arginine vasopressin release, and enhanced renal sympathetic activity may cause retention of Na and water, and the increase in atrial natriuretic hormone release responding to the plasma volume expansion may bring about the diuresis and natriuresis.

Adult↗

A case of syndrome of inappropriate secretion of antidiuretic hormone associated with diabetes mellitus.

A 46-year-old man, presenting with headache, nausea, and lassitude, was diagnosed as having diabetes mellitus and hyponatremia, and admitted to Tohoku University Hospital. Insulin treatment improved the hyperglycemia but aggravated hyponatremia, which was proved to be elicited by the inappropriate secretion of antidiuretic hormone (SIADH). An acute water load failed to suppress ADH release in the supine posture but slightly increased plasma atrial natriuretic peptide (ANP). On the other hand, plasma ADH markedly increased in response to an upright posture, accompanied by a fall in blood pressure and a rise in heart rate. After treatment with droxidopa "a sympathomimetic drug", ambulatory blood pressure gradually increased and hyponatremia disappeared. However, blood pressure and ADH responses to upright posture were not improved by treatment with the drug. Moreover, plasma ADH was still not sufficiently suppressed by acute water loading in the supine position, but plasma ANP markedly increased, thereby resulting in urinary dilution and natriuresis. These results suggest that exaggerated ADH release (SIADH) was brought about by the baroreceptor reflex stimulated by the postural hypotension, and also by the impaired osmoregulation associated with diabetic neuropathy, and that droxidopa improved cardiovascular function and increased ANP release with resultant urinary dilution and natriuresis in spite of slightly increased ADH release.

Blood Pressure↗

Responses of atrial natriuretic peptide, vasopressin, aldosterone and renal function to intracerebroventricular infusion of angiotensin II in dogs.

To assess the mechanisms how angiotensin II (Ang II) given intracerebroventricularly (i.c.v.) induces natriuresis, the effects of Ang II (10 ng/kg/min, for 30 min) on the renin-angiotensin-aldosterone system, the release of vasopressin (AVP) and atrial natriuretic peptide (ANP) and on cardiovascular and renal functions were investigated in anesthetized dogs. In control dogs, vehicle alone (artificial cerebrospinal fluid) was infused at a rate of 10 microliters/min. Ang II given i.c.v. produced a gradual increase in urine flow, urinary sodium and potassium excretion and osmolar clearance, but had no effect on plasma ANP, aldosterone, arterial blood pressure, and renal blood flow. However, i.c.v. Ang II increased plasma AVP and decreased heart rate, plasma renin activity, inulin clearance and filtration fraction. In the cotrol group, vehicle treatment had no effect on these parameters except for decreases in inulin clearance and filtration fraction. These results suggest that circulating ANP and blood pressure may not play an important role in i.c.v. Ang II-induced natriuresis, but increased AVP release and decreased renal sympathetic nervous activity may contribute to the natriuresis.

Aldosterone↗

Glucocorticoid-induced central diabetes insipidus in a case of malignant lymphoma.

A 37-year-old man was diagnosed as malignant lymphoma infiltrating in the central nervous system with hypopituitrism and secondary glucocorticoid deficiency. In this case, plasma arginine vasopressin (AVP) increased, but glucocorticoid administration decreased plasma AVP and increased urine volume with a reduction in urinary osmolality, indicative of the presence of glucocorticoid-induced diabetes insipidus. At the terminal stage, plasma AVP did not increase in response to the withdrawal of glucocorticoid and urine volume remained decreased, suggesting the presence of masked diabetes insipidus. Autopsy showed an infiltration of lymphoid cells around the cerebral ventricles and necrosis in the hypothalamo-hypophyseal system. These findings suggested that glucocorticoid might centrally play an important role in the regulation of AVP release, and its deficiency potentiated AVP release.

Adult↗

Effect of vasopressin on cardiovascular and renal functions and ANP release under plasma volume expansion.

To assess the mechanisms whereby arginine vasopressin (AVP) increases atrial natriuretic peptide (ANP) release and to examine whether AVP-mediated ANP release affects the effect of AVP on the cardiovascular and renal function, AVP was infused continuously at a rate of 20 ng.kg-1.min-1 for 75 min following 200 ng/kg bolus injection under stepwise increases in plasma volume in anesthetized dogs. Moreover, the effect of an AVP antagonist, a V1 blocker, 1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-2-(o-methyl)tyrosine AVP (TMeAVP), on these parameters was also investigated. In the control study, saline alone was infused. AVP infusion increased total peripheral resistance (TPR), pulmonary capillary wedge pressure (PCWP), and plasma ANP, but decreased cardiac index (CI) and heart rate (HR) without increases in mean arterial blood pressure (MABP). Stepwise rises in plasma volume further increased plasma ANP, CVP, CI and PCWP, but gradually decreased TPR. TMeAVP curtailed AVP-induced increases in TPR and plasma ANP as well as decreases in CI and HR. The replacement of ANP to prevent a fall in plasma ANP following TMeAVP never affected cardiovascular function. AVP infusion increased plasma volume accompanied by a fall in urinary Na excretion (UNaV) and urine flow (UF) under the stepwise plasma volume expansion compared to the control group, but did not affect mean circulatory filling pressure (MCFP). ANP administration enhanced UNaV and UF and decreased MCFP. These results indicate that AVP may preferentially increases ANP release via the increased cardiac afterload, not preload, but increased plasma ANP per se may not be involved directly in the AVP-induced cardiac suppression.

Animals↗

Involvement of ovarian steroids and endogenous opioids in the fasting-induced suppression of pulsatile LH release in ovariectomized rats.

The participation of the ovarian steroids and opioid peptides in the suppression of pulsatile LH release during acute fasting was examined in rats. Ovariectomized rats bearing silicone elastomer implants of oestradiol and/or progesterone were fasted for 48 h and subsequently blood samples were taken every 6 min for 3 h. Pulsatile LH release was suppressed after 48 h of fasting in the ovariectomized rats implanted with oestradiol but not in the oil-implanted controls. This suppression was enhanced after the administration of progesterone together with oestradiol. In a second experiment, ovariectomized rats bearing implants of oestradiol or oil were fasted for 48 h and injected s.c. (2.5 mg/kg body weight) with an opioid antagonist, naloxone hydrochloride, immediately before blood sampling. In the fasted oestradiol-treated ovariectomized rats, naloxone was able to prevent the suppression of pulsatile LH release. In the absence of oestradiol, however, naloxone was without effect on LH release in either the fasted or unfasted animals. These experiments indicate that the suppression of pulsatile LH release after 48 h of fasting is dependent upon oestradiol and that endogenous opioids are involved in the suppression.

Animals↗

[Autologous blood transfusion aided with erythropoietin in transurethral resection of the prostate].

Erythropoietin (EPO) with an established clinical efficacy in renal anemia has in recent years become applied as an aid to autologous blood transfusion in surgical patients. This report describes our experience with autotransfusion along with the use of EPO in transurethral resection of the prostate (TUR-P), indicating its usefulness. Ten patients with benign prostatic hypertrophy aged 60 to 74 years received 3000 units of EPO, with an iron preparation, nine times beginning 3 weeks prior to operation. Autologous blood of 300 ml was collected from the patient each at 2 and 1 week before operation and was used at TUR-P. Five other patients who underwent TUR-P with the same volume of autotransfusion accompanied by preparative medication with the iron alone served as controls. In the EPO treated group (mean age, 68.3 years) the mean value for hemoglobin concentration (Hb) was 14.0 +/- 1.6 g/dl on the day of operation, which showed a recovery rate of 94.9 +/- 5.4% (Hb recovery rate) as against the pre-EPO treatment value (mean: 14.8 +/- 1.3 g/dl). This Hb recovery rate was significantly greater (p less than 0.001) when compared to 82.2 +/- 2.5% in the control group (mean age, 68.2 years). Of the EPO treated patients, those in their sixties (n = 6; mean age, 66.3 years) exhibited a significantly higher Hb recovery rate (98.3 +/- 3.5%) than the rate (89.9 +/- 3.0%) for patients in their seventies (N = 4; mean age, 71.3 years) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Transfusion, Autologous↗

[Timing of administration of granulocyte colony stimulating factor after cytotoxic chemotherapy in hematological malignancies].

We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) given to 30 patients with hematological malignancies after cytotoxic chemotherapy. The first course of chemotherapy was not treated with rhG-CSF (control), and in the second to fourth courses, rhG-CSF was given by one of the following three ways to the patients (not necessarily in this order): 1) 10 days of administration starting 48 hr after chemotherapy, 2) 5 days of administration starting 48 hr after chemotherapy, and 3) 5 days of administration after the leukocyte counts reached to less than 2,000/microliters. The leukocyte nadirs were significantly higher in the course with 10 days of administration compared with the control course. The time needed for recovery from the leukocyte nadir was significantly shorter in 10-day course and 5-day course after the leukocyte counts reached to less than 2,000/microliters. The therapy spans became significantly shorter with all of the three patterns of administration of rhG-CSF compared with the control course. The number of days on which the leukocyte counts became less than 2,000/microliters were significantly fewer in 10-day course and 5-day course after the leukocyte counts became less than 2,000/microliters. These findings showed that rhG-CSF prevented severe neutropenia after cytotoxic chemotherapy, and (or) assisted the rapid recovery from neutropenia. These effects depend on the timing of its administration.

Acute Disease↗

[Chronic lymphocytic leukemia with peripheral T lymphocytes expressing CD 2+, CD 3+, CD 4-, CD 8-, CD 16+, and CD 56+ and lymph-node lymphocytes expressing CD 2+, CD 3-, CD 4-, CD 8-, CD 16+, CD 38+, and CD 56+].

A 33-year-old man was hospitalized because of thrombocytopenia and severe splenomegaly. On admission 78% of peripheral lymphoid cells were abnormally large, with pale cytoplasm. Flow cytometry of the abnormal lymphocytes showed that they expressed CD 2, CD 3, CD 11, CD 16, and CD 56, but not CD 4 nor CD 8, so they were T-cell large granular lymphocytes (T-LGL). Abnormal lymphocytes obtained from a lymph node expressed CD 2, CD 16, CD 38, and CD 56, but not CD 3, CD 4, and CD 8, so they were natural killer(NK) cells. Splenectomy was performed and the operative specimen showed diffuse infiltration of pleomorphic lymphocytes, probably chronic lymphocytic leukemia cells. After splenectomy, the platelet count returned to normal but the lymphocytosis continued. Two years after discharge, chemotherapy was done because of thrombocytopenia and hepatomegaly. The patient died of disseminated intravascular coagulation arising from sepsis. The differences and similarities between peripheral and lymph-node lymphocytes suggest that LGL and NK cells may be differentiated from the same kind of cell, somewhat differentiated from stem cells.

ADP-ribosyl Cyclase↗

[Expression of CD56 antigen on acute nonlymphocytic leukemia].

CD56 antigen (detected by NKH-1) is distributed on NK cells, monocytes, and ectodermal neural cells. In this study, the blasts of 29.2% of 27 patients with acute nonlymphocytic leukemia (ANLL) expressed CD56 antigen, but not CD16, CD2, or CD3 antigen. Leukemic cells isolated from 3 patients with CD56-positive ANLL did not have NK activity. There were no significant differences between CD56-positive and CD56-negative ANLL in CD13-positive cases, CD33-positive cases, and HLA-DR-positive cases. These results suggest that CD56-positive ANLL could be so-called mixed-lineage leukemia (lymphoid-associated antigen in ANLL).

Antigens, CD↗

Positive effect of granulocyte-colony stimulating factor on erythropoiesis in humans.

We studied the effects of granulocyte-colony stimulating factor (G-CSF) on human erythropoiesis in vivo. Changes in the peripheral blood were analyzed in 9 subjects; 3 healthy volunteers, 3 patients with pancytopenia and hypersplenism and 3 patients with chronic renal failure and severe anemia being treated with hemodialysis. We monitored erythropoiesis according to the number of highly fluorescent cells (HFC) present in the peripheral blood after staining with Auramine 0. These cells are relatively immature reticulocytes that contain much RNA. All subjects received recombinant human G-CSF at a daily dose of 100 micrograms/m2 administered intravenously for 3 to 5 days. Plasma erythropoietin was measured in patients receiving dialysis before and several times after its administration. The number of HFC increased significantly in all subjects. In 1 of 3 patients receiving dialysis, the plasma erythropoietin increased transiently but insignificantly. These findings show that G-CSF affects human erythropoiesis in vivo, but that the mechanism of its effect did not involve an increase in plasma erythropoietin.

Adult↗