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Biomedical subjects

H Kaji

Publications and source records attributed to H Kaji.

At least 253 records · Page 14Linked to original sources

Central nervous system effect of calcitonin: stimulation of prolactin release in rats.

Effect of [Asu 1,7]eel calcitonin (CT) on prolactin (PRL) release was examined in male rats under urethane anesthesia. Intravenous injection of 4-20 micrograms [Asu1,7]eel CT did not modify plasma PRL levels. Injections of 0.5-2.5 micrograms [Asu1,7]eel CT into the lateral ventricle produce a significant and dose-related increase of plasma PRL within 10 min of injection. When intraventricularly injected in an equimolar dose (0.74 nmol/10 microliters), eel CT11-32, eel CT15-32, [Asu1,7]eel CT1-16 and [Asu1,7]eel CT1-9 showed 44.8, 25.7, 19.9 and 10.1% the potencies of [Asu1,7]eel CT, respectively, in stimulating activity of PRL release. The rise of plasma PRL after [Asu1,7]eel CT injection were significantly less or abolished not only in hypothalamic-lesioned rats but also in rats with complete deafferentation. Pretreatment with alpha-methyl-p-tyrosine (250 mg/kg, 12 h before) but not with p-chlorophenylalanine (300 mg/kg, 72 and 24 h before) resulted in a suppression of [Asu1,7]eel CT-induced PRL release. These results suggest the following: first, PRL release is stimulated by centrally injected [Asu1,7]eel CT, the action site of which may exist in the extrahypothalamic area; second, brain catecholamines may be involved in the mechanism of [Asu1,7]eel CT-evoked PRL release; third, the C-terminal portion of the peptide may play an important role in stimulating PRL release.

Animals↗

Effects of hydrocortisone and aspirin on protein synthesis and post-translational protein modification in cultured cells.

Arginyl-tRNA transferase is suggested to function as a post-translational modifier of proteins through the addition of arginine to the NH2-terminus of specific acceptor proteins. Both hydrocortisone and aspirin produced an age-dependent stimulation of protein synthesis in normal human fibroblasts (IMR90), while producing an inhibition of protein synthesis in SV40 virus-transformed IMR90 cells. The effect of aspirin was confined primarily to the cytoplasmic compartment, whereas hydrocortisone produced its effect at both cytoplasmic and nuclear levels. Neither hydrocortisone nor aspirin had a direct effect on arginyl-tRNA transferase activity in vitro; however, hydrocortisone resulted in a marked increase in the availability of chromosomal proteins subject to modification by arginyl-tRNA transferase. This stimulatory effect was attenuated by increasing culture age. The modified chromosomal proteins were found to be dissociated from native chromatin, suggesting that arginylation either triggered their release or prevented reassociation with chromatin thereafter. Hydrocortisone produced a moderate decrease in the availability of chromosomal proteins for arginylation in SV40 virus-transformed cells, and this effect was not modulated by aging phenomena.

Acyltransferases↗

Influence of drugs on macromolecular synthesis during cell synchronization.

A cell culture system has been used to examine the effect of various pharmacologic agents on DNA synthesis with the hope of utilizing this system for the evaluation of drugs at the cellular level. Glucocorticoids have been shown to have a differential effect on growth dependent on the cell type studied. For this reason steroidal anti-inflammatory agents were chosen to study in our culture system. Aspirin, a non-steroidal anti-inflammatory agent, was also studied for a comparison with glucocorticoids. The CNS stimulants, caffeine and amphetamines, were studied for their effects on non-target cells in culture and compared with the response of target cells. Doxorubicin, an anti-neoplastic agent, has been shown to depress growth in a variety of cells. This drug was also studied in our culture system. We have found that steroidal anti-inflammatory drugs induced a dose-dependent stimulation of DNA synthesis in normal human fibroblasts that was also age-dependent, while decreasing DNA synthesis in SV40 virus transformed cells. Aspirin (25 micrograms/ml) exhibited a similar response. Human fibroblasts were found to be responsive to the CNS stimulants, exhibiting a dose-dependent decrease in DNA synthesis when exposed to caffeine. Amphetamine (200 microM) depressed DNA synthesis in normal fibroblasts and increased it in SV40 virus transformed cells. All cells studied exhibited a depression of DNA synthesis when treated with doxorubicin (0.1 microgram/ml).

Amphetamines↗

Determination of true specific activity of superoxide dismutase in human erythrocytes.

1. Activities, contents and true specific activities of superoxide dismutase (SOD) were determined in human erythrocytes of 105 normal healthy subjects. 2. The mean SOD activity assayed by the inhibition of xanthine autoxidation was 11.0 x 103 units/g of haemoglobin (Hb). 3. The mean SOD content assayed by an immunochemical method was 456 micrograms/g of Hb. 4. Both activity and content of SOD showed normal distributions, and no significant variations with regard to sex and age were detected. 5. A highly positive correlation between activities and contents of SOD was observed in normal healthy subjects (r = 0.77, P less than 0.001). 6. True specific activity was calculated from levels of activity and content of SOD. The mean true specific activity of SOD in human erythrocytes was 23.7 units/micrograms of SOD. 7. There was no significant difference in true specific activity between young and old subjects.

Age Factors↗

Effect of vasoactive intestinal polypeptide on growth hormone secretion in perifused acromegalic pituitary adenoma tissues.

The effects of vasoactive intestinal polypeptide (VIP), dopamine, and somatostatin (SRIF) on GH secretion were examined in vitro in perifused pituitary adenoma tissues obtained at surgery from seven patients with acromegaly. The perifusion of VIP at 5 x 10(-8) M resulted in a significant increase in effluent GH levels in five of the seven adenomas. A dose-related GH response was observed from 5 x 10(-9) to 5 x 10(-7) M VIP in two adenomas examined. SRIF at 5 x 10(-8) to 10(-7) M suppressed not only baseline secretion of GH but also inhibited GH rises elicited by VIP in six of the seven adenomas. Dopamine at 5 x 10(-7) to 5 x 10(-6) M decreased the baseline secretion of GH in six of the seven adenomas. In four of the six adenomas responsive to dopamine, dopamine suppressed VIP-induced GH release when perifused simultaneously. In the remaining two dopamine-sensitive adenomas in which VIP alone failed to affect GH release, the inhibition by dopamine of GH release was blocked by VIP perifused concomitantly with dopamine. Synthetic TRH or theophylline perifused at the end of the experiment stimulated GH release in all of the adenomas, indicating the viability of tumor cells throughout the study. These results suggest that VIP stimulates GH release by its direct action on pituitary adenoma cells of acromegalic patients and that VIP, SRIF, and dopamine interact at the pituitary level in modulating GH secretion from these adenomas.

Acromegaly↗

Effect of temperature on normal and SV40-transformed human fibroblasts.

The effect of a temperature shift from low (36 degrees C) to high (40 degrees C) temperature on human fibroblasts (IMR90) at various population doubling levels and IMR90 cells transformed by SV40 virus infection at a population doubling level of 30 (SV40/IMR90) was examined. Both IMR90 and SV40/IMR90 cells showed a decrease in cell saturation density at confluency, whereas an increase in population doubling time and protein content was noted when the cells were shifted up to 40 degrees C from 36 degrees C. The modification of IMR90 chromosomal proteins by arginyl-tRNA transferase was increased by the temperature shift, whereas NH2-terminal arginylation of SV40/IMR90 chromatin was not altered. Similarly, no appreciable change in 2-deoxyglucose uptake was noted with SV40/IMR90 cells at either temperature, although 2-deoxyglucose uptake by IMR90 cells was increased by the temperature shift. Additionally, the rate of 2-deoxyglucose uptake showed no difference between IMR90 and SV40/IMR90 cells. The above results support previous findings that environmental alterations, such as temperature shift can cause acceleration of cellular senescence. These findings also imply that cellular senescence remains fixed when viral transformation occurs and is rendered refractory to further age-associated alterations.

Acyltransferases↗

Intraventricularly injected growth hormone stimulates somatostatin release into rat hypophysial portal blood.

The effects of GH on the release of somatostatin from the hypothalamus were assessed by measuring the concentrations of immunoreactive somatostatin (IRS) in hypophysial portal blood of urethane-anesthetized male rats. A significant and dose-related increase of IRS in hypophysial portal blood was observed during 20-80 min after a single injection of rat GH (5 and 25 micrograms) into the third ventricle. An intraventricular injection of ovine LH or vehicle alone did not affect IRS values in hypophysial portal blood. When rat GH was repeatedly injected into the cerebral ventricle at 75-min intervals, IRS in hypophysial portal blood rose following each injection in a similar pattern with a latency of 30-45 min. These findings suggest that the release of somatostatin from the hypothalamus is regulated, at least in part, by GH. Furthermore, in view of the inhibitory effect of somatostatin on GH secretion, stimulation by GH of somatostatin release into hypophysial portal blood may be involved in the mechanism by which GH regulates its own secretion.

Animals↗

[A case report of a primary pure squamous cell carcinoma of the stomach associated with dermatomyositis (author's transl)].

A 54-yr-old man was admitted to Hokkaido University Hospital, complaining of fever, multiple arthralgia, edematous erythema and face and muscular weakness of extremities during the last 2 months. He was diagnosed as dermatomyositis by acceleration of ESR, elevation of GOT, GPT, CPK, aldolase, moderate increases of collagen fibers in biopsy specimen of skin and his clinical signs. Although stools were positive for occult blood, the routine radiographic examination failed to detect the bleeding site in the upper GI. tract. However, in the double contrast picture of the stomach, a very fine abnormal linear shadow was observed at the upper corpus of the lesser curvature. This linear shadow was a margin of the tumor, retrospectively. About 4 months later, abnormal pain occurred and a mass was palpable in the left lumbar region, suggesting a pancreatic tumor. He was operated on excising the tumor, but was performed only exploratory laparotomy because of the presence of intra-abdominal metastases. Death occurred 40 days after the operation and necropsy was done. The gross anatomical findings of the abdomen showed a stomach tumor as large as an infant's head and its metastases to pancreas, lymph nodes, and greater and lesser omentum. Esophageal mucosa including esophagocardiac junction was intact. Histological examination of the intragastric tumor revealed a typical squamous cell carcinoma with keratinization. According to the absence of the components of adenocarcinoma and squamous metaplastic gastric mucosa of non-cancerous areas in the stomach, it seemed likely to be a heterotopic squamous cell carcinoma. It was unknown about the precedence between the stomach cancer and dermatomyositis. There have been 11 cases of primary pure squamous cell carcinoma in the world literature since 1968, but this is the first case report of coexistence of these two diseases.

Carcinoma, Squamous Cell↗

Biochemical aspect of dimethyl sulfide breath test in the studies on methionine metabolism.

Dimethyl sulfide concentration in expired alveolar gas (abb. alv-DMS) was determined following oral or intravenous administration of DL-, L- or D-methionine in healthy volunteers. Fasting level of alv-DMS was 1.9 +/- 1.3 ng/dl (mean +/- SD) in all the experimental subjects (N = 38). Following ingestion of 2.0 g of DL-methionine, alv-DMS increased to a peak of 37.1 +/- 21.7 ng/dl. Following administration of 1.0 g of D-methionine, the peak values of alv-DMS were 66.0 +/- 42.1 ng/dl (mean +/- SD) (orally) and 60.0 +/- 19.9 ng/dl (intravenously). In contrast, 2.0 g of L-methionine administration caused quite a little increase in alv-DMS; 4.6 +/- 2.6 ng/dl (orally) and 4.2 +/- 2.1 ng/dl (intravenously). In view of these results, it is apparent that the increase in alv-DMS following administration of methionine is certainly related to D-methionine metabolism. The threshold level for DMS exhalation in normal subjects was between 0.5 and 1.0 g for D-isomer and more than 2.0 g for L-isomer of methionine. Since the behavior of methyl mercaptan in expired alveolar gas (abb. alv-MM) was different from and disproportionate to that of alv-DMS, the increase in alv-DMS following D-methionine administration seemed to be caused by the mechanisms other than MM formation.

Adolescent↗