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Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

At least 487 records · Page 27Linked to original sources

Suppression of antipyretic response in rabbits by intraventricular protein synthesis inhibitor, anisomycin.

Fevers induced by intravenous injection of endogenous pyrogen (EP) and intraventricular prostaglandin E2 (PGE2) were significantly prolonged when protein synthesis inhibitor, anisomycin was administrated intraventricularly 30 min before or 1 hr after injection of EP or PGE2. The present results show that protein synthesis in the central nervous system is involved in the development of antipyresis.

Animals↗

Restraint induced stress elicits acute-phase response in rabbits.

We investigated whether a restraint induced stress elicits an acute-phase response which includes changes in the plasma trace metals, fibrinogen and the circulating leucocyte count. The present results showed that restraint-stress induces significant increases in the plasma concentrations of copper and fibrinogen and decreases in those of iron and zinc in rabbits, indicating that some of acute-phase response are produced without fever mediated by endogenous pyrogen.

Animals↗

A variant Burkitt-type translocation (2p-;8q+) in a patient with diffuse large cell lymphoma.

A case of diffuse large cell lymphoma with t(2p-;8q+) is reported. Immunologically the lymphoma cells were shown to be of B-cell origin and positive for surface gamma and kappa chains, B4, CALLA, and Ia1 markers. Karyotypically three major clones were detected: 47,XX, + 12,t(2;8)(p11-13;q24) (52%); 47,XX, + 12 (26%); and 46,XX,t(2;8)(p11-13;q24) (15%). A t(2p-;8q +) has been exclusively reported in cases of Burkitt's lymphoma or Burkitt-type acute lymphocytic leukemia. The present case is the first one with t(2p-;8q +) observed in non-Burkitt-type lymphoid malignancy of the B-cell lineage. The t(2p-;8q +) may play a primary role in the early stage of transformation of B cells, and trisomy 12 may provide them secondarily with an advantage for tumor progression. The phenotypic pictures provided by 8q24 rearrangements seem to be heterogeneous, as previously suggested.

Adult↗

The value of lymph-node dissection in patients with differentiated thyroid cancer.

The perithyroidal and ipsilateral cervical lymphatic system not only is commonly involved by thyroid cancer but also is a common site of recurrence. Modified radical neck dissection, with preservation of the sternocleidomastoid muscle and spinal accessory nerve, is the treatment of choice for patients with clinically evident lymph node metastases due to differentiated thyroid cancer. It is also recommended, by us, for patients over 40 years of age who have primary thyroid tumors greater than 1.5 cm in size whether or not nodes are clinically palpable. This is because at least 75 per cent of these patients have metastases, and their discernment at operation is unreliable. With more aggressive surgery, the recurrence-free survival rate can be improved substantially without cosmetic deformity or postoperative dysfunction.

Age Factors↗

Loss of intracellular peroxidase and anaplastic change of differentiated carcinoma of human thyroid gland.

Ultrastructural localization of endogenous peroxidase (peroxidase) in differentiated thyroid carcinoma was studied in 2 cases of follicular carcinoma and 12 of papillary carcinoma. The reaction product for the enzyme was observed in cancer cells which had a round and smoothly-contoured nucleus and rather few number of microvilli (positive cells) and the product localized mainly in the rough-surfaced endoplasmic reticulum and perinuclear cisternae. The positive cells resembled normal follicular cells in localization sites of the reaction product and ultrastructural features. On the contrary, in cancer cells having an irregularly-outlined nucleus with or without intranuclear cytoplasmic inclusion and many microvilli, no reaction product was visualized (negative cells). The positive cells were frequently found in 2 follicular carcinomas and 2 papillary carcinomas. Only a few number of positive cells presented in 2 papillary carcinomas. The remaining 8 papillary carcinomas were composed only of negative cells. Histologically, follicles with colloid were frequently found in carcinomas with abundant positive cells, whereas they were few in number in carcinomas containing only negative cells. These findings suggest that loss of peroxidase activity in cancer cells of follicular cell origin correlates with anaplastic change of the cancer cells.

Carcinoma↗

Ultrastructural localization of endogenous peroxidase activity in benign thyroid diseases.

Ultrastructural localization of endogenous thyroid peroxidase under benign pathological conditions such as toxic diffuse goiter, non-toxic multinodular goiter, and adenoma, and in normal tissue was studied. Peroxidase activity was visualized by a cytochemical reaction for electron microscopy. In toxic diffuse goiters and most non-toxic multinodular goiters, reaction product for peroxidase was observed not only in the cytoplasm but also at the external surface of microvilli of follicular cells. In normal thyroid tissues and adenomas, peroxidase was visualized only in the cytoplasm. Peroxidase activity at the external surface of microvilli of the follicular cells was found in the tissues obtained from the goiters which showed "hot" radioiodine scintigram. These findings suggest that follicles with peroxidase activity at the external surface of microvilli in non-toxic multinodular goiter are "autonomous follicles" and that peroxidase at the external surface of microvilli plays some role in active iodine uptake.

Adenoma↗

Evidence for separate mechanisms of induction of biphasic fever inside and outside the blood-brain barrier in rabbits.

1. Intravenous bacterial endotoxin, or endogenous pyrogen, in high concentration both caused biphasic fever in rabbits. In low concentration they produced only the first phase of fever. 2. Subcutaneous indomethacin suppressed the first phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the second phase. 3. Intraventricular cerebral injection of indomethacin reduced the second phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the first phase. 4. Intraventricular cerebral injection of endotoxin or of endogenous pyrogen caused slow monophasic fever. This was suppressed by intraventricular, but not by subcutaneous, indomethacin. 5. It is concluded that the first phase of biphasic fever is caused by pyrogen acting via structures outside the blood-brain barrier, presumably peripheral nerves, and the second phase by pyrogen acting via structures within the blood-brain barrier, presumably hypothalamic neurones.

Animals↗

Fever induced in rabbits by intraventricular injection of rabbit and human serum albumin.

1. Intraventricular injection of rabbit and human serum albumin, and rabbit endogenous pyrogen produced dose-dependent fevers in rabbits. The pyrogenicity of albumin was less than one-twentieth of the pyrogenicity of endogenous pyrogen. 2. Fevers induced by ventricular albumin were significantly suppressed by intraventricular injection of indomethacin which is a cyclooxygenase inhibitor. In contrast, subcutaneous injection had no effect. 3. Ventricular endogenous pyrogen induced several of the acute phase responses, i.e. decreases in the plasma concentration of iron and zinc, and increases in both the plasma concentration of copper and the white blood cell count. Albumin induced none of these responses. 4. It is concluded that fever induced by ventricular albumin is processed by prostaglandins synthesized within the central nervous system. However, ventricular albumin does not activate the central mechanism to induce acute phase responses.

Animals↗

Fever and acute phase response induced in rabbits by human recombinant interferon-gamma.

1. Intravenous (I.V.) and intracerebroventricular (I.C.V.) injections of human recombinant interferon-gamma (IFN-gamma) produced dose-dependent fevers in rabbits. The fever induced by I.V. injection was monophasic and the maximum elevation occurred 80-110 min after injection. The fever induced by I.C.V. injection was observed from about 20 min after injection and was remarkably prolonged over 4 h. 2. The development of pyrogenic tolerance to IFN-gamma was observed when rabbits were given I.V. injections on 3 successive days. Furthermore, the pyrogenicity of IFN-gamma was significantly attenuated by heating at 60 degrees C for 40 min. The I.V. injection of IFN-gamma enhanced the febrile response induced by endotoxin but had no effect on that induced by endogenous pyrogen. 3. The I.V. injection of a large dose of IFN-gamma (6 x 10(6) units/kg) induced an acute phase response, which included a reduction in plasma concentration of iron and zinc. 4. The present results suggest that IFN-gamma released from lymphocytes is one of the endogenous mediator proteins responsible for producing fever and acute phase response.

Acute-Phase Reaction↗

Separate mechanisms inside and outside the blood-brain barrier inducing metabolic changes in febrile rabbits.

1. We investigated the acute phase response induced by either intravenous (I.V.) or intracerebroventricular injections of bacterial endotoxin or endogenous pyrogen. These caused either monophasic or biphasic fever, and the response includes changes in plasma concentration of iron, zinc, copper, fibrinogen and in circulating leucocyte count.2. The I.V. injection of a small dose of endotoxin or endogenous pyrogen produced a monophasic fever, while a large dose produced a biphasic fever. The ventricular injection of endogenous pyrogen produced a fever similar to the second phase of the biphasic fever.3. The I.V. injection of a small dose of endotoxin or endogenous pyrogen produced a low plasma zinc 8 h after injection, while the ventricular injection of endogenous pyrogen produced a low plasma zinc 24 h after injection. The I.V. injection of a large dose of endotoxin or endogenous pyrogen induced a low plasma zinc 8 and 24 h after injection, suggesting that the hypozincaemia induced by the large dose was mediated by both peripheral and central action of endogenous pyrogen with different time courses.4. The I.V. injection of the small dose did not affect the level of the plasma copper concentration but the I.V. injection of the large dose and the ventricular injection increased it 24 h after injection. It is considered that the plasma copper concentration is mainly controlled by the central action of endogenous pyrogen.5. The changes in the plasma iron and fibrinogen concentration and the circulating white blood cell count induced by the different doses and by the different routes showed very similar patterns, indicating that these are simultaneously controlled by both peripheral and central actions of endogenous pyrogen.6. The present results show that there are two separate mechanisms involved in the acute phase response, one inside and one outside the blood-brain barrier. From the consideration that endogenous pyrogen released from the phagocytic leucocytes induces fever and acute phase response by its action on both the peripheral target organs and the central nervous system, it is suggested that endogenous pyrogen acts both centrally and peripherally, in the same manner as other hormonal agents such as corticosteroids.

Journal Article↗

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

Animals↗

Sex-related differences in fever development of rats.

Lipopolysaccharide (LPS) or partially purified endogenous pyrogen (EP) was injected intravenously into rats of both sexes to induce fever. In LPS fever, which was easily produced in 24-h dehydrated rats with an intravenous injection of LPS, the female rats showed an attenuated febrile reaction as measured by both the maximum increase of rectal temperature (Tre) and the thermal response index (TI). Although castrated female rats showed the same magnitude of febrile reaction to that in normal female rats, castrated male rats had less of a febrile response than normal male rats. During EP fever, the maximum increase of Tre and TI between the male and female rats was also observed to be different. However, castration of rats of both sexes did not affect the febrile reaction to intravenous injection of EP. Ten-week-old female rats, treated by a subcutaneous injection of testosterone propionate on the 1st day after birth, produced a similar magnitude of febrile reaction to that in the normal male rats that were comparable in age. It is concluded that there are sex-related differences in fever development, due both to EP production and structural sexual differences in the central nervous system pathways regulating fever.

Animals↗

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in guinea pig brain slices.

To investigate the direct effects of endogenous pyrogen (EP) and prostaglandin E2 (PGE2) on the activity of neurons in the preoptic and anterior hypothalamic (PO-AH) region, single-unit activity was recorded from brain tissue slices prepared from the PO-AH region of guinea pigs. When EP was applied into the perfusate 18% of warm-responsive neurons decreased their activity, and 23% of warm-responsive neurons increased their activity. Most of the thermally insensitive neurons did not respond to EP. PGE2 inhibited 29% of warm-responsive neurons and facilitated 15% of them. Moreover, when EP and PGE2 were applied to the same neurons at different times, the same directions of changes in neuronal activity were observed in 72% of total neurons examined. These results suggest that EP and PGE2 change the neuronal activity of the thermoresponsive neurons in the PO-AH region involved in fever induction. However, by these results, the direction of neuronal response induced by these substances could not be generally categorized based on the thermoresponsiveness of the individual neuron.

Animals↗

Effect of PGE2 on preoptic and anterior hypothalamic neurons using brain slice preparation.

In the present study, effects of prostaglandin (PG) E2 on the hypothalamic neurons were investigated using slice preparations of rats. Warm- (57%) and cold-responsive (33.3%) and thermally insensitive (42.3%) neurons were facilitated by PGE applied in a culture chamber. Some neurons (5.1%) showed inhibitory response to PGE2. The remaining neurons did not show any responsiveness to PGE2. Moreover, we also examined the effects of PGE2 on the hypothalamic neurons both in normal Krebs-Ringer solution and synaptic blocking medium (low Ca2+, high Mg2+). Most of the neurons (12/15) retained their responsiveness to PGE2 in the synaptic blocking medium, indicating that PGE2 has a direct action on the hypothalamic neuron. Therefore, it is conceivable that neurons in the preoptic and anterior hypothalamic region that respond to PGE2 might play an important role in the development of fever. However, characteristics of neurons responding to PGE2 were not determined based on their thermoresponsiveness.

Animals↗

Effect of photoperiod, injection of pentobarbitone sodium or lesion of the suprachiasmatic nucleus on pre-partum decrease of blood progesterone concentrations or time of birth in the rat.

In Sprague-Dawley rats kept under 14L:10D (lights on 05:00-19:00 h), parturition occurred during the light phase on Day 23, and the pre-partum decrease in progesterone concentrations was observed between 07:00 and 15:00 h during the light period on Day 22. When the rats were transferred to reversed light-dark regimen (lights on 17:00-07:00 h) on Day 7, the progesterone decrease and parturition still occurred during the light period on Day 21 and 22-23, respectively. However, when rats were kept in constant darkness from Day 7, parturition occurred independently of the time of day between Day 22 and 24. A gradual decline of progesterone concentrations was randomly observed in individual rats. In Wistar rats kept under the usual light-dark regimen, parturitions were biphasic, occurring during the light periods on Day 22 and 23. The progesterone decrease occurred at the usual time even when the lighting regimen was changed only on the day of the expected progesterone decrease. However, treatment with pentobarbitone sodium at 15:00, 19:00 or 21:00 h, but not at 12:00 or 23:00 h, on Day 21 resulted in a delay of progesterone decrease and of parturition. Complete lesion of the suprachiasmatic nucleus on Day 13 or 14 led to advancement and random distribution of the time of birth. These results suggest that the time of parturition and of pre-partum progesterone decrease may be closely associated with an endogenous circadian system, and a luteolytic factor involving the nervous system may be present during a limited period before parturition.

Animals↗

Effect of implantation of carbachol pellet near the suprachiasmatic nucleus on the free-running period of rat locomotor activity rhythm.

To clarify the effect of a cholinergic agent on free-running period of circadian rhythm, locomotor activities were continuously recorded in the rat implanted with a paraffin pellet mixed with or without carbachol near the suprachiasmatic nucleus. Implantation of carbachol, but not paraffin alone, resulted in shortening of the free-running period under constant darkness.

Animals↗