Tachykinins are widely distributed in mammalian central nervous system and exert a variety of actions through individual specific receptors. Neurotransmitter functions of substance P (SP), a member of mammalian tachykinins, have been firmly established in the spinal cord; SP is highly concentrated in the superficial layers of the dorsal horn, is released upon electrical stimulation, produces a slow excitatory postsynaptic potential in second-order neurons and is inactivated by peptidases. Since SP is contained in unmyelinated primary afferent fibers, which mediate nociception, SP is thought to transmit nociceptive information and contribute to occurrence of pathological pain states such as inflammation and nerve injury. Based on these findings, great effort has been devoted to developing NK-1 tachykinin receptor antagonists as a potent antinociceptive drug, but up to the present such effective drugs are unavailable. Tachykinin receptor antagonists have been also attracting much attention as a novel therapeutic drug for anxiety and depression other than pain. The amygdala, a key brain structure associated with emotional responses, is thought to be a target of tachykinin receptor antagonists for exerting psychopharmacological actions. Indeed, tachykinins enhance inhibitory synaptic transmission in the basolateral complex of the amygdala. Further study of tachykininergic transmission in the central nervous systems will open novel fields for pharmacology and therapeutics in neuropsychiatric disorders.

抄録全体を表示

Objective: Endometrial perfusions were measured by Doppler ultrasound to evaluate the influence of spontaneous menstrual cycles and to study the effect of clomiphene citrate.
Methods: Flow waveforms in right and left uterine arteries were obtained by using transvaginal color Doppler ultrasonography in infertile women with 60 spontaneous menstrual cycles and 37 clomiphene citrate stimulated cycles from the follicular to the luteal phase.
Results: In the spontaneous menstrual cycles, the uterine arterial blood flow increased significantly from the follicular phase to the day of ovulation and then increased markedly to about 200∼230% of the follicular phase after the 6th day of ovulation. In the clomiphene citrate stimulated cycles, the uterine arterial blood flow did not change during the periovulatory period and then increased significantly to about 180∼220% of the follicular phase after the 6th day of ovulation.
Conclusions: In the present study, the clomiphene citrate stimulated cycles showed lower endometrial perfusion during the periovulatory period compared with those in the spontaneous menstrual cycles. The results suggest that the assessment of endometrial perfusion with Doppler ultrasound can be used to reveal unexplained infertility problems in induced ovarian cycles.

抄録全体を表示

Depression commonly involves abnormalities of the sleep-wake rhythm, the temperature rhythm, and other biological rhythms. The changes of these biological rhythms are caused in remission by medications. However, it has yet to be clarified whether the biological rhythms are changed as a result of recovery from depression or from the direct pharmacological effects of the antidepressants. Therefore, we have undertaken a study on the direct effects of the antidepressants trazodone and imipramine on the biological rhythms of healthy volunteers.
The study involved 12 healthy male volunteers (ages 21∼28 years, mean age 23.9±1.7 years) who had given written informed consent. Placebo, trazodone, and imipramine were each administered in a single blind manner four times a day, during the three-day study period. The total daily dosage of trazodone was 100 mg (50 mg in one subject), and of imipramine 40 mg (20 mg in one subject). Subjects were submitted to polysomnography (PSG) and body core temperature (rectal temperature) measurements during the study period. We compared the data concerning the antidepressants to those of the placebo.
The results show that, with regard to the sleep rhythm, trazodone significantly increased slow wave sleep (SWS), but no changes were observed in REM (rapid eye movement) sleep. Imipramine significantly decreased REM sleep and prolonged the REM cycle. With regard to the temperature rhythm, trazodone showed a tendency to advance the appearance time of the minimal temperature. Imipramine significantly lowered the maximal temperature and decreased the difference between the maximal and the minimal temperature, but no changes in the phases were observed. Neither antidepressant had any effect on the temperature cycle.
Trazodone and imipramine showed different effects on PSG. Furthermore, they had different effects on the temperature rhythm. The changes of the sleep-wake rhythm were greater than those of the temperature rhythm. Although the two antidepressants had different mechanisms of action, it is worthy of note that both directly influenced the biological rhythms of healthy volunteers.

抄録全体を表示

The purpose of this study was to evaluate a quantitative analysis of the nociceptive threshold, using the current perception threshold (CPT), in women with normal pregnancies and to assess the relationship between nociceptive thresholds and ovarian sex steroids. The subjects consisted of 10 women with singleton pregnancies and 14 age-matched healthy female volunteers. The CPTs (5,250, and 2,000 Hz) of the dominant ankle section were determined with a Neurometer CPT/C (Neurotron, Baltimore, MD). Blood samples were collected after these examinations, and the total 17β-estradiol (E₂) and progesterone concentrations in sera were measured. The present findings clearly indicated that the CPTs at 2,000 Hz in women at term in normal pregnancies were significantly higher than those in nonpregnant women (p<0.05). At 5 and 250 Hz, there was no significant difference between pregnant and nonpregnant women. While there was also no significant correlation between CPT and E₂, and progesterone, there was significant correlation between CPT and the ratio of 17 β-estradiol/progesterone (E₂/P) at 2,000 Hz (p<0.05, r=0.67). We suggest from these data that changes in pressure sensitivity occur at term in pregnancy, and that other factors, possibly stimulated by both E₂ and progesterone, may play an important role in this change.

抄録全体を表示

The possibility of the participation of mast cells in human parathyroid hormone secretion was studied with regard to the frequency, distribution, and sub-types of mast cells and the content of in-tissue histamine, a chemical mediator in mast-cell granules, in human parathyroids with various pathological conditions. The above factors were compared between those of a 'normal' parathyroid group and those of 'pathological' parathyroids associated with adenoma and hyperplasia.
Specimens were scanned for the mean value of the mast cell number per field of microscopic view and for the ratio of the mast cell number in glandular parenchymal tissue to that in interstitial tissue. The activated state of the mast cells was examined through classifying the mast cells into two sub-types, mucosal mast cells and connective-tissue mast cells. The high-performance liquid chromatography (HPLC) method was used for assay of in-tissue histamine. The frequency of mast cells showed no difference between the groups, whereas the distribution of mast cells, showed a distinct difference. The occurrence rate of mast cells in glandular parenchymal tissue in the 'pathological' group presented an increase as compared with that in the 'normal' group. Furthermore, the occurrence rate of mucosal mast cells in an activated state also showed an increase. This suggests that mast cells are likely to participate in parathyroid hormone secretion. The histamine-content in the 'normal' group was significantly larger than that in the 'pathological' group, which was a different outcome from that observed in mast cells from the results of light microscopy. This may require taking into consideration the difference in the histamine content of the mast cells themselves between that of mucosal mast cells and connective-tissue mast cells.

抄録全体を表示

Gross anatomic, histologic and ultrastructural studies were made on 32 floppy aortic valves (FAVs) resected at the time of aortic valvular replacement for aortic regurgitation. Patients with the FAVs had relatively long clinical courses and had severe aortic regurgitation with mild symptoms of heart failure. The sizes of the mechanical valves implanted in the patients with FAVs were not large, indicating that the aortic regurgitation in these patients was not worsened by dilatation of the aortic ring. Two types of FAVs were recognized grossly, according to whether they showed abnormal cuspal thickening or thinning. Accumulations of myxoid material in the spongiosa were found in all FAVs, regardless of cuspal gross morphology. Histologically, the collagen fibers were sparse and irregularly arranged and elastic fibers were disrupted and finely granular in the myxomaotus areas of FAVs. Ultrastructurally, the myxomatous material consisted of numerous star-shaped proteoglycan granules associated with spiraling collagen fibrils and abnormal elastic fibers. Numerous spiraling collagen fibrils were observed especially at the border area of myxomatous change that extended from the spongiosa into the fibrosa. Abnormal elastic fibers had either a granular appearance of their amorphous components without microfibrils, or irregularly arranged masses of microfibrils without amorphous components. These abnormalities of connective tissue components, resulting from defective formation and/or increased degradation were similar to those in floppy mitral valves, and were related to the floppiness of cardiac valves.

抄録全体を表示

The monoclonal antibody HISL-19 was originally generated after immunizing BALB/c mice with human islet cells. We used this antibody to study a wide variety of neuroendocrine (NE) and non-NE tumors by immunohistochemical, immunoelectron microscopic, and biochemical (Western blotting) techniques. Of the thyroid tumors, HISL-19 specifically immunoreacted with medullary carcinoma of the thyroid (MCT); of the pancreatic tumors, it reacted with islet cell tumors such as insulinomas and a gastrinoma; of the adrenal tumors, it reacted with pheochromocytoma. HISL-19 showed particularly strong immunoreactivity to a gross granular material at the perinuclear area in the MCT and malignant pheochromocytoma but not in the benign pheochromocytoma, although the latter cells showed a faint and homogenous positive reactivity in the cytoplasm. The strongly HISL-19-positive material was found to consist of newly synthesized antigenic proteins with a molecular weight between 60 and 65 kilodaltons (kDa) by Western blotting. Immunoelectron microscopic analysis revealed that this antigenic protein was located in the secretory granules that appear markedly in malignant endocrine tumors, usually located close to the nucleus. Thus, HISL-19 is a useful and specific marker for the immunohistochemical diagnosis of NE cell tumors. The specific antigenic proteins of HISL-19 were defined in MCT and malignant pheochromocytoma. These proteins are speculated to be actively synthesized and more highly produced in the secretory granules of malignant endocrine tumors than benign ones. Thus, a preoperative immunohistochemical study using HISL-19 might be useful for predicting the grade of malignancy of endocrine malignant tumors and thus help determine an appropriate operative procedure, in addition to being a useful marker of neuroendocrine cell tumors.

抄録全体を表示

The subjects were 160 pregnant women with no complications who were examined with indirect calorimetry by a single observer; 20 healthy age-matched non-pregnant women were used as controls. Assessment was performed 12 hours after oral intake of food. Each measurement of resting energy expenditure divided by the body surface area was analyzed and compared with that of the controls. In pregnant women, the mean resting energy expenditure divided by the body surface area did not significantly increase until 32 weeks' gestation. Energy expenditure increased significantly by about 300∼600 kJ/m² between before 31 weeks' gestation and the end of pregnancy. Significant changes occurred in the 32∼35 and 36∼40 weeks' gestational stages (3,790±370,4,110±385 kJ/m²) (p<0.05). Resting energy expenditure increases at conception, and does not increase until 32 weeks' gestation, but increases gradually from 32 weeks' gestation to term in normal pregnant women as assessed by indirect calorimetry.

抄録全体を表示

We present two rare cases of volar and dorsal fractures of the middle phalanx at the proximal interphalangeal joint (PIPJ). The first case was a 16-year-old girl. She hurt her middle finger while playing basketball. A lateral radiograph revealed volar and dorsal fractures of the middle phalanx. She underwent external immobilization of the PIPJ in 30°of flexion with a splint for 3 weeks. The fractures healed 7 weeks after the injury with neither tenderness nor limitation of range of motion. The second case was a 16-year-old boy. He injured his index finger while playing basketball, and underwent immobilization of the PIPJ for 3 weeks. At 10 weeks after the injury, the dorsal fracture was almost healed, but the displacement of the volar fragment had worsened. At a 3-year follow-up, the dorsal fragment was healed, but the volar fragment remained in a site of nonunion. However, there was neither residual deformity nor restriction of movement.

抄録全体を表示

Several studies have reported the efficacy of donepezil (a cholinesterase inhibitor) in patients with Alzheimer's Disease, not only for memory disturbances but also for psychotic and behavioral disturbances.
We have experienced one such case that was a 74-year-old female patient with Alzheimer's Disease. Donepezil remarkably improved, for the most part, these symptoms in this case.
The scale of Mini-Mental State Examination (MMSE) was improved from 21/30 to 26/30, and the Alzheimer's Disease Assessment Scale (ADAS) was improved from 21.7/70 to 16.3/70. It took about 8 weeks of treatment with donepezil to achieve these results, although some adverse effects associated with the use of donepezil were found in this case. It became difficult for the nursing staff to give care because of hyperactivity and self-assertion.
However, the relationship between donepezil and these behavioral disturbances was not clear.
This case indicates that donepezil may exacerbate symptoms in Alzheimer's Disease patients who have psychotic and behavioral problems.
From a clinical point of view, we concluded that donepezil is therapeutically efficacious for Alzheimer's Disease sufferers, but that some problems still exist.

抄録全体を表示