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A Gram-stain-negative, non-spore-forming, aerobic, oligotrophic bacterium (strain 262-7T) was isolated from a crack of white rock collected in the Skallen region of Antarctica. Strain 262-7T grew at temperatures between −4 and 30 °C, with optimal growth at 25 °C. The pH range for growth was between pH 6.0 and 9.0, with optimal growth at approximately pH 7.0. The NaCl concentration range allowing growth was between 0.0 and 1.0 %, with an optimum of 0.5 %. Strain 262-7T showed an unprecedented range of morphological diversity in response to growth conditions. Cells grown in liquid medium were circular or ovoid with smooth surfaces in the lag phase. In the exponential phase, ovoid cells with short projections were observed. Cells in the stationary phase possessed long tentacle-like projections intertwined intricately. By contrast, cells grown on agar plate medium or in liquid media containing organic compounds at low concentration exhibited short- and long-rod-shaped morphology. These projections and morphological variations clearly differ from those of previously described bacteria. Ubiquinone 10 was the major respiratory quinone. The major fatty acids were C17 : 1ω6c (28.2 %), C16 : 1ω7c (22.6 %), C18 : 1ω7c (12.9 %) and C15 : 0 2-OH (12.3 %). The G+C content of genomic DNA was 68.0 mol%. Carotenoids were detected from the cells. Comparative analyses of 16S rRNA gene sequences indicated that strain 262-7T belongs to the family Sphingomonadaceae , and that 262-7T should be distinguished from known genera in the family Sphingomonadaceae . According to the phylogenetic position, physiological characteristics and unique morphology variations, strain 262-7T should be classified as a representative of a novel genus of the family Sphingomonadaceae . Here, a novel genus and species with the name Polymorphobacter multimanifer gen. nov., sp. nov. is proposed (type strain 262-7T = JCM 18140T = ATCC BAA-2413T). The novel species was named after its morphological diversity and formation of unique projections.

Cytogenetic analysis of germ-line cells prior to intracytoplasmic sperm injection (ICSI) treatment is thought to be necessary for infertile males with an identified chromosomal abnormality. We analyzed the chromosomal karyotype of human spermatozoa from an oligoasthenozoospermic carrier of a reciprocal translocation t(10; 21). Cytogenetic analysis of 39 spermatozoa was performed by spectral karyotyping (SKY) and by ICSI into mouse oocytes. The motile morphologically normal spermatozoa were injected into mouse oocytes. Of these spermatozoa, 38 (97.4%) were activated. Twenty-one (53.8%) of the activated oocytes formed two pronuclei. Metaphase chromosome spreads from 13 spermatozoa were analyzed. Only one spermatozoon was normal and 2 spermatozoa exhibited balanced translocation. Nine and one spermatozoa showed abnormalities related and unrelated to the translocation, respectively. The numbers of normal/balanced spermatozoa were lower than those in previous reports analyzing reciprocal translocations using a previously described technique involving penetrated golden hamster oocytes. After genetic counseling with the carrier and his partner, ICSI treatment was performed. Healthy female and male infants were delivered at 37 weeks gestation via a Caesarean section. The female infant was a carrier of the reciprocal translocation and the male infant was confirmed normal on prenatal diagnosis at 16 weeks gestation. For genetic counseling prior to ICSI treatment, the incidence of unbalanced type spermatozoa after swim-up or Percoll gradient treatment should be investigated and discussed with couples having fertility problems related to oligozoospermia autosomal structural abnormalities.

右被殻出血後に発話の反復現象と，助詞，文末，語尾の省略を呈した50 歳代，右利き女性を報告した。本症例は，語の反復と音節の反復が同程度に認められたため，同語反復症と症候性吃音の両者を合併していると考えた。モーラ指折り法を用いた発話訓練を行ったところ，同語反復症および省略現象は軽減したが，症候性吃音は一時的な軽減にとどまった。 本症例の発話の反復現象は，前頭葉を含む右半球の広範な血流低下により，発話運動の抑制機能不全が生じたことや，左右半球間の発話運動に関する協調が崩れたことに起因する可能性が考えられる。また，本症例の示した省略現象には，注意やpacing の著明な障害が関与している可能性が推察された。さらに，発話障害に関する無関心さが，本症例における発話の反復現象や省略現象を助長させている可能性が示唆された。

Background: Ovarian hyperstimulation syndrome (OHSS) appears to be caused by increased capillary permeability in the vascular endothelial cells. Such cells secrete excess amounts of von Willebrand factor (vWF), a large adhesive glycoprotein.

We present a case of a 46,XY der(13;14) Robertsonian translocation carrier whose spermatozoa were karyotyped after injection into mouse oocytes. Fresh semen samples as well as recovered samples were used. There was no significant difference in the survival rate of mouse oocytes (fresh: 78.1% versus frozen: 81.7%), activation rate (fresh: 84.0% versus frozen: 90.6%), fertilization rate (fresh: 72.0% versus thawing of frozen: 76.5%) between fresh or frozen spermatozoa. Metaphase chromosome spreads from 45 spermatozoa were analysed. The frequency of spermatozoa that were chromosomally unbalanced with respect to the translocation was 8.9%, and the frequency of abnormalities unrelated to translocation was 4.4%. An excess of spermatozoa with balanced chromosomes was observed: compared with normal, 23 (51.1%) versus 16 (35.6%) respectively; but this segregation difference was not statistically significant (chi(2) = 0.9, P > 0.3). After genetic counselling with the carrier and his partner, intracytoplasmic sperm injection treatment was performed. Healthy female and male infants were delivered at 36 weeks gestation via a Caesarean section. Both babies were carriers for the balanced Robertsonian translocations detected for prenatal diagnosis at 16 weeks gestation. The present study demonstrates that patients can be given further information about the proportion of the spermatozoa which carry a chromosomal abnormality.

We investigated prospectively the clinical efficacy of a newly developed continuous autotransfusion system of ascites (CATSA) without protein supplement in patients with severe ovarian hyperstimulation syndrome (OHSS). Peritoneovenous shunting was used to recirculate ascites. The CATSA was performed for 5 h at a rate of 100-200 ml/h once a day. Eighteen patients were treated with the CATSA (CATSA group) and 36 were treated with an intravenous 37.5 g/day of albumin supplement (albumin group). Hospital stay was significantly shorter in the CATSA group than in the albumin group (10.0 +/- 5.7 versus 13.9 +/- 6.2 days, P < 0.01). Haematocrit value reached

Human elongated spermatids from azoospermic patients were inserted into mouse oocytes by intracytoplasmic sperm injection (ICSI). The injection resulted in survival rates of 46.5% (180 out of 387) and activation rates of 36.1% (65 out of 180). The rate of two pronuclear (2PN) formation was 35.4% (23 out of 65). Only 34.8% (eight out of 23) metaphase chromosome spreads from 2PN zygotes could be analysed; however, all were of normal karyotype. Cytogenetic analysis at the first metaphase revealed that human elongated spermatid chromosomes were able to undergo replication in a heterogeneous environment.

Departments of 1 Obstetrics and Gynaecology and 2 Pediatrics, Jichi Medical School, Minamikawachi-machi, Tochigi, 329-04 Japan 3 To whom correspondence should be addressed The outcomes of twins conceived by 136 women after medical assistance (MA) such as ovulation induction with or without assisted reproductive techniques, and twins conceived spontaneously (SP) by 72 women were compared. All 208 women were monitored from ,20 weeks gestation; they all delivered at o24 weeks gestation. The chorionicity of the placenta was diagnosed antenatally and confirmed after delivery. There were 10 perinatal deaths; the physical and neurological status of the remaining 406 infants was assessed at 1 year of corrected age. There were no differences in gestational age at birth, the birth weights of the larger and smaller twins, the birth weight discordance, or the incidence of life-threatening major malformations between groups. Adverse infant outcomes, such as death, cerebral palsy and mental retardation occurred in nine (3.3%) of 272 MA twins compared with 12 (8.3%) of 144 SP twins (P , 0.05). The placenta was monochorionic in only three (2.2%) of 136 MA twin pregnancies compared with 41 (57%) of 72 SP twin pregnancies (P , 0.001). Of the 21 infants with adverse outcomes, nine had monochorionic placentas. Thus, the risk of an adverse outcome was 2.8-fold higher (95% confidence interval (CI) 1.2‐6.4) in monochorionic twins than in dichorionic twins (10 versus 3.7%; P , 0.05). There was no difference in the incidence of adverse infant outcomes between SP (4.8%) and MA (3.4%) twins with dichorionic placentas. These findings suggest that ovulation induction in itself was not associated with an adverse outcome of twin pregnancies. The lower frequency of monochorionic placentas in MA twins may have been responsible for the lower risk of an adverse outcome in MA twins.

The objective of this study was to determine whether or not abnormalities in the autosomal structure of the male partner have any influence on fertilization and early embryo development after intracytoplasmic sperm injection (ICSI). Thirty-seven couples in whom the male partners were examined by the same andrologist were included in this study. Six couples (group I) in whom the male partner possessed autosomal structural abnormality underwent seven ICSI cycles. As a control group, 31 couples (group II) in which the male partner was karyotypically normal underwent 41 ICSI cycles. Although the normal fertilization rates seen in group I were significantly higher than those in group II (P < 0.05), there was no significant difference in the cleavage rates between the two groups. We did not perform the analysis of the female partner's chromosomes, but we surmise that structural autosomal abnormalities in the male partner do not adversely influence fertilization at ICSI and early development of embryos.

A Gram-stain-negative, non-spore-forming, rod-shaped, aerobic bacterium (strain 107-E2T) was isolated from freshwater samples containing microbial mats collected at a lake in Skarvsnes, Antarctica (temporary lake name, Lake Tanago Ike). Strain 107-E2T grew between 5 and 25 °C, with an optimum of 23 °C. Moreover, colony formation was observed on agar media even at −5 °C. The pH range for growth was between 6.0 and 9.0, with an optimum of pH 7.0–8.0. The range of NaCl concentration for growth was between 0.0 and 0.5 % (w/v), with an optimum of 0.0 %. No growth was observed in media containing organic compounds at high concentrations, which indicated that strain 107-E2T was an oligotroph. In the late stationary phase, strain 107-E2T produced a dark brown water-soluble pigment. Esterase, amylase and protease production was observed. Antimicrobial-lytic activities for Gram-negative bacteria and yeast were observed. Ubiquinone-8 was the major respiratory quinone. The major fatty acids were iso-C15 : 0, iso-C17 : 1ω9c and iso-C15 : 1 at 5. The G+C content of genomic DNA was 66.1 mol%. Analysis of the 16S rRNA gene sequences revealed that strain 107-E2T belonged to the genus Lysobacter , and low DNA–DNA relatedness values with closely related species distinguished strain 107-E2T from recognized species of the genus Lysobacter . The phylogenetic situation and physiological characteristics indicated that strain 107-E2T should be classified as a representative of a novel species of the genus Lysobacter , for which the name Lysobacter oligotrophicus sp. nov. is proposed. The type strain is 107-E2T ( = JCM 18257T = ATCC BAA-2438T).

Objective: To evaluate the clinical performance of gamete intrafallopian transfer (GIFT) and in vitro fertilization and embryo transfer (IVF-ET). Methods: Infertile women were divided into 2 groups: for GIFT, 239 patients (326 cycles) with at least 1 patent tube; and, for IVF-ET, 125 patients (210 cycles) with bilateral tubal occlusion. A specially designed retractor was developed to replace the gametes into an appropriate section of the Fallopian tube accurately and safely. Several parameters, including the pregnancy and delivery rates of each group, were compared. Results: The success rate per trial in the GIFT group was approximately 1.5 times higher than that in the IVF group (pregnancy rate: 44.2% vs. 31.0%, p < 0.01; delivery rate: 33.4% vs. 22.9%, p < 0.01). The pregnancy and delivery rates of GIFT decreased steadily with the number of trials. These apparent decreases were not observed up to the 3rd trial in IVF-ET cases. Conclusions: GIFT with a minilaparotomy procedure yielded significantly higher success rates than IVF-ET. Accordingly, GIFT is considered to be the first treatment choice in infertility cases with at least 1 patent Fallopian tube.

左辺縁葉後端部の小出血で選択的健忘症状を呈した53歳の男性例を報告した.全身痙攣後に一過性意識障害を呈し, 意識障害の改善と共に健忘が明らかになった.健忘は, 言語性優位の著明な前向性健忘と軽度の逆向性健忘で, 障害はエピソード記憶に選択的で, 意味記憶, 手続き記憶は保たれていた.急性期のX線CTでは左辺縁葉後端部に高吸収域を認め, 亜急性期のMRI (T2強調) では同部の皮質と皮質下白質に限局した低信号域を認めた.文献報告例との対比から左辺縁葉後端部病変による健忘は前向性健忘が主体であり, 言語性優位である可能性が示唆された.

The authors investigated the lesions and symptoms of five patients who presented with monoparesis of an upper limb due to cortical infarction. The location of the cortical motor hand area seems to be in the middle to lower portion of the anterior wall of the central sulcus. Severity of finger paralysis associated with impairment of this area varied in different fingers and occurred in two patterns: one variant predominantly affected the radial side, and the other predominantly affected the ulnar side.

We retrospectively analyzed the clinical features of two cases of neurodegenerative disease, whose initial symptoms were motor speech disorder and dementia, brought to autopsy. We compared the distributions of pathological findings with the clinical features. The main symptom of speech disorder was dysarthria, involving low pitch, slow rate, hypernasality and hoarseness. Other than these findings, effortful speech, sound prolongation and initial difficulty were observed. Moreover, repetition of multisyllables was severely impaired compared to monosyllables. Repetition and comprehension of words and sentences were not impaired. Neither atrophy nor fasciculation of the tongue was observed. Both cases showed rapid progression to mutism within a few years. Neuropathologically, frontal lobe degeneration including the precentral gyrus was observed. The bilateral pyramidal tracts also showed severe degeneration. However, the nucleus of the hypoglossal nerve showed only mild degeneration. These findings suggest upper motor neuron dominant motor neuron disease with dementia. We believe the results indicate a subgroup of motor neuron disease with dementia whose initial symptoms involve pseudobulbar palsy and dementia, and which shows rapid progression to mutism.

皮質性中枢性顔面単麻痺を呈した8例のMRI病変と臨床症状を対比し, 中心前回運動野の体部位局在について検討した.また, 顔面単麻痺の程度と性質, さらに顔面随意運動と感情運動時の運動麻痺の態度を観察し, 顔面筋支配の中枢性経路について考察した.MRI上の病変部位は冠状断像から, 中心溝, 中心前回を同定し, これを通る断面像から大脳縦裂を上端とし, Sylvius裂を下端とする大脳皮質を3等分し, 上方1/3, 中央1/3, 下方1/3とした.8例の共通病変は中心前回の中央1/3に存在し, それより, 下方進展例では, 嚥下・構音障害, 舌運動障害がみられ, 一方, 深部白質進展例では, 半側空間無視, 運動性失語などの合併が認められた.8例全例が, 顔面の随意運動時, 感情運動時共に同様な運動麻痺の態度を示し, 顔面随意運動と感情運動に関与する経路はいずれも, 中心前回運動野周辺では近接して走行している可能性が示唆された.

This case report illustrates the successful use of assisted reproductive technologies (ARTs) in a patient receiving conservative treatment for endometrial adenocarcinoma. A 31-year-old infertile woman, diagnosed as FIGO stage Ia endometrial adenocarcinoma (grade 1), received oral medroxyprogesterone acetate 400 mg/day for 12 weeks. Endometrial curettage was performed and the absence of endometrial carcinoma was confirmed. A single pregnancy was achieved with in vitro fertilization and embryo transfer. A healthy female infant was born via cesarean section at 42 weeks’ gestation. The carcinoma has not recurred, and the patient now desires a second child. We conclude that ART combined with progesterone treatment might be a powerful option for the treatment of infertile patients with early stage, well-differentiated endometrial adenocarcinoma.

左中心前回下部の脳梗塞により prosody の障害を主体とする持続性で重度の語唖症状を呈した症例を報告した。語唖症状の代償機能については，劣位半球対称領域 (Nielsen，1946＝劣位半球代償説) または Broca 野の周辺領域 (Levineら, 1979＝優位半球広範囲障害説) の役割を重視する二つの考え方が示されている。本症例は右 (劣位側) 中心前回下部に陳旧性病変を有しており，そこに存在するはずの語唖に対する代償機能が働かなかったと考えると，本症例にみられた語唖症状の持続が説明 (劣位半球代償説) 可能であると思われた。

We report a clinicopathological study of a patient suffering from frontotemporal dementia (FLD) with severe dysarthria and concomitant motor neuron disease (MND). The patient was a 52-year-old woman with almost simultaneous emergence of severe dysarthria and FTD. The severe dysarthria subsequently evolved into anterior opercular syndrome. Motor neuron signs then emerged, and the patient developed akinetic mutism approximately 2 years after the onset of the disease. The patient died of pneumonia after a 7-year clinical illness. Pathologically, severe and widespread degeneration in the frontal and temporal lobes, including the anterior opercular area, limbic system, basal ganglia, spinal cord and cerebellum, and frequent ubiquitin- and tau-negative basophilic inclusions were observed. The pyramidal tracts and anterior horns of the cervical cord also showed marked degeneration. Cases showing basophilic inclusions reported so far have been divided into two groups: early onset FTD and MND with basophilic inclusions. Our case presented clinicopathological features of both FTD and MND, which suggests that cases showing basophilic inclusions may constitute a clinicopathological entity of FTD/MND.

A right-handed Japanese man with no consanguinity exhibited personality changes, speech disorder and abnormal behaviors, such as stereotypical, running-away, environment-dependent, and going-my-way behaviors, since the age of 49 years. At age 52 years, neuropsychological examination revealed frontal lobe dysfunctions, mild memory impairment, and transcortical sensory aphasia. MRI showed symmetrical severe atrophy of the anterior part of the temporal and frontal lobes. The clinical diagnosis was FTD. He died at age 54 years after a clinical illness of approximately 5 years. Numerous argyrophilic grains were observed throughout the limbic system, temporal lobe, frontal lobe and brainstem. In addition, there were many tau-positive neurons and glial cells. These findings are all compatible with argyrophilic grain disease (AGD). Our case, however, is atypical AGD because of the young age of onset of the disease and sharply circumscribed cortical atrophy exhibiting severe neuronal loss and gliosis. Our case, together with some other similar cases of atypical AGD, gives rise to the possibility that this type of AGD would constitute a part of pathological background of FTD.

A total of 1,923 follicular human ova were collected for use in intracytoplasmic sperm injection (ICSI). Timed ovulation was induced by means of a standard ovarian stimulation protocol involving set dosages of follicle stimulating hormone (FSH), human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (hCG). Prior to performing ICSI, all of the ova were subjected to thorough examination which led to the discovery of only two parthenogenetic oocytes, also referred to as parthenogens, out of the total 1,923. These oocytes were retrieved from different patients. Although genetic analysis revealed that one of the parthenogens had a haploid number of chromosomes, it was impossible to analyze the second because it had not yet reached the metaphase stage. The 0.1 percent incidence of spontaneous parthenogenesis in this study clearly indicates that this phenomenon is extremely rare.

To assess the possibility that number of days of hospital stay increases with an increasing number of conceptuses in patients with ovarian hyperstimulation syndrome (OHSS).We reviewed 100 OHSS patients who were treated with a conservative therapeutic approach; 15 patients conceived but experienced spontaneous abortion by 8 weeks' gestation (SA group), 24 patients conceived a single fetus (singleton group), 16 patients conceived 2 fetuses (n = 14) or 3 fetuses (n = 2) (multiple group), and 45 patients did not conceive (NC group). The number of days of hospital stay, number of days of albumin supplementation, and hospital days when patients exhibited a urine volume ofor = 1200 mL/day and a hematocrit of40% were compared among the four groups.The number (SD) of days of hospital stay was 23.6 (9.0) days for the multiple group, 16.5 (7.7) days for the singleton group, 13.9 (7.6) days for the SA group, and 11.6 (4.8) days for the NC group. The orders of the other three variables were the same as that of the number of days of hospital stay, in that a larger number of days was observed with an increasing number of conceptuses.Pregnant women sustained OHSS for a longer time with an increasing number of conceived fetuses.

Precocious puberty has been defined as the development of secondary sex characteristics before 8 years of age in girls. In the past, therapy with progestational agents, such as medroxyprogesterone acetate or cyproterone acetate had been used. The gonadotropine releasing hormone agonist has been used widely. The ethiologies of delayed sexual development are numerous. A series of 191 patients with delayed pubertal development is reported in this study. Gonadal dysgenesis is 39/119(32.8%), physiologic delay is 27/119(22.7%), Rokitansky syndrome is 17/119(14.3%), hyperprolactinemia is 11/119(9.2%). The girls with physiological delay, hyperprolactinemia or poly cystic ovary syndrome, have subsequent normal reproductive potential. In the treatment of abnormal pubertal development, the individual treatment is important.

To investigate the neuropsychological mechanisms of kinesthetic alexia, we asked 7 patients who showed kinesthetic alexia with preserved visual reading after damage to the left parietal region to perform tasks consisting of kinesthetic written reproduction (writing down the same letter as the kinesthetic stimulus), kinesthetic reading aloud, visual written reproduction (copying letters), and visual reading aloud of hiragana (Japanese phonograms). We compared the performance in these tasks and the lesion sites in each patient. The results suggested that deficits in any one of the following functions might cause kinesthetic alexia: (1) the retrieval of kinesthetic images (motor engrams) of characters from kinesthetic stimuli, (2) kinesthetic images themselves, (3) access to cross-modal association from kinesthetic images, and (4) cross-modal association itself (retrieval of auditory and visual images from kinesthetic images of characters). Each of these factors seemed to be related to different lesion sites in the left parietal lobe.

Objective: To investigate the feasibility of using late spermatids in intracytoplasmic sperm injection (ICSI) for patients in which there is a total lack of normal and testicular sperm. Design: Clinical study. Setting: Private fertility center with adjacent laboratory facilities. Patient(s): Thirty-six males diagnosed with azoospermia underwent testicular biopsy and the resulting spermatids from nine patients were used to fertilize oocytes retrieved from their respective wives by ICSI. Intervention(s): Intracytoplasmic spermatid injection of oocytes with late spermatids obtained by testicular biopsy. Main Outcome Measure(s): Fertilization, pregnancy, and delivery rates. Result(s): Three of the cases resulted in pregnancies with childbirth occurring in all three, identical twins in one, and individual singletons in the other two cases. Conclusion(s): It is possible to achieve successful levels of pregnancy and childbirth in cases of azoospermia by intracytoplasmic injection of late spermatids.

In order to prove the acute stimulatory effects of estrogen on pituitary gonadotropin release, we have performed the present experiments in 8 women with a hypergonadotropic state due to surgical castration or primary ovarian failure. They received gonadotropin releasing hormone (Gn-RH) for 12-21 h at the constant rate of 20 micrograms/h. In 5 of the women, estradiol-17 beta was concomitantly administered at the rate of 20 micrograms/h from 6 h after the start of Gn-RH infusion. Blood samples were collected frequently throughout the experiments for the analysis of LH, FSH and estradiol. In response to the sole stimulation of Gn-RH, remarkable and prompt rises in LH (313.5%), but to a lesser degree in FSH (194.2%), were observed within the initial 3 h, and their high levels were maintained throughout the experimental period. However, the additional administration of estradiol brought on a further sudden rise in both gonadotropins levels: 178.3% for LH and 163.5% for FSH within 2 h. These high levels were sustained during estradiol infusions. In 2 of them, blood samples were obtained for several hours after cessation of estradiol infusion. The circulating gonadotropin level dropped precipitously close to the baseline level within 3 h after estradiol infusions. Our data indicate that estrogen has an acute and strong augmentative effect on Gn-RH induced gonadotropin release in addition to its conventional negative and positive feedback effects.

Gonadotropins-releasing hormone (Gn-RH) in selected regions of the female rat brain was measured by radioimmunoassay. Detectable immunoreactive Gn-RH was found in the anterior hypothalamic-septal region and in the mid-hypothalamic (arcuate-median eminence) region. Gn-RH was several times higher in the middle region than in the anterior region. Gn-RH was undetectable in the posterior hypothalamic region, frontal cerebral cortex and pineal glands, as well as in random blood samples, and low to undetectable in anterior pituitary glands. Gn-RH activity varied during the estrous cycle and after castration. In the mid-hypothalamic region, Gn-RH content was lowest throughout diestrus and in late morning and early afternoon of proestrus, and highest early in the morning of proestrus and during estrus. A significant decrease at mid-day was only found on the day of proestrus, a few hours prior to the critical period for LH release. In the anterior hypothalamic region, low Gn-RH activity was found from 1200 h of estrus to 1200 h of diestrus-2. A comparatively higher activity was seen at 1700 h of diestrus-2 and also from 1400 h of proestrus to 0800 h of estrus. Twenty-one days after ovariectomy, Gn-RH in the mid-hypothalamic region was significantly lower than the lowest values seen during the estrous cycle, while Gn-RH in the anterior hypothalamic region remained between low and high values seen during the cycle, being significantly higher than the low values. The changes observed during the estrous cycle and after castration suggest that gonadal steroids play a direct role in the control of hypothalamic Gn-RH. These data also demonstrate that Gn-RH varies in a different way in the anterior and mid-hypothalamic regions.

The method of pulsatile administration of gonadotropin-releasing hormone (Gn-RH) has been proven as a useful means for induction of ovulation in anovulatory women. In our series of clinical trials, 23 out of 29 anovulatory patients ovulated with pulsatile administration of Gn-RH. Seven patients who ovulated volunteered for the present study with daily hormonal analysis and follicular sonometory . Two patients have oligomenorrhea, 3 patients secondary amenorrhea-1st grade (the sole administration of gestagen required for withdrawal bleeding) and the remaining 2 patients secondary amenorrhea-2nd grade (the combined administration of estrogen and gestagen required for withdrawal bleeding). A diagnosis of hyperprolactinemia was made for one patient with secondary amenorrhea-1st grade. Pulsatile administration of Gn-RH was performed by the use of a self-administered infuser . The infuser was connected to an i.v. indwelling catheter via a specially designed blood backflow eliminater . Five micrograms or less of Gn-RH was given every 2 hr from 07:00 to 23:00 hr daily. Five patients received HCG during the preovulatory period. In one patient, a short term treatment of HMG was added to Gn-RH treatment. Follicular sonometry revealed the development of a single dominant follicle which reached between 20 and 28 mm (23.7 +/- 0.12 mm, mean +/- S.E.) in diameter at the preovulatory period. Disappearance of a dominant follicle was recognized in the early luteal phase. Characteristic increases in estradiol were recognized concomitantly with the development of a dominant follicle. Progesterone levels after ovulation were within the limits of its normal "luteal phase" rise. The present data suggest that pulsatile administration of low dose Gn-RH with nocturnal interruption of treatment is effective for normal progress of follicular development in various types of anovulatory patients, culminating in single ovulation. This paper includes the discussion on our method which may be responsible for a high success rate of ovulation induction.

Hypothalamic-pituitary stalk portal blood was collected from 12 female rhesus monkeys. The pituitary stalk was approached transorbitally and cut at the level of the diaphragma sellae under direct visualization. After complete heparinization of the animal, stalk portal blood was obtained continuously, for periods of 30 minutes to 9 hours, using a constant exfusion pump at a rate of 30 to 40 mul/min. The mean GnRH in portal blood, as measured by radioimmunoassay, was 66 +/- 6.6 pg/ml (+/- SE) in 7 ovariectomized animals and 51 +/- 5.3 pg/ml (+/- SE) in 2 monkeys during the early follicular phase. Fluctuations in portal blood GnRH were most prominent in ovariectomized animals, with peak levels of 200-800 pg/ml and intervals of 1 to 3 hours between pulses. Peaks of GnRH during the early follicular phase did not exceed 200 pg/ml. The administration of estradiol (1000 ng, iv) to 3 monkeys did not decrease GnRH levels within the next 2 hours. These data provide direct evidence for a hypothalamic mediation of pituitary LH pulsatile release.

修治附子および烏頭の aconitine 類と総 alkaloids 量を測定するとともに, 各種漢方薬中に加えてその煎液中に移行する総 alkaloids 量をも測定した。修治附子は烏頭に比べて総 alkaloids の含有量が高かつた。しかし原型の aconitine 類は烏頭のほうが高く, なかでも hypaconitine の量が4.9倍高かった。また各種漢方薬中に加えた場合, 総 alkaloids の残存率は烏頭よりも修治附子のほうが高く, この値は混じる薬方により影響をうけることが明らかとなった。修治附子または烏頭を単剤で煎じた場合より各種薬方中に加えた場合のほうが, 総 alkaloids の残存率は減少した。同一の附子片に含まれる有効成分でも煎液への残存率, 残存量は混ずる薬方により異なり, それが臨床的に有効にして副作用の軽減をもたらす可能性が示唆された。

Several N,N-dialkylselenocarbamate complexes of tin(IV), (CH3)2Sn[OSeCNR2]2 (1), (CH3)2ClSn[OSeCNR2] (2) (R=CH3 and C2H5) and (CH3)3Sn[OSeCN(CH3)2] (3), have been prepared, and their infrared and proton magnetic resonance spectra have been examined. The results indicate that in 1 and 2 the selenocarbamate ligands are coordinated to the tin atom in a bidentate manner, although the coordination of the oxygen atom is weak. On the other hand, 3 has a tetra-coordinate tin with a free carbonyl bond. The configurations of these complexes are discussed and compared with those of the corresponding thio-, dithio-, diseleno-, and thioselenocarbamate complexes of tin(IV).

The effects of either single injection or continuous infusion of synthetic Gn-RH on plasma hCG levels were studied in 5 pregnant women (14-38 week gestation). No definite increase of hCG level was seen in all the cases studied. In view of large dosages of Gn-RH used in this study in comparison with its minimum effective dose for the pituitary gonadotropin release, Gn-RH seems unlikely to play a role in hCG secretion during human pregnancy.

In order to elucidate the positive feedback mechanism of estrogen on gonadotropin release in women, the responses of plasma LH and FSH to the constant infusion of estradiol-17 beta for a prolonged period were studied. The infusion was initiated on various days of the follicular phase and maintained for 36-66 hr at a constant rate of 500 or 1,000 microgram/24 hr. When the stimulus of estradiol was sustained for more than 30 hr in the women of the middle or late follicular phase, a positive feedback effect to elicit gonadotropin surges was observed during the maintenance of the infusion. In contrast, the stimulus of estrogen was ineffective in the early follicular phase, even if sustained for a longer period up to 66 hr. Gonadotropin levels, also, increased after the end of infusion. The magnitude of the responses, however, was much smaller, as compared to spontaneous preovulatory gonadotropin surges. In all cases, the effect of estradiol was greater for LH than for FSH. It is suggested that: 1) Preovulatory gonadotropin surges are triggered by estrogen increments rather than the withdrawal of the negative feedback effect of estrogen. 2) Low levels of estrogen for a certain period of the early follicular phase may play an important role in priming the control system which responds to the positive feedback effect of estrogen.

The present experiments were performed to study the effects of preovulatory levels of estrogen on GnRH-induced gonadotropin release. Twelve female volunteers in various phases of the menstrual cycle received estradiol infusion for 66 h at a constant rate of 500 micrograms/24 h which is grossly equivalent to its production rate during the preovulatory follicular phase. In 8 of the women, GnRH was administered concomitantly from 6 h after the initiation of estradiol infusion. The administered doses of GnRH were 2.5 and 5 micrograms/h. Blood samples obtained throughout the infusion were analysed for LH, FSH, estradiol and progesterone. The sole administration of estradiol failed to induce the positive feedback effect on gonadotropin release within the experimental period in the early follicular phase (days 3-7) in 4 women. In 5 women treated during the follicular phase, remarkable LH releases were induced after a lag period by the infusion of both GnRH and estradiol. The induced LH surge formed a prolonged biphasic pattern. Although a similar pattern of FSH was observed in some cases, its response was minimal compared with that of LH. In 3 women during the luteal phase, however, a combined administration of estradiol and GnRH induced only a short term release of LH which was terminated in only 12 h. The present data indicate that 1) Preovulatory levels of estrogen affect the late part of the LH surge which is induced by constant administration of low doses of GnRH resulting in a prolonged biphasic release of LH, and 2) These effects of both hormones are not manifest in the presence of high levels of progesterone. These results indicate the possibility of a role of GnRH and estrogen in the mechanism of the prolonged elevation of a gonadotropin surge at mid-cycle.

In order to reevaluate the earlier varying data regarding circulatory gonadotropin-releasing hormone (GnRH), we assayed extracted GnRH from the plasma frequently collected at mid-cycle in 11 women. For the analysis of episodic GnRH patterns and basal levels, blood samples were obtained at 6 h intervals for 72 h and at 15 min intervals for 2 h every 12 h throughout the experimental period. All blood samples were assayed for GnRH and selected samples for LH, FSH, estradiol and progesterone. For GnRH assay, 5 or 6 ml of blood was mixed with 60 mg of ethylenediaminetetraacetic acid, disodium salt, and 3 mg of phenylmethylsulfonyl floride immediately after blood collection. These enzyme inhibitors prevented the destruction of GnRH in the blood at room temperature for at least 4 h. Plasma GnRH was extracted through several steps including florisil absorption, acidic extraction and washing with organic solvent. Nonspecific immunoreactivity in the plasma was markedly decreased through this extraction process. Our assay values (approximate range, 0.1-2.0 pg/ml) of plasma GnRH in normal women corresponded to the low range of those obtained by others who used the alcohol extraction method. The basal levels of GnRH did not change significantly throughout 3 different periods, i.e., before, during and after the LH surges, and fluctuated between a small range of 0.11 and 1.44 pg/ml. Although the peak levels of GnRH observed in its episodic patterns did not change between the periods before and during the LH surges, they decreased significantly after the LH surge compared with those seen during the LH surges (0.93 +/- 0.07 vs 1.17 +/- 0.09 pg/ml, p less than 0.05). The present data demonstrate that immunoreactive GnRH in the extracted peripheral plasma does not change significantly in its mean, basal and peak levels during the periovulatory period except for a minor but significant decrease in the peak levels shortly after an LH surge.

The present experiments were performed to elucidate the mechanism of the selection and maturation of a dominant follicle in women. Eight normally menstruating women undergoing myonectomy or tubal surgery volunteered for the present study. In 3 patients who were operated on Day 9-11, a visual dominant follicle was removed. The other 5 patients underwent the removal of a newly developing corpus luteum on Day 15-21. After taking 3 or 4 preoperative blood samples in the morning after their hospitalization, blood was obtained at 3 or 6 h intervals for the first 36-45 h and at 1-3 day intervals thereafter for 21-34 days. Serum FSH, LH, estradiol and progesterone were measured by radioimmunoassay. Follicleectomy was followed by a sudden drop in estradiol and a minor increase in progesterone. FSH increased for a few days and then declined. There was a drastic, but short-term increase in LH following follicleectomy which was performed before a preovulatory gonadotropin surge. A LH surge occurred 10.7 +/- 1.2 days (mean +/- S.E.) after follicular ablation followed by a luteal phase. In contrast, there was no remarkable LH release in 4 out of 5 patients who underwent luteectomy. A slightly higher level of FSH was sustained for 2-7 postoperative days. "Luteal phase" rises in estradiol and progesterone terminated promptly following luteectomy. A LH surge was observed 14.2 +/- 1.7 days after surgery followed by a luteal phase. After either type of operation, a sustained increase in FSH was followed by a gradual increase in estradiol which preceded a gonadotropin surge. These hormonal sequences resemble those seen in the normal follicular phase. The present data demonstrated that follicleectomy and luteectomy bring on some characteristic hormonal changes which may exert stimulatory or suppressive effects on the selection and maturation of a dominant follicle after the removal of a main ovarian cyclic structure culminating in ovulation at a certain interval.

The developmental appearance of immunoreactive gonandotropin releasing hormone (Gn-RH) was measured by radioimmunoassay in male and female rats from the 12th day of gestation to adulthood. Gn-RH content of the whole hypothalamus of both sexes increased from birth to 21 days of age. By the 28th day, Gn-RH content in females had approximately reached adult levels, while that in males continued to increase. Adult male rats exhibited significantly higher levels than adult females. The ontogeny of the regional differences previously observed in cycling female rats (4) was also studied. Regional analysis of Gn-RH development was characterized in the anterior hypothalamus by the rapid attainment of adult levels by day 7. In striking contrast, in the mid-hypothalamic region, Gn-RH content increased gradually, rising dramatically just prior to vaginal opening. The developmental pattern of Gn-RH content is consistent with the maturation of those hypothalamic structures concerned with synthesis, transport and storage of Gn-RH. The regional patterns observed may thus represent sequential maturation of the neural pathways involved.

The degree of follicular development was examined in a patient with 17 alpha-hydroxylase deficiency that accounted for impairment of estrogen and androgen biosynthesis. The ovarian content of P was markedly higher than those of any other steroids requiring 17 alpha-hydroxylation for synthesis. The morphologic analysis of the ovaries demonstrated that normal follicles could not develop to more than 2.2 mm in diameter, and most follicles with diameters of 1.0 mm or more yielded to atresia. It is known that estrogen and FSH act synergistically on the growth of the follicles. Our data suggest that the follicles can develop up to the size of 2.2 mm in diameter at most with the sole stimulation of gonadotropin.

5-HTP (5 mg/100 g body weight), a precursor of serotonin, was administered intravenously to pituitary stalk sectioned rats. Plasma prolactin levels were initially increased 30 and 60 min after the injection of 5-HTP and thereafter decreased. Pituitary prolactin content was decreased 60 min after the stalk section as compared to those seen following sham operation. The treatment of 5-HTP induced a moderate increase in pituitary prolactin content in the stalk sectioned rats. In order to confirm the complete disconnection of pituitary stalk after the operation, 2.5 micrograms of dopamine hydrochloride was given into the lateral ventricle of stalk sectioned rats. Plasma prolactin did not change following the administration. Our results demonstrate that 5-HTP acts either directly at the pituitary level or via some mechanism yet to be determined.