Estrogenic Induction of NADPH- Diaphorase Activity in the Preoptic Neurons Containing Estrogen Receptor Immunoreactivity in the Female Rat

Nitric oxide and estrogen have been shown to play a critical role in the control of female reproductive function. In order to determine an anatomical relationship between nitric oxide generating neurons and estrogen target neurons, NADPH-diaphorase histochemistry was combined with estrogen receptor immunohistochemistry in the female medial preoptic area. While only a few weakly stained neurons for NADPH-diaphorase were found in ovariectomized control rats, a drastic increase in NADPH-diaphorase activity was observed in the medial preoptic nucleus of estradiol-treated ovariectomized animals. The total number of NADPH-diaphorase neurons in the estradiol-treated group increased three-fold relative to controls, and more than 80% of those neurons contained estrogen receptor-immunoreactivity in their nuclei. Since neuronal NADPH-diaphorase is nitric oxide synthase, the present result suggests that nitric oxide synthase activity can be positively regulated by estradiol in neurons containing estrogen receptor in the female medial preoptic nucleus.     

NEW METHOD OF STENTING TREATMENT FOR MALIGNANT DUODENAL STENOSIS: USING DOUBLE‐BALLOON ENTEROSCOPY

Recently, a self‐expandable metallic stent has been recognized for treatment of malignant duodenal stenosis. But the complications by stenting are important problems even now. In the present study, we report our new method of duodenal stenting by using of double‐balloon enteroscopy considered safe and effective.     

Disappearance of Philadelphia chromosomes after remission induction in lymphoid crisis of chronic myelogenous leukemia]

The authors report a rare case of chronic myelogenous leukemia (CML) in which the Ph1 clone disappeared after remission induction of lymphoid crisis. A 58-year-old man was admitted to our hospital because of fever in July 1988. The white cell count was elevated. Bone marrow aspirate showed hypercellularity with myeloid hyperplasia. In the chromosomal analysis, Ph1 chromosomes were detected in 100% of bone marrow cells analysed. Diagnosis of CML was made and treatment was initiated with recombinant interferon-alpha 2a. Hematological remission without cytogenetic improvement was achieved. In March 1990 he developed lymphoid crisis with proliferation of CD10-positive cells. The chromosomal analysis revealed additional abnormalities including, 45, X, -Y, t(9;22) (q34;q11), +1, -8. With vincristine 0.6 mgX4, pirarubicin 15 mgX4, dexamethasone 40 mgX4 therapy complete remission was obtained. In December 1990 the Ph1 positive clone completely disappeared judging from normal karyotypes in the chromosomal analysis and the disappearance of M-bcr gene rearrangement.     

Assessment of urinary beta-core fragment of hCG as a tumor marker of cervical cancer]

Beta-core fragment (beta-CF), a fragment of the hCG beta-subunit missing its carboxyterminal peptide, can be detected in the urine of women throughout pregnancy or in trophoblastic disease. It is also found in the urine of patients with nontrophoblastic cancers. We examined the beta-CF level in urine samples from patients with cervical cancer and assessed its value as a tumor marker. beta-CF was measured by an enzyme immunoassay with hCG beta-core directed monoclonal antibody No. 229. Based on the cut-off value (0.2ng/ml) from control subjects, the overall positivity rate for urinary beta-CF in the cervical cancer group was 45% (57 of 128 patients), increasing from 32% (23 of 73) in stage I to 100% (2 of 2) in stage IV. These positivity rates exceeded or equaled those of the other markers, SCC, CEA, CA19-9 and CA125, simultaneously measured in the patients' serum. There was no significant difference between the positivity rates for the two histological types of cancer, squamous cell carcinoma and adenocarcinoma. Serial determination in 28 patients with increased urinary beta-CF prior to therapy showed that 24 patients had a decreased concentration after successful treatment, but 2 of 4 patients with still increased urinary beta-CF during or after treatment subsequently relapsed. The determination of urinary beta-CF may provide a useful tool in monitoring the response to treatment in patients with cervical cancer.     

Electron microscopic study of muscle spindle in human interarytenoid muscle

Using transmission electron microscopy, the fine structure of the muscle spindle in the interarytenoid muscle was studied. The specimen was made from a fresh adult male larynx which had been surgically removed. The muscle spindle showed the following characteristic features: (1) the capsule was thin, with only a small number of layers of capsular sheet cells; (2) the periaxial space was narrow and there were abundant collagenous fibrils; (3) the sensory endings consisted of irregularly coiled terminal axons with varicose swellings, and some endings penetrated the sarcoplasm; (4) one nuclear chain fiber terminated on the capsule, while the other branched into two bundles; and (5) special sarcoplasmic inclusions, possibly related to the sensory endings, were also observed. These findings suggest that the muscle spindle in the interarytenoid muscle is not only a very sensitive stretch receptor, but also a pressure receptor.     

Bilateral symmetric tonic posturing suggesting propagation to the supplementary motor area in a patient with precuneate cortical dysplasia.

We report a patient manifesting seizures with bilateral symmetric tonic posturing, which were markedly reduced after resection of the left precuneus. A 16-year-old man had sudden onset, complex partial seizures with bilateral symmetric tonic posturing since the age of eight years. Magnetic resonance fluid-attenuated inversion-recovery imaging revealed a hyperintense lesion in left precuneus. In almost all focal seizures recorded during an invasive EEG evaluation, ictal onset was detected from the inferomesial aspect of the lesion, but fast paroxysmal discharges from the ipsilateral supplementary motor area (SMA) were observed just before the clinical onset. After surgical excision of the EEG onset zone, including the lesion, seizure frequency was markedly (> 95%) reduced. By the 20th month after surgery, there were only brief nocturnal seizures involving slight elevation of both shoulders and slight abduction of both arms, with preservation of consciousness occurring once every few days. Invasive EEG findings and surgical outcome suggested that the epileptic activity originating from the epileptogenic zone may have propagated to the symptomatogenic zone including mainly the ipsilateral SMA. In summary, we report an interesting case of bilateral symmetric tonic posturing suggesting propagation to the SMA. MRI and invasive EEG confirmed the epileptogenic focus as a precuneate cortical dysplasia lesion.[Published with video sequences].     

Potentiation of vincristine and actinomycin D by a new synthetic imidazole anti-tumor agent YM534 active against human cancer cells and multidrug-resistant cells

Ethyl 6-p-5-(l-imidazolyl) pentyloxyphenoxy-2, 2-dimethylhexanoate hydrochloride (YM534) is a new synthetic anti-tumor compound. Combinations of YM534 with other anti-cancer agents were examined to ascertain whether YM534 potentiated other anti-cancer agents against the KB cell line and its multidrug-resistant counterpart, VJ-300. YM534 potentiated the cytotoxic action of vincristine and actinomycin D about 2-fold against KB cells, but not those of daunomycin and adriamycin. By contrast, YM534 only slightly reversed drug-resistance to adriamycin and daunomycin in VJ-300 while it reversed 5-fold vincristine resistance and 60-fold actinomycin D resistance in VJ-300. The reversal effect of YM534 on actinomycin D and vincristine-resistance in VJ-300 cells appeared to be due to enhanced accumulation of [3H] actinomycin D and [3H] vincristine in VJ-300 cells by YM534. YM534 inhibited efflux of actinomycin D and vincristine from VJ-300 cells, and it also enhanced cellular uptake of these anti-cancer agents. YM534 enhanced cellular accumulation of both actinomycin D and vincristine in the sensitive KB cells. YM534 is thus a unique anti-cancer agent since combinations of other anti-cancer agents with YM534 are expected to augment anti-tumor activity of them. By contrast, YM212, a carboxy analog of YM534, had much less activity to potentiate vincristine and actinomycin D). YM534 at 100-1000 microM almost completely inhibited the photoaffinity labeling of [3H] azidopine to the 170-kD P-glycoprotein of VJ-300 cell membranes, but YM212 showed much less inhibitory action on the photoaffinity labeling. YM534 could also inhibit the photoaffinity labeling of deglycosylated P-glycoprotein.