Localization and neuronal response of RFamide related peptides in the rat central nervous system

RFamide related peptides (RFRP)-1 and RFRP-3 are neuropeptides derived from the same preproprotein. We have examined the distribution of RFRP-1 and RFRP-3 immunoreactivities (irs) in the rat central nervous system using specific antibodies. Neuronal cell bodies containing both RFRP-1 and RFRP-3 were detected within the caudal portion of the hypothalamus, the periventricular nucleus (PerVN), and the portion around or above the ventromedial nucleus of the hypothalamus. Both immunohistochemical and in situ hybridization analyses showed that neurons containing RFRP immunoreactivity and mRNA were distinct from those of neuropeptide FF, which contains the same structure at the C-terminus, Pro-Glu-Arg-Phe-NH2, as RFRP-3. Fibers containing both RFRP-1 and RFRP-3 were widely distributed in the brain: the lateral septal nucleus in the telencephalon, the paraventricular thalamic nucleus, various hypothalamic nuclei, the periaqueductal gray in the midbrain, the parabrachial nucleus in the pons, and the nucleus tractus solitarius (NTS) in the medulla oblongata. Only RFRP-1-ir was detected within the posterior gray horn in the spinal cord. Only RFRP-3-ir was detected in several thalamic nuclei and the spinal cord, especially at the posterior intermediate sulcus and within the anterior gray horn. Intracerebroventricular administration of RFRPs induced c-Fos expression in the anterior portion of the NTS, locus coeruleus, the nucleus of incertus, supraoptic nucleus, PerVN and the arcuate nucleus of the hypothalamus. These results show that RFRP-1 and RFRP-3 are widely distributed in the rat central nervous system and might be involved in various functions such as the neuroendocrine system or pain modulation.     

A new regimen for TS-1 therapy designed to minimize adverse reactions by introducing a one-week interval after each two-week dosing session

It has been reported that the response rate to TS-1 of advanced recurrent gastric cancer was the highest rate (46.5%) of effectiveness among anti-cancer agents, but the incidence of adverse reactions to this drug has been found to be as high as 83.2%, with grade 3 or severer reactions occurring in 20.3% of patients. Taking into consideration the post-marketing survey finding that adverse reactions to the drug first appear 2-3 weeks after the start of oral TS-1 therapy, we attempted a new dosing regimen for this drug, wherein each session of therapy lasted for 2 weeks, with a one-week interval between two consecutive sessions (herein-after called "the 2-week regimen"). This regimen was employed based on the expectation that the adverse reactions to the drug would be minimized and that the consecutive dosing period could be prolonged, while keeping the anti-cancer potency at a level similar to that expected with the 4-week dosing regimen with a 2-week interval between sessions (the 4-week regimen). The subjects were 38 patients with advanced or recurrent stomach cancer who were treated with TS-1 at our center between September 1999 and November 2001. Twenty-four patients treated using the 4-week method until January 2001 were taken as a historical control, and compared with 14 patients treated using the 2-week method from February 2001 and afterwards. The incidence of adverse reactions was 71% in the 2-week regimen group against 92% in the 4-week regimen group. The incidence of grade 3 or severe adverse reactions was 8% in the 2-week group and 21% in the 4-week group. Thus, the incidence of adverse reactions was lower in the 2-week group. The percentage of patients who complied with the dosing instructions completely during a 6-month period, as evaluated by the Kaplan-Meier method, was 86% in the 2-week group and 58% in the 4-week group. The response rate, as calculated in patients whose lesions could be evaluated, was 25% in the 2-week group and 19% in the 4-week group. These results suggest that the 2-week regimen may allow safer outpatient drug therapy using TS-1 and merits a trial when considering the QOL of patients. We propose conducting a phase-II multi-center clinical study of this regimen in the near future.     

Structural quantification in osteoarthritis of the knee using power spectral analysis

An exact diagnosis of osteoarthritis is very important to prevent deterioration of ADL (activities of daily living) of the elderly. However, it is very difficult to diagnose the stage of osteoarthritis, and only a few indices for structural quantification of osteoarthritis have been reported. The purpose of this research is to investigate a new index for the bone structure in osteoarthritis. We examined right knees of 41 women aged from 34 to 85 years. Directivity index (DI) is a new index of bone structure calculated by directivity of the power spectrum from radiographs of tibial bone using fast Fourier transform (FFT). DI was obtained by subtracting the integral power value at 0 and 90 degree directions on the x-y plane of the two-dimensional power spectrum of tibial bone from the integral power value at a direction of 45 degrees. A significant relationship between the state of the knee joint by X-ray inspection and DI was indicated by evaluation of the correlation coefficient. However, no significant relationship was found between the state of the knee joint by X-ray inspection and the first moment of the Fourier power spectrum or the fractal dimension. There is a possibility that DI can estimate slight deformation of bone structure in osteoarthritis. In the future, we will apply DI to the prevention of osteoarthritis and a deterioration of ADL in the elderly.     

Primary squamous cell carcinoma of the breast during lactation: a case report

A case of primary squamous cell carcinoma of the breast during lactation is reported. The patient was a 32-year-old woman, in post-partum lactating 18 months after delivery, who was referred to our hospital following detection of a lump in her left breast during physical examination in mass screening for breast cancer. The tumor, palpated in the upper outer quadrant of the left breast, was firm, well-defined and 2.8 x 2.6 cm in size. Ultrasonograms identified an irregular-shaped hypoechoic lesion and mammograms revealed a well-defined, circumscribed tumor. Based on these findings, breast cancer was suspected and an excisional biopsy was performed. The resected specimen was a firm, solid and circumscribed tumor with central hemorrhage. Microscopic findings demonstrated that the tumor consisted of an invasive ductal carcinoma with marked squamous metaplasia, such as keratinization and squamo-columnar junction. Breast-conserving surgery was performed and no lymph node involvement was noted. Both estrogen and progesterone receptors of the tumor were negative. Generally, the size of both squamous cell carcinoma and carcinoma during the lactation period tends to be larger than ordinary carcinomas. In this case, the cancerous lesion was detected at a relatively early stage. Although the cancerous lesion was detected at a relatively early stage and no lymph node involvement was noted, lung metastases occurred within 12 months of the surgery. Malignant potential is generally considered to be high in cases of squamous cell carcinoma of the breast with lactation and thus intensive treatment potentially resulting in severe side effects was considered to be necessary for this patient.     

Dorsal dislocation of the D.I.P. joint with fracture of the volar base of the distal phalanx

Between 1978 and 1985, we treated 12 cases of dorsally displaced fracture-dislocation of the I.P. joint of the thumb or of the D.I.P. joint of the finger, with a volar bony fragment. All were treated surgically, active exercise being started three to five weeks later. At the last follow-up, averaging 6.4 years (range 4.3-10 years) after operation, none of the joints was painful but the range of motion was somewhat limited.     

Antitumor effect of K18 on metastatic models

K18 is a newly synthesized antitumor agent which is the conjugate form of human immunoglobulin with p-di (2-chloroethyl)-amino-L-phenylalamine (melphalan). The antitumor effect of K18 on two animal metastatic models was investigated: (a) Lewis lung carcinoma was transplanted into thigh muscle of mice, followed by the reaction of the primary lesion, or the tumor was transplanted through the tail vein: (b) a renal model was also created, where colon-26 was inoculated into the renal capsule of BALB/c mice. Oral administration of K18 resulted in the decrease in the number of nodules in the lung in the case of tumor transplantation through tail vein.     

An Autopsy Case of Binswanger's Disease without Hypertension and Associated with Cerebral Infarction in the Terminal Stage

Abstract: We report here an autopsy case of Binswanger's disease (BD) without hypertension and associated with cerebral infarction in the terminal stage. The female patient, who was 74 years old at the time of death, had initially demonstrated manic-depressive disorder-like mental disorder, followed by dementia and neurological deficits. A brain CT scan showed white matter low attenuation bilaterally and symmetrically. BD was clinically diagnosed despite the lack of hypertension. In the terminal stage, she suffered an infarction in the left anterior cerebral artery region, and died of pneumonia. Neuropathologically, we found the infarction of the left anterior cerebral artery region, demyelination, fibrillary gliosis, lacunae and arteriosclerosis of the small arteries and arterioles in the white matter.     

Intra-articular calcifying synovial sarcoma mimicking synovial chondromatosis

 A case of intra-articular calcifying synovial sarcoma of the right knee joint in a 27-year-old man is reported. Prior to admission the patient had been suffering pain in the right knee for 5 years. Plain radiographs showed multiple calcified densities in the anterior aspect of the right knee closely mimicking synovial chondromatosis. Histological examination revealed that the lesion was a synovial sarcoma with extensive calcification subjacent to the synovial surface. Although intra-articular calcifying synovial sarcoma is very rare, it is important to be aware of the fact that synovial sarcoma, as well as synovial chondromatosis, can be present as a calcified lesion in the joint cavity.