Endoscopic and Histologic Findings of Intraductal Lesions Presenting with Nipple Discharge

Abstract:   To improve the utility of mammary ductoscopy, we investigated the correlation between endoscopic findings and histologic findings using intraductal biopsy specimens. Seventy-one intraductal biopsy specimens obtained from 63 patients between October 2001 and March 2004 were analyzed retrospectively. All specimens were obtained from monotonous intraductal lesions immediately after observation by mammary ductoscopy and were composed of a pure histologic subtype. With regard to endoscopic findings, color was classified as yellow, red, white, or colorless, and morphology was classified as spherical, lobular, mulberry, or amorphous. The histologic subtype was classified as papillotubular, papillary, degenerated, papillary cancer, solid-type ductal carcinoma in situ (DCIS), or cribriform cancer. The relationship between histologic diagnosis, color, and morphology was investigated. Intraductal biopsy specimens included 25 specimens of carcinoma and 46 specimens of papilloma. There was no significant correlation between color and diagnosis. Fourteen of 25 carcinoma specimens were amorphous, and amorphous morphology was significantly suggestive of malignancy (p < 0.001). Further, cribriform cancer was associated with amorphous morphology and yellow color. Morphology may be a useful endoscopically delineated parameter for differentiating intraductal lesions.      

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.     

Reduced expression of deleted colorectal carcinoma (DCC) protein in established colon cancers.

Using a bacterial fusion protein, a deleted colorectal carcinoma (DCC)-specific monoclonal antibody (MAb) 127-22 was established. Although MAb 127-22 reacted with almost all normal tissues, it did not react or only weakly reacted with many cancer cell lines, including colonic cancer lines, in flow cytometry. In Western immunoblots, the MAb reacted with a single 190-kDa molecule in a myeloma line Ara-10 extract. This component was scarcely detected in colonic cancer cell lines. Immunoblots of samples from 25 pairs of colonic cancers and adjacent normal tissues and from five adenoma tissues revealed that all normal colonic and adenoma tissues significantly expressed the DCC protein, whereas colonic cancer tissues showed poor expression. These results indicate not only deletion of and lowered mRNA expression of the DCC gene, but also marked reduction of DCC protein occurred in colonic cancer tissues. In addition, colonic cancer patients with liver metastasis expressed significantly lower levels of DCC than those without, suggesting the prognostic value of DCC expression.     

Role of the submandibular glands in in vivo mechanisms of plasma inactive renin release in the rat

In our present studies, we evaluated the role of the submandibular glands (SMG) on plasma inactive renin (PIR) releasing mechanisms in rats using some agents which are known to stimulate plasma active renin (PAR) release. The results were analyzed between sialoadenectomized (SX) and sham-operated (control: C) rats. Twenty-four h after the operation, PAR releasing agents, furosemide (FRO) 2.5 mg/rat/h with prior iv bolus 5 mg, captopril (CAP) 5 mg/rat/h with prior iv bolus 10 mg, 1-Sar-8-Ile-angiotensin II (Ang II A) 300 ng/kg/min, prostaglandin E1 (PGE1) 100 ng/kg/min, and prostaglandin I2 (PGI2) 100 ng/kg/min, were infused through femoral venous cannulae. Blood samples were taken through femoral arterial cannulae into test tubes containing 2 mg EDTA-2Na. PAR was assayed by RIA, and total renin was obtained after tryptic activation. According to the responses of PIR, the agents used were categorized into three patterns: FRO increased PIR, both PGs lowered PIR, and, CAP and Ang II A had no effect on PIR release. The PIR release mechanisms by FRO were further investigated by 20 mg FRO ip injection in totally nephrectomized rats. PIR increased even in nephrectomized rats, but the increase was totally canceled by the following SX. In conclusion, FRO alone among some agents studied is able to stimulate PIR release only under the existence of SMG.     

Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia

Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes.