A stereomicroscopic study of the mastopathic human breast

Summary The stereomicroscopic study of cystic disease of the breast revealed the presence of abnormal ductules near the terminal sites of the original lactiferous ducts. This alteration was the key feature of cystic disease since the involution of abnormal ductules possibly may have induced the stricture of the original duct by increasing fibrosis around the site of duct evolution. The phenomenon could contribute to the creation of cystic dilatation of distal ducts and acini. Multiple large cysts characterizing the morphology of cystic disease may represent the end stage of distended ducts and acini. Prolonged and repeated unbalanced stimulation of hormones could produce progressive and regressive alternations in the same breast. This modifies the original alteration into more pleomorphic and complicated types.

---

Stereomikroskopische Studie der durch Mastopathie veränderten menschlichen MammaII. Die peripherische Form der Milchgangsevolution und ihre Beziehung zur Cystenmamma

Zusammenfassung Die stereomikroskopische Untersuchung sog. Cystenmmamen zeigt, daß die Cysten durch Ektasie der sog. Kanälchen-Endäste entstehen. Dagegen werden die Stamm-Milchgänge einer Involution zugeführt. An der Cystenbildung beteiligen sich auch die Acini. Als morphogenetische Reize kommen hormonelle Dysregulatonen in Frage. Durch die unterschiedliche Ausbildung der Kanälchen proliferation einerseits, die Involution sowie Cystenbildung andererseits resultiert ein buntes, wenig einheitliches Bild.

---

---

Clinical Investigator, Veterans Administration Hospital, San Francisco, California, U.S.A., Former Postgraduate Student, Faculty of Medicine, Tokyo Medical and Dental University, Japan.

---

This investigation was carried out at the Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University from 1958 to 1960 and was partially supported by a special research grant of the Japanese Ministry of Education.     

Effect of serum amyloid P component level on transthyretin-derived amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy.

To elucidate the pathogenesis of amyloid deposition associated with familial amyloidotic polyneuropathy (FAP), we developed several transgenic mouse lines carrying the human mutant transthyretin (TTR) gene. We found that human TTR and mouse serum amyloid P component (SAP) are deposited as amyloid in tissues of these mouse lines. Because SAP is a major acute-phase reactant in mice, we asked whether repeated injections of Escherichia coli lipopolysaccharide (LPS) would enhance the amyloid deposition in one of these transgenic mouse lines. During the course of repeated LPS injections, serum levels of SAP in the transgenic mice remained between severalfold to about 50-fold higher than seen in the absence of stimulation. As no significant difference was detected in the onset, progression, and tissue distribution of TTR-derived amyloid (ATTR) deposition between the LPS-stimulated and unstimulated transgenic mice, the induction of SAP synthesis by acute inflammation probably does not affect the onset and extent of ATTR deposition.     

Histopathological study on the PTHrP-induced incisor lesions in rats

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). The present study elucidates the histopathological characters of incisor lesions in the HHM rat model. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks, after which the mandibular incisors were collected. Incisor fractures were observed grossly. Microscopically, hypercalcified dentin, dentin niche with osteodentin, and thinning of dentin were observed. Hypercalcified dentin was observed as a basophilic line of calcified dentin without associated odontoblastic changes, whereas dentin niche and thinning of dentin occurred with osteodentin and loss of cell height, respectively. In contrast with hypercalcified dentin, which was distributed throughout the dentin, dentin niche and thinning of dentin were localized to the labial area of the apical and middle region, and to the labial and lingual areas of the middle and incisal region, respectively. These results suggest that hypercalcemia affected the entire calcification process resulting in hypercalcified dentin, and that high PTHrP concentrations affected selective populations of odontoblasts resulting in formation of dentin niche and thinning of dentin. The localization of dentin niche and thinning of dentin also suggest that PTHrP may also be involved odontoblastic development in the rat.     

Human cytomegalovirus infection in foci of Langerhans cell histiocytosis

 Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFα. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection. Received: 24 November 1998 / Accepted: 24 April 1998     

Effects of anxiolytic drugs on escape behavior induced by dorsal central gray stimulation in rats.

Each animal was chronically implanted with bipolar electrodes in dorsal central gray matter (DCG) and was trained to press a lever to decrease the DCG-stimulation current. Chlordiazepoxide (5-20 mg/kg, PO), diazepam (2-10 mg/kg, PO) and bromazepam (1-5 mg/kg, PO) produced dose-dependent increases in the DCG-stimulation threshold 1-4 h after administration without affecting motor performance. Meprobamate (200 mg/kg, PO) and pentobarbital (10 mg/kg, PO) also slightly increased the stimulation threshold. Their potency was in the order of bromazepam greater than diazepam greater than chlordiazepoxide greater than pentobarbital greater than meprobamate. The increase in the threshold induced by diazepam (10 mg/kg, PO) was inhibited by the GABA antagonists, bicuculline (1 mg/kg, IP) and picrotoxin (0.1 mg/kg, IP). These results suggest that decreased susceptibility to brain stimulation is involved in suppressing effects of anxiolytic drugs on the escape behavior, and also that the antiaversive action of benzodiazepines may be related to a GABAergic mechanism.     

An Immunohistochemical Study

C cell proliferation of the thyroid, which was designated as primary C cell hyperplasia (PCCH), was demonstrated in aged Fischer 344 rats in high incidence using the immunohistochemical method for calcitonin. It developed from mild to severe PCCH and resulted in nodular PCCH and tumor formation. The combined incidence of PCCH and nodular PCCH was increased with age and appeared in 60.7% of 7–15 month old group and 92.7% of 16–24 month old group possibly as a preneoplastic C cell lesion. It is almost an equivalent C cell lesion reported in the human thyroid with familial C cell carcinoma and therefore this Fischer 344 rat can provide a useful animal model to study familial C cell tumor of the thyroid.     

Involvement of nitric oxide in glucose toxicity on differentiated PC12 cells: prevention of glucose toxicity by tetrahydrobiopterin,a cofactor for nitric oxide synthase

Effects of high concentrations of glucose on cell survival of differentiated PC12 cells were examined. Seven day-culture with D-glucose (9.0-27.0 mg/ml as 2-6-fold of the optimal level) induced cell death in a dose-related manner but 3-day culture with high concentrations of glucose had no effect on cell viability. L-glucose had no effect on viability of PC12 cells, suggesting that D-glucose toxicity was independent of its osmolarity effect. Seven-day culture with D-glucose (13.5 mg/ml as 3-fold of the optimal level) increased nitric oxide metabolites (NOx) in the culture medium. Glucose-induced increase in NOx was eliminated by 0.1 mM L-nitro-arginine methylester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Intracellular Ca(2+) concentration was increased by D-glucose in a dose-related manner, suggesting that D-glucose activated NOS by increasing intracellular Ca(2+) concentration in PC12 cells. Glucose-induced cell death was blunted by 0.1 mM L-NAME, showing that nitric oxide (NO) was involved in the glucose toxicity to PC12 cells. Tetrahydrobiopterin (BH(4)), a cofactor for NOS, attenuated both glucose-induced cell death and NOx production at 1 microM but not at 10 microM. The effects of BH(4) on glucose-induced cell death and NOx production were not mimicked by reducing agents such as ascorbate and cysteine. These results taken together suggest that high concentrations of glucose induced cell death via NO production and that low concentration of BH(4) had a protective effect against glucose neurotoxicity in differentiated PC12 cells.