Breast cancer with reactive multinucleated giant cells: report of three cases

We report here three cases of breast cancer with reactive multinucleated giant cells. The patients were among the 605 patients with breast cancer seen in the past 17 years at Tenri Hospital; the incidence of this variety of breast cancer was 0.5%. Enzyme histochemical and electron microscopic examination suggested that the giant cells were of histiocytic origin. However, results of immunohistochemical technique, S-100 protein, lysozyme, nonspecific cross-reacting antigen with carcinoembryonic antigen, alpha-1-antitrypsin, and alpha-1-antichymotrypsin, all currently used as markers of histiocytes, were negative. Because of the rarity of this variety of breast cancer, the biological significance of these unusual findings remains unknown.     

Novel single nucleotide polymorphisms of the human nuclear factor kappa-B 2 gene identified by sequencing the entire gene

The nuclear factor kappa-B 2 (NFKB2) gene is a member of the NFKB/Rel gene family, which is known to be a pivotal regulator of the acute phase of the inflammatory response and of immune responses. We identified three novel single nucleotide polymorphisms (SNPs) and determined their allelic frequencies, as determined by the sequencing of 48 alleles of the entire gene in a Japanese population sample. Two of the three polymorphisms were identified at nucleotide (nt) position 1837 (T/C) and nt position, 1867 (GG/G) in the upstream region of the gene. The other polymorphism was identified at nt position 2584 (G/T) within intron 1. These polymorphisms will be useful in genetic studies of the processes involved in inflammatory responses and in bone differentiation. Received: October 17, 2000 / Accepted: October 23, 2000     

Frequent allelic loss at the TOC locus on 17q25.1 in primary breast cancers

Sporadic breast cancers often show allelic losses on the long arm of chromosome 17. Since the BRCA1 gene lies at 17q21.1 and the TOC locus, associated with esophageal cancer, lies at 17q25.1, either gene could be the target of those losses. We examined both loci in 178 primary breast cancers, using microsatellite markers covering the relevant regions of 17q, and observed allelic losses in 97 tumors (55%). Losses were most frequent at markers around the TOC locus (48% at D7S1839 and 43% at D17S1603), where we identified a distinct commonly deleted region within a I -cM interval. Another larger, separate commonly deleted region including the BRCA1 gene was also identified, which exhibited 45% of allelic loss (at D17S934). Allelic loss on 17q was more frequent in tumors of the solid-tubular histologic type (P = 0.0129) and in estrogen-negative and progesterone-negative tumors (P = 0.0281 and 0.0196, respectively). The results indicated that BRCA1 and TOC are independent targets of allelic loss on 17q in primary breast cancers, and that inactivation of the TOC locus in particular may play an important role in the genesis of sporadic breast tumors.     

Role of complement in acute tubulointerstitial injury of rats with aminonucleoside nephrosis.

The present work was designed to elucidate the in vivo role of complement in the proteinuria-associated tubulointerstitial injury. Rats were intravenously injected with puromycin aminonucleoside, and massive proteinuria was observed within 5 days. Prominent tubulointerstitial injury characterized by proximal tubular degeneration, tubular dilatation, and leukocyte infiltration were observed 7 days after injection. C3 and C5b-9 were observed in the luminal side of proximal tubular cells. Renal function, assessed by inulin and para-aminohippurate clearance, was significantly decreased. To-assess the role of complement in this model, rats were injected with either cobra venom factor or soluble recombinant human complement receptor type 1 starting at day 3. These manipulations significantly improved tubulointerstitial pathology and para-aminohippurate clearance without affecting the degree of proteinuria. Deposition of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by cobra venom factor. In rats treated with soluble complement receptor, C3 was still detected in the tubules, but deposition of C5b-9 was not observed. Soluble complement receptor was detected at the site of C3 deposition and in the urine. These data strongly suggest that complement plays a pivotal role in proteinuria-associated tubulointerstitial injury and that systemic complement depletion or inhibition of complement in the tubular lumen may diminish the tubulointerstitial damage.     

Quantitative analysis of the velocity characteristics of optokinetic nystagmus and optokinetic after-nystagmus

1. Velocity characteristics of optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN) induced by constant velocity full field rotation were studied in rhesus monkeys. A technique is described for estimating the dominant time constant of slow phase velocity curves and of monotonically changing data. Time constants obtained by this technique were used in formulating a model of the mechanism responsible for producing OKN and OKAN.2. Slow phase velocity of optokinetic nystagmus in response to steps in stimulus velocity was shown to be composed of two components, a rapid rise, followed by a slower rise to a steady-state value. Peak values of OKN slow phase velocity increased linearly with increases in stimulus velocity to 180 degrees /sec. Maximum slow phase eye velocities in the monkey are 2-3 times as great as in humans.3. At the onset of OKAN, slow phase velocity falls by about 10-20%, followed by a slower decline to zero. Peak OKAN slow phase velocities were linearly related to optokinetic stimulus velocities up to 90-120 degrees /sec. Above 120 degrees /sec OKAN slow phase velocity saturated although OKN slow phase velocity continued to increase.4. The charge and discharge characteristics of OKAN were studied. The OKAN mechanism charged in 5-10 sec and discharged over 20-60 sec in darkness. The time constants of decay in OKAN slow phase velocity decreased as stimulus velocities increased. They also decreased on repeated testing. In several monkeys there was a consistent difference in the rate of decay of OKAN slow phase velocity to the right and left.5. Extended visual fixation discharged the activity responsible for producing OKAN. Short fixation times caused only a partial discharge of the OKAN mechanism. Following brief periods of fixation, OKAN resumed but with depressed slow phase velocities.6. A model based on a state realisation of a peak detector was formulated which approximately reproduces the salient characteristics of OKN and OKAN. This model predicts the three dominant characteristics of OKAN: (1) charge over 5-7 sec, (2) slow discharge in darkness, and (3) rapid discharge with visual fixation. With the addition of direct fast forward pathways, it also correctly predicts the rapid and slow rise in OKN. We postulate that OKAN is produced by a central integrator which is also active during OKN. Presumably this integrator acts to maximize velocities during OKN and to smooth and stabilize ocular following during movement of the visual surround.     

Lung adenocarcinoma with bronchioloalveolar carcinoma component is frequently associated with foci of high-grade atypical adenomatous hyperplasia

We assessed the occurrence of atypical adenomatous hyperplasia (AAH) in whole lung lobes with primary cancer lesions. Following surgical resection, tissue specimens were sliced to a thickness of 4 mm (3,641 specimens from 61 cases; mean = 59.7 specimens per case). A total of 119 AAH foci were found and an association was evident in 25 (57%) of 44 adenocarcinomas, 3 (30%) of 10 squamous cell carcinomas, and 2 (29%) of 7 other lung cancers. Histologic evaluation showed that 108 AAH foci were categorized as low-grade and the other 11 as high-grade AAH. These 11 foci of high-grade AAH were present in 7 patients with adenocarcinoma, and in 1 patient there was a synchronous double primary lung adenocarcinoma. High-grade AAH was closely associated with bronchioloalveolar carcinoma (BAC) type adenocarcinoma, and low-grade AAH with non-BAC adenocarcinoma. The mean +/- SD Ki-67 labeling index in high-grade AAH (3.5%+/-2.9%) was significantly higher than for the low-grade index (1.4%+/-1.6%). We propose that foci of high- but not low-grade AAH may be potential precursor lesions of lung adenocarcinoma, especially with the BAC component.     

HLA class I distribution in Japanese patients with schizophrenia

Several Caucasian studies and one Japanese study have observed associations between human leukocyte antigen (HLA) class I specificities, including A24 (9) and A26 (10) and schizophrenia. Most of those studies were conducted in 1970s and early 1980s, when the typing technique of HLA was not adequately reliable. Also, an operational diagnostic system was not employed in many of the studies. The present study investigated frequencies of HLA-A specificities in schizophrenia patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392) from population in the southwestern part of Japan. HLA-B and -C specificities were studied in addition. Frequencies of subjects possessing A24 and A26 were not different between the patients and controls (54% and 24% in the patients and 62% and 24% in the controls, respectively). No significant difference was found in frequencies of other class I (A, B, and C) specificities between the patients and the controls. Thus, the present study provided no evidence for an association between the HLA class I specificities, including A24, A26, and others, and schizophrenia in the Japanese population.     

Patterns of differentiation in various sympathetic efferents induced by hypoxic and by central thermal stimulation in decerebrated rabbits

Summary The patterns of regional changes of sympathetic efferent activity evoked by thermal stimulation of the spinal cord and by arterial and primary tissue hypoxia were investigated in decerebrated, anesthetized and immobilized rabbits. Decerebration was performed either at the mid- or infracollicular level. The responses of the decerebrated rabbits evoked by spinal thermal stimulation were the same as those of intact rabbits, i.e., splanchnic and cardiac sympathetic activity increased and cutaneous sympathetic activity decreased during warming, while the reverse response was elicited by cooling. It is concluded that the typical thermoregulatory response pattern of the sympathetic nervous system can be produced also after the loss of hypothalamic integration, i.e., by integrative mechanisms in the lower brain stem and the spinal cord. In contrast, the responses of decerebrated rabbits to arterial and primary tissue hypoxia differed from those of intact rabbits in that they consisted in an overall activation in all investigated sympathetic branches. It is confirmed by this result that suprabulbar integration is essential for the generation of the inhibitory components in the differential sympathetic responses to hypoxia, which typically consist in cutaneous and cardiac sympathetic inhibition with splanchnic activation during arterial hypoxia and in cutaneous sympathetic inhibition with cardiac and splanchnic sympathetic activation during primary tissue hypoxia.