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To investigate the contributions of adenoid and tonsil sizes to obstructive sleep apnea syndrome (OSAS) in normal-weight children in two age categories: preschool and schoolchildren.Fifty-eight normal-weight (body mass index z-score2) symptomatic children with OSAS (apnea-hypopnea index ≥ 2) were evaluated. The patients were divided into two age categories: preschool (age6; n=33) and schoolchildren (age ≥ 6; n=25). Polysomnographic findings and adenoid and tonsil sizes were compared. The relative contributions of body mass index and adenoid and tonsil sizes were also investigated with a regression analysis.Adenoid grade and apnea index correlated significantly in preschool children (r=0.45, p0.01). On regression analysis, adenoid grade was a significant predictor of the apnea index in preschool children. The influence of adenoid hypertrophy decreased from preschool to schoolchildren. Tonsil size had little influence on the apnea index in either group.Adenoid hypertrophy was a major contributor to OSAS in normal-weight preschool children. The upper airway morphology of younger children with OSAS differed from that of older children with OSAS.

We studied the change in the hypothalamo-pituitary-adrenal gland (HPA) axis upon adding prior toluene inhalation to our previous formaldehyde inhalation experiments to determine whether short term exposure to relatively high levels of toluene triggers multiple chemical sensitivity (MCS). Data come from immunocytochemical, morphometrical and RT-PCR measurements. Four groups of adult female mice were exposed to differing concentrations (0, 80, 400, and 2,000 ppb) of formaldehyde for 16 hr/day, 5 days/week for twelve weeks, after the mice were exposed intranasally to 500 ppm toluene per mouse for 6 hr/day, for 3 days. We found that the number of corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons was up-regulated according to the amount of formaldehyde as well as inhalation of formaldehyde alone in our previous experiment. The proportion of adrenocorticotropin hormone (ACTH)-ir cells increased according to the formaldehyde concentration, though there was no significant difference between the 400 and 2,000 groups. The number of ACTH-ir cells was higher in the 400 group than in the other groups (0, 80, and 2,000). Expression of ACTH-mRNA was also up-regulated according to the quantity of formaldehyde. The sinusoid in the anterior pituitary showed more dilatation in the 400 and 2,000 groups than in the control group, especially in the 2,000 group. We propose that exposure to toluene prior to inhalation of formaldehyde has no effect on the HPA axis and as a trigger of MCS, although greater sinusoid dilatation was found in the anterior pituitary gland at higher concentrations of formaldehyde.

We have examined alterations in the hypothalamo-pituitary GH-somatic growth axis and the hypothalamo-pituitary LH-ovarian axis in a line of transgenic ICR mice expressing human GH (hGH) under the influence of the whey acid protein promoter. Transgenic female mice weighed twice as much as control females and were infertile. The size of the anterior pituitary (AP) was 1/3 that of the controls. In transgenic mice, acinar cells in the mammary and mandibular glands displayed hGH-immunoreactivity, and plasma hGH was detected by radioimmunoassay. In the medial basal hypothalamus (MBH) of transgenic females, the immunoreactive-GHRH level was decreased (P

Mitochondria occasionally increase in size in response to metabolic injury. Numerous studies have reported giant mitochondria in patients with various diseases and animals with metabolic injuries, but there are few reports on giant mitochondria in normal cells under physiological conditions. Here, we report giant mitochondria in normal gastric parietal cells. Stomachs of guinea pigs fed freely, fasted or fasted and then injected with histamine were processed for electron microscopy. Giant mitochondria >2 microm in the diameter of their major axis were observed in resting-type parietal cells in the gastric glands of animals fasted for 60-72 h, whereas acid-secreting-type parietal cells found in those fed ad libitum did not contain giant mitochondria. Giant mitochondria showed unusual structures, especially in their cristae: they contained closely packed, tubular and concentric cristae as well as amorphous and pleomorphic inclusion bodies in their matrix. We observed giant mitochondria consisting of several segments, suggesting the fusion of several normal-sized mitochondria. Histamine injection decreased in a frequency of giant mitochondria in accordance with a decrease in a frequency of resting-type parietal cells. This is the first report of giant mitochondria in gastric parietal cells under physiological or near physiological conditions. Gastric parietal cells might be a good model for examining mitochondrial fusion and fission in a physiological state accompanied by the morphological change of the cells in the membrane system from an acid-secreting to resting type.

We examine sexual dimorphism in growth hormone-releasing hormone (GHRH) in the arcuate nucleus (ARC), and somatostatin (SS) in the periventricular nucleus (PeN) of the hypothalamus, and investigate when it becomes evident. Using immunohistochemical staining and morphometry, we observed ARC GHRH-immunoreactive (ir) neurons, ARC SS-ir neurons and PeN SS-ir neurons in male and female mice at 5, 20, 30, 40 and 60 days old. The number of ARC GHRH-ir neurons was significantly higher in males than females, after 20 days old. ARC SS-ir neurons showed no significant differences between sexes. On the other hand, PeN SS-ir neurons were significantly more numerous in males at 30, 40 and 60 days than in females. During postnatal development, these GHRH- and SS-ir neurons changed in different patterns from ages 20 to 60 days. The number of ARC GHRH-ir neurons in both sexes decreased from 5 to 20 days, increased until day 40, and then decreased at day 60, while ARC SS-ir neurons in both sexes increased from day 5 to day 60. PeN SS-ir neurons in both sexes increased from days 5 to 20 to 116% in males and 189% in females. Furthermore, in male mice, the increase continued until 40 days of age, while in females, there was no significant difference from days 20 to 60. There were no apoptotic cells; a few proliferating cell nuclear antigen (PCNA) stained cells were found in the ARC and PeN. Our results suggest that the sex difference of ARC GHRH neurons and PeN SS neurons appears by stimulation with testosterone during the development life. The developmental fluctuation in the number of ARC GHRH-ir neurons may not be modulated by testosterone, but by ARC SS neurons.

Quantitative changes of lung tissue components (air spaces lined by PAS-positive and PAS-negative epithelium, blood vessels and interstitium) were investigated in developing rats from fetal day 18 through neonatal day 1. The volume of the left lung increased significantly from fetal day 18 through neonatal day 1. The percentage and volume of the air spaces increased strikingly between fetal days 20 and 21. However, the percentage of the air spaces lined by PAS-positive epithelium decreased significantly from fetal days 20 to 21, and that of the spaces lined by PAS-negative epithelium increased between the two days. The proliferating cell nuclear antigen (PCNA)-positive cells were rich in the interstitium and epithelium of the air spaces on fetal days 18 and 19. The percentage of the interstitium decreased significantly from fetal day 18 through neonatal day 1, showing remarkable decrease between fetal days 20 and 21. From fetal day 20 onward, the PCNA-positive cells decreased in number and located in the epithelium of the conducting air ways and interstitium. Based upon these findings, the present study suggests that the period from fetal days 20 to 21 is a critical time for the development of fetal lung: the period before fetal day 20 is that for proliferation and the period after fetal day 21, functional differentiation of the lung.

In the murine uterus granulated metrial gland (GMG) cells appear only during normal pregnancy. GMG cells belong to a member of natural killer (NK) cells and play an important role in fetus survival and placental growth. Our previous study revealed that mouse GMG/uterine NK (uNK) cells in the late pregnancy rapidly disappear from the uterus, due to the degenerative change classified as necrosis. But there are few reports regarding appearance and morphology of uNK cells during late pregnancy. We examined histologically and histochemically how and when uNK cells undergo cell death. The uNK cells in the metrial gland increased in number and reached maximum until day 12 of pregnancy. Sudden disappearance, however, occurred after day 15 and the granules reduced in both number and size. In situ DNA fragmentation detection revealed that DNA fragmented uNK cells increased in number during days 13 to 15 and reached 70.2% at day 15 of pregnancy. From days 13 to 17, uNK cells were positive against anti-perforin antibody. Ultrastructurally, uNK cells at day 15 showed poor organelles and unusual granules in structure. In uNK cells at day 17, condensation of nucleus chromatin, reduction in size and phagocytosis into other uNK cells were observed. These results suggested that uNK cells undergo at least two types of cell death, classified as necrosis and apoptosis, at the different stages of pregnancy, and that perforin is not a mediator for cell death.

Background The pituitary gland of the dog is different from all animals and is described as “typical” for mammals. How might this complex pituitary gland of the dog be formed in fetal life? The current study examined the fetal development of the complex and unique dog pituitary and the ontogeny of specific cell types in the pars distalis. Methods Adenohypophysis of the beagle, from 25 to 60 days of gestation and at 2 days of age, was studied by immunocytochemical and histological staining. Results At 25 days gestation, the primordium (Rathke's pouch) of the adenohypophysis began to form by an upward evagination from the epithelium of the primary oral cavity. At 38 days, the pituitary gland showed the same morphology as in adult dogs, being merely smaller. Five walls of Rathke's pouch (anterior wall [A], lateral walls [L], posterior wall [P], and upper wall [U]) were found at 25 days, and by 38 days they had specialized into specific regions of the adenohypophysis through complex and unique processes. The pars intermedia was derived from the U and the dorsal area of the A. The pars tuberalis was derived from the dorsal area of the A. The pars distalis was formed by more singular processes: the peripheral areas of the pars distalis were first formed by A and P; then the ventral lumen of the extensive Rathke's lumen surrounded by these areas was filled up by proliferation of cells, although the dorsal lumen remains as Rathke's lumen after 38 days. The blood capillaries may play an important role in the development of parencymal cells in the Rathke's pouch during canine fetal life. At 30 days gestation, the first adrenocorticotropic hormone cells were found in the anterior- and posterior-ventral regions (derived from middle and ventral areas of the A and the P) of the pars distalis anlage, and blood capillaries invaded the parenchymal cells from the mesencyme surrounding the anlage. At 38 days, portal vessels without capillary loops in the median eminence had appeared, and growth hormone and luteinizing hormone cells appeared in the ventral areas of A and P in the pars distalis. By 52 days, when capillary loops were seen in the portal vessels in the median eminence, these types of cells spread through the whole pars distalis. Conclusion These areas in the epithelium of Rathke's pouch at 25 days may differentiate into specific regions of the pars distalis during subsequent fetal life, through complex processes that are characteristic to the canine species. Anat. Rec. 251:143–151, 1998. © 1998 Wiley-Liss, Inc.

Background The present study was designed to clarify development of filtration property of fetal renal glomerulus when maternal kidney is dysfunctional. Materials and Methods Maternal bilateral ureteral ligation was performed on days 17, 19, and 21 of pregnancy. One day after each operation, cationized ferritin (CF), native ferritin (NF), and horseradish peroxidase (HRP) were injected, respectively, in the fetuses. Distribution of the tracers in the fetal kidneys was investigated electron microscopically. Results On fetal day 20, clustered CF particles were present in the laminae rarae interna and externa of the glomerular basement membrane of the fetuses from ureter-ligated mothers, while the clusters were arrayed in three to four layers in that of the fetuses from sham-ligated ones. On fetal day 22, a relatively large amount of CF particles was present in the lamina rara externa in the fetuses from ureter-ligated mothers when compared to that in the age-matched control fetuses. On fetal days 20 and 22, the number of NF particles was decreased, and shortening of the time for filtration of HRP through the glomerular basement membrane was observed in the fetuses from the ligated mothers. Conclusions These results suggest that dysfunction of maternal kidneys causes accelerated formation of fetal glomerular basement membrane and stimulates glomerular function in filtration in fetal rat kidney. Anat. Rec. 249:181–186, 1997. © 1997 Wiley-Liss, Inc.

The kidneys of fetal rats from uninephrectomized mothers were investigated morphometrically on days 18, 20, and 22 of gestation. Maternal uninephrectomy was performed on day 5. On days 20 and 22, the proximal tubular cell height in fetuses from uninephrectomized mothers was significantly lower than that in fetuses from sham-operated mothers. The luminal diameter, length and total volume of the proximal tubule were significantly larger in fetuses from uninephrectomized mothers than in those from sham-operated mothers. The total glomerular volume of mature type in fetuses from uninephrectomized mothers was significantly larger than that in fetuses from sham-operated mothers. On day 18, maternal uninephrectomy caused no significant difference in any kind of parameters used for the proximal tubule, but induced an increase in the total glomerular volume of immature type. These results suggest that maternal uninephrectomy stimulates morphological development of the proximal tubule in the fetal kidney.

Persistent obstructive sleep apnoea syndrome (OSAS) occurs in approximately 20% of normal-weight children after adenotonsillectomy (TA) and, in nearly 70% of them, it is caused by adenoid regrowth. Patients with severe or moderate OSAS showed a high incidence of persistent disease even after TA. Allergic disease, severity and large adenoid size are associated with adenoid regrowth and persistent disease.To investigate factors contributing to persistent OSAS and adenoid regrowth after TA in normal-weight children.This was a prospective, observational study at a single institute and involved 49 normal-weight children with severe or moderate OSAS (apnoea-hypopnoea index, AHI, ≥ 5) who underwent TA. Background information, nasal endoscopic data and pre- and postoperative polysomnographic data were collected. A third polysomnography (PSG) was performed 1.5 year postoperatively in children who subsequently developed symptoms of sleep disturbance.Thirteen children (27%, 13/49) were symptomatic 1.5 years after TA. Allergic rhinitis (38.5% vs 11.1%, p = 0.03) and allergic disease (69.2% vs 30.6%, p = 0.02) were seen more frequently in these children. A third PSG confirmed persistent disease (AHI ≥ 5) in nine children (18.4%, 9/49). Six children (12.2%, 6/49) were diagnosed as having adenoid regrowth and three (6.1%, 3/49) underwent revision adenoidectomy.

Cyclic variation of heart rate (CVHR) associated with sleep apnea/hypopnea episodes has been suggested as a marker of sleep disordered breathing (SDB). This study examined the utility of ECG-based CVHR detection for diagnosing SDB using simultaneous polysomnography as the reference standard. We used a previously developed automated CVHR detection algorithm (autocorrelated wave detection with adaptive threshold, ACAT) that provides the number of CVHR per hour (CVHR index). The ACAT was refined using a polysomnographic database of 194 subjects with various severities of SDB and then, applied to a single channel ECG obtained during standard overnight polysomnography in 862 consecutive subjects referred for SDB diagnosis. Using multiple thresholds of CVHR index ≥38 and

Adenohypophysis was immunocytochemically examined in an infertile female transgenic (Tg) mouse which carried human growth hormone (hGH) gene and had a high circulating level of hGH. No GH positive cells were detected. This confirmed the extrahypophyseal (ectopic) production of hGH and was coincident with the disappearance of parenchymal cells showing affinity to azocarmine in Azan staining. The normal frequency of ACTH positive cells was in accordance with the previous suggestion based on the changes found in zona fasciculata cells of the adrenal cortex. Most interesting findings were the detection of many PRL positive cells and the ovarian histology with nearly normal characteristics except for the presence of thick capsule and interstitial gland-like structure composed of large and light cells. Ovarian histology was also clearly different among individual Tg mice, even though they stemmed from the same line or progenitors, and had a similar phenotype. The current immunocytochemical observation well documented the changes revealed with Azan staining in the adenohypophysis about GH but not about PRL or ACTH. Thus, the immunocytochemical analysis of the adenohypophysis will provide useful methodology in assessment of endocrinological circumstances of Tg mice.

Background— Despite the adverse cardiovascular consequences of obstructive sleep apnea, the majority of patients remain undiagnosed. To explore an efficient ECG-based screening tool for obstructive sleep apnea, we examined the usefulness of automated detection of cyclic variation of heart rate (CVHR) in a large-scale controlled clinical setting. Methods and Results— We developed an algorithm of autocorrelated wave detection with adaptive threshold (ACAT). The algorithm was optimized with 63 sleep studies in a training cohort, and its performance was confirmed with 70 sleep studies of the Physionet Apnea-ECG database. We then applied the algorithm to ECGs extracted from all-night polysomnograms in 862 consecutive subjects referred for diagnostic sleep study. The number of CVHR per hour (the CVHR index) closely correlated ( r =0.84) with the apnea-hypopnea index, although the absolute agreement with the apnea-hypopnea index was modest (the upper and lower limits of agreement, 21 per hour and −19 per hour) with periodic leg movement causing most of the disagreement ( P Conclusions— The automated detection of CVHR with the ACAT algorithm provides a powerful ECG-based screening tool for moderate-to-severe obstructive sleep apnea, even in older subjects and in those with cardiac autonomic dysfunction.

Female mice were divided into androgenized (AF) and control (CF) groups. The AF mice were injected subcutaneously with testosterone propionate (Tp) and the CF mice with sesame oil at 5 days of age. Mammotropes (PRL cells) and somatotropes (GH cells) in the adenohypophyses of these mice when they became adults were studied with immunohistochemistry and morphometry by light microscopy correlated with routine electron microscopy. In CF mice, almost all of the PRL-immunoreactive cells (about 43% of all parenchymal cells) were type I (classical) PRL cells, and almost all of the GH-immunoreactive cells (about 30% of all parenchymal cells) were type I (classical) GH cells. Type II PRL cells accounted for about 0.4% of parenchymal cells, and type II GH cells were about 2.5% of all parenchymal cells. In AF mice, the percentages of PRL and GH cells were not significantly different from those of CF mice. Mammosomatotropes (Ms cells) in both groups were less than 1% of all parenchymal cells. Numbers of all parenchymal, PRL and GH cells, however, were increased significantly in AF mice when compared to those in CF, because the adenohypophysis was increased in volume in AF mice. Type I PRL cells were larger in AF than in CF. The ultrastructure suggested that type I PRL cells may show increased PRL synthesis and secretion in AF mice. Furthermore, AF mice, in which the hypothalamus is masculinized by the neonatal treatment with Tp, retained feminine characteristics in the population and size of PRL cells and GH cells in the adenohypophysis.

To investigate the relationship between pulmonary congestion and bronchial responsiveness, we measured bronchial responsiveness to acetylcholine in 51 patients with left heart disorders. The measurement of bronchial responsiveness was performed by inhaling doses of acetylcholine chloride (0.08 to 20 mg/ml) and calculating the PC20-FEV1. The median value for PC20-FEV1 was above 20 mg/ml in the subjects without history of congestive heart failure (n = 18), was 5.29 mg/ml in the subjects with clinical evidence of congestive heart failure in the past days (n = 18; p less than 0.01), and was 5.74 mg/ml in the subjects with clinical evidence of congestive heart failure at the time of study (n = 15; p less than 0.01). The hemodynamic variables by cardiac catheterization and the clinical symptoms were not correlated with the grade of bronchial responsiveness. These results suggest that the bronchial responsiveness was increased in most of the patients with chronic congestive heart failure. We concluded that continuous pulmonary congestion may contribute to the pathogenesis of bronchial hyperresponsiveness.

To assess the clinical significance of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia (NSIP) pattern (IP/NSIP groups), we measured the levels of serum (n = 14) and bronchoalveolar lavage fluid (BALF, n = 10) CA19-9 in IP/NSIP groups.The serum levels of CA19-9 did not correlate with the serum levels of LDH, of KL-6, or of SP-D or with the intensity of chest Ga-67 scintigraphy. There were no significant differences between the serum CA19-9 levels before therapy and those after therapy in improving patients. The levels of CA19-9 in fibrotic NSIP groups (serum:n = 7, 138.3 + /- 79.6 U/ml BALF: n = 5, 845.8 + /- 334.2 U/ml) were significantly higher than those in cellular NSIP groups (serum: n = 7, 12.8 +/-2.1 U/ml, BALF: n = 5, 40.8 +/- 16.2 U/ml). Immunohistochemical stains of CA19-9 showed the strong positivity in the bronchiolar epitheliums located in severe fibrotic lesions and the mucus within the lumens of microscopic honeycomb. The serum levels of CA19-9 were increased in both worsening patients.We speculated that the serum levels of CA19-9 may reflect the progression of lung fibrosis but not the disease activity in IP-NSIP groups.

Recently, a noninvasive medical device (SD-101) capable of detecting breathing pattern changes in a subject lying supine or on the side has been developed. We therefore tested whether the SD-101 would be useful for diagnosing sleep apnea syndrome (SAS). Seventy patients who had been suspicious of SAS were enrolled (M/F = 61/9, mean age +/- SD = 46.6 +/- 14.7 y/o). They took 2 distinct screening tests for SAS (using the SD-101 and one of the most popular screeners for SAS in Japan (Apnomonitor III: AP, Chest Co., Tokyo)) and a simultaneously performed standard polysomnography (PSG). All patients were then asked to respond to a questionnaire on awareness of invasiveness experienced during each study (both from the screeners and from the standard PSG). The data were then compared with those from PSG mainly using correlation coefficients and the x2 test for analysis of subjective invasiveness. Statistical significance was defined as a p value of less than 0.05. As a result, the apnea-hypopnea index (AHI) from SD-101 (r=0.947, p0.0001) had a significantly higher correlation coefficient (p0.0001) than that from the AP (r=0.601, p0.0001) in relation to that from PSG. The SD-101 had a significantly lower invasiveness than either AP or PSG (p0.0001). In conclusion, SD-101 could be much more useful for checking AHI than other conventional screeners, such as AP, which suggests that SD-101 is more useful for defining SAS.

We have observed growth hormone-releasing hormone (GHRH)-immunoreactive (ir) neurons in the arcuate nucleus (ARC), somatostatin (SS)-ir neurons in the periventricular nucleus (PeN), and pituitary growth hormone (GH)-ir cells in female C57BL/6J mice at 2 months old (2 M), 4, 12 and 23 M, using immunocytochemical and morphometric methods. The number of GHRH-ir neurons decreased with age. The number of SS-ir neurons increased from 2 to 4 M, but decreased after 4 M. The volume of the anterior pituitary and the number of adenohypophysial parenchymal cells fell from 12 to 23 M. The proportion of GH-ir cells decreased significantly from 2 to 4 M and decreased in number from 12 to 23 M as well as in size from 2 to 4 M and from 12 to 23 M. Our results show that both GHRH-ir neurons and SS-ir neurons are fewer in old female mice, but the ratio of the number of SS-ir neurons to GHRH-ir neurons increases in old females. We suggest that the fall in the number and size of GH-ir cells in the pituitary gland with age may be involved in the increase in the ratio of the number of SS-ir neurons to GHRH-ir neurons in the hypothalamus in female mice, as well as in males.

Mitochondria occasionally increase in size in response to metabolic injury. Numerous studies have reported giant mitochondria in patients with various diseases and animals with metabolic injuries, and there are few reports on giant mitochondria in normal cells under physiological conditions. Here, we report a reversible formation of giant and normal-sized mitochondria in gastric parietal cells of guinea pigs. We morphometrically analyzed the frequency distribution of mitochondrial area on ultrathin sections of parietal cells in guinea pigs fed freely (control group), starved for 60–72 hr (starvation group), and starved and then injected with histamine (histamine group). The distribution was significantly different between the control and starvation group and between the starvation and histamine group: the histogram of the starvation group significantly shifted toward large mitochondria compared with that of the control or histamine group; the frequency of mitochondria more than 2 μm2 in size was significantly higher in the starvation group than that in the control or histamine group. This is the first report that clearly demonstrated the presence of giant mitochondria in gastric parietal cells under the starved condition and a mitochondrial recovery in a normal size after the administration of histamine. Because gastric parietal cells change their membrane system according to the state of gastric acid secretion, the present data may offer new insight into the morphological changes in gastric parietal cells. Anat Rec Part A 278A:533–539, 2004. © 2004 Wiley-Liss, Inc.

We examine the effect on the hypothalamus-pituitary-adrenal gland (HPA) axis of prolonged exposure to low levels of formaldehyde in female C3H/He mice, using immunocytochemical and RT-PCR methods. Two groups of female mice were exposed to differing concentrations (0, 80, 400, 2000 ppb) of formaldehyde inhalation for 16 h/day, 5 days/week, for 12 weeks. The corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons in the hypothalamus were then examined, together with the adrenocorticotropin hormone (ACTH)-ir cells and ACTH mRNA in the pituitary. One group comprised sham control mice. The other group was made allergic by injection of ovalbumin (OVA) and alum prior to exposure to formaldehyde, since most sick building syndrome (SBS) sufferers are women with allergic disease. These animals were further exposed to aerosolized OVA as a booster four times during the exposure period. Our results showed a dose-dependent increase in the number of CRH-ir neurons in the non-allergy (NAG) group. A similar pattern was found in ACTH-ir cells and ACTH mRNA. The allergy (AG) model group showed an increase in basal levels of all markers of HPA activity. Moreover, the AG mice appeared to respond to the lowest concentration of formaldehyde, and all indices of HPA activity were reduced at the highest concentrations of formaldehyde. These results relate to an important clinical issue and also have implications in the broader area of HPA regulation. We conclude that our experimental system may be a suitable animal model for SBS and/or multiple chemical sensitivity (MCS).

Gicerin, an immunoglobulin superfamily protein, is expressed abundantly in the embryonic tissues and plays an important role in development through its cell adhesive activity. Interestingly, re-expression of gicerin is found in a variety of tumors. In the present study, the possible role of gicerin in the progression of mammary carcinoma was investigated. The normal mammary glands of mice were negative for gicerin, but sporadic mammary carcinoma cells expressed gicerin strongly on their surface. A mouse mammary carcinoma cell line, JYG-B, which is gicerin-negative was employed for introducing gicerin cDNA and the resultant gicerin transfectants were subsequently analyzed. In vitro, self-aggregation activity of the gicerin-transfectants progressed. For an in vivo study, invasive and metastatic potential of the cells was examined by a subcutaneous implantation into nude mice. The invasion of gicerin transfectants into the surrounding tissue was enhanced and severe metastasis to the lungs occurred. These findings suggest that gicerin is an effector for the malignant progression of mammary carcinoma.

Objective—To determine the effect of age on immunocytochemical staining characteristics of adenohypophyseal cells of Mongolian pony mares and stallions. Animals—35 Mongolian ponies. Procedure—Pituitary glands from 1- to 22-year-old horses of both sexes were collected at a commercial slaughterhouse in China and allocated into 7 groups according to age and sex: prepubertal stallions (n = 5; 1 to 2 years old), young stallions (6; 3 to 7 years old), middle-aged stallions (4; 10 to 12 years old), old stallions (5; 15 to 22 years old), young mares (3; 3 to 7 years old), middle-aged mares (5; 10 to 12 years old), and old mares (7; 15 to 22 years old). Pituitary glands were processed for microscopy, and sections were immunocytochemically stained for various pituitary hormones. The percentages and cell areas of 6 types of adenohypophyseal cells were determined by use of morphometry. Results—Age-related alterations in adenohypophyseal cells were detected in horses > 15 years old. Percentage of somatotrophs decreased with age regardless of sex, and percentage of lactotrophs increased with age in stallions. In old mares, percentage of follicle-stimulating hormone cells increased, whereas cell area of follicle-stimulating hormone and luteinizing hormone cells decreased. Differences between sexes for percentage of somatotrophs and lactotrophs, and cell area of follicle-stimulating hormone and luteinizing hormone cells were not evident in old horses. Conclusions and Clinical Relevance—Differences among percentages and cell areas of pituitary cell types in old horses may be associated with degeneration of the sex organs. (Am J Vet Res 2000;61: 826–831)

The present study was designed to clarify lung-kidney interrelation in fetal rats. On fetal day 20, liquid paraffin (LP) was injected into fetal thoracic cavity to produce pulmonary hypoplasia. No significant difference in body and renal weights were noted between the LP injected and control fetuses. The weight of lung, however, was significantly lower in the LP injected fetuses than in the control ones. Histological examinations on the lung and kidney of the LP injected fetuses revealed that the lung was hypoplastic characterized by rich interstitium and reduced air spaces. In the kidney, mature types of glomeruli and profiles of proximal tubules near them were increased in number. Furthermore, strong expression of EGF immunoreactivity was noted in the apical cytoplasm of epithelium of the proximal tubules in the LP injected fetuses. These findings indicate that lung-kidney interrelation exists in fetal rats during late gestational days, and suggest that interruption of the lung development induces accelerated growth of the kidney in fetal rats.

During pregnancy, a population of uterine NK cells, commonly called granulated metrial gland (GMG) cells, differentiates in the uterus of both immune competent and various immunodeficient mice. Regulatory mechanisms controlling the differentiation of GMG cells are not fully known. It has been proven that GMG cells are derived from bone marrow, appear under the influences of progesterone and estrogen, do not require the presence of an embryo, and are associated in rodents with decidualization of the uterine stroma. Mice of genotype aly/aly are genetically deficient in lymph nodes and Peyer's patches due to a lymphoid-associated mesenchymal disorder. They are considered to be a useful model for the study of interactions between lymphocytes and stromal components. This immunodeficient animal is completely different from nu/nu and scid/scid mice who differentiate GMG cells during pregnancy. To determine whether the differentiation of GMG cells depends on mesenchymal interactions in the uterus, aly/aly mice were studied histologically between days 10 and 14 of pregnancy for differentiation of GMG cells and development of the metrial gland. Metrial gland tissue was present and appeared normal in aly/aly mice. There were no significant differences in the distribution of GMG cells in comparison to control pregnant aly/+ mice. Fewer GMG cells were present in aly/aly mice than aly/+ mice on days 12 and 14 of pregnancy. The features of individual GMG cells were different on days 10 and 12 of pregnancy. GMG cells in aly/aly mice were small in size and the granules were poorly developed. By day 14, however, GMG cells acquired a mature size and the granules appeared mature. It is likely that GMG cell differentiation was delayed in pregnant aly/aly mice, due to a mesenchymal disorder affecting metrial gland development in this animal.

We report four cases of acute pneumonitis due either to interferon, or a herbal drug, "Sho-saiko-to", or both in combination, in patients with chronic active hepatitis, focusing on its pathogenesis and response to prednisolone therapy. These cases shared common clinical features: fever, dry cough, dyspnoea, hypoxaemia, diffuse infiltrates both on chest radiography and chest computed tomography, restrictive pulmonary functional impairment, and alveolitis on examination of transbronchial lung biopsy, all of which suggest acute interstitial pneumonia. Furthermore, lymphocytosis was observed in association with the dominant CD8+ T-cell subset in bronchoalveolar lavage fluid. A lymphocyte stimulation test using peripheral blood was positive to interferon in one case and to Sho-saiko-to in another. All patients responded to oral prednisolone therapy. Peripheral soluble interleukin-2 receptor levels decreased in parallel with improvement in the clinical course. All patients were free of symptoms with a follow-up of 1-3 yrs. We conclude that interferon- and/or Sho-saiko-to-induced acute pneumonitis may be due to allergic-immunological mechanisms rather than toxicity, and that peripheral levels of soluble interleukin-2 receptor appear to be good markers of disease activity.

Morphology of granulated metrial gland (GMG) cell, a uterine natural killer (NK) cell, was reported to be normal in pregnant uteri of NK cell-deficient mice and T-cell- and B-cell-deficient mice, but little is known about the number of GMG cells. To determine whether the number of GMG cells is influenced by such mutations, their number in the bg mice (genotype C57BL/6J-bg/bg) and SCID mice (genotype C.B-17/Icr-scid/scid) was compared to that of control mice on day 12 of gestation. GMG cells in these mutant mice were normal in number. Thus, the present results support the previous reports that GMG cells can differentiate normally in bg mice and that the GMG cell differentiation is not affected by functional T- nor B-cells.

Adenohypophyses of porcine fetuses from 25 to 110 days of gestation were studied by immunohistochemical staining to ascertain the ontogeny of specific cell types and their spatial distribution in the pars distalis. No hormonecontaining cells were found before 30 days of gestation. ACTH cells were observed first at 40 days, while GH and LH cells appeared first at 60 days. PRL cells were initially detected at 105 days. ACTH immunoreactive cells were also observed in the pars intermedia at 40 days. Blood capillaries were interposed between cell cords of the pars distalis after 40 days of gestation. ACTH cells were evenly distribution in all areas of the pars distalis except the rostal area (sex zone). GH cells were densely distributed in lateral wings of the pars distalis and immediately anterior to Rathke's lumen. PRL cells resembled GH cells in their distribution pattern, but PRL cells were fewer in number. LH cells were scattered in the sex zone of the pars distalis from 60 to 80 days of gestation. After 90 days, they became scattered throughout the pars distalis but were more numerous in the sex zone than in other areas. The inductive elements of adenohypophysial cells from Rathke's pouch epithelia are discussed. We hypothesize that cell cords of specific areas facing Rathke's lumen may differentiate into specific cell types of the pars distalis during fetal life. © 1992 Wiley-Liss, Inc.

The number of prolactin and growth hormone cells was estimated in the mouse anterior pituitary gland. During postnatal development in females, the number of prolactin cells showed a rectilinear increase from about 0·3 × 104 at 20 days of age to about 21 × 104 in adult female mice, while growth hormone cells gradually increased from about 7 × 104 on day 20 to about 20 × 104 on days 60–70, with a plateau level of about 14 × 104 cells around puberty. Prolactin cells were more abundant in adult female (about 21 × 104) than in male (about 5 × 104) mice, while there were fewer growth hormone cells in adult females (about 20 × 104) than in males (about 25 × 104). Ovariectomy before puberty induced the male pattern of pituitary development by inhibition of the increase in the number of prolactin cells and stimulation of that of growth hormone cells. In animals ovariectomized just before puberty (30–35 days of age) or 5 days after vaginal opening (40–45 days of age) the number of prolactin cells showed no further increase after the day of operation. On the other hand, when animals were ovariectomized at 10 days of age, the number of prolactin cells increased to the level found in 30-day-old normal control females. This implies that the increase in prolactin cells between 10 and 30 days of age is not dependent on the ovary, although after puberty the increase does depend on the presence of the ovary.

With the use of monosodium L-glutamate (MSG) treatment and ovariectomy, we studied how the arcuate nucleus and ovary are involved in the maturation of GH, PRL, and nongranulated cells in the anterior pituitary lobe during postnatal development. From day 1 to day 7 female pups were injected sc daily with MSG (2 mg/g BW) (MSG mice) or distilled water (control mice). Just before puberty (at 30 days of age) some control and MSG mice were ovariectomized (OVX) (control + OVX mice and MSG + OVX mice, respectively). All animals were killed at 60-70 days of age by decapitation. Populations of GH, PRL, and nongranulated cells in the anterior pituitary lobe were calculated by applying morphometric procedures. Percentages of GH, PRL, and nongranulated cells in MSG mice were not different from those of control mice. In control + OVX mice the percentage of GH cells was greater than that of control mice, while PRL cells were markedly decreased. On the other hand, in MSG + OVX mice the percentage of PRL cells was less than that of MSG mice, while GH cells showed no difference; nongranulated cells were increased. The number of parenchymal cells in the anterior pituitary lobe in MSG mice was approximately two thirds that of control mice. The parenchymal cells in control + OVX mice were the same in number as those in control mice, while those in MSG + OVX mice were approximately half the number of the parenchymal cells in MSG mice. Numbers of GH and PRL cells in MSG mice were half those of control mice. There was no difference in the number of nongranulated cells between MSG and control mice. GH cells in control + OVX mice were more abundant than those of control mice, while PRL cells were fewer. On the other hand, both GH and PRL cells in MSG + OVX mice were fewer when compared with those of MSG mice. The numbers of nongranulated cells in most groups showed no significant differences among each other. All of these data taken from control mice were the same as those taken from normal mice. These results suggest that the arcuate nucleus in the hypothalamus stimulates the differentiation of GH and PRL cells during postnatal life, and that the ovary stimulates the differentiation of PRL cells through a direct effect on the anterior pituitary lobe but inhibits that of GH cells via the arcuate nucleus in the hypothalamus, while the differentiation of nongranulated cells is little affected.

PRL and GH cells in the adenohypophysis of adult mice were studied with immunohistochemistry and stereological morphometry by light and electron microscopy. We compared findings for males and females. In female mice, most PRL-immunoreactive cells (43% of all parenchymal cells) and most GH-immunoreactive cells (33% of all parenchymal cells) were classical PRL cells (type I PRL cells) or GH cells (type I GH cells), respectively. Besides these classical types of cells, we found PRL- and GH-immunoreactive (type II PRL and GH) cells that contained small (approximately 100-200 nm in diameter) and round secretory granules. However, in female mice type II PRL or GH cells accounted for less than 3% of all parenchymal cells, as was also true for type II GH cells in the males. The percentages of type I and type II PRL cells in male mice were about the same (approximately 10% of all parenchymal cells). Only a few mammosomatotropes (0-0.6% of all parenchymal cells) were found in the mouse adenohypophysis of either sex. All mammosomatotropes were type II cells; none were PRL or GH cells of the classical type. This immunohistochemical study confirmed our previous findings by conventional electron microscopy that there are marked sex differences in the proportions of PRL and GH cells in the adult mouse adenohypophysis; PRL cells are more abundant in the female mice, and GH cells are more abundant in the males.