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Figure 20. Pancreatic islets of Syrian hamster. a) Distribution of islets of different sizes. Anti-chromogranin A, staining X 20. b) Conglomerate of islets forming a snake-like shape. H&E, X 32. c) Similar “snake-like” islets in culture. The brown-stained material is insulin. Anti-insulin antibody, X 32. d) A conglomerate of islets in a human pancreas. H&E, X 32. increases by 8 μm (12.6 ± 3.4 to 20.7 ± 2.3 μm). Mucous-producing cells are found near the opening into the duodenum and are prominent throughout the entire length of the common duct of 56-week-old animals. Mucous droplets form on the epithelial surface, and often conglomerate to amorphous caps. Cell borders are easily distinguishable, while another cell type has microvilli on its surface and ciliated cells are found only occasionally. Compared with the four-week-old hamsters, the epithelial height in the common duct of these animals does not increase markedly on the average (22.4 ± 2.9 μm). The endocrine portion of the hamster pancreas (islets of Langerhans) resembles that of other mammals with the exception that their distribution throughout the pancreas is fairly constant in this species and averages 1.0 islet/ sq mm (0.8 to 1.5 sq mm). These figures apparently are consistent with findings in other rodents 102 . Also, as in other mammals, the islets in hamsters are arranged pe- 20 ripherally around the ducts in a bud-like fashion. These slightly oval structures, which are inconspicuous in H&E stained histological sections by their light appearance, are more or less well defined and show a remarkable variation in size, which can be best demonstrated in tissues stained with anti-chromogranin A antibody (Fig. 20a). Some islets are composed of a few cells, whereas others may be as large as 500 μ or more. Cell counts of 50 islets of Langerhans in a histology section showed a range from 18 to 267 cells per islet 107 . Attachment of 8-10 islets to each other, forming a snake-like configuration, was observed in the pancreas in only two cases (Fig. 20b). Remarkably, this configuration was also seen in cultured islets (Fig. 20c), indicating strong attachment factors in islet cells. Islet conglomerate can also be seen in the human pancreas, especially in diabetics (Fig. 20d). This finding indicated that these islets are nonfunctional.
Figure 21. SEM view of a well-delineated islet against acinar cells (AC) and containing tightly packed islet cells, capillaries (arrows) and interstitial spaces (IS). A section of a ductule is also seen (arrowhead). X 520. Scanning electron microscopically (SEM), on the cut surface, the islets of Langerhans vary in size and shape from spherical to ellipsoidal (Fig. 21). At 56 weeks, those in hamsters are approximately 100 μ larger than those in the four-week-old animals. As clusters, the islet cells are arranged in irregular strands and separated by sinusoids, which in older hamsters exhibit larger diameters than in those of young animals. Although a true capsule is missing in two-week-old animals, fairly well developed connective tissue can be found around the islet after four weeks of age. An age relationship seems to exist relative to islet size. In our study of 100 islets in hamsters at the ages of 18, 57, and 123 weeks, 6, 10, and 9% of the islets, respectively, measured less than 50 μ. Eighty-nine, 90, and 82% of them, respectively, measured between 50μ and 300 μ. In older animals, about 20% of the islets had a size of 500 μ. Hamster islets are considerably larger than those in humans, which generally range from 75 to 100 μm, 110 although sizes of up to 300 μ have been found. 111 ; 112 Apparently, the hamster islets are not much different from those of the guinea pig 102 . Apparently, new islets are formed budding from ducts and ductules during the animal's entire lifespan, as has been observed in the guinea pig 102 , and show a slightly decreasing trend with age. This phenomenon of new islet cell formation, termed nesidioblastosis by Laidlaw 113 , could 21 correspond to "Endophytie," as described by Muller 107 . Transmission electron microscopically (TEM), the hamster islets appear as small cell clusters separated by fenestrated sinusoidal capillaries and occasional small interstitial spaces (Fig. 22). Figure 22. TEM view of an islet, which is composed primarily of insulin cells. There are several capillaries (c) and interstitial spaces (IS), in which lymphocytes are seen. At the lower right corner, a section of a ductules is present. X 2,907. As in other animals, the peripheral cells more often tend to be α-cells containing numerous granules with a moderate to intensely stained central portion surrounded by a clear halo within the enveloping single membrane. The β-cells have more irregular cores, which tend to be somewhat smaller in proportion to the membrane enclosure and occasional crystalloid cores are noted among the population. Granular endoplasmic reticulum tends to be fairly abundant in some of these cells and the Golgi apparatus is often somewhat linear in appearance rather than sharply circular, as noted in the acinar cells. Golgi complexes often appear in multiple sites in a single cell. Mitochondria tend to be somewhat dense with a predominantly elongated form. As described in other species 114 , some β-cells possess one or two cilia, which project into the sinusoidal spaces (Figs. 23,24).
Page 2 and 3: Proof Copy The Hamster as a Pancrea
Page 4 and 5: 11. Etiology of Induced Pancreatic
Page 6 and 7: This book is dedicated to the late
Page 8 and 9: with his researchers and provided h
Page 10 and 11: The first experimental pancreatic t
Page 12 and 13: immunodeficiency) mice, which have
Page 14 and 15: CHAPTER 3 Hamsters in Toxicological
Page 16 and 17: Figure 1. Comparative data on the a
Page 18 and 19: CHAPTER 4 The Pancreas of the Syria
Page 20 and 21: This designation, although arbitrar
Page 22 and 23: through the common duct into the gu
Page 24 and 25: shape with an almost transparent cy
Page 26 and 27: of the ducts (i.e., the wider the l
Page 30 and 31: Figure 23. Two cilia in a normal ha
Page 32 and 33: Figure 27. An islet with mostly typ
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Page 38 and 39: CHAPTER 6 Spontaneous Diseases of t
Page 40 and 41: incidence) and almost regularly inv
Page 42 and 43: Figure 37. Patterns of islet cell t
Page 44 and 45: Figure 39. The molecular structure
Page 46 and 47: mg/kg body wt resulted in pancreati
Page 48 and 49: Lesions were also found in the peri
Page 50 and 51: high protein diet. These findings w
Page 52 and 53: eached 50%, which was a significant
Page 54 and 55: CHAPTER 8 Metabolic Studies on Panc
Page 56 and 57: 450 3A family was involved, directl
Page 58 and 59: The ability of MOP to damage pancre
Page 60 and 61: (along with traces of BHP, but no u
Page 62 and 63: CHAPTER 9 Drug-Metabolizing Enzymes
Page 64 and 65: Accordingly, in the rat and possibl
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Page 68 and 69: BOP by subcutaneous injection (5 mg
Page 70 and 71: Figure 52. The patterns of hamster
Page 72 and 73: experiments, SZ-induced diabetes si
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The normoglycemia in SZ-treated ham
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CHAPTER 11 Etiology of Induced Panc
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Among 75 adenocarcinomas, 14 (19%)
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egularly show hypertrophy and hyper
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Figure 69. Top: Hyperplastic centro
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Figure 71. Pseudoductular formation
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Figure 73. Ductular complexes showi
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Figure 75. Intra-insular ductular p
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Figure 77. a) A cystic ductule with
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Figure 79. Islet cell neogenesis. T
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Figure 81. Alteration of large and
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aising the question of the possible
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Classification of pancreatic tumors
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include those lesions which consist
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Figure 92. Intra-ductal papillomas.
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Figure 96. a) Intra-ductal carcinom
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Figure 98. Ductular (tubular), well
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Figure 103.a) Tubular mucinous carc
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Squamous cell carcinoma. Pure squam
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Figure 110. poorly differentiated p
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Figure 114. Giant cell carcinomas o
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Mixed Cell Carcinomas. As in humans
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These findings ubiquitously point t
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Figure 125. Top: Under SEM tumors p
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14a. Blood group antigen expression
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Table 2. Expression of Human Tumor
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There seemed to be differences betw
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Figure 137. Gold-labeled anti-A ant
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Table 3. Lectin-binding patterns in
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As part of our comparative studies,
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DCC, and Rb-1 suppressor genes and
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Figure 142. Karyotype of the normal
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present crucial factors. Progress h
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Figure 145. Human islets in culture
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Figure 147. Human islets in culture
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Figure 150. Chromosomal pattern of
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Carbonic anhydrase was demonstrated
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Figure 154. a) KL5N cells grew in r
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Figure 156. Tumor growth in the ham
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Figure 160. Mono nucleated and poly
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formed a large encapsulated mass wi
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1 cm in the first and the second ge
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Consequently, it must be concluded
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e transferred from the M3:5 medium,
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decrease in the HI° histone was fo
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easonably controlled environment of
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Consumption of HF diets after eight
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saturated fat on pancreatic carcino
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suggested that the enhancement of P
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wt at six and seven weeks of age. T
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synthesis and release of large amou
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pancreatic ductular carcinoma incid
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modifying effect of PH on pancreati
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predominant form of DNA alkylation
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the following 37 weeks. Additional
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tritiated thymidine (unpublished),
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or at the time of cellular regenera
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hamsters receiving the 2% BHA suppl
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the inhibition of pancreatic cancer
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diet in comparison with hamsters fe
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diet supplemented with 2% (group 1)
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single subcutaneous injection of BO
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Figure 168. Pancreatography by retr
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Although we have identified insulin
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Figure 169. Perivascular iendocrine
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ducts and in the micro carcinoma (F
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CHAPTER 19 Prevention and Therapy o
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proMMP-2 is highly activated in PC
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plus adenocarcinomas were significa
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and the combination of 5-fluorourac
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duct carcinogenesis. OPB-3206 may b
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thus receive the highest photodynam
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The same applies to hyperplastic an
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Figure 177. Serial sectioning of a
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atypical-to-malignant and were remo
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CHAPTER 21 Conclusions from the Stu
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While these precursor cells may be
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transform the cultured human islet
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Figure 181. After massive degenerat
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27. Caygill CP, Hill MJ, Hall CN, K
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68. Nakase A, Koizumi T, Fujita N,
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116. Pour PM, Kazakoff K, Dulaney K
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162. Pour P, Althoff J, Nagel D. In
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203. Lawson T, Kolar C. Mutation of
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246. Rettie AE, Korzekwa KR, Kunze
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289. Bell RH, Jr., McCullough PJ, P
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335. Pour PM, Uchida E, Burnett DA,
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375. Resau JH, Hudson EA, Jones RT.
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419. Schreiber AB, Winkler ME, Dery
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463. Fitzgerlad P, Sharkey F, Fogh
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507. Herrington MK, Permert J, Kaza
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548. Permert J, Ihse I, Jorfeldt L,
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586. Nishikawa A, Furukawa F, Kasah
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627. Rao MS, Scarpelli DG, Reddy JK
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