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We consider single machine batching and scheduling problem in which the processing time of each job is known, but the setup time is a random variable from the distribution with an unknown parameter. Batch sizes are determined sequentially, that is, the size and jobs of the rst batch are determined by using the prior knowledge and observed the value of a setup time, then the size and jobs of the second batch are determined by using the value of the rst setup time, and so on. Since this problem is a sequential decision problem, it is formulated by dynamic programming and several properties are obtained.

Lysyl oxidase initiates cross-linkage of collagen and elastin by catalysing the formation of a lysine-derived aldehyde. In order to study cross-linking in scleroderma, we used monoclonal antibodies to lysyl oxidase to determine the localization of this enzyme in systemic and localized scleroderma, and compared the distributions obtained with that in normal skin. Using an indirect immunofluorescent antibody method and an avidin-biotinylated enzyme complex method, 11 cases of diffuse type of systemic scleroderma and seven cases of localized scleroderma were studied. In the oedematous stage of systemic scleroderma, intracellular and extracellular lysyl oxidase were remarkably increased in the dermis, particularly in groups around blood vessels. In the sclerotic stage of systemic scleroderma, lysyl oxidase was detected intracellularly in fibroblasts and extracellularly among collagen bundles between the lower dermis and the subcutaneous fat tissue. In localized scleroderma, a marked increase in lysyl oxidase was observed in mononuclear cells and fibroblasts near blood vessels in the lower dermis and in the subcutaneous fat tissue, in addition to the extracellular deposits between collagen bundles. The increase in lysyl oxidase in localized scleroderma was much more common than in the oedematous stage of systemic scleroderma. These findings indicated that intracellular and extracellular expression of lysyl oxidase expression was greater in sclerodermatous skin than in normal skin.

Intelligent actuators have contributed to constructing products such as machines, robotic systems and to factory automation. The stroke is measured by using a sensor located on one end of an actuator. This stroke sensing system is not only very complex but also sensitive to vibration, dust and fumes. To solve this problem, a new actuator has already been developed. This actuator's piston rod has highly accurate magnetic scales made by laser beam irradiation. This allowed the development of a scaling rod, which satisfies both accuracy and intensity. Manufacturing cost is, however, very high, and the applications are restricted to special use. Therefore, the purpose of this paper is the development of a new manufacturing process with plastic forming in order to improve productivity. In this method, magnetic scales are made by rotary forming. Only the plastic deformation parts become ferromagnetic because of transformation-induced martensite by transformation-induced plasticity (TRIP) effect on the surface of a nonmagnetic rod. Using this method, a reasonable and accurate regular magnetic interval and the stroke's high degree of accuracy is achieved.

Recent development of marine magnetic gradient systems, using arrays of sensors, has made it possible to survey large contaminated areas very quickly. However, underwater Unexploded Ordnances (UXO) can be moved by water currents. Because of this mobility, the cleanup process in such situations becomes dynamic rather than static. This implies that detection should occur in near real-time for successful remediation. Therefore, there is a need for a fast interpretation method to rapidly detect signatures of underwater objects in marine magnetic data. In this paper, we present a fast method for location and characterization of underwater UXOs. The approach utilises gradient interpretation techniques (analytic signal and Euler methods) to locate the objects precisely. Then, using an iterative linear least-squares technique, we obtain the magnetization characteristics of the sources. The approach was applied to a theoretical marine magnetic anomaly, with random errors, over a known source. We demonstrate the practical utility of the method using marine magnetic gradient data from Japan.

A 64-year-old woman was transferred to the intensive care unit with dyspnea and palpitation on effort. Chest x-ray film showed cardiomegaly and pulmonary congestion. We carefully examined for sarcoidosis as a differential diagnosis of heart failure. Serum lysozyme was mildly high, but human atrial natriuretic peptide (HANP) and brain natriuretic peptide (BNP) were strikingly high. Angiotensin converting enzyme was within normal limit. Chest roentgenogram did not reveal bilateral hilar lymphadenopathy. Atrioventricular conduction block was not observed on electrocardiogram. Echocardiographic examination showed left ventricular global hypokinesis with septal thinning and enlargement. Mitral valve regurgitation was recognized by Doppler evaluation. Coronary arteriography showed normal coronary arteries. Endomyocardial biopsy revealed noncaseous epithelioid granulomas containing, Langhans type giant cell accompanied by fibrosis and lymphocyte infiltration. From these data cardiac sarcoidosis was diagnosed. Gallium scintigraphy showed diffuse uptake only in the heart. Treatment with oral prednisolone 20 mg/day was started. Her symptoms improved by several weeks after the medical treatment. In addition, both the value of HANP and BNP were markedly decreased and echocardiogram showed improvement of cardiac systolic function. In Japan, there is a higher incidence of cardiac sarcoidosis than in the West. The prognosis of this condition associated with cardiac dysfunction is reported to be very poor. When progressive heart failure in older patients is seen, cardiac sarcoidosis should also be kept in mind. Endomyocardial biopsy play an important role as the only accurate technique for the diagnosis of cardiac sarcoidosis.

The same kind of n jobs are processed one by one sequentially by a single machine and any number k of them may be processed as a batch. A setup time is necessary before the processing of the first job in a batch. The completion times of all the jobs in a batch are the same as the completion time of the last job in the batch and the processing time of the batch is the sum of a setup time and k times of the processing time of a job. The processing time of the job is known, but the setup time is the random variable which is distributed in the gamma distribution with the parameter whose value is unknown a priori. A conjugate prior distribution for the value is considered. The first batch size is decided by using the prior distribution, the setup time is observed, and then the second batch size is decided by using the posterior distribution revised by using the observed value of the setup time in the first batch. This process is repeated until all the jobs have been processed. The objective is to minimize the expected total completion times. This problem is formulated by using dynamic programming and both the several properties derived from the recursive equations and the critical values for the optimal strategy are derived.

We study an example of R. Bellman's gold-mining problem related to a programming job on the computer. The problem is formulated by dynamic programming and the optimal strategy is explicitly derived. The Bayesian version when the parameter involved is unknown is also solved by the same method. It is shown that the optimal strategy in each of two versions has the “no-island” (or, in other words, “control-limit”) property.

Sirs, Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia due to an idiopathic chronic granulomatous inflammation of the cavernous sinus [9]. THS usually improves with corticosteroids, however, in cases showing an insufficient effect of corticosteroid therapy or side effects, alternative therapies such as immunosuppressive agents [3] or focal radiation therapy have been reported [2, 5–7]. We describe a patient with THS who was successfully treated with radiation monotherapy. A 36-year-old man with chronic hepatitis B and impaired glucose tolerance since age 30 developed acute left orbital pain and double vision at the end of July 2006. Neurologic examination on 3 August 2006 demonstrated only mild restriction of abduction of the left eye. Magnetic resonance imaging (MRI) of the brain showed no abnormality including the cavernous sinus region at that time. His illness progressed rapidly and he was admitted to our hospital on 14 August 2006. On admission, body temperature and blood pressure were normal. Neurologic examination demonstrated almost complete ophthalmoplegia in all directions and blepharoptosis without pupil abnormality on the left. Spontaneous left ophthalmic pain was also reported. There were no ophthalmic symptoms on the right and there were no symptoms of lower cranial nerves on both sides. Urinalysis and routine hematological examination were normal. Blood chemistry examination demonstrated mild elevation of aspartate aminotransferase (60 IU/L; normal range 11–34 IU/L), alanine aminotransferase (151 IU/L; normal range 6–39 IU/L) and glycohemoglobin A1c (6.1%; normal range 4.3–5.8%). Surface antigen and core antibody of hepatitis B virus were positive. The following immunological and inflammatory investigations were normal or negative; antinuclear antibody, cytoplasmic and perinuclear antineutrophil cytoplasmic antibody, angiotensin converting enzyme level and b-D-glucan. Chest radiography and Gallium scintigraphy of the whole body showed no abnormality suggestive of systemic inflammatory disease. Cerebrospinal fluid examinations were normal including cytology and culture for bacteria and mycobacteria. Brain MRI showed abnormal soft tissue enhanced with gadolinium within the left cavernous sinus (Fig. 1). Based on a diagnosis of THS, we first considered corticosteroid therapy for THS with simultaneous antiviral therapy for hepatitis; however, the patient refused corticosteroid therapy because of the possible exacerbation of hepatitis. One week after admission, the left pupil was dilated and light response was diminished, indicating progression of THS. Thereafter, the patient received a total of 30 Gy in 15 fractions focused on the left cavernous sinus by three-dimensional conformal radiotherapy (3D-CRT). Left blepharoptosis and ophthalmoplegia gradually improved within 2 weeks after the initiation of radiation therapy; blepharoptosis had almost completely disappeared by the middle of October 2006. Ophthalmoplegia also Y. Furukawa W. Yamaguchi K. Ito T. Hamada H. Miyaji Department of Neurology, Fukui Prefectural Hospital, Fukui, Japan

We diagnosed phakomatosis pigmentovascularis type IIIb in an 11-month-old baby who had a giant nevus spilus, a nevus flammeus, and moyamoya disease. Development of the patient was normal until 6 months of age when he developed a sudden onset of focal seizures and left hemiparesis. This patient represents the sixth case of phakomatosis pigmentovascularis type IIIb, including three cases in the Japanese literature, reported thus far. However, to our knowledge, this is the first case with an association to moyamoya disease.

Langerhans cells (LCs) are activated in the epidermis by external and internal stimuli, such as antigens and cytokines, respectively. To reveal the morphologic and functional properties of in vivo-activated LCs during inflammation, we injected the streptococcal preparation OK-432 intradermally into the earskin of mice and performed time-course analyses by immunofluorescence and electron microscopy. Cellular infiltrate appeared in the dermis at 6 h after OK-432 injection and had progressively extended to the dermoepidermal junction at 12 and 24 h. Immunostaining for class II antigen revealed that LCs were enlarged and extended long dendrites during inflammation. Acidic compartments such as lysosomes and multivesicular bodies also increased in number and Golgi apparatuses developed as demonstrated by electron microscopy and morphometric analysis. Birbeck granules, although not showing numerical changes, were translocated from the Golgi area to the subplasmalemmal area. After epicutaneous application of cationic ferritin, LCs often contained endosomes as the result of engulfment by the cytoplasmic projections. The present results indicate that nonspecifically induced dermal inflammation is capable of inducing activation of LCs in vivo, and that in vivo-activated LCs have the capacity for active endocytosis and intracellular digestion or processing.

We diagnosed a unique case of Merkel cell carcinoma (MCC) coexisting with Bowen's disease on the sole of the foot of a 72-year-old man who had worked for about 4 years in a factory handling inorganic arsenic. He had a past history of arsenical keratosis and multiple Bowen's disease. The tumour first appeared as a reddish macule and then showed marked growth over the next month. The tumour was excised and the specimen was examined histopathologically. The tumour consisted of two components: a group of atypical cells representing Bowen's disease in the epidermis and another group of atypical cells with a trabecular pattern characteristic of MCC in the dermis. Neither group of cells showed transitional findings, and the tumour elements were divided by a clear basement membrane. The tumour cells in the dermis were positive for neurone-specific enolase, and on electron microscopy had dense core granules in the cytoplasm. Inorganic arsenic can cause various cutaneous neoplasms, but to our knowledge, this is the first report of a case of MCC associated with Bowen's disease.

Background: The thymus plays important roles in host defense, which may be impaired after burn injury. The effects of thermal injury on thymocytes were investigated in male Wistar rats. Methods: Changes in thymus weight and content of glutathione and corticosterone were determined after burn injury. Apoptosis of thymocytes was detected by electrophoresis of DNA, and lymphocyte subsets were characterized by flow cytometry. The effects of adrenalectomy and the glucocorticoid receptor antagonist RU486 in burned animals were also studied. Results: The weight of the thymus decreased progressively after burn injury, and this effect was accompanied by increases in the corticosterone concentration in plasma and the thymus and apoptosis of CD4 + CD8 + thymocytes. Administration of RU486 or adrenalectomy inhibited burn-induced thymocyte apoptosis. Conclusion: Thermal injury increases the corticosterone concentration in plasma and the thymus and triggers thymocyte apoptosis.

When we make document files by a computer or a wordprocessor, we sometimes meet with the accident that all the files having been stored in the floppy disk are lost and cannot be reconstructed. In order to avoid this kind of accident, we sometimes make a backup copy of the floppy disk which is useful when the original floppy disk is broken. We make a stochastic model which is useful to make a decision about whether or not to make a backup disk when there are k files in the floppy disk whose backup copy does not exist, we should make remaining n new files, and the probability that the accident occurs is p. The problem is formulated by dynamic programming and several properties of the optimal strategy are obtained. The case that the true value of p is unknown is also discussed and several properties have been obtained.

A 79-year-old Japanese male presented our clinic with a painful eruption on the left edge of the tongue. The lesion was a shallow ulcer surrounded by a elevated indulated border. The size was 40mm in diameter. The histopathological examination of the tumor showed squamous cell carcinoma. He was treated by radiation and resection of the left side of the tongue. One and half year after operation, he is still alive

This paper describes the clinical findings and treatment of the recurrence basal cell carcinoma (BCC).1. The recurrence BCCs were located mostly on periorbital and perialar nasi.2. Histologically, all recurrence BCCs were the morphea-like type.3. As for the treatmen tfor BCC, the first complete surgical removal was essential.4. The authors tried to score the prognosis of recurrence BCC.

We consider a kind of reconnaissance problem which has an application to distributed failure detection. The problem can be considered as a multistage two-person zero-sum game. The two-person, player A and player B, consists of a transport ship and a terrorist, respectively, where the ship is equipped with an unmanned reconnaissance boat. The ship circulates ports again and again and the terrorist may lay a naval mine on the shipping route. For safety, the ship dispatches the unmanned reconnaissance boat and removes the risk of a mine. However, it is very rare that the terrorist lays the mine, while the circulation of the reconnaissance boat is very costly. So, we introduce a mine-preparing probability, represented by geometric distribution, preceding the terrorist’s strategy. The ship has to determine when it should dispatch the boat so that it can maximize its expected payoff. First, we assume that the mine is laid at each beginning of a stage and investigate two cases, a game continuation case and a game termination case, after the ship has been broken by a mine. Next, we assume that the mine may be laid at any timing of a stage and investigate two methods, dispatching two boats and dispatching one boat, for the game continuation case. Finally, we state that the problem can also be applied to a failure detection problem in a distributed system if we regard the ship as a token and the terrorist as an adversary who causes a failure.

For repeated operation of a detonation chamber, evaluation of its fatigue damage and estimation of time to crack initiation are of considerable importance from the aspect of safe operation. This paper proposes the use of a sufficiently conservative operation control fatigue evaluation curve, based upon the ASME Code fatigue design curve and the best fit laboratory air curve upon which the design curve is derived, in order to define operational points for actions to inspect for possible fatigue damage and initiate repairs, as needed. The paper also recommends appropriate actions to verify that any needed repairs maintain structural integrity during subsequent operations.

Cutaneous metastases from pancreatic carcinoma are uncommon. Eight cases have been described in the literature. The metastases display some common features such as umbilical nodules and the histologic pattern of adenocarcinoma. Our patient had erythematous infiltrated plaques in the left axilla and on the upper portion of the chest. A skin biopsy specimen disclosed many poorly differentiated atypical cells throughout the dermis. The diagnosis was confirmed by positive immunohistochemical staining for carbohydrate antigen 19-9.

A patient with primary anaplastic large-cell lymphoma of the skin with characteristic clinical findings is described. The diagnosis was made on the basis of histologic and immunohis-tochemical findings. Thephenotypeof the tumor cells was not determined, but rearrangement of the T-cell receptor β gene indicated that the tumor was of T-cell lineage. Despite high-grade malignancy of the tumor cells, the patient unexpectedly had a benign clinical course. The findings in this case suggest that regressing atypical histiocytosis and lymphomatoid papulosis type A are subsets of anaplastic large-cell lymphoma.

We report a case of adult T-cell leukaemia/lymphoma (ATLL), in whom the polymerase chain reaction (PCR) on genomic DNA from saliva demonstrated the monoclonal integration of human T-cell lymphotropic virus type-1 (HTLV-1) proviral DNA in lymphocytes in the saliva. These results provided evidence of the possibility of saliva-borne transmission of HTLV-1.

We report a Japanese patient with congenital hypomelanosis with a segmental pattern on the lett abdomen, whorl-like pattern on the back; mosaic pattern on the chest, right abdomen, and proximal extremitiea; and with yellow hair on a portion of the scalp. Chemical analysis of the yallow hair revealed decreased eumetanin content, whereas the pheometanin content was normal.

Summary The activity and gene expression of ornithine decarboxylase (ODC, an indicator of tumour promotion) were induced by the phorbol ester tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in mouse skin. In the present study, the effect of colchicine, a microtu-bule-disrupting agent, on ODC activity and its gene expression were investigated. On administration of colchicine (100 μg) intraperitoneally 1·5 h before TPA treatment, ODC activity and ODC mRNA levels stimulated by TPA were suppressed to about 52 and 64%, respectively. These results suggest the involvement of a microtubule or colchicine-sensitive substrate in the signal transduction system for gene expression.

We report the case of a Japanese female infant with Chédiak-Higashi syndrome born to consanguineous parents. At birth she had fair skin but, when she was three months old, marked hyperpigmentation of the sun-exposed skin areas developed. Microscopic examination of blood and electron microscopic examination confirmed the diagnosis. She enjoyed good health until she was two years old when she had pneumonia with marked hepatosplenomegaly. It is important for dermatologists and pediatricians to be aware of the skin manifestations of this disease because hyperpigmentation after sun exposure may be a characteristic, initial feature of this condition.

Vogt-Koyanagi-Harada disease is a rare disease characterized by uveitis, meningitis, dysacusis, alopecia, poliosis, and vitiligo. We describe a 48-year-old patient with Vogt-Koyanagi-Harada disease associated with thin inflammatory raised erythema and plaque-type inflammatory erythema superimposed on vitiligo. Interestingly, inflammatory raised erythema was separated from the perfect vitiligo, and the incomplete vitiligo lay between them initially. Thereafter, incomplete vitiligo became completely depigmented with diminution of inflammatory raised erythema. This is the second case of vitiligo with inflammatory raised borders associated with Vogt-Koyanagi-Harada disease. Our results of immunohistochemical and electron microscopic studies suggested the involvement of T-cell-mediated cytotoxicity and apoptosis in the development of skin lesions.

The problem considered in this paper is to decide when to stop a sequence of the independent random variables from the uniform distribution on the interval (-1,u). Suppose that the true value of u is unknown and there is the prior knowledge that u has the Pareto distribution with parameters w and a as a prior distribution. The .objective is to maximize the total expected discounted sum of the observations. This problem is formulated by dynamic programming and the optimal strategy is denoted by the critical value function whose value for any parameter vector-value is easily calculated.

Chemotherapy-induced acral erythema (CAE) is an uncommon and distinct reaction seen in patients receiving high-dose chemotherapy. The exact pathogenic mechanisms of this disorder are still unknown. We report a 27-year-old woman who presented with red, swollen and painful macules on both palms, clinically consistent with this disease. Histological examination demonstrated vacuolar degeneration of the basal cell layer and spongiotic blisters in the epidermis, especially in the atrophied eccrine ducts and papillary oedema with mild perivascular infiltration of mononuclear and hypersegmented neutrophils. Immunohistochemistry showed that the infiltrating mononuclear cells were CD3-CD16+CD56+ leucocyte function antigen-1+, possibly natural killer cells. The eccrine ducts expressed HLA-DR and intracellular adhesion molecule-1 (ICAM-1). Our findings suggest that cell-to-cell interaction between NK cells and keratinocytes in the eccrine apparatus may induce CAE and may be involved in the pathogenesis of the skin reaction in our patient and possibly in this disease.

We describe a combined cutaneous hamartoma in a 57-year-old man, which comprised a vellus hair cyst, an epidermoid cyst and an intradermal melanocytic naevus in a single facial tumour. The vellus hair cyst was filled with keratinous material with unusual slit-like lacunae. While numerous cases of epidermoid cyst have been reported in association with an intradermal melanocytic naevus, our case is a rare example of a lesion combining several hamartomatous elements.

Two patients with epidermolysis bullosa dystrophica recessiva who had squamous cell carcinoma are presented. Case 1 is a 40–year-old woman who had ulcers on her left lower leg. Case 2 is a 42–year-old man who had a tumor on his left first toe. Wide surgical excision with skin coverage by autograft was performed in case 1. Amputation of the toe in case 2 was performed. A review of the cases of epidermolysis bullosa dystrophica associated with cancer reported in Japan is also presented.

By using antibodies to type I, III, IV, V, and VI collagens and laminin, we examined the localization of interstitial collagens and basement membrane components with indirect immunofluorescence and immunoelectron microscopy (IEM). Furthermore, the morphological changes of these collagens in malignant transformation were investigated. In neurofibroma, IEM showed type I, III, and V collagens to be present diffusely on cross-striated collagen fibrils, whereas type VI collagen was present between the fibrils. Type IV collagen and laminin were observed to surround tumor cells. In neurofibrosarcoma, tumor collagen bundles that reacted with antibodies to type I, III, V, and VI collagens were irregularly arranged. Immunofluorescent deposits that reacted with anti-type IV collagen and anti-laminin antibodies were decreased in number, showing a thin and sparse arrangement.

糖尿病患者にみられたカポシ肉腫を報告した。患者は69歳男子。1982年頃に右足踵から足底にかけて, 紅色∼暗赤色の丘疹, 小結節が出現し, 徐々に増数増大, 疼痛を伴うようになってきた。組織学的にカポシ肉腫と診断され, 5年後には左足, 両手にも皮疹が出現した。糖尿病に対して, インスリン, 経口血糖降下剤投与を行い, さらにアクチノマイシンD, ビンクリスチンによる化学療法を行ったが, 発病約5年後に消化管出血のために死亡した。剖検では, 消化管, 副腎, 横隔膜, リンパ節など多臓器にカポシ肉腫が認められた。

Recently, we have reported two cases with endothelin (ET)-secreting tumor presenting with hypertension and elevated plasma endothelin-1 (ET-1) levels. The present study examines the histopathology of the ET-secreting tumor in one of these cases. The neoplasm was located in the skin and microscopically characterized as a malignant hemangioendothelioma by remarkable intravascular proliferations of atypical endothelium with the expression of Factor VIII-related antigen in the tumor cells. The tumor enlarged rapidly with rising ET-1 and blood pressure levels. The ET-1 content and its messenger RNA expression in the tumor extract were higher than those from normal parts of skin. ET-1 may play a pathophysiological role in patients with ET-secreting malignant hemangioendothelioma.

43歳, 男性。平成元年7月頃より四肢に無症候性の皮疹が出現し, 次第に全身に拡大した。約1ヵ月後に当科を受診したが, 末梢血検査にて異型リンパ球が11%に見られ, HTLV-1抗体は256倍を示した。皮疹部組織を用いたDNA assayにてHTLV-1 proviral DNAを証明し, ATLと診断した。ステロイド剤外用のみにて皮疹の出没を繰り返していたが, 突然, 急性転化し, 化学療法にも反応せず死亡した。

Balb 3T3 fibroblasts were cultured in type I collagen gel and the effects of tretinoin (all-trans-retinoic acid) were examined on cell growth and the gel contraction produced by cells. Cell proliferation was suppressed and the degree of gel contraction was enhanced by the addition of 10−7 and 10−6 M tretinoin. Growth and gel contractility of transformed cells derived from the Balb 3T3 cells were not influenced by this agent. Addition of 12-O-tetradecanoylphorbol ester, which is known to antagonize tretinoin in several biological processes, enhanced gel contraction synergistically with tretinoin. These results suggest that tretinoin influences cell-to-collagen interactions.

A primary adenoid cystic carcinoma of the skin is reported. Light microscopy revealed pseudocysts. PAS-positive basement membrane and true glandular lumen, which in aggregates are specific for adenoid cystic carcinoma. Perineural invasion was also observed. Ultrastructural examinations revealed three types of cystic spaces; pseudocysts, true glandular lumens and intercellular spaces. Enzyme histochemical examinations showed positive reactions for eccrine enzymes, including phosphorylase and succinic dehydrogenase and negative for apocrine enzymes. Immunolocalization of collagens and laminin revealed that basement membranes of the pseudocysts involve Type V collagen as well as Type IV collagen and laminin.

Three patients with subungual exostoses, two involving the great toe and one the fourth toe, are presented. Local excision was performed, and the specimens were processed for light and electron microscopy. Light-microscopic study revealed that the tumours consisted of a proliferative fibrocartilaginous cap that merged into mature trabecular bone at its base. Electron-microscopic examination revealed that the tumour was composed of two types of cells: one was rich in cell organelles including rough endoplasmic reticulum, well-developed Golgi apparatus, and glycogen granules; the other cell had few such cell organelles. The former cells seemed to be osteoblasts actively engaged in bone formation, and the latter to be osteocytes related to those situated deeper in bone matrix in normal bone. However, ossification or calcification in subungual exostosis is rather casual, and osteocytes in this disorder may lack the capacity to elaborate compact bone.

A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma.

The proliferation and cell cycle phase composition of human dermal fibroblasts cultured on or in type I collagen lattices (reconstituted dermis model) were examined. On collagen lattices, as compared with conventional cultures on plastic dishes, the proliferation of human dermal fibroblasts was suppressed, being arrested at about one-half the saturation density after 10 days of culture. In collagen lattices, proliferation was further suppressed, being nearly arrested within 4-7 days of culture. Cells were analyzed for cell cycle phases by two-color flow cytometry using DNA staining and S phase cell staining with FITC-conjugated antibromodeoxyuridine antibody. After 5 days of culture, the number of S phase cells on collagen lattices was 49.3% of that on plastic dishes, with an increase in G0G1 phase cells of 79.8%. In collagen lattices, the number of S phase cells was very small (4.3% of all cells), and most of the cells accumulated in G0G1 phase. These findings suggest that the cell cycle of fibroblasts is arrested at G0G1 phase by their interaction with collagen. On the basis of these results, the reconstituted dermis model using collagen lattice is considered to be analogous to the dermis in vivo with respect to cell growth and cell cycle phase composition.

To elucidate the interaction between melanoma and its matrix, we cultured B16 murine melanoma cells on and in type I collagen gel and evaluated specified functions of melanoma cells; tyrosinase activity and melanin-synthesizing capacity. Proliferation of cells cultured in these environments was markedly suppressed compared with that of cells cultured conventionally on plastic. On the other hand, the tyrosinase activity of cells cultured in or on collagen gel was two to three times higher than that of cells cultured on the plastics, while their melanin production was approximately double that achieved during conventional culture of cells. In conclusion, collagen gel influenced the growth and cell-specific functions of the melanoma cell. The culture system using collagen gel as substrate may be useful for the investigation of the interaction between melanoma and its matrix.

Four types of fibroblastic cell lines at various stage of differentiation, which had been derived from syngeneic mice, were cultured in collagen lattices (reconstituted dermis model). Lattice contraction, growth in the lattice, and cell morphology were compared. The following cell lines were used: [I] precrisis cells within several subcultures derived from the skin of Balb/c mice, [II] an established normal cell line derived from syngeneic mice (Balb/3T3 clone A31), and [III] two transformed lines (Balb/3T12-3, 3T3-B-SV40) originating from [II]. The cells adopted a bipolar spindle form in the collagen lattice. Lattice contraction was the most marked with cell type [I] followed in order by [II] and [III]. Relative growth in the lattice occurred in the reverse order (III greater than II greater than I). These findings suggested a correlation between lattice contraction and growth in the lattice and also between the extent of differentiation and lattice contraction.

Human dermal fibroblasts were cultured in a hydrated type I collagen lattice. When collagen fibers were arranged in one direction, fibroblasts were arranged in the same direction. Cell proliferation was markedly suppressed in the collagen lattice as compared with that on plastic, with growth being arrested after day 5. No differences in proliferation were observed between aligned cells and randomly oriented cells. Flow cytometry with DNA staining was performed to analyze each phase of the cell cycle of fibroblasts. Among the 10,000 cell population, S phase cells on day 2 of culture accounted for 43% on plastic but were markedly inhibited to 25% in the lattice. On day 4, S phase cells accounted for 33% on plastic but only for 10% in the lattice. These findings suggest that cell advancement to the S phase is markedly inhibited in the collagen lattice, resulting in accumulation of most of cells in the G0G1 phase. The present study clearly showed that culture in the collagen lattice allowed alignment of fibroblasts with a definite orientation as observed in vivo and produced a status resembling that in vivo in terms of proliferation and cell cycle phase composition.