Somatic alterations of the DPC4 and Madr2 genes in colorectal cancers and relationship to metastasis.

The DPC4 and Madr2 genes are located at 18q21, and the LOH on chromosome 18q21 has been shown to occur frequently in colorectal cancers. To investigate the role of these genes in advanced colorectal cancers, we analyzed 29 colorectal specimens for alterations in the DPC4 and Madr2 genes. Twelve (63.2%) of 19 informative primary colorectal cancers showed allelic loss of chromosome 18q21.3 marker. An alteration of the DPC4 gene sequence was identified in 6 (20.7%) of 29 colorectal carcinomas, and the distinct Madr2 gene mobility shifts were present in 3 (10.3%) cancers. Somatic mutations were identified in these tumors by sequencing analysis. DPC4 gene alterations of 4 cases were detected in Mad homology 2 domains. There was no significant correlation between the somatic alteration of Madr2 and clinicopathological findings. However, the frequency of DPC4 mutation was significantly higher in tumors associated with liver metastasis than in those without such metastasis. Our findings suggest that somatic alteration of the DPC4 gene may play a role in tumorigenesis and liver metastasis of human colorectal cancers.

Clinical significance of combined immunohistochemical detection of CD44v and sialyl LeX expression for colorectal cancer patients undergoing curative resection.

To evaluate their prognostic value, the expressions of CD44v and sialyl LeX (SLX) in colorectal cancers were studied immunohistochemically. Tissue specimens were reacted with monoclonal antibodies (mAb) CD44-1V and CSLEX-1. Of the 145 colorectal cancer patients undergoing curative resection, 59 (40.7%) were positive for mAb CD44-1V, and 40 (27.6%) were positive for mAb CSLEX-1. There was a significant correlation between the combined expression of SLX and CD44v8-10 and lymph node metastasis. The patients with tumors negative for CD44v8-10 and SLX had the most favorable prognoses. Conversely, the patients with tumors positive for both CD44v8-10 and SLX had a high recurrence rate and the poorest prognoses. In a multivariate analysis using the Cox regression model, the combined expression of SLX and CD44v8-10 emerged as an independent prognostic indicator. These results suggested that the combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance.

Clinical significance of serum levels of CD44 variant exons 8-10 protein in colorectal cancer.

We examined serum levels of a CD44 splice variant that contained variant exons 8-10 (CD44v8-10) as a tumor marker in colorectal cancer patients. We performed enzyme-linked immunosorbent assays in 81 sera obtained from 71 colorectal cancer patients and 10 healthy controls. Serum CD44v8-10 levels were significantly higher in the colorectal cancer patients than in the healthy controls (0.209 +/- 0.098 versus 0.114 +/- 0.019 OD; P < 0.01). There was a close correlation between immunohistochemical expression and serum CD44v8-10 levels. Surgical resection of the tumors resulted in a reduction of serum CD44v8-10 levels. There was no significant correlation between serum CD44v8-10 level and serosal invasion or histologic type. However, a significant correlation was observed between serum CD44v8-10 level and lymphatic or venous invasion. In addition, serum CD44v8-10 levels were significantly higher in carcinomas associated with lymph node or liver metastasis than in those without metastasis. These findings suggest the usefulness of serum CD44v8-10 level in the prediction of colorectal cancer metastasis.

[Telomerase activity in colorectal carcinoma and its relationship to clinicopathological findings].

Telomerase is thought to be responsible for cell immortality. The telomerase activity in carcinomas has been remarked since 1995. We examined telomerase activity in colorectal carcinoma by TRAP (Telomeric repeat amplification protocol) assay, and investigated its relationship to clinicopathological findings. We could analyse telomerase activities in 33 cases (66%) of 50 colorectal carcinomas, whereas the activity was not found in all 13 cases of noncancerous colorectal mucosa. There was no relation between the telomerase activity and the clinicopathological findings or metastatic status. We confirmed telomerase activities in much of colorectal carcinomas in spite of their progression. The carcinoma cells might be immortal from their early stage of progression by means of telomerase activity.

Significance of tumor marker SLX in colorectal cancer.

We examined serum SLX for its significance as a tumor marker in 109 colorectal cancer patients. There a close correlation with immunohistochemical expression of SLX and serum SLX level. Serum SLX was positive in 16.5% of 109 patients with colorectal cancers. There was no significant correlation between serum SLX level and histologic type or primary tumor status. There were significant correlations between serum SLX positive rates and both lymph node and hematogenous metastasis. In 7 SLX positive cases who underwent curative resection, 4 patients had already recurrence in the liver. Our findings suggest that serum SLX values may be a biologic marker of metastasis.

Immunoglobulins specific to mosquito salivary gland proteins in the sera of persons with common or hypersensitive reactions to mosquito bites.

Using the immunoblot technique, we analyzed the quality and quantity of IgG, IgG4, and IgE specific to mosquito salivary gland (hereafter abbreviate as SG) components of Aedes albopictus in the sera of volunteers with common reactions and of 3 patients with severe reactions. In the volunteers with delayed reactions only or with both delayed and immediate reactions, IgG against SG components of A. albopictus formed several faint or moderately stained bands. Those with immediate reactions showed several intense bands and many other weak bands. In volunteers, who had been bitten by Aedes sp. frequently but had no skin reaction, and in severe cases, many intense IgG bands were observed. IgG4 bound to SG components were found in the sera of the common reaction group at the levels of 24 and 48 kD, but, in one severe case, no bands were observed, although the total IgG was very high. IgE levels specific to SG components were much higher in severe cases than in the volunteers. These results indicate that high titers of specific IgG and IgE and lack of IgG4 for particular components of SG may lead to severe allergic reactions in severe cases. Immunoblotting analysis of the antibodies also verified the possibility of developing in vitro tests to identify causative species of the mosquito for severe cases.

A quantitative study of specific immunoglobulins to mosquito salivary gland antigen in hypersensitive and common types of mosquito bite reaction.

This study was designed with two purposes: first, to elucidate immunologic mechanisms in different cutaneous reactions, particularly in hypersensitivity to mosquito bites, and, second, to develop a more reliable and safer method of identifying the causative species of mosquito in severe cases. The amounts of IgG, IgG4 and IgE specific to the mosquito salivary gland extract of Aedes albopictus were determined in the sera of 116 volunteers with normal reactions, either immediate or delayed, and 4 patients with severe systemic symptoms caused by mosquito bites. Titers of IgG and IgE in the severe cases were considerably higher than in volunteers with normal reactions, but there were no differences in IgG4 titers between the two groups. These results indicate that high titers of IgG and IgE may be involved in development of systemic symptoms in severe cases and verify the possibility of in vitro tests to identify causative species of the mosquito.

[Delusions of parasitosis--report of 94 cases].

The present article describes 94 patients (34 male and 60 female) with delusions of parasitosis, admitted to our dermatology clinic between 1978 and 1989. The female to male ratio was to one under the age of 45, and 1:2.1 over 45. The mean age of onset in males was 46.4 years, and in females, 52.8. In nine patients (6 male and 3 female), the delusions began shortly after their retirement, while in seven (1 male and 6 female) after separation from their families. The ratio of the number of patients living alone to that of patients living with their families was one to two, three times higher than that of the general population (1:6). About half of the patients had no skin lesions, while half the rest had excoriations. Three had eczematous lesions caused by the application of insecticides. In 58 patients, the creatures of delusion were mites. Most patients complained of some kind of cutaneous sensations of the skin, such as itching, tickling and prickling, while only two complained of auditory sensations. The color of creatures of delusion was black or white. Folie á deux was observed in 23 groups and affected both sexes.

[Familial cases of cutaneous myxomas and spotty pigmentation (Carney's complex)].

In 1985, Carney et al reported a complex of myxomas, spotty pigmentation, and endocrine overactivity and subsequently demonstrated dominant inheritance of the condition. The criteria for diagnosis of the complex is the presence of two or more of the following conditions: (1) cardiac myxoma, (2) cutaneous myxoma, (3) mammary myxoma, (4) spotty mucocutaneous pigmentation, (5) primary pigmented nodular adrenocortical disease (Cushing's syndrome), (6) testicular tumors (sexual precocity), (7) pituitary adenoma secreting growth hormone (acromegaly or gigantism). We encountered a family with an affected mother and daughter. Case 1 was a 43-year-old woman with multiple cutaneous myxomas, mammary myxomas and spotty mucocutaneous pigmentation. Case 2, the 19-year-old daughter of case 1 had multiple cutaneous myxomas and spotty cutaneous pigmentation. These two cases both met the criteria for the diagnosis of the complex. Our report is believed to be the first report on the complex in Japan.

Cutaneous reactions caused by experimental exposure to jellyfish, Carybdea rastonii.

Dermatitis caused by contact with tentacles of jellyfish was studied on 25 volunteers. Two tentacles cut from a living jellyfish, Carybdea rastonii, were applied on each of the forearms and skin reactions were observed. All volunteers complained of severe pain, which lasted from 10 min to 8 hrs. Erythema and wheal appeared within 3 to 4 min and enlarged for 15 to 20 min. Erythema subsided within 24 hrs to 3 days in all but two individuals. Seven to 13 days after the application, linear erythema and papulo-vesicular lesions with pruritus were observed on the forearms of 15 out of 25 volunteers tested. These flare-up lesions lasted for one week leaving slight pigmentation. Histological findings from the flare-up lesions corresponded to those of allergic contact dermatitis. The lymphocyte response to the jellyfish venom in the subjects who had recurring lesions was greater than that in either the subjects with no recurring lesions or the control group, who was never exposed to jellyfish.

A study of mosquito salivary gland components and their effects on man.

To evaluate the mechanism of mosquito bite reaction in man, salivary gland extracts from female Aedes albopictus were prepared. When the extract of the gland was analysed by ion-exchange high performance liquid chromatography the amount of histamine in a pair of salivary glands of one mosquito was found to be below the limit of detection, an amount which is insufficient to produce an immediate reaction. Salivary gland extracts were fractionated to higher and lower molecular weight components. Intradermal injection tests with salivary gland extracts, which contained less than 100 ng of protein showed that the higher molecular weight fraction (molecular weight greater than 10,000) elicited an immediate and a delayed reaction similar to a bite reaction.

Clinical observations of mosquito bite reactions in man: a survey of the relationship between age and bite reaction.

To evaluate the mechanism of mosquito bite reaction in man, the reaction to Aedes albopictus was observed in 162 subjects ranging in age between 1 to 68 years old. Bite reactions were found to consist of both an immediate and a delayed reaction. The eruption and time course of the immediate reaction were consistent with type I hypersensitivity. The eruption and time course of the delayed reaction were consistent with cutaneous basophil hypersensitivity. Positive rates of immediate reaction increased from early childhood to adolescence and decreased with age from adulthood. The appearance and intensity of the delayed reaction decreased with age. Mosquito bite reactions in human beings exposed continuously and regularly are known to change from stage 1 to stage 5 (stage 1; no reaction, 2; delayed reaction only, 3; immediate and delayed reaction, 4; immediate reaction only, 5; no reaction). Analysis of the relationship between age and bite reaction in this study indicated that the principle held true even when the exposures were irregular or at random.

A case of secondary syphilis with a solitary pulmonary lesion.

This study describes a case of secondary syphilis with a papular eruption and penile ulceration. A chest roentgenogram showed a solitary lesion in the left middle lung field. Histological examination revealed epithelioid cell granuloma in both the penile ulcer and the lung lesion. After antisyphilitic treatment, the lung lesion shrunk remarkably and at the same time the skin eruption and the systemic symptoms also improved.

Concurrent multiple morphea and neonatal lupus erythematosus in an infant boy born to a mother with SLE.

An infant boy born to a mother with systemic lupus erythematosus developed multiple morphea and annular erythematous lesions. The annular lesions appeared on his face, back, chest and extremities one month after birth and faded within 7 months. The sclerotic lesions progressed until the age of 6 months and remain on his back, chest, right cheek, the nape of the neck and left shoulder at the age of 3 years. Histological findings in the sclerotic lesions were consistent with scleroderma. Serological tests, performed at 14 months of age, were within normal limits. The mother developed acute SLE and died of cardio-renal failure 8 months after the delivery. It is highly probable that maternal factors transferred through the placenta caused the sclerotic lesions in the infant.

Delayed flare-up reactions caused by jellyfish.

Four patients had a recurrence of cutaneous lesions 1 week after being stung by jellyfish. Three patients had flare-up lesions after only one exposure to jellyfish. All of the recurring lesions were vesicular erythema, and the histological findings of case 3 corresponded to that of allergic contact dermatitis.

Immunologic cross-reaction between human and mouse tyrosinases.

Human tyrosinase, partially purified from metastatic malignant melanoma, reacted with antiserum prepared against tyrosinase purified from Harding-Passey mouse melanoma melanosomes, although the human and mouse tyrosinases were not completely identical immunologically. The human tyrosinae showed only one band on disc electrophoresis which corresponded in mobility to T2 tyrosinase of mouse.