[Subcutaneous sparganosis: a case report].

This case report presents the diagnosis and treatment of a case with subcutaneous sparganosis.

Genomic FHIT analysis in RER+ and RER- adenocarcinomas of the pancreas.

Alterations of the candidate tumor suppressor gene FHIT have been reported in multiple tumor types, including pancreatic carcinoma. The mechanism of FHIT genomic inactivation is unusual, most frequently occurring by homozygous deletion, whereas only rare cases have missense mutations. Altered (shortened) transcripts and reduced protein expression are reported, but a genetic basis for these is often inapparent. We studied FHIT genomic alterations of pancreatic carcinomas. Loss of heterozygosity (LOH) was found in 41% of 93 carcinomas without microsatellite instability (RER(-)), but no mutations were found by genomic sequencing. Homozygous deletions inside the FRA3B fragile site were found in four RER(-) tumors, but only two affected the FHIT coding region. In contrast, FHIT alterations were found in the three RER(+) pancreatic carcinomas screened; two had FHIT homozygous deletions affecting exon 5 and the third had a heterozygous missense mutation (H76N). The excess occurrence of homozygous deletions at this site in RER(+) pancreatic cancers is statistically significant (P < 0.01). Since homozygous deletions have not previously been reported in RER(+) carcinomas at any genomic site, an extremely high rate of site-specific deletion must exist within the FRA3B-related FHIT gene. Consequently, the paucity of documented inactivating point mutations cannot be used to judge the presence or absence of putative FHIT-related selective pressures that act during tumorigenesis of RER(-) neoplasia. Nonetheless, the identification of a heterozygous mutation as the sole sequence abnormality might raise doubt as to whether strong selective pressures are afforded by FHIT genomic inactivation in this tumor type. Genes Chromosomes Cancer 27:239-243, 2000.

Novel homozygous deletions of chromosomal band 18q22 in pancreatic adenocarcinoma identified by STS marker scanning.

The identification of homozygous deletions in sporadic neoplasms has been pivotal in the positional cloning of several tumor suppressor genes. Chromosomal arm 18q harbors the DPC4, SMAD2, and DCC genes and is suspected on the basis of high frequencies of allelic loss to harbor additional tumor suppressor genes. We applied high-resolution sequence-tagged site (STS) marker scanning to a panel of 106 pancreatic adenocarcinomas to identify novel regions of homozygous deletions on 18q. Three homozygous deletions were identified. Physical mapping of these deletions showed them to be nonoverlapping, but clustered in an approximately 7- to 10-Mb region of chromosome band 18q22. Each deletion spanned physical distances of nearly 1.3 to 3 Mb. A number of transcribed genes map within these deletions. The identification of these homozygous deletions might aid in the identification of novel tumor suppressor genes on chromosomal arm 18q. Genes Chromosomes Cancer 25:370-375, 1999.

Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers.

Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder characterized by hamartomatous polyps in the gastrointestinal tract and by pigmented macules of the lips, buccal mucosa, and digits. Less appreciated is the fact that PJS also predisposes patients to an increased risk of gastrointestinal cancer, and pancreatic cancer has been reported in many PJS patients. It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS. We investigated the role of STK11/LKB1 in the development of pancreatic and biliary cancer in patients with and without the PJS. In a PJS patient having a germline splice site mutation in the STK11/LKB1 gene, sequencing analysis of an intestinal polyp and pancreatic cancer from this patient revealed loss of the wild-type allele of the STK11/LKB1 gene in the cancer. Inactivation of STK11/LKB1, by homozygous deletions or somatic sequence mutations coupled with loss of heterozygosity, was also demonstrated in 4-6% of 127 sporadic pancreatic and biliary adenocarcinomas. Our results demonstrate that germline and somatic genetic alterations of the STK11/LKB1 gene may play a causal role in carcinogenesis and that the same gene contributes to the development of both sporadic and familial forms of cancer.

High-resolution deletion mapping of chromosome arm 1p in pancreatic cancer identifies a major consensus region at 1p35.

Chromosomal arm 1p has long been suspected, on the basis of loss of heterozygosity (LOH) and other data, to harbor a tumor suppressor gene important in pancreatic carcinomas and other tumors. We constructed a high-resolution map of LOH at I p in a panel of pancreatic adenocarcinomas. Using 44 markers, we identified LOH on I p in 49% of 43 cancers. Breakpoints in 1p were identified in 15 of the carcinomas and could be used to ascertain consensus patterns. We found a major consensus region of LOH at 1p35 between loci D1S233 and D1S247. This region participates in the majority of LOH events on 1 p in pancreatic cancer. These data provide a roadmap for further regional mapping, homozygous deletion searches, comparison to LOH patterns seen in other tumor types, and prioritization of studies using candidate genes.

Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene.

Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a component of a stress and cytokine-induced signal transduction pathway involving MAPK proteins. The MKK4 protein has been implicated in activation of JNK1 and p38 MAPK on phosphorylation by conserved kinase pathways. A recent report on the deletion and mutation of the MKK4 gene in human pancreatic, lung, breast, testicle, and colorectal cancer cell lines suggests an additional role for MKK4 in tumor suppression. Both the gene function and the infrequency of mutations might be considered atypical for many human tumor suppressor genes, and constitutional DNA was not previously available to determine whether the reported sequence variants had preceded tumor development. Here, we report that homozygous deletions are detected in 2 of 92 pancreatic adenocarcinomas (2%), 1 of 16 biliary adenocarcinomas (6%), and 1 of 22 breast carcinomas (when combined with reported sequence alterations, 3 of 22 or 14%). In addition, in a panel of 45 pancreatic carcinomas prescreened for loss of heterozygosity, one somatic missense mutation of MKK4 is observed and confirmed in the primary tumor (2%). Mapping of the homozygous deletions further indicated MKK4 to lie at the target of deletion. The finding of a somatic missense mutation in the absence of any other nucleotide polymorphisms or silent nucleotide changes continues to favor MKK4 as a mutationally targeted tumor suppressor gene. Coexistent mutations of other tumor suppressor genes in MKK4-deficient tumors suggest that MKK4 may participate in a tumor suppressive signaling pathway distinct from DPC4, p16, p53, and BRCA2.

Evaluation of combined assays of serum ferritin, alpha-1-antitrypsin and alpha-fetoprotein in liver cancer.

Serum ferritin (SF), alpha-1-antitrypsin (AAT) and alpha-fetoprotein (AFP) were examined preoperatively in 66 patients with intrahepatic space-occupied lesions revealed by B-real time ultrasonography. Elevated SF levels (> 300 micrograms/L in males and > 180 micrograms/L in females), AAT levels (4.2 g/L), and AFP levels (> 20 micrograms/L) were shown in 84%, 71% and 66% respectively of 55 patients with liver cancer. Combined analysis indicates that if all the three tests are negative, liver cancer can be essentially excluded; and positive AFP can rule out hepatic hemangioma. So combined assays of SF, AAT and AFP are valuable in the diagnosis and differential diagnosis of liver cancer.

Histopathology and immunohistopathology of lymph nodes of the first autopsy with HIV positivity in China.

Nineteen lymph nodes of a HIV-positive boy were studied histologically and immunohistologically. According to Stutte's classification of HIV-related lymphadenopathy, 84% of the lymph nodes were at the third or fourth stages in relation to clinical status ARC/AIDS. Lymph follicle atrophy, angiogenesis, histiocytic proliferation and destruction of the normal reticulum frame were observed. Immunohistochemical studies showed most of the remaining lymphocytes to be T cells and changes in the distribution of S-100 positive cells. Ki 1 positive cells existed mainly at the second stage. The significance of these changes is discussed.

[Immunological investigation in hemophiliacs with and without human immunodeficiency virus (HIV) infection].

Immunological studies were carried out in three HIV-seropositive hemophiliacs and the results were compared with those of 26 HIV-seronegative hemophiliacs 18 normal controls. In the three HIV-seropositive hemophiliacs it was demonstrated that there was a decrease in peripheral helper T cells, a fact significantly different from normal controls (P less than 0.05); there was an increase in peripheral suppressor T cells and a decrease in helper to suppressor T cell ratio, another fact significantly different from normal controls (P less than 0.005, P less than 0.002 respectively) as well as HIV-seronegative hemophiliacs (P less than 0.02). In addition, all three HIV-seropositive hemophiliacs had anergy for 1:2000 OT test. It appeared that these immunological abnormalities are the results of HIV infection. The number of peripheral helper T cell and suppressor T cells and the ratio of helper to suppressor cells in the HIV-seronegative hemophiliacs did not differ from those in normal controls. Among 15 HIV-seronegative hemophiliacs tested with 1:2000 OT, only two showed anergy. The findings in our study differed somewhat from those reported abroad. This difference may be due to the fact that our hemophilic patients had been treated with much smaller doses of blood products for alleviating coagulation defects.

PIP: A comparison was made of the immunological function of three HIV seropositive hemophiliacs, 26 HIV-seronegative hemophiliacs, and 18 controls. The 26 HIV-seronegative hemophiliac patients included 13 who had received transfusions of factor VIII and IX concentrates imported to China from the US. Among the three HIV-seropositive hemophiliacs, a lower level of peripheral helper T cells, higher level of peripheral suppressor T cells, and lower ratio between T helper cell and T suppressor cells were observed compared with the controls and the HIV-seropositive hemophiliac group. The differences between the three HIV-seropositive hemophiliacs and the other two groups were statistically significant. In addition, the three cases had no reaction to 1:2000 OT tests. The abnormal immunological functions in the three HIV-seropositive hemophiliacs might be affected by the HIV infection. The number of peripheral helper T cells, the suppressor T cells, and the ratio of helper to suppressor cells in the 26 HIV-seronegative hemophiliacs did not significantly differ from the those of the control group. Among the 15 HIV-seronegative hemophiliacs who were given 1:2000 OT tests, only two had negative reactions. The finding from this study differed from findings of the immunological deficiencies among hemophiliac patients in studies conducted in other countries. This difference may be due to the fact that hemophilic patients in Zhejiang Province, China, were treated with much smaller doses of blood products for alleviating coagulation defects.

Immunologic investigation of Chinese hemophiliacs with and without human immunodeficiency virus infection.

Cellular and humoral immune functions in Chinese hemophiliacs with and without human immunodeficiency virus (HIV) infection were compared with those of healthy controls. There was a significant increase in peripheral T8 cells and a significant decrease of peripheral T4 cells as well as the T4/T8 ratio in 3 hemophiliacs with HIV infection when compared with 26 hemophiliacs without HIV infection and 18 healthy controls (P less than 0.005, P less than 0.05 and P less than 0.002, respectively). In contrast, there were no statistical differences in the above mentioned parameters between hemophiliacs without HIV infection and healthy controls. All the three HIV seropositive hemophiliacs had anergy for 1:2000 OT test whereas among the 15 HIV seronegative hemophiliacs, only two had anergy for 1:2000 OT test. These results demonstrate that the immunological abnormalities of the 3 HIV seropositive hemophiliacs were attributed to HIV infection, and that even though hemophiliacs without HIV infection had been treated with blood products, their immune functions are generally normal. These findings are somewhat different from those reported abroad. This difference may be due to the fact that Chinese hemophiliacs are often treated with much smaller dose of blood products as a part of the treatment of their coagulative defects.

Clinical analysis of four Chinese hemophiliacs with human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) is now considered as the causative agent of acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia who received lyophilized commercial factor VIII and IX concentrates of American origin. At a prevalent survey from September to December 1985, HIV antibodies were found in all four patients with hemophilia treated with the batch number W87307, 955 I.U. of American commercial factor VIII concentrate supplied by Armour Pharmaceutical Company, USA. One of the sero-positive patients developed AIDS-related complex (ARC) and died of cerebral hemorrhage. The other three sero-positive patients had abnormalities in cell-mediated immunity. Of them two developed left lumbosacral radiculopathy and hemorrhagic herpes zoster and one remained well so far.

[Clinical analysis of 4 Chinese hemophiliacs with human immunodeficiency virus infection].

Human immunodeficiency virus (HIV-is) now considered the causative agent of acquired immunodeficiency syndrome(AIDS). A high risk of AIDS has been reported among patients with hemophilia who received lyophilized commercial factor VIII and IX concentrates of American origin. In a prevalence survey conducted from September to December 1985, HIV antibodies were found in all the 4 patients with hemophilia treated with the batch number W87307, 955 I.U. of American commercial factor VIII concentrate supplied by Armour pharmaceutical Company U.S.A. One of the seropositive patients developed AIDS-related complex (ARC) and died of cerebral hemorrhage. The other three sero-positive patients had abnormalities in cell mediated immunity; among them two developed left lumbosacral radiculopathy and hemorrhagic herpes zoster and one remains well so far.

Clinical significance of urine ferritin determination in urologic malignancies.

Urine and serum ferritin levels were measured by a double-antibody radio-immunoassay in 96 normal adults and 57 patients with urologic malignancies. In the 96 adults, the urine ferritin levels ranged from 0 to 28 ng/ml. Elevated urine ferritin levels were observed in all 7 patients with renal pelvic carcinoma, 4 of 13 patients with renal carcinoma, 1 of 13 patients with well-differentiated (Grade I) bladder carcinoma, 8 of 19 patients with median-differentiated (Grade II) bladder carcinoma, and all 5 patients with poorly-differentiated (Grades III, IV) bladder carcinoma. These results indicated that urine ferritin assay was helpful in discriminating well-differentiated bladder carcinoma from the poorly-differentiated (P less than 0.01) in addition to differentiating renal pelvic carcinoma from renal carcinoma (P less than 0.05).

Detection of antibody to LAV/HTLV-III in sera from hemophiliacs in China.

Using ELISA, Western blots and immunofluorescence techniques, we identified seropositivity for lymphadenopathy-associated virus/human lymphotropic virus-III (LAV/HTLV-III) in 4 of 18 hemophiliacs and 1 AIDS patient. The four seropositive patients had received factor VIII prepared by Armour Company. The hemophiliacs are all asymptomatic. Given this documentation of introduction of LAV/HTLV-III into China, a national surveillance program is underway.

PIP: The detection of human immunodeficiency virus (HIV) in hemophiliacs treated with factor VIII has prompted the Government of China to institute a national surveillance program. An earlier survey of 310 healthy individuals and leukemia patients from 8 provinces failed to yield any sera positive for antibodies to HIV. However, given the documented high seroprevalence rate among hemophiliacs, the sera of 28 Chinese hemophiliacs and 1 acquired immunodeficiency syndrome (AIDS) patient were analyzed by enzyme-linked immunosorbent assay (ELISA). Antibodies to HIV were detected in the AIDS patient and in 4 of the hemophiliacs. All 4 of the seropositive cases were from a group of 18 hemophiliacs who had received factor VIII produced by the US-based Armour Company. This suggests that HIV infection was transmitted to China from the US via blood products at a frequency of 22%. At the time of the study, all 4 seropositive hemophiliacs were asymptomatic.