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Biomedical subjects

T S Yen

Publications and source records attributed to T S Yen.

At least 19 recordsLinked to original sources

Cytomegalovirus peritonitis in a patient with the acquired immunodeficiency syndrome.

Peritonitis has been reported infrequently in patients with the acquired immunodeficiency syndrome (AIDS). Intestinal or colonic perforation resulting from cytomegalovirus (CMV) enteritis is the most common cause of peritonitis in these patients. We report a patient with CMV peritonitis occurring in the absence of perforation (primary peritonitis) to alert physicians to this potentially treatable disorder.

Abdominal Pain

Congenital defect in sinusoidal smooth muscles: a cause of organic impotence.

We report 2 cases of primary impotence due to a congenital defect in the compliance of the sinusoidal spaces secondary to fibrosis and atrophy of the smooth muscles. Both patients were young adults at presentation. Diagnosis of this rare entity was achieved by penile Doppler ultrasound and cavernosometry/cavernosography of the cavernous bodies. Both patients underwent placement of a penile prosthesis, during which biopsy samples of the cavernous tissue were obtained, and diagnosis was confirmed by light and electron microscopy.

Adult

Chronic verrucous varicella-zoster virus infection in patients with the acquired immunodeficiency syndrome (AIDS). Histologic and molecular biologic findings.

Verrucous skin lesions have been attributed to various herpes viruses in immunosuppressed patients, including those with human immunodeficiency virus infection (HIV). We examined such lesions from six HIV-infected patients to determine the range of microscopic findings present and to establish which herpesviruses were present. Verrucous epidermal hyperplasia, pseudocarcinomatous hyperplasia, and massive hyperkeratosis correlate with the warty clinical appearance of the lesions. Herpetic cytopathic changes, including multinucleated epidermal giant cells, steel-gray nuclei, necrotic acantholytic keratinocytes, and Cowdry type A nuclear inclusions were seen most prominently in the dells between papillations and in adnexal epithelium. In two cases, increased numbers of spindled cells were seen in the dermis. Immunoperoxidase staining with anti-type IV collagen antibodies demonstrated that these findings were not those of Kaposi's sarcoma, but represent a fibrotic reaction to the infection. Viral cultures of four of the cases demonstrated the presence of varicella-zoster virus, whose presence was detected by the polymerase chain reaction in paraffin-embedded lesional tissue from all six cases. Polymerase chain reaction did not show the presence of cytomegalovirus, herpes simplex, Epstein-Barr, or human papillomavirus. We conclude that these unusual verrucous lesions are a chronic manifestation of herpes zoster infection and that the reported presence of other agents in such lesions is probably coincidental.

Acquired Immunodeficiency Syndrome

Metastasis-associated alterations in phospholipids and fatty acids of human prostatic adenocarcinoma cell lines.

Metastatic variants of human prostatic adenocarcinoma cell lines (DU-145, LNCaP, and ND-1) were studied by using soft agar colony forming efficiency, nude mice tumorigenicity, in vitro invasion assay, and type IV collagenase assay. The DU-145 and ND-1 cell line showed higher metastatic potential than LNCaP. Lipids from DU-145, ND-1, and LNCaP cells were extracted and analyzed by thin-layer chromatography and gas-liquid chromatography. The major lipids were phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, fatty acids, and cholesterol. The sphingomyelin level was significantly higher in highly metastatic cells (DU-145 and ND-1) compared with the lower metastatic variant (LNCaP). The increase in the synthetic pathway and decrease in degradation pathway of sphingomyelin in microsomal fractions was sufficient to account for the measured increase in sphingomyelin in DU-145 cells compared with LNCaP cells. The major fatty acids of these lipids were palmitic (16:0), stearic (18:0), oelic (18:1), and arachidonic acid (20:4). The arachidonic acid level was significantly decreased in DU-145 and ND-1 compared with LNCaP cells. Electron microscopic studies showed no significant changes in the morphology of DU-145, ND-1, and LNCaP cells. The results of these investigations demonstrate for the first time that sphingomyelin and arachidonic acid contents are different in high and low metastatic variants of human prostatic adenocarcinoma cell lines.

Adenocarcinoma

Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus.

To investigate the status of urinary kallikrein excretion (UKE) in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years), comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/- 5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours. Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years), comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients were further divided into two groups. Group A (n = 21) had regular blood sugar control, while Group B (n = 9) had poor blood sugar control. The autonomic nervous function was tested in 15 patients to study its relationship with UKE. UKE was measured by spectrophotometric assay of the kallikrein enzymatic product on the synthetic substrate S-2266. Autonomic function was evaluated by cardiovascular reflex tests. The results showed that UKE was elevated in Group B, but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/- 2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/- 0.04 nkat. mL/day.minute). There was no significant correlation between UKE or the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood pressure change. These results suggest that NIDDM patients have abnormal urinary kallikrein excretion levels that are influenced by blood sugar control. The abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal kallikrein-kinin system exists in NIDDM patients.

Adult

Biochemical, cytogenetic, and morphological characteristics of human primary and metastatic prostate cancer cell lines.

Metastatic properties of human prostatic cancer cell lines (ND-1 and DU-145) were examined using various biochemical techniques. DU-145 cells had a higher metastatic potential than ND-1 cells. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with considerable structural rearrangement. ND-1 cells had a modal chromosome number range lower than DU-145 cells (45-66, compared to 54-62). Ploidy analysis revealed that DU-145 cells showed hyperdiploidy with a greater amount of proliferation than the majority of ND-1 cells. Electron microscopic studies revealed little change in the cell morphology of either line. DU-145 cells had lower phosphatidyl choline levels and higher sphingomyelin levels than ND-1. DU-145 cells had much lower arachidonic acid levels than ND-1 cells. SDS-polyacrylamide gel electrophoresis revealed protein differences between the two cell lines. This study demonstrates for the first time that lipids, proteins and cytogenetic parameters differ in human primary and secondary prostate cancer cell lines.

Adenocarcinoma

Selective cutaneous hyperpigmentation in mice following zidovudine administration.

BACKGROUND AND DESIGN: C57BL/6N mice fed zidovudine in their drinking water develop selective hyperpigmentation of the tails and footpads. Zidovudine-fed and identical control mice were observed and sequential biopsy specimens were obtained. Routine light microscopy, electron microscopy, and image analysis of unstained biopsy specimens were used to evaluate the extent, nature, and amount of cutaneous hyperpigmentation. RESULTS: Beginning at day 14 selective hyperpigmentation of the tails and footpads of the mice was noted. Histologic evaluation revealed a gradual increase in melanin, beginning in the lower levels of the epidermis, with eventual pigmentation of the stratum corneum. Electron microscopy demonstrated a sixfold increase in melanosomes in the tail skin of the zidovudine-fed mice. Using image cytometry, melanin was quantitatively shown to increase, paralleling the clinically apparent hyperpigmentation. The hyperpigmentation was reversible on discontinuation of zidovudine. CONCLUSIONS: This animal model parallels the human in developing reversible and selective hyperpigmentation on administration of zidovudine. In this model the increased pigmentation is due to increased numbers of melanosomes within epidermal keratinocytes. Image cytometry may be useful in semiquantitatively studying the pathogenesis of various disorders of hyperpigmentation.

Animals

The hepatitis B virus S promoter comprises A CCAAT motif and two initiation regions.

The hepatitis B virus S (major surface gene) promoter is embedded in two overlapping open reading frames and specifies several transcripts with heterogeneous 5' termini. We have identified the cis-elements necessary for S promoter function. A single upstream CCAAT element is essential for high level expression in both liver and non-liver cells. No TATA box is present, but two regions surrounding the initiation sites can function separately as initiating elements. These results show that the S promoter has a simple requirement for upstream activating sequences, but a complex initiation region. Therefore, it may provide a suitable model system for studying transcription initiation in non-TATA type promoters.

Base Sequence

High-protein ascites in patients with the acquired immunodeficiency syndrome.

Diseases of the liver or peritoneum resulting in ascites have been infrequently reported in patients with the acquired immunodeficiency syndrome. Since 1985, eight noncirrhotic patients with the acquired immunodeficiency syndrome presenting with new onset high-protein ascites have been evaluated. All but one patient had nondiagnostic paracentesis studies. Laparoscopy with biopsy of identified abnormalities or percutaneous omental biopsy were diagnostic in four patients. Non-Hodgkin's lymphoma was the cause in three patients, and disseminated cryptococcosis occurred in one patient. In the four other patients, chronic nonspecific peritonitis was found at laparoscopy; follow-up of these latter patients, including exploratory laparotomy in one patient and autopsy in two patients, disclosed no specific cause. Patients with the acquired immunodeficiency syndrome and high-protein ascites of uncertain etiology should undergo directed peritoneal evaluation as a potentially treatable disorder may be found. However, despite extensive evaluation, a subset of patients in whom no specific cause can be identified still remains.

Acquired Immunodeficiency Syndrome

Midgestational excisional fetal lamb wounds contract in utero.

Clinical observations and experimental data suggest that fetal wound healing is very different from adult wound healing. An understanding of the biology of scarless fetal wound healing has tremendous clinical potential for modulating postnatal wound problems. In this study, the fetal lamb model was used to assess excisional fetal skin wound contraction in utero. Full-thickness 9-mm punch biopsy wounds were created on fetal lambs at 100 days' gestation (term, 145 days). Half of the wounds remained exposed to amniotic fluid, whereas the other half were covered by a silastic patch to exclude amniotic fluid. Wounds were harvested 3, 7, or 14 days later and wound areas were calculated. Exposure to amniotic fluid retarded wound contraction significantly at 3 days, but by 14 days all wounds had completely contracted and reepithelialized. Myofibroblasts are an important cellular element of wound contraction. The presence of wound myofibroblasts was documented by both transmission electronmicroscopy and immunocytochemistry with antimuscle actin antibody. It is concluded that fetal lamb wounds contract in utero and exposure to amniotic fluid appears to retard fetal skin wound contraction only during the early healing process.

Amniotic Fluid

Leaky transcription termination produces larger and smaller than genome size hepatitis B virus X gene transcripts.

The genomic DNA of hepatitis B virus (HBV) is circular and has only one known transcription termination site. The HBV X protein coding sequence is flanked by this transcription termination site at the 3' end and a promoter element at the 5' end. Transcription initiating from the X promoter and terminating at the termination site would produce a transcript 0.7 kb in length, which we have detected in cell lines that produce HBV particles. Unexpectedly, a 3.9-kb transcript containing two copies of the X gene sequence was also detected in these cell lines. Polymerase chain reaction analysis indicates that this 3.9-kb transcript contains sequences from both upstream and downstream of the termination site. Thus, transcription of this 3.9-kb transcript initiates from the X promoter, reads through the termination site, and terminates the second time it encounters the site. Analysis using an SV40-derived vector indicates that the transcription termination site in the HBV genome is also leaky for X gene transcription when a heterologous promoter initiates the transcription. Based on these results, the mechanism of how the transcription termination of HBV mRNA is regulated is discussed.

Animals

Identification of herpes simplex virus DNA in lesions of erythema multiforme by the polymerase chain reaction.

An association between erythema multiforme and herpes simplex virus infection has been supported by clinical studies and by the detection by immunofluorescence of herpes viral antigen in sera and skin biopsy specimens of patients with erythema multiforme. In rare cases, the virus has also been isolated in cultures of skin biopsy specimens of erythema multiforme. To investigate further the association between erythema multiforme and herpes simplex virus, we used the polymerase chain reaction for herpes simplex virus to examine skin lesions from patients with erythema multiforme. In this study herpes simplex virus DNA was detected in 11 of 31 biopsy specimens of erythema multiforme; six additional cases showed equivocal amplification results, which is suggestive of low amounts of viral DNA. Seven skin and mucosal biopsy specimens with the histologic changes of herpes virus infection served as positive controls: all were positive for herpes simplex virus DNA. Viral DNA was not detected in control biopsy specimens from skin excised for unrelated conditions. These studies support the association of herpes simplex virus in the pathogenesis of some cases of erythema multiforme. The polymerase chain reaction provides a quick and effective method of detecting herpes simplex virus in lesions of herpes-associated erythema multiforme. Furthermore, the polymerase chain reaction may delineate those cases of erythema multiforme that are etiologically related to herpes virus infection and therefore might be treated with acyclovir to prevent recurrence.

Aged

Granulomatous vasculitis occurring after cutaneous herpes zoster despite absence of viral genome.

Granuloma annulare, sarcoidal and other granulomatous dermatitides, pseudolymphoma, lymphoplasmacytoid lymphoma, and Kaposi's sarcoma have been described as sequelae of herpes zoster. We report a new postzoster reaction, granulomatous vasculitis, that caused flat-topped papules restricted to the affected dermatome. Polymerase chain reaction failed to detect varicella-zoster virus in a biopsy specimen. These results suggest that granulomatous vasculitis occurs without persistence of the viral genome and, perhaps, is a reaction to minute amounts of viral proteins.

Adult

Primitive polypoid granular-cell tumor and other cutaneous granular-cell neoplasms of apparent nonneural origin.

Most cutaneous and noncutaneous granular-cell tumors are currently thought to be of Schwann-cell derivation. We present seven unusual cutaneous granular-cell lesions in which Schwann-cell origin can be excluded or is inapparent. Four of these lesions are of a previously undescribed type, and, unlike conventional granular-cell tumors of the skin, show a polypoid configuration, numerous mitoses, cytologic atypia, and a primitive immunophenotype. We propose the term "primitive polypoid granular-cell tumor" for these lesions. One occurred in a child, and three in adults. There have been no metastases to date, with follow-up periods of 2, 4, 4, and 16 years, respectively, although one tumor recurred locally. Additional cases and longer follow-up may be required to rule out the possibility that primitive polypoid granular-cell tumor is a low-grade malignancy. Two other granular-cell lesions represent variants of leiomyosarcoma, one of which widely metastasized. The last case is a granular-cell form of nodular basal-cell carcinoma. Cutaneous granular-cell neoplasms can show varying differentiation and behavior. Pathologists should not equate the occurrence of cytoplasmic granularity in a cutaneous neoplasm with the diagnosis of granular-cell schwannoma.

Adult

Leukocyte filtration removes infectious particulate debris but not free virus derived from experimentally lysed HIV-infected cells.

We used in vitro model of storage-induced leukocyte degradation in blood to experimentally characterize the infectivity of the debris of lymphocytes harboring human immunodeficiency virus (HIV-1). The leukocyte filtration process removed both intact HIV-infected H9 cells and the particulate debris, but failed to remove the cell-free HIV released from lysed cells. These data suggest that the leukocyte filtration of donor blood soon after collection would optimally reduce the particulate infectious burden of blood for transfusions.

Blood Transfusion

Mutual functional antagonism of the simian virus 40 T antigen and the hepatitis B virus trans activator.

The hepatitis B virus X protein (pX) trans activates transcription of a wide variety of viral and cellular genes, apparently by interacting with multiple cellular transcription factors. It has been shown previously that the simian virus 40 early-region gene products (large-T and small-t antigens) prevent trans activation by pX. We show here that this phenomenon can be ascribed solely to the large-T antigen and that T antigen binds to pX in vitro. Mapping studies reveal that the region of large-T antigen around residues 125 and 126 is critical for this binding and also for the ability of T antigen to prevent trans activation by pX. Furthermore, pX in turn interferes with two of the known functions of T antigen, transcriptional trans activation and simian virus 40 DNA replication. We propose that pX and T antigen inactivate each other by forming a nonfunctional complex in vivo.

Animals

The ubiquitous transcription factor Oct-1 and the liver-specific factor HNF-1 are both required to activate transcription of a hepatitis B virus promoter.

The liver-specific transcription factor HNF-1 activates transcription of several mammalian hepatocyte-specific genes. The hepatitis B virus preS1 promoter shows hepatocyte specificity, which has been ascribed to binding of HNF-1 to a cognate DNA sequence upstream of the TATA box. We show here that there is an adjacent site that binds the ubiquitous transcription factor Oct-1. Both the Oct-1 and HNF-1 sites are necessary for liver-specific transcription of the preS1 promoter, but neither site alone activates transcription. The Oct-1 site is also necessary for activation of the preS1 promoter in HeLa cells, expressing transfected HNF-1. Our results show that while Oct-1 is not restricted to hepatocytes, it nevertheless can play a critical role in the expression of a liver-specific gene.

Base Sequence