Search PubMed⌕ Search

Biomedical subjects

M Sacks

Publications and source records attributed to M Sacks.

At least 19 recordsLinked to original sources
PubMed2004

Measles virus: evidence of an association with Hodgkin's disease.

The quest for an infectious agent that may account for cases of Hodgkin's disease (HD) especially in young adults has proven vain until lately. We have recently reported findings that suggested the presence of measles virus (MV) antigens and MV RNA in the tissues of patients with HD. Support for an association between MV and HD has been provided by recent epidemiological findings relating the occurrence of HD to exposure to measles in pregnancy and the perinatal period. We now present further evidence of this putative association based on immunohistochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridisation studies (ISH) on HD tissues. Biopsies from 82 (54.3%) of our cohort of 154 patients showed a positive immunostain with at least two of the anti-measles antibodies used. Latent membrane protein-1 immunostaining for Epstein-Barr virus was positive in 46 (31.1%) of the patients examined. Reverse transcriptase-PCR and ISH for measles RNA were positive in seven and 10 of 28 patients, respectively. Preliminary clinicopathological associations between MV and HD are noted in this study, but no causal relationship can be claimed at this stage.

Adolescent↗
PubMed2003

New candidate virus in association with Hodgkin's disease.

Epidemiologic and molecular investigations of Hodgkin's disease (HD) suggest a strong infectious association. The Epstein-Barr virus (EBV), together with its viral proteins, is expressed in Hodgkin-Reed-Sternberg (HRS) cells in the lymph nodes involved by HD. EBV is more likely to be related to childhood and older adult cases of HD and is much less frequently expressed in young adult HD patients, the group most expected to be associated with an infectious agent. In addition, the "hit and run" theory of EBV infection remains speculative and no other lymphotropic viruses studied to date seem to satisfy the quest for a new candidate virus in young adults with HD. We have recently found preliminary evidence suggesting a possible association between the measles virus (MV) and HD. This evidence is the subject of the present review.

Adolescent↗
PubMed2000

2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism.

An 4-mo-old male was found to have an isolated increase in 2-methylbutyrylglycine (2-MBG) and 2-methylbutyrylcamitine (2-MBC) in physiologic fluids. In vitro oxidation studies in cultured fibroblasts using 13C- and 14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in Escherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female fetus, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.

Amino Acid Metabolism, Inborn Errors↗
PubMed2000

Differential expression of sialyl and non-sialyl-CD15 antigens on Hodgkin-Reed-Sternberg cells: significance in Hodgkin's disease.

CD15 expression has been used for years to confirm the diagnosis of Hodgkin's disease (HD). Little is, however, known on the relevance of the CD15 antigen to the pathobiology of the disease and there is conflicting evidence as to the prognostic value of its expression. To investigate the significance of the differential expression of CD15 in Hodgkin's disease, a retrospective study of 102 patients with "classical" Hodgkin's disease was performed. Immunohistochemical studies were carried out using antibodies against two types of CD15: non-sialylated CD15 (LeuM1 and 80H5) and sialylated CD15 (FH6 and CSLEX1). Cases that were negative for non-sialylated CD15 or positive for the sialylated variant were stained again following neuraminidase pretreatment. The cohort included 27 patients in whom sequential biopsies were available. Both CD15 expression in its non-sialylated form and absence of sialyl-CD15 expression correlate with a favorable outcome. Subsequent biopsies show a preferential expression of sialyl-CD15, notably in bone marrow metastases. Our findings suggest that, in the progression of HD towards a widely disseminated disease, the LewisX moiety of the CD15 antigen on the tumor cells acquires a sialyl-group. This change may confer on the tumor cells the capacity to metastasize.

Actuarial Analysis↗
PubMed2000

Hodgkin's lymphoma in the Bedouin of southern Israel: epidemiological and clinical features.

BACKGROUND: A previous study on Hodgkin's lymphoma in southern Israel found that Bedouin patients had an increased rate of Epstein-Barr virus expression in their tumor cells. OBJECTIVES: To determine the influence of the patients' communities on the pattern of disease in HL. METHODS: We compared the clinical features, demographic data, stage at diagnosis, treatment modality and outcome, as well as laboratory findings, in four community-based subgroups. These groups comprised kibbutz residents (n = 11), Bedouin (n = 19), new immigrants from the former USSR (n = 22), and town-dwellers (n = 82). RESULTS: The Bedouin patients differed significantly from the new immigrants and town-dwellers, particularly regarding the rate of EBV sequences in the tumor tissues, and a poorer response to treatment. The kibbutz patients did not differ significantly from the other populations regarding most of the parameters studied, but showed an intermediate expression of EBV antigens compared to Bedouin patients and the rest of the cohort. CONCLUSIONS: This study indicates that HL may behave differently in different population groups in a given geographic area. Notably, the Bedouin patients showed markedly different clinical and biological patterns of this malignancy.

Adolescent↗
PubMed1999

Mechanisms of bioprosthetic heart valve failure: fatigue causes collagen denaturation and glycosaminoglycan loss.

Bioprosthetic heart valve (BPHV) degeneration, characterized by extracellular matrix deterioration, remodeling, and calcification, is an important clinical problem accounting for thousands of surgeries annually. Here we report for the first time, in a series of in vitro accelerated fatigue studies (5-500 million cycles) with glutaraldehyde fixed porcine aortic valve bioprostheses, that the mechanical function of cardiac valve cusps caused progressive damage to the molecular structure of type I collagen as assessed by Fourier transform IR spectroscopy (FTIR). The cyclic fatigue caused a progressive loss of helicity of the bioprosthetic cuspal collagen, which was evident from FTIR spectral changes in the amide I carbonyl stretching region. Furthermore, cardiac valve fatigue in these studies also led to loss of glycosaminoglycans (GAGs) from the cuspal extracellular matrix. The GAG levels in glutaraldehyde crosslinked porcine aortic valve cusps were 65.2 +/- 8.66 microg uronic acid/10 mg of dry weight for control and 7.91 +/- 1.1 microg uronic acid/10 mg of dry weight for 10-300 million cycled cusps. Together, these molecular changes contribute to a significant gradual decrease in cuspal bending strength as documented in a biomechanical bending assay measuring three point deformation. We conclude that fatigue-induced damage to type I collagen and loss of GAGs are major contributing factors to material degeneration in bioprosthetic cardiac valve deterioration.

Animals↗
PubMed1999

Apoptotic index as a prognostic factor in Hodgkin's disease.

Hodgkin's disease (HD) is an unusual malignant neoplasm, mainly because of the rarity of tumor cells in the diseased tissues, but also due to a relatively favorable response to treatment. In a previous study, we have shown a variable degree of apoptosis in lymph nodes from HD patients. We now looked for clinicopathological correlations of apoptosis with special emphasis on the prognosis in this disease. A retrospective study of 92 patients was carried out, using in situ end labelling of DNA fragments and an apoptosis detection kit. An apoptotic index (Al) was calculated in each case, as the percentage of apoptotic Hodgkin-Reed-Sternberg cells out of the total number of tumor cells in 10 selected high power fields. An association between a high Al and advanced stages was noted. A Kaplan-Meier analysis showed a negative correlation between Al and survival (p=0.05). In a multivariable analysis adjusting for Ann Arbor stage, a high Al carried a 3.27 fold risk of dying of HD (OR=3.27; Cl=0.89-11.94). However, in our limited cohort of HD patients, Al was not an independent prognostic factor. The results of this study confirm the important role played by apoptosis in HD and suggest that the apoptotic index is probably a negative prognostic marker in this disease. Its assessment in patients with HD may provide a new, important clinical tool.

Adult↗
PubMed1998

Silica-induced pulmonary inflammation in rats: activation of NF-kappa B and its suppression by dexamethasone.

The goal of this study was to examine the relationship of the transcriptional regulatory factor nuclear factor-kappaB (NF-kappa B) to the early inflammatory events involved with silica exposure. Male F-344 rats received an intratracheal (i.t.) instillation of silica (100 mg/kg in a volume of 1 ml/kg) of saline. At 1, 3, 6, and 18 h postinstillation, and the rats were sacrificed and underwent bronchoalveolar lavage (BAL) for functional analysis of inflammation. Beginning at 1 h postinstillation, the silica-instilled (Si) rats displayed significant increases in neutrophils in BAL fluid compared to the saline controls. BAL cells from the Si group displayed a significant increase in luminol-dependent chemiluminescence (LDCL) compared to the controls. NF-kappa B activation was measurable at 3 h postinstillation, and this activation continued throughout the 18-h time course. Treatment with dexamethasone (5 mg/kg) at -3 h prior to silica instillation, at the time of instillation (0 h), and +1.5 h postinstillation resulted in both a reduction in NF-kappa B expression (by 70%) at 3 h postinstillation and corresponding reductions in LDCL, BAL cell count, and BAL neutrophils. These results show that activation of NF-kappa B is associated with silica-induced pulmonary inflammation, and the inhibition of its activation correlates temporally with suppression of inflammation.

Animals↗
PubMed1995

HIV-related cases among 2,094 admissions to a psychiatric hospital.

OBJECTIVE: Admissions to an acute care psychiatric hospital were studied to determine what proportion of admissions were for HIV-related psychiatric disturbances, what evidence exists that the HIV-related admissions constitute a new population of psychiatric inpatients, and whether any psychiatric variables distinguish patients with HIV-related disorders from patients without such disorders. METHODS: Charts for 2,094 consecutive admissions to the hospital in a three-year period were reviewed. Chi square analyses and t tests were used to compare various groups of HIV-related admissions and non-HIV-related admissions on sociodemographic characteristics, length of stay, history of psychiatric hospitalization, and other clinical measures. RESULTS: One-hundred and sixty-three admissions (7.8 percent of the total admissions) were judged to be HIV related. The largest category of HIV-related admissions, nearly half, were patients experiencing functional or psychological complications of HIV infection or risk. AIDS-phobic patients, who expressed irrational concerns about infection, accounted for 20.2 percent, and patients with organic manifestations for 18.4 percent. If the AIDS-phobic, HIV-bereaved, and factitious HIV-positive admissions were excluded, the rate of HIV-related admissions was 5.2 percent. CONCLUSIONS: Psychiatric hospitals can expect a significant but not overwhelming number of HIV-related admissions.

Adolescent↗
PubMed1994

Gamma/delta T-cell lymphoma involving the subcutaneous tissue and associated with a hemophagocytic syndrome.

A case of gamma/delta-positive T-cell lymphoma localized primarily in the subcutaneous adipose tissue and associated with an extensive hemophagocytic syndrome and a rapid, fatal outcome is presented. Previous reports of gamma/delta cutaneous and subcutaneous T-cell lymphomas are reviewed. To define the characteristics of a T-cell subset of neoplastic cells bearing the gamma/delta receptor in a subcutaneous lymphoma, we undertook clinical and laboratory examinations, morphological evaluation of biopsies, electron microscopy, and extensive immunohistochemical studies. Immunohistochemical studies showed that the neoplastic cells expressed the gamma/delta T-cell receptor (CD3+, C gamma M1+) and were CD2+, CD43+, CD45+, CD45RO+, PCNA+, but were beta F1-, CD1-, CD4-, CD8-, CD15-, CD20-, CD25-, CD30-, CD45R-, CD57-, CD68-, Mac 387-, and HLA Dr-. To the best of our knowledge, this is the first report of a subcutaneous T-cell lymphoma of gamma/delta type involving the subcutaneous tissue and associated with a hemophagocytic syndrome.

Adipose Tissue↗
PubMed1994

Undetected HIV infection among patients admitted to an alcohol rehabilitation unit.

Of 300 patients admitted to an alcohol rehabilitation unit, serological testing of discarded admission blood samples revealed that 31 (10.3%) had HIV infection. Chart records indicated that four patients were known to be HIV infected on admission, and HIV infection was detected in another three patients during hospitalization; however, 24 (77.4%) of the HIV-positive patients were discharged with their HIV infection still undetected.

Adult↗
PubMed1994

Effectiveness in psychiatric care. III: Psychoeducation and outcome for patients with major affective disorder and their families.

This hypothesis-generating study had the objective of dissecting the process of psychiatric care in an attempt to understand outcomes for patients and their families. In all, 24 patients who carried a DSM-III diagnosis of major affective disorder were identified 12-18 months after hospital admission. The patients, their families, and their doctors were interviewed using instruments measuring delivery of treatment and achievement of treatment goals; findings were then correlated with resolution of the index episode and patient global outcome. Delivery of patient and family psychoeducation was associated with better resolution of the index episode and better global outcome.

Depressive Disorder↗
PubMed1992

Undetected HIV infection among acutely ill psychiatric inpatients.

Serological testing of waste bloods revealed that 25 (7%) of 350 acutely ill psychiatric inpatients had HIV infection. Eight of the 10 HIV-positive patients whose serological status was not recorded on admission were discharged with their status still unrecorded and presumably undetected. Thirty-nine (51%) of the 77 inpatients with HIV-related risk behaviors identified on admission were discharged with no record of their having been serologically tested before or during hospitalization.

AIDS Serodiagnosis↗
PubMed1992

The ethical man.

Sorting out the painful dilemmas of medicine is an everyday duty for Stanford Medical School's biomedical ethicist Ernle Young.

California↗
PubMed1992

Effectiveness in psychiatric care: IV. Achieving effective medication management for major affective disorder.

Although effective medications for the treatment of Axis I disorders have been developed, achieving adequate, let alone, optimal medication regimens has been difficult. This hypothesis-generating study had the objective of dissecting the process of medication-management among 24 previously hospitalized affective disorder patients, their families, and their doctors in Italy, Japan, and the United States as well as identifying their outcomes. The data demonstrated significant positive associations between outcome and delivery of adequate medication as well as psychoeducation (about the illness and its treatment) to both patient and family. These results suggested that, regardless of country, medication was necessary but insufficient without the practitioner delivering a family intervention and psychoeducation.

Affective Disorders, Psychotic↗