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Biomedical subjects

M A Rodriguez

Publications and source records attributed to M A Rodriguez.

At least 73 records · Page 4Linked to original sources
PubMed1998

Stage I Hodgkin disease: radiation therapy and chemotherapy at the University of Texas M. D. Anderson Cancer Center, 1996-1997.

PURPOSE: To summarize 30 years of experience in treatment of and prognosis for stage I Hodgkin disease. MATERIALS AND METHODS: The authors reviewed retrospectively the cases of 196 patients seen and followed up at one institution from 1967 to 1997. All patients were treated with radiation therapy, and 46 also received combination chemotherapy as part of their initial treatment. Radiation therapy techniques included involved or regional-field irradiation in 83 patients, extended field irradiation (mantle or inverted Y) in 74, and subtotal nodal irradiation in 39 (median radiation doses for subclinical and clinical disease were 30 and 40 Gy, respectively, at 1.5-2.0 Gy per fraction). Of 46 patients treated with combination and radiation therapy, 26 received subtotal nodal irradiation; in the remaining 20, chemotherapy was combined with more limited-field radiation therapy. Follow-up ranged from 3 to 356 months (median, 144 months). RESULTS: The actuarial overall survival, disease-specific survival, and freedom from progression at 10 and 20 years were 82% and 66%, 94% and 91%, and 77% and 70%, respectively. In multivariate analysis, age adversely influenced overall survival, and female sex favorably affected freedom from progression. Mixed cellularity histology and mantle field technique adversely influenced disease-specific survival. Laparotomy significantly influenced disease-specific survival but not overall survival. CONCLUSION: Radiation therapy results in an excellent outcome in patients with favorable stage I Hodgkin disease. Pathologic staging is no longer necessary.

Adolescent↗
PubMed1998

Abnormal pattern of tyrosine phosphorylation in unstimulated peripheral blood T lymphocytes from patients with systemic lupus erythematosus.

Previous reports have shown abnormal responses mediated via the TCR/CD3 pathway in T lymphocytes from systemic lupus erythematosus (SLE) patients. Recently, we and others have reported augmented TCR/CD3-mediated responses in lupus T cells. It is possible that the pattern of downstream biochemical signals triggered by TCR/CD3 ligation may be altered in T lymphocytes from patients with SLE, thus leading to abnormal distal cell responses. In this paper we have examined the phosphorylation of proteins on tyrosine residues in peripheral blood T lymphocytes from a group of SLE patients and controls. We found a lower frequency of constitutively tyrosine-phosphorylated 119- and 113-kDa substrates and an enhanced frequency of tyrosine-phosphorylated 66- and 25-kDa proteins in unstimulated cultures of SLE T lymphocytes, suggesting an altered pattern of tyrosine phosphorylation in T cells from patients in vivo. Additionally, the protein tyrosine phosphatase (PTP) activity of CD45 immunoprecipitates was lower in unstimulated lupus T cells and was enhanced after stimulation via the CD3 pathway in lupus but not control T lymphocytes. The present results seem to suggest abnormal regulation of in-vivo tyrosine phosphorylation in T cells from patients with SLE.

Adolescent↗
PubMed1998

Chromosome breaks and sister chromatid exchange as predictors of second cancers in Hodgkin's disease.

Hodgkin's disease (HD) survivors face an increased risk of developing second cancers. We evaluated baseline cytogenetic biomarkers, sister chromatid exchange (SCE) and chromosome breaks [spontaneous (SCB) and bleomycin-induced (BIB)], as predictors of second cancer risk in a cohort of 105 adult HD patients. During follow-up, seven second cancers occurred. SCBs and BIBs showed no association with risk of second primaries. Multivariate Cox regression revealed that high levels of SCEs (relative risk (RR)=11.3, p=0.02) and age (RR=1.08, p=0.02) predicted second cancer risk. Histology, stage, and treatment were not associated with elevated risk. In conclusion, baseline SCE frequencies may be a useful biomarker for identifying HD patients at increased risk of developing second cancers. These results need to be verified in a larger cohort with a longer follow-up time.

Adolescent↗
PubMed1998

Ninety-six-hour paclitaxel infusion with mitoxantrone and ifosfamide/mesna and consolidation with ESHAP for refractory and relapsed non-Hodgkin's lymphoma.

A prospective phase II study was carried out in 48 patients with relapsed or refractory non-Hodgkin's lymphoma using paclitaxel 27.5 mg/M2 i.v. by continuous infusion over 24 hours daily on days 1, 2, 3, and 4 in combination with mitoxantrone 8 mg/M2 i.v. on day 1 and ifosfamide/mesna 1.33 grams/M2 i.v. daily on days 1, 2, and 3 (MINT). Responding patients completed four cycles of MINT and were consolidated with etoposide, solumedrol [methylprednisolone], high-dose cytarabine [Ara-C], and platinum (ESHAP). Forty-eight patients were entered in the study between 1994 and 1996 at The University of Texas M. D. Anderson Cancer Center. Overall response after the first four cycles of MINT was 67% (16% complete response [CR]+ 51% partial response [PR]) and after consolidation with ESHAP it was 49% (26% CR + 23% PR). Variables associated with an improved CR rate and better failure-free survival included the number of prior treatments and the response to prior treatment. A comparison with a similar group of patients treated with mesna, ifosfamide, mitoxantrone, and etoposide (MINE)-ESHAP revealed no major differences in outcome.

Adult↗
PubMed1998

Factors affecting patient-physician communication for abused Latina and Asian immigrant women.

BACKGROUND: Domestic violence is one of today's most serious health issues. Abused Latina and Asian immigrant women face unique barriers to the discussion of abuse with health care providers. This research was undertaken to identify any provider-related factors that may affect patient-provider communication for these women. METHODS: Qualitative data were collected using semistructured focus group interviews with abused Latina and Asian immigrant women. Participants were recruited through urban community-based organizations. Twenty-eight immigrant women with histories of domestic violence participated in four focus groups: two groups of Latina women and two groups of Asian women. Iterative readings by independent researchers identified provider-related factors affecting patient-provider communication. RESULTS: The study participants identified the provider behaviors that demonstrate trust, compassion, and understanding as elements that improve patient-provider communication. In addition, participants wanted providers to initiate discussions about partner abuse. CONCLUSIONS: Improved understanding of factors that may affect abused immigrant patients' communication may assist health care providers in offering meaningful support and assistance to these patients. Providers, administrators, policy makers, and educators should consider these factors when developing policy, protocols, and educational curricula for a variety of health care settings.

Adolescent↗
PubMed1998

Patient attitudes about mandatory reporting of domestic violence. Implications for health care professionals.

As of January 1994, California physicians are required to report to police all patients who are suspected to be victims of domestic violence. This article describes the results from a focus group study of abused women (n = 51) that explored their experiences with and perspectives on medical care. The eight focus groups included two Latina (total n = 14), two Asian (total n = 14), two African-American (total n = 9), and two Caucasian (total n = 14) groups of women who had been the victims of domestic abuse within the previous 2 years. The women were recruited through community-based organizations in the San Francisco Bay Area. With regard to physician reporting of domestic violence to police, five themes were identified: fear of retaliation by the abuser, fear of family separation, mistrust of the legal system, desire for police protection, and preference for confidentiality and autonomy in the patient-health professional relationship. Our results indicate that mandatory reporting may pose a threat to the safety and well-being of abused women and may create barriers to their seeking help and communicating with health care professionals about domestic violence.

Adult↗
PubMed1997

Long-term outcome of treatment for Ann Arbor stage 1 Hodgkin's disease: patterns of failure, late toxicity and second malignancies.

PURPOSE: Radiation therapy results in excellent short-term survival in patients with early-stage Hodgkin's disease. However, the optimal therapeutic scheme that achieves the highest disease-free survival with the minimum long-term toxicity is yet to be determined. An analysis of the patterns of failure and late complications after radiation therapy was conducted to address this question. METHODS AND MATERIALS: A retrospective study was conducted of 145 patients with Stage I Hodgkin's disease treated at M. D. Anderson Cancer Center from 1967 through 1987. Follow-up extended from a minimum of 30 to 339 months, with a median period of observation of 16.5 years. All the patients were treated with radiation therapy and, and 16 received combination MOPP-based chemotherapy as part of their initial treatment. The radiotherapy technique, was involved/regional in 71 (49%), extended in 62 (43%), and subtotal nodal irradiation in 12 patients. The median total dose was 40 Gy. RESULTS: The actuarial freedom from progression at 10 and 20 years was 76% and 69%, respectively. Forty of 145 patients relapsed (27.6%). The site of primary disease was cervical adenopathy in 30 (75%), axillary in 7 (17.5%), mediastinal in 2 patients and subdiaphragmatic in one patient. Twenty-two patients were treated with involved/regional technique (55%), 17 with extended (42.5%), and 1 with subtotal nodal irradiation technique. There were three in field and four marginal recurrences. Six relapses occurred in non-irradiated nodal regions at the same side of the diaphragm and 17 in non-irradiated transdiaphragmatic lymph nodes (57.5%). Nine patients (22.5%) relapsed with visceral disease. Nineteen patients (47.5%) relapsed within the first 2 years, 15 (37.5%) 3 to 10 years after diagnosis and the remaining 6 (15%) after 10 years. Eleven of 40 patients died of disease after the first or subsequent relapses (27.5%). Three of six patients with late relapses had progression in viscera but only two died with disease. Thirty-eight of 145 patients developed late toxicity from the treatment (26.2%). Twenty-three patients experienced ischemic heart disease (15.9%), only 13 of whom received mediastinal irradiation (9%). Fifteen patients developed secondary malignant solid tumors (10.3%). Nine of those (6.2%) occurred within the irradiation field (two were also treated with chemotherapy). Two additional patients, one of whom received chemotherapy as part of the initial treatment, died of acute myelogenous leukemia. Non-Hodgkin's lymphoma and lung cancer were the most common second malignancies. CONCLUSIONS: Limited field radiotherapy results in a significant number of relapses in non-irradiated, especially transdiaphragmatic lymph nodes. Subtotal nodal irradiation can prevent some relapses and therefore improve freedom from progression. Careful design of the treatment fields may decrease the risk of morbidity and mortality from coronary artery disease and second malignancies in early-stage Hodgkin's disease. Careful long-term surveillance may permit early detection and management of late relapses and treatment complications.

Adolescent↗
PubMed1997

Paclitaxel activity for the treatment of non-Hodgkin's lymphoma: final report of a phase II trial.

In order to determine the activity of paclitaxel in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II clinical trial in which eligible patients received paclitaxel 200 mg/m2 intravenously over 3 h. Treatment was repeated every 3 weeks. Patients achieving complete or partial responses after two courses of paclitaxel continued to receive therapy for a maximum of eight courses, otherwise they were removed from the study. Of 96 evaluable patients, 45 (47%) had primary refractory disease, and 51 (53%) had relapsed lymphoma. The median number of prior treatment regimens was two (range one to 10 regimens). 45 patients had lowgrade, 44 had intermediate-grade, and seven had mantle cell lymphoma. 24/96 patients responded (10 complete and 14 partial remissions) for an overall response rate of 25% (95% CI 17-35%). Patients with relapsed lymphoma had a higher response rate than those with primary refractory disease (19/51 = 37% v 5/45 = 11%; P < 0.01), and patients with relapsed intermediate-grade lymphoma had a higher response than those with relapsed low-grade lymphoma (9/18 = 50% v 10/31 = 32%; P = 0.22). The treatment was very well tolerated with the most common side-effects being alopecia (100%), peripheral neuropathy (35% of > or = grade II), and arthralgia/myalgia (25% of > or = grade II). After the first course of paclitaxel, grade III/IV thrombocytopenia and neutropenia were observed in 21% and 23% of the patients respectively. 23 episodes of neutropenic fever developed after 250 courses of paclitaxel therapy (8%). We conclude that paclitaxel, at this dose and schedule, is an active new drug for the treatment of non-Hodgkin's lymphoma. The activity of paclitaxel combination programmes are currently under investigation.

Adult↗
PubMed1997

Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease.

PURPOSE: Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD). PATIENTS AND METHODS: Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy. RESULTS: Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels. CONCLUSION: NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.

Adult↗
PubMed1997

Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants.

PURPOSE: Clinical data and histologic material were retrospectively analyzed in 46 cases of previously untreated mantle cell lymphoma (MCL) to more fully characterize the clinical response pattern of these lymphomas and to determine whether growth pattern significantly affected clinical outcome. MATERIALS AND METHODS: The histologic pattern was classified as diffuse (61%), nodular (13%), and mantle zone (26%) in accordance with stated criteria. RESULTS: Bone marrow infiltration was detected in 69% of cases; the frequency of involvement correlated with histologic pattern, being most common in diffuse variants and least common in mantle zone variants. Other sites of extranodal involvement were observed in 50% of cases. Cyclin-D1 staining revealed nuclear positivity in 23 of 25 patients (92%) and no difference was observed between the various histologic patterns. Rearrangement at the bcl-1 major translocation cluster (MTC) was detected in seven of 21 cases, without regard for histologic pattern. Complete response rates to doxorubicin-based regimens showed a striking correlation with histologic pattern. Seventy-three percent of patients with a mantle zone pattern attained a complete response compared with only 25% of patients with a nodular pattern and 19% with a diffuse pattern. Three-year survival rates were 100%, 50%, and 55% for patients with mantle zone, nodular, and diffuse histologic patterns, respectively. CONCLUSION: We conclude that (1) diffuse and nodular MCL are associated with a poor treatment response and a poor overall survival rate; (2) the mantle zone variant exhibits the clinical attributes of a low-grade lymphoma; and (3) the poor survival rates of patients with nodular and diffuse MCL suggest that these variants be classified as intermediate-grade lymphomas. However, the trend of the time to treatment failure curve does not indicate that current regimens can cure MCL.

Adult↗
PubMed1997

Phase I study of fludarabine and paclitaxel for the treatment of low-grade non-Hodgkin's lymphoma.

We conducted a phase I clinical trial of a new combination of fludarabine and paclitaxel in which 19 patients with histologically confirmed recurrent low-grade non-Hodgkin's lymphoma (NHL) were treated at five dose levels. Fludarabine was administered intravenously by bolus for 5 days and paclitaxel was given by intravenous (I.V.) continuous infusion for 96 or 72 hours starting day 1. Courses were repeated every 4 weeks. Patients whose disease responded received a maximum of six courses. All 19 patients received at least one course and could be evaluated for toxic effects, and 18 patients could be evaluated for response. The maximum tolerated dose (MTD) was 20 mg/m2/day I.V. bolus for 5 days of fludarabine plus 60 mg/m2/day I.V. of paclitaxel given as a continuous infusion over 72 hours. The limiting toxic effect was neutropenic fever, which was observed in five of the seven patients treated at the highest dose level. Grade 3 non-hematologic toxic effects of stomatitis (14%), neuropathy (14%), and hypotension (14%) were also observed at the highest dose level. No grade 4 non-hematologic toxic effects or treatment-related deaths occurred. One patient had herpes zoster infection of the skin 1 year after the completion of therapy. The overall response rate was 50%, with the two patients whose disease completely responded remaining disease free at 22 and 17 months. Patients with no prior exposure to either paclitaxel or fludarabine had 62% response rate. We conclude that the combination of fludarabine and paclitaxel appears to have promising activity for the treatment of recurrent low-grade NHL.

Adult↗
PubMed1997

Paclitaxel (Taxol) for the treatment of lymphoma.

Paclitaxel (Taxol) was recently tested in patients with relapsed and refractory lymphoma in two phase II clinical trials using two different infusion schedules. The first, reported from the NCI (USA), used a 96-hour intravenous continuous infusion schedule, and the second, from our group, used a 3-hour infusion. In the NCI trial, 29 evaluable patients were treated with 140 mg/m2 every three weeks, which achieved a 17% response rate (all PRs); while we treated 96 evaluable patients with 200 mg/m/ every three weeks, which achieved a 25% response rate (10 CRs and 14 PRs, 95% CI: 17%-35%). In our trial, patients with relapsed (not primary refractory) intermediate-grade lymphoma had a response rate of 50%, and those with relapsed low-grade lymphoma had a response rate of 31%. In a follow-up trial, 12 patients who failed to respond to 3-hour infusion of paclitaxel were crossed over to receive paclitaxel by 96-hour infusion. None of the 12 evaluable patients achieved a major clinical response. Similarly, of 25 patients treated with cyclosporine A and paclitaxel after failing therapy with single-agent paclitaxel, only one patient (4%) responded. We conclude that paclitaxel has a promising single-agent activity, most prominently in patients with relapsed intermediate-grade lymphoma. Paclitaxel-based combination programs are currently being evaluated in our institution.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Organisation of the cerebellar nucleus of the dogfish, Scyliorhinus canicula L.: a light microscopic, immunocytochemical, and ultrastructural study.

Elasmobranchs possess a well-developed cerebellum with an associated cerebellar nucleus. To determine whether the organization of this nucleus is comparable with that of the deep cerebellar nuclei of mammals, we studied the dogfish cerebellar nucleus with light microscopic methods (Nissl stain, Golgi method, reduced silver stain, NADPH-diaphorase histochemistry and immunocytochemistry) and with electron microscopy. We found the dogfish cerebellar nucleus to consist of about 1,050 large neurons, the ratio of Purkinje cells to cerebellar nucleus neurons being about 17:1. Immunocytochemistry showed large glutamatergic neurons in the main portions of the nucleus and small glutamate- and/or alpha-aminobutyric acid (GABA)-immunoreactive cells in the subventricular region of the nucleus. Large glutamatergic neurons corresponded to bipolar or triangular cells revealed by Golgi methods. Application of horseradish peroxidase to the cerebellar cortex produced the labelling of beaded fibres of Purkinje cells in the cerebellar nucleus. Unlike in mammals, GABAergic innervation of the cerebellar nucleus was scare: Purkinje cell axon terminals in the cerebellar nucleus did not appear to be GABA-immunoreactive, most GABAergic fibres being found in the subventricular neuropile. Some fibres immunoreactive to serotonin and somatostatin were also observed in the subventricular neuropile of the cerebellar nucleus. Three neuron types were distinguished with electron microscopy (types A to C). Type A cells were abundant and smooth-surfaced, and appeared to correspond to Golgi-impregnated neurons and large glutamate-immunoreactive cells. Type B neurons were scarce and possessed dendrites covered by sessile or stalked spines. Type C neurons were small cells located mainly in the medialmost region of the nucleus and corresponded to subventricular glutamate- and GABA-immunoreactive cells. Six types of synaptic bouton were observed (types I to VI). The most abundant (type I boutons) made symmetrical contacts and appeared to correspond to Purkinje cell axons. Type I boutons were the only type observed on perikarya and initial axon segments of type A cells. Type IV and type V boutons made complex glomerular-like asymmetrical contacts with spines of type B cells. Type VI boutons appeared to correspond to peptidergic and/or monoaminergic axons. The functional significance of these results is discussed.

Animals↗
PubMed1996

NADPH-diaphorase histochemistry reveals oligodendrocytes in the rainbow trout (teleosts).

We studied the distribution of NADPH-diaphorase (NADPHd) in the brain of the rainbow trout. Not only neurons but also tanycytes and oligodendrocytes showed NADPHd positivity. Interestingly, staining of oligodendrocytes was delicate and revealed fine characteristics of these cells, comparable to those revealed by classical 'oligodendrocyte methods' in mammals (such as the rich branching of processes and their association with myelin sheaths). NADPHd histochemistry indicated that trout oligodendrocytes are heterogeneous as regards cell size, shape and number of processes, and that there is a positive correlation between the size of axons and that of the associated oligodendrocytes. NADPHd histochemistry thus appears to be a useful method for the study of oligodendrocyte populations in bony fishes. Furthermore, this is the first report of NADPHd activity in oligodendrocytes of any vertebrate.

Animals↗
PubMed1996

Breaking the silence. Battered women's perspectives on medical care.

OBJECTIVE: To determine the barriers to identification and management of domestic violence from the battered women's perspective. DESIGN: Qualitative research methods using semistructured focus groups. SETTING: Urban and suburban community-based organizations serving women and their families in the San Francisco Bay (Calif) area. PARTICIPANTS: Fifty-one women with histories of domestic violence comprised eight focus groups divided as follows: two groups of Latino (n=14), two groups of white (n=14), Asian (n=14), and two groups of African-American (n=9) women. RESULTS: Participants from all ethnic groups identified major factors that affect identification and management of battered women in the health care setting. Factors that interfere with patient disclosure included threats of violence from the partner, embarrassment, adherence to gender roles, concerns about police involvement and lack of trust in the health care provider. One factor that predisposed a woman to seek help from providers was a need for the providers to exhibit compassion, awareness, and respect for the patient's need to make the final decisions about her situation. Most participants said that providers should take the initiative to ask directly about domestic violence, establish a supportive patient-provider relationship, and refer battered women to available community resources. The major institutional barriers to using the health care system included the high cost of medical care and long waiting periods. CONCLUSIONS: Many battered women experience social, institutional, and provider barriers to obtaining help from the health care system for problems related to domestic violence. Providers as well as institutions can overcome these barriers through an understanding of the social context of domestic violence and the victim's needs. Identification may be improved through a trusting patient-provider relationship and by direct questioning about domestic violence.

Adolescent↗
PubMed1996

Mantle cell lymphomas.

MCLs are thought to arise from a subset of B cells that normally express the CD5 antigen and that reside in the mantle zone of secondary lymphoid follicles. Although expression of the CD5 antigen is also seen in small lymphocytic lymphoma and chronic lymphocytic leukemia, MCL differs from SLL/ CLL in several ways. Whereas trisomy of chromosome 12 is the hallmark cytogenetic abnormality of SLL/CLL, the translocation (11;14) (q13q32) is the most frequent karyotypic abnormality in MCL. The histologic pattern of MCL is most frequently diffuse. However, this lymphoma can grow in a unique pattern called 'mantle zone MCL,' indicating that the malignant cells expand the mantle of the follicle and grow around a normal germinal center. If the germinal center is also replaced by the malignant cells, but the follicular architecture remains, the pattern appears nodular. The clinical presentation of MCL is usually only seen with advanced disease stage, particularly in patients with diffuse MCL. The bone marrow is the most frequently affected extranodal site, followed by the gastrointestinal tract. The histologic pattern of disease in the lymph nodes correlates with clinical outcome. Patients with diffuse MCL have poor response to frontline combination chemotherapy including doxorubicin, whereas patients with mantle zone MCL have excellent complete remission rates. The therapeutic response correlates in turn with worse survival outcome for patients with diffuse MCL compared to mantle zone MCL. The few patients with nodular MCL had clinical behavior similar to diffuse MCL. The chemotherapeutic response of diffuse and nodular MCL, however, is quite poor, and we would propose that new investigational approaches be considered in the front-line therapy of these disorders.

Antibiotics, Antineoplastic↗
PubMed1996

A protein tyrosine kinase associated with the ATP-dependent inactivation of adipose diacylglycerol acyltransferase.

The activity that has been previously reported to reversibly inactivate adipose glycerolphosphate acyltransferase (GPAT) and diacylglycerol acyltransferase (DGAT) in vitro in the presence of ATP is shown here to be partially purified from adipose tissue with an apparent molecular weight of 68 kDa. The activity responsible for inactivating DGAT is associated with a kinase activity as determined by phosphate incorporation both into microsomal proteins and into a synthetic tyrosine-containing peptide as substrate for protein tyrosine kinase. Two microsomal polypeptides of 53 and 69 kDa are major substrates of this kinase. Both DGAT inactivating and kinase activities assayed from the purified sample have been found to be insensitive to the Ser/Thr kinase inhibitor H-7 while being sensitive to genistein and tyrphostin-25. A crude protein phosphatase preparation from liver was capable of reversing the effects of both activities. The purified sample was also shown to inactivate GPAT in the presence of ATP. These results suggest that a protein tyrosine kinase, in concert with a protein tyrosine phosphatase, may regulate the activities of DGAT and GPAT by a phosphorylation-dephosphorylation mechanism.

Acyltransferases↗