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Biomedical subjects

H Jaffe

Publications and source records attributed to H Jaffe.

At least 19 recordsLinked to original sources
PubMed1992

A high-molecular-weight squid neurofilament protein contains a lamin-like rod domain and a tail domain with Lys-Ser-Pro repeats.

Previous studies have shown that two low molecular-weight neurofilament (NF) proteins (NF-60 and NF-70) from the squid Loligo pealei are translated from mRNAs that are splice variants of a single squid NF gene. In this study, we report the isolation and characterization of cDNA clones encoding a high-molecular-weight squid NF protein (NF-220), the mRNA of which derives from the same squid NF gene. All three proteins are identical in their amino-terminal and lamin-like rod domains but differ in their carboxyl-terminal tail regions. In contrast to the short tail domains of NF-60 and NF-70, the NF-220 protein has a longer tail domain containing an acidic cluster of amino acids immediately followed by repeated copies of the sequence motif Lys-Ser-Pro. The Lys-Ser-Pro domain is similar to that of mammalian medium NF (NF-M) and high NF (NF-H) proteins, where the serines are highly phosphorylated. Except for these Lys-Ser-Pro motifs, there is surprisingly little structural similarity between the squid NF-220 protein and mammalian NF-M and NF-H proteins. Furthermore, the location of introns in squid NF-220 protein shows that it is more closely related to nuclear lamins and type III intermediate-filament proteins than to vertebrate NF proteins.

Amino Acid Sequence↗
PubMed1992

Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS.

The causal agent of Kaposi's sarcoma is unknown. That the disorder is ten times more common in homosexual or bisexual men with the acquired immunodeficiency syndrome (AIDS) than in other human immunodeficiency virus (HIV) transmission groups suggests that a certain aspect of their behaviour exposes them to the agent or facilitates its spread. We therefore assessed social and demographic characteristics, including sexual behaviour, of 65 homosexual or bisexual men with AIDS from London. Sexual practices in which there was contact with partner's faeces before AIDS developed were the main determinants of Kaposi's sarcoma risk. Risk increased with frequency of insertive "rimming" (oral-anal contact): Kaposi's sarcoma developed in 18% of the men with AIDS who reported never having practised insertive rimming compared with 50% who practised it less than once a month, 73% between once a week and once a month, and 75% or more once a week (two-sided exact p-value for trend less than 0.001). 45 men had been interviewed about their sexual practices before AIDS developed, and 20 were interviewed at the time the syndrome developed. The findings were similar and statistically significant when each group was analysed separately. The men with Kaposi's sarcoma also tended to be more sexually active and were more likely to engage in other sexual activities that entailed contact with faeces than were the men who had other features of AIDS only. Other behaviours and exposures, including the use of "poppers" (nitrite inhalants), were not related to Kaposi's sarcoma risk, after taking into account whether the subjects had practised insertive rimming. The data suggest that faecal-oral contact is the main route of transmission of the agent of Kaposi's sarcoma in homosexual or bisexual men with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Osteoclastic superoxide generation: taking control of bone resorption using modulators of superoxide concentrations.

We have examined the role of superoxide in bone resorption by stimulating defective superoxide production and bone resorption in patients with osteopetrosis and inhibiting superoxide production and bone resorption in murine calvarial explants. Interferon gamma treatment did stimulate superoxide generation and bone resorption in patients with osteopetrosis as evidenced by a reduction in bone volume and an increase in biochemical markers of bone resorption. Further, lowering the superoxide concentrations within calvarial osteoclasts using a scavenger, desferal manganese, decreased bone resorption. We conclude that superoxide generation by osteoclasts is necessary for normal osteoclastic function.

Animals↗
PubMed1991

AIDS-associated non-Hodgkin lymphoma.

Non-Hodgkin lymphoma is associated with HIV infection. We investigated the epidemiology and aetiology of AIDS-related non-Hodgkin lymphoma by analysing data from cases reported to the Centers for Disease Control, Atlanta, USA, up to June 30, 1989. During this period 97,258 AIDS cases were reported, of whom 2824 (2.9%) had non-Hodgkin lymphoma. The condition was about 60 times more common in AIDS patients than in the general US population. 1686 cases were immunoblastic lymphoma, 548 primary lymphoma of the brain, and 590 Burkitt's lymphoma, a condition which is not normally associated with immunosuppression. The proportion of AIDS patients with immunoblastic lymphoma increased from 0% in those under 1 year old to 3.5% in those aged 50 or more. Primary lymphoma of the brain was constant at 0.6% for all ages. The frequency of Burkitt's lymphoma increased from zero in infants to a peak at 10-19 years of age (1.8%). Each type of lymphoma was twice as common in whites as in blacks and in men as in women. Lymphoma was most common in patients with haemophilia or clotting disorders and least common in those born in the Caribbean or Africa who had acquired HIV by heterosexual contact. Epidemiological data suggested that whilst infectious agents (eg, Epstein-Barr virus) may be associated with development of non-Hodgkin lymphomas in AIDS patients there was probably no single cause for all the types of lymphoma. Perhaps the most puzzling question is why Burkitt's lymphoma is commonly associated with HIV infection but not with other types of immunosuppression.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Is risk of Kaposi's sarcoma in AIDS patients in Britain increased if sexual partners came from United States or Africa?

OBJECTIVE: To determine whether the risk of Kaposi's sarcoma in patients with AIDS is increased by sexual contact with groups from abroad with a high incidence of Kaposi's sarcoma. DESIGN: Analysis of risk of Kaposi's sarcoma in patients with AIDS, according to country of origin of their sexual partners. SETTING: United Kingdom. PATIENTS: 2830 patients with AIDS reported to the Communicable Disease Surveillance Centre and the Communicable Disease (Scotland) Unit up to March 1990, of whom 566 had Kaposi's sarcoma. MAIN OUTCOME MEASURES: Percentage of patients with AIDS who had Kaposi's sarcoma. RESULTS: 537 of 2291 homosexual or bisexual men (23%) with AIDS had Kaposi's sarcoma; 10% (14/135) of the men and women who acquired HIV by heterosexual contact had Kaposi's sarcoma. None of the 316 subjects who acquired HIV through non-sexual routes had Kaposi's sarcoma. Kaposi's sarcoma was more common among homosexual men whose likely source of infection included the United States (171/551, 31%) or Africa (9/34, 26%) than among those infected in the United Kingdom (119/625, 19%) (p less than 0.05). CONCLUSION: The data suggest that Kaposi's sarcoma is caused by a sexually transmissible agent which was introduced into the British homosexual population mainly from the United States [corrected].

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pharmacokinetics of peptide T in patients with acquired immunodeficiency syndrome (AIDS).

1. The pharmacokinetics of Dala1-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiency disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intravenous (i.v.) or intranasal (i.n.), via metered sprayer, administration. 2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearance rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA. 3. Bioavailability, determined for a 2 mg test dose in six individuals was 9.3 +/- 6.9 nmol/L. Peak plasma levels of 41 +/- 30 nmol/L after 10 mg i.n., 2.8 +/- 5.9 nmol/L after 2 mg i.n., and 0.13 +/- 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Phase I evaluation of recombinant tumor necrosis factor given in combination with recombinant interferon-gamma.

In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.) injection of IFN-gamma, followed 5 min later by an i.m. injection of TNF-alpha, each agent in different sites, every other day for ten doses over 20 days. Patients received 10, 50, or 100 micrograms/m2 of each agent throughout the treatment course. No dose modifications were made. Patients suffering serious toxicity had therapy stopped and were considered to be off-study. All patients experienced fatigue, and 36% spent over half their time in bed on treatment days. Fever and chills were nearly universal. Mild to moderate elevations in serum transaminase levels were noted in 44% of patients, and 44% developed transient microscopic hematuria. Although 81% of patients had anorexia, only 17% of patients lost more than 3 kg of body wt during the 3 weeks of therapy. Because two of three patients receiving 100 micrograms/m2 of both agents developed serious toxicity (one fever greater than 105 degrees F, one thrombocytopenia 43,000/mm3), the MTD was established to be 100 micrograms/m2 of IFN-gamma plus 50 micrograms/m2 of TNF-alpha. The use of aspirin did not significantly alter the toxic effects of the agents. One patient with melanoma had a mixed response and one patient with mesothelioma transiently cleared his ascites of malignant cells.

Adult↗
PubMed1990

Identification of a domain in cytochrome C that displaces [3H]TCP binding from rat brain membrane receptors: synthesis of beta-neuroprotectin.

1. A stereospecific radioreceptor binding assay for the phencyclidine analogue, [3H]TCP, was utilized to screen for inhibition of binding in extracts of rat brain. 2. Extracts were prepared from rat cerebral cortex and hippocampus by methods employing aqueous acid. The extracts were fractionated by reversed phase-HPLC (RP-HPLC) and tested for activity in the radioreceptor assay. Three zones of activity were detected. The middle zone was further purified by high performance-size exclusion chromatography (HP-SEC). 3. Size exclusion chromatography revealed a single zone of activity corresponding to mol. wts of ca 12,000-31,000 daltons. A fraction from this zone was digested with trypsin, and the resulting enzyme fragments, isolated by a combination of HP-SEC and RR-HPLC, were identified as fragments of rat cytochrome C. 4. Horse cytochrome C was digested with trypsin and the fragments were similarly purified on the basis of the [3H]TCP binding displacement assay. The fragments were sequenced and found to be trypsin cleavage products of a single largely invariant domain of the cytochrome C molecule: Lys-Lys-Lys-Asp-Glu-Arg-Ala-Asp-Leu-Ile-Ala-Tyr-Leu-Lys-Lys. 5. beta-neuroprotectin (D)-Ala-Asp-Leu-Ile-Ala-Tyr-Leu-NH2, inhibits [3H]TCP binding and provides protection against NMDA mediated neuronal cell death at low concentrations.

Amino Acid Sequence↗
PubMed1990

Isolation and identification of a peptide from rat brain which inhibits [3H]TCP binding.

1. A stereospecific radioreceptor binding assay for the phencyclidine analogue [3H]TCP was utilized to screen for inhibitors of binding in extracts of rat brain. 2. Extracts were prepared from rat cortex and hippocampus by methods employing aqueous acid or acidified methanol. Samples were fractionated by reversed phase-HPLC (RP-HPLC) and tested for activity in the radioreceptor assay. Three zones of activity were detected. The most active fraction was further purified by high performance-size exclusion chromatography. 3. Size exclusion chromatography revealed two zones of activity, corresponding to mol. wts of 4000-8000 Da and 1000-2000 Da. Final purification of the lower molecular weight material was achieved by RP-HPLC. 4. Two well-separated peaks were shown to be homogeneous. Their amino acid sequences were determined by automated Edman degradation and data base searching identified these two peaks as the undecapeptide Substance P and its oxidized counterpart (Substance P sulfoxide). 5. Comparative HPLC of synthetic Substance P, or its sulfoxide, as well as spectral analysis confirmed the identity of the isolated peptides. 6. Synthetic Substance P inhibits specific [3H]TCP binding in the radioreceptor assay.

Amino Acid Sequence↗
PubMed1989

Primary structure of two neuropeptide hormones with adipokinetic and hypotrehalosemic activity isolated from the corpora cardiaca of horse flies (Diptera).

The primary structures of two neuropeptides, Tabanus atratus adipokinetic hormone (Taa-AKH) and Tabanus atratus hypotrehalosemic hormone (Taa-HoTH), from the corpora cardiaca of horse flies (Diptera: Tabanidae) have been determined. Amino acid sequences of Taa-AKH (less than Glu-Leu-Thr-Phe-Thr-Pro-Gly-Trp-NH2) and Taa-HoTH (less than Glu-Leu-Thr-Phe-Thr-Pro-Gly-Trp-Gly-Tyr-NH2) (where less than Glu = pyroglutamic acid) were determined by automated gas-phase Edman degradation of the peptides deblocked by pyroglutamate aminopeptidase and by fast atom bombardment mass spectrometry. The hormones were synthesized, and the natural and synthetic peptides exhibited identical chromatographic, spectroscopic, and biological properties. When assayed in adult face fly males, Taa-AKH and Taa-HoTH demonstrated hyperlipemic activity, in addition, Taa-HoTH also demonstrated a significant hypotrehalosemic activity.

Amino Acid Sequence↗
PubMed1988

Isolation and primary structure of a neuropeptide hormone from Heliothis zea with hypertrehalosemic and adipokinetic activities.

A neuropeptide was isolated from the corpora cardiaca of the corn earworm moth Heliothis zea, and purified by sequential gradient elution in three reversed phase-high performance liquid chromatographic steps. The primary structure, pGlu-Leu-Thr-Phe-Ser-Ser-Gly-Trp-Gly-Asn-NH2 was determined by automated gas-phase Edman degradation of the peptide deblocked with pyroglutamate aminopeptidase, and confirmed by fast atom bombardment mass spectrometry. The hormone was synthesized and the natural and synthetic peptides had identical chromatographic and spectroscopic properties. Both natural and synthetic hormones caused the elevation of trehalose and lipid levels in the hemolymph of adult H. zea males.

Amino Acid Sequence↗